REUMADAGARNA 2014 - Svensk Reumatologisk Förening
ReumaBulletinen tidskrift för svensk reumatologisk förening • nummer 96 • 2/2014 REUMADAGARNA 2014 Program Abstracts Innehåll · 2/2014 ReumaBulletinen ReumaBulletinen är Svensk Reumatologisk Förenings tidskrift och utkommer med sju nummer per år Ansvarig utgivare Ralph Nisell Reumatologiska kliniken Karolinska Universitetssjh 171 76 Stockholm Tel 08-517 760 93 [email protected] Redaktör Tomas Bremell Reumatologi Sahlgrenska Universitetssjh Gröna Stråket 12 413 45 Göteborg Tel 031-342 33 78 [email protected] 3 Välkommen till Reumadagarna i Örebro 4 Reumatologkliniken vid Örebro universitetssjukhus 10Mötesprogram 14 Reumadagarna 2014 - Abstracts 48 Reumakalender Red.medlemmar Ido Leden [email protected] Bengt Lindell [email protected] Milad Rizk [email protected] Ioannis Parodis [email protected] Produktion Mediahuset i Göteborg AB Marieholmsgatan 10C 415 02 Göteborg www.mediahuset.se Tel 031-7071930 Annonser Dan Johansson [email protected] Olle Lundblad [email protected] Layout Eva-Lotta Emilsdotter [email protected] Tryck Åkessons Tryckeri AB Box 148 361 22 Emmaboda www.akessonstryck.se Distribution Distribueras som posttidning ISSN 2000-2246 (Print) ISSN 2001-8061 (Online) Utgivningsplan 2014 Nummer Manusstopp Utgivning Nr 1 RB Nr 2 RB Nr 3 RB Vetenskap Nr 4 RB Nr 5 RB Nr 6 RB Vetenskap Nr 7 RB 24 januari 7 februari 7 mars 22 april 1 september 30 september 10 november 28 februari 19 mars 16 april 28 maj 8 oktober 5 november 18 december Omslagsbild: Tidig bokskog Skäralid, Skåne Foto: Sven-Olov Ohlsson, Kristianstad www.svenskreumatologi.se ReumaBulletinen Nr 96 · 2/2014 1 Nationella ST-läkardagarna 2014 ST-läkardagarna kommer att äga rum måndag 19 maj från kl. 12.00 till tisdag 20 maj kl. 14.30 i Hotell Gamla Fängelset, Storgatan 62, Umeå Tema Infektioner – som orsak eller verkan Det blir intressanta föreläsningar av infektionsläkare, lungläkare, neurolog och reumatologer. Vi kommer också att diskutera patientfall och deltagare som så önskar är välkomna att anmäla fall för diskussion.Vi får också aktuell information av Svensk Reumatologisk Förenings (SRF:s) nya Yngreläkarrepresentant Yulia Stennikova. Kostnad: Hemmakliniken står för resekostnaden och anmälningsavgift. 500 SEK för medlem i SRF, 2000 SEK för ickeSRF-medlem. Anmälningsavgiften återbetalas ej vid sen avanmälan. Mer detaljerat schema och anmälningsblankett kommer som länk på SRF:s hemsida under februari månad. Välkomna till två givande dagar i Europas kulturhuvudstad 2014! Ewa Berglin ST-studierektor Reumatologiska kliniken Norrlands Universitetssjukhus [email protected] 070-286 45 49 2 ReumaBulletinen Nr 96 · 2/2014 Lotta Ljung Överläkare ORDFÖRANDE · Ralph Nisell Välkommen till Reumadagarna i Örebro (USÖ). Även SveReFo, FRS (reuma-sjuksköterskorna) och Reumatikerförbundet har parallella program under onsdagen och torsdagen. Vi tycker att agendan ser mycket spännande ut och vi hoppas på bra och givande Reumadagar 2014. Du är mycket välkommen, och hoppas vi ses i Örebro! Ska vi kalla vårt årliga reumatologiska möte som vi tidigare har benämnt ”Vårmötet” för ”Reumatologi-dagarna” eller något enklare för ”Reumadagarna”? Eller ska det rent av vara ”veckan” istället för ”dagarna”? D essa frågor ställde sig Svensk Reumatologisk Förenings (SRFs) styrelse för ett år sedan. Orsaken till namnbytet var två, dels ville vi markera att något nytt har hänt, dels infaller det framöver återkommande reumatologiska mötet i månadsskiftet augusti/september med start 2015. Specialnummer Detta nummer av Reumabulletinen, nr 2, är ett specialnummer och har helt fokus på Reumadagarna, som i år således hålls i Örebro den 1-4 april. Det är första gången vårt svenska reumatologi-möte pågår under fyra dagar. Att mötet nu har förlängts beror på att det vetenskapliga programmet har flyttats från Riksstämman till dessa Reumadagar. Detta innebär att reumatologiska abstracts och posters vilka tidigare år har presenterats i månadsskiftet november/december (Riksstämman) nu istället kommer med på detta möte. Notera dessutom att föreläsningar, För mer information var god se: www.reumadagarna2014.se Vår-reuma-hälsningar! ”Reumadagarna hålls i Örebro den 1-4 april” prisutdelningar, mm också har flyttats till Reumadagarna. Spännande agenda ”Reumadagarna 2014” arrangeras i samarbete med SRF och den Reumatologiska kliniken på Universitetssjukhuset i Örebro Ralph Nisell Ordf SRF Boel Mörck Vice ordf SRF Christopher Sjöwall Vetensk sekr SRF Marie Vallgårda Lokalt ansvarig Reumadagarna Sara Bucher Vchef Reumatologiska kliniken USÖ ReumaBulletinen Nr 96 · 2/2014 3 REUMATOLOGKLINIKEN I ÖREBRO · Eva Nordin Reumatologkliniken vid Örebro universitetssjukhus Vissa kallade henne modig, andra ifrågasatte hennes omdöme då hon som nybliven specialist tackade ja till att bli verksamhetschef för reumatologkliniken vid Örebro universitetssjukhus. Själv är Sara Bucher entusiastisk och väl medveten om de utmaningar hon står inför. Den 1-4 april är kliniken värd för Reumadagarna i Örebro. F rån tågstationen är det en rak promenadväg på ungefär en kvart till sjukhusets huvudentré. Det har gått cirka 14 år sedan det fick status som universitetssjukhus, och sedan våren 2011 bedrivs här utbildning av läkare i nära samarbete med Örebro universitet. För att möta de nya kraven på forskning och utbildning satsar Örebro läns landsting för fullt på nya byggnationer; ett nytt Campus håller att byggas, men det är bara en del i en större byggnadsförnyelse som syftar till att utveckla universitetssjukhuset. En arkitekttävling har också genomförts och flera förslag har tävlat om uppdraget att utforma ett nytt högspecialitetshus som ska rymma såväl öppen som slutenvård inom områden som ögon, öron-näsa-hals, käkkirurgi, plastikkirurgi, hud, handkirurgi och anestesi. – Det finns stora ambitioner från både sjukhusledningen och landstinget. Samtidigt inser jag också att det finns flera stora utmaningar för att klara de uppdrag som ryms inom ett universitetssjukhus, säger Sara Bucher. Uppförsbackarna är många. I slutet av januari publicerade Dagens Medicin en rankinglista över Sveriges bästa universitetssjukhus. Örebro hamnade på näst sista plats. I genomgången hade man tittat på parametrar som medicinsk kvalitet, vårdgaranti, patientenkäter, ekonomi, hygien, läget på akuten, vårdplatsläge. Man hade också utgått från registerdata från Öppna jämförelser, patientenkäter och mätningar av olika slag. – Vi behöver arbeta intensivt och målmedvetet de närmaste åren för att utvecklas till ett fullfjädrat universitetssjukhus. Om jag går till min egen verksamhet har Reumatologkliniken i Örebro varit en av Sveriges största kliniker, i dag är det en av landets minsta. Vi befinner oss också i en omfattande omorganisation, tre sjukhus ska slås ihop i en och samma förvaltning och myck- 4 ReumaBulletinen Nr 96 · 2/2014 et är ännu oklart kring hur den nya organisationen skall se ut. Det skapar osäkra förutsättningar för verksamheterna i det korta perspektivet. Helt klart är att vi inte kommer slås samman med andra specialiteter till en storklinik, säger Sara Bucher. Från specialist till verksamhetschef Det är måndag förmiddag på Reumatologkliniken. Sara har just kommit tillbaka efter en sportlovsvecka tillsammans med sin familj och har just den här dagen bakjour. Det dröjer inte länge förrän telefonen ringer och kollegor knackar på dörren för konsultation. På skrivbordet ligger boken ”Den kommunikativa chefen- en handbok om kommunikation för chefer i Örebro läns landsting”. På en stol vid fönstret vilar en oljemålning som föreställer ett nyfött barn framför ett sjukhus. Den är målad av Saras syster som är konstvetare och arbetar med konstutsmyckningar inom vården. – Jag är uppvuxen i en akademisk familj med stort kulturintresse. Det har präglat mig. Kulturen är en viktig del i den medmänskliga kommunikationen, och det finns mycket forskning som visar den betydelsefulla roll och den läkande kraft som konsten, musiken och litteraturen har. Det har bara gått cirka sju veckor sedan Sara Bucher tillträdde som verksamhetschef. Hon är 38 år och blev klar specialist i reumatologi i december förra året. Hon gjorde sin AT i Karlskrona och sökte sig till Örebro 2006 för att göra sin specialisttjänstgöring. Sara Bucher är född i Örebro och ville gärna arbeta på ett universitetssjukhus, men också komma tillbaka till hemstaden. Även Saras man gillar staden, han är utbildad planarkitekt och arbetar i Örebro kommun. Tillsammans har de två barn och gillar de fördelar som finns med att bo i en mindre stad än Stockholm. Vardagslivet är lite enklare; närheten till skola och arbete väger tungt. Varje morgon promenerar Sara till arbetet och får då en stund för sig själv. – Jag brukar stänga av mobilen och försöka vara närvarande i det som är, en slags mindfulnessövning innan arbetsdagen startar. Långsiktigt perspektiv Kliniken har sökt ny verksamhet under ett par års tid och i juni 2013 övergavs kravet på att sökande skulle vara specialist i Reu- matologi. I november stod det klart att Sara Bucher skulle ta över chefskapet. Men det var det inte en självklarhet att hon skulle söka tjänsten. Hennes ursprungliga plan var att arbeta som reumatolog några år för att bli en duktig kliniker, gärna med en möjlighet att också forska. – Jag satt med i klinikledningen när vi letade efter en ny verksamhetschef, men det växte inte kandidater på träd. När kravet på att vara specialist släpptes såg jag chansen och möjligheterna att arbeta med målet och visionen att utveckla Reumatologkliniken till en välfungerande universitetsklinik med akademisk höjd och med en god arbetsmiljö. Sara Bucher går mot strömmen. Ledarskapet i hälso- och sjukvården har länge betraktats som en ödesfråga. Undersökningar visar att det är svårt att hitta ledare i läkarkåren. Många läkare har valt läkaryrket för att de vill arbeta med patienter och/ eller forska, och prioriterar inte att axla ett Sara Bucher REUMATOLOGKLINIKEN I ÖREBRO · Eva Nordin Sara Bucher chefskap. På läkarutbildningen finns heller inte mycket om ledarskap som förbereder läkare för chefsrollen. – Jag är genuint intresserad av ledarskapsfrågor, hur man får människor att blomma och bli motiverade att prestera. På läkarutbildningen ansvarade jag för utbildningsfrågor, jag har också arbetat fackligt. – Mitt förordnande är på fyra år, men jag vill gärna stanna åtta år. Det är ett bra tidsperspektiv och det ger också en stabilitet och tydlighet, vilket är viktigt i den situation vi befinner oss i. Resan mot en universitetsklinik Reumatologiska kliniken i Örebro bildades 1966. Upptagningsområdet omfattar cirka 280 000 invånare. Kliniken som ansvarar för cirka 3 500 patienter (enstaka regionpatienter kommer från Värmland) har cirka 600 nybesök samt 2 800 återbesök per år. Kliniken uppfyller till stor del vårdgarantin för nybesök inom 60 dagar, men en otillfredsställande andel av återbesöken sker inom avtalad tid. Kliniken är i dag underdimensionerad. Läkargruppen består av sju specialister, varav en är disputerad och en är dubbelspecialist i företagshälsovård, samt två ST-läkare. Enligt Svensk Reumatologisk Förenings beräkningar skulle kliniken behöva 14 specialister för att klara sitt uppdrag. Kliniken ställs dessutom inför ytterligare en utmaning då fyra av de sju specialisterna är över 60 år och flera står inför pension. – En stor utmaning är att kunna säkra utbildningskvaliteten och behålla den kliniska kompetensen då flera av våra seniora och erfarna läkare inom en snar period kommer att sluta. Vi kommer att behöva rekrytera nio specialister. Jag har redan nu fått löfte om att nyanställa tre ST-läkare samt en specialist, och det är en bra början, säger Sara Bucher. En annan stor utmaning är att utveckla kliniken till en välfungerande universitetsklinik. Det saknas i dag forskning vid kliniken; den höga produktionen i kombination med underbemanning har gjort det svårt att frigöra tid och resurser för forskning. I dag når kliniken inte upp till kraven på en universitetsklinik när det gäller kvalitetsarbete och medicinsk vetenskap. Frågan är högt prioriterad, menar Sara Bucher. – En förutsättning för att lyckas med målet är att vi kan rekrytera flera läkare. Mina specialistläkare ansvarar för cirka 550 patienter, många fler än riksgenomsnittet. – Vi har just påbörjat resan mot att bli en riktig universitetsklinik med en kreativ forskningsmiljö och en vetenskaplig produktion. På sikt ser jag det som naturligt att klinik och forskning går hand i hand. Vi försöker nu identifiera viktiga forskningsområden och söker samarbeten med Örebro universitet för att skapa broar mellan klinik och akademi. Klinisk inflammationsforskning är ett prioriterat område för sjukhuset och finns i dag vid ett flertal kliniker inom exempelvis medicin, infektion, kardiologi, hud och urologi. På universitetssidan finns etablerad immunologisk forskning med fokus på inflammationsforskning. Sara Bucher vill gärna skapa ett brett forskningsnätverk av kliniker och institutioner där reumatologi är en viktig del av det framtida forskningssamarbetet. Sara Bucher inser att det kommer att krävas en stor målmedvetenhet, men också prestigelöshet. Det är många frågor och områden hon måste erövra, såväl inom sin egen organisation som inom landstinget. – Jag är relativt ung, nyfiken och analytiskt lagd. Men jag har ingen lång erfarenhet av varken klinisk reumatologi eller forskning. För mig handlar det om att vara nyfiken, men också om att våga be om hjälp. Jag har tillgång till en fantastisk mentor i min egen organisation, jag har också stöd i Svensk Reumatologisk Förening, som jag är en del av. Sedan finns det en starkt uttalad ambition i landstinget att man ska satsa på forskning. En tredje utmaning är att leverera bra beslutsunderlag till politiker och tjänstemän så att vården kan utvecklas på ett kvalitets- säkert sätt utifrån patienters behov. Landstinget i Örebro har tydligt markerat att de vill ta avstånd från New Public Management och i mycket större utsträckning satsa på kvalitetsindikatorer och värdebaserade ersättningar, menar Sara Bucher. – Det finns en bra viljeinriktning. Vi ligger bra till i Öppna jämförelser, men när det gäller nationella riktlinjer för rörelseorganens sjukdomar så återstår en hel del att göra vad gäller implementering. Jag ser riktlinjerna som ett bra verktyg och en möjlighet att uppnå de mål som tydligt finns uttryckta i riktlinjerna. Vill vara ett föredöme för yngre Trots ett tungt ansvar som verksamhetschef, har Sara Bucher varit mån om att få fortsätta arbeta kliniskt. Hon ansvarar för cirka 250 patienter och har mottagning ungefär en vecka i månaden. Var sjätte vecka är hon bakjour. Det är fantastiskt, menar hon, att arbeta inom en specialitet där landvinningarna inom forskning och behandling närmast kan betraktas som revolutionerande. Sara beskriver reumatologi som en intellektuell specialitet med stor humanism. Hon hoppas att hon som verksamhetschef ska kunna vara ett föredöme för yngre läkarstuderande och även inspirera fler att välja specialiteten. – Det finns fortfarande gamla föreställningar om att man som reumatolog jobbar med äldre och besvärliga människor som har ont. Men jag brukar säga att man får möjligheten att arbeta som Dr House. Man ställs ofta inför kliniskt knepiga frågeställningar som kräver breda och omfattande kunskaper, men också kreativitet och analytisk förmåga. Om några veckor står Reumatologiska kliniken som värd för Reumadagarna i Örebro. Även i år kommer Svenskt Reumaforum, Föreningen Reumasjuksköterskor samt Reumatikerförbundet att vara medarrangörer och hålla i ett eget program med fokus på patient, omvårdnad och rehabilitering. Vid sidan av det vetenskapliga programmet, kommer även ett symposium om pedagogik att hållas: ”Dagens pedagogiska utmaning: Allt ljus på den informerade patienten och den självständiga studenten?”. – Örebro universitet har en mycket dynamisk och modern syn på pedagogik. Vi är mycket aktiva att bygga och utveckla den verksamhetsförlagda delen av läkarutbildningen, och är av åsikten att det behövs mer fokus på pedagogik under läkarutbildningen. Till exempel är utbildning inom teamet, inklusive patienten, särskilt viktigt inom reumatologin. Därför arrangerar vi ett symposium med pedagogik, säger Sara Bucher. ReumaBulletinen Nr 96 · 2/2014 5 Fakta Reumatologkliniken vid Örebro universitetssjukhus Anställda Kliniken har 27 anställda varav 7 specialistläkare, samt 2 STläkare. Upptagningsområde Cirka 280 000 invånare. Enstaka regionpatienter kommer från Värmland (myosit och systemisk skleros samt enstaka second opinion). Slutenvård Bedrivs med fem platser för medicinsk utredning (varav två är sju-dygnsvård) samt tre för slutenvårdsrehabilitering och två som behandlingsplatser. Vid kliniken finns även dagvårdsrehabilitering. Varje vecka ges cirka drygt 40 infusionsbehandlingar. Poliklinisk verksamhet Vid mottagningen görs varje år cirka 3 500 läkarbesök, 800 sjuksköterskebesök samt 1300 besök till arbetsterapeuter och kuratorer. Här finns flera specialmottagningar och tidig artrit-mottagning. Det saknas i dagsläget en självständig sjuksköterskemottagning. Beredskap Verksamheten innehåller reumatologjour och beredskap dag- och kvällstid för specialister. Här finns även konsultverksamhet och telefonrådgivning. Mot slutet av specialisttjänstgöringen deltar de även i konsultverksamhet. Klinikens läkare deltar i medicinklinikens jourverksamhet med ett dag/kvällspass var tredje vecka. Kvalitetsgranskade Kliniken har genomgått flera SPUR-inspektioner, 1998 och 2007. I februari 2014 genomfördes den senaste inspektionen, rapporten är i skrivande stund inte publicerad. I Örebro bygger man för fullt. Ett nytt högspecialitetshus ska byggas och en arkitekttävling har utlysts. Här är en del av ett av förslagen från Centrum för vårdens arkitektur på Chalmers. Koordinator sökes till Svensk Reumatologisk Förenings kansli Svensk Reumatologisk Förening (SRF) söker en koordinator på heltidstjänst till vårt kansli med arbetsplatser både vid Reumatologkliniken Karolinska Universitetssjukhuset Solna och QRC (Kvalitetsregistercentrum) Solna. Din funktion blir att vara en kombination av kanslichef, administratör, projektledare och verksamhetsutvecklare. • Ge administrativt stöd till/föra protokoll för SRF styrelse, dess Registerråd samt arbetsgruppen ARTIS (Anti-Reumatisk Terapi I Sverige) • Sprida och popularisera resultat från forsknings- och utvecklingsarbete • Ansvara för dokumenthanteringssystem Du bör vara utåtriktad, service-minded, initiativrik, ha administrativ kompetens och vana av självständigt arbete. Mycket god samarbetsförmåga är ett krav. Forskningskompetens liksom tidigare erfarenhet av registerarbete är meriterande. Din ansökan skickas till SRF-ordförande Ralph Nisell ([email protected]), senast den 27 mars. Huvudsakliga arbetsuppgifter: • Vara kontaktperson för medlemmar, SRQ (Svensk Reumatologis Kvalitetsregister), företag och vid uppdragsforskning • Ansvara för utveckling och förbättring av hemsida och andra kontaktytor • Organisera och administrera SRFs nationella möten 1-2 gånger per år 6 ReumaBulletinen Nr 96 · 2/2014 Din arbetsgivare blir ”SRF Service AB”. Förutom CV skriv även ett kort personligt brev där det framkommer varför just du söker denna tjänst. Stor vikt läggs vid personlig lämplighet. Tillträde enligt överenskommelse. REUMATOLOGKLINIKEN I ÖREBRO · Eva Nordin Intervju med Maria Berglund Maria Berglund är ST-läkare i reumatologi och har haft en tjänst på kliniken i ett år. Hon tog sin läkarexamen i Danmark och gjorde sin AT i Örebro. Under den valfria klinikplaceringen valde hon Reumatologkliniken. Och där han hon stannat. S pecialiteten är spännande på många sätt tycker hon. – Jag gillar den delen som handlar om att utforska och vara nyfiken, det krävs en slags Sherlock Holmes förmåga för att bli en duktig kliniker, och det gillar jag. Det är också en specialitet där samspelet mellan läkare och patient är väldigt viktigt. Det finns i dag omfattande behandlingar, samti- digt är flera av dem förknippade med svåra biverkningar. Det gäller att vara lyhörd för patientens behov och sätta sig in i patientens perspektiv och de förväntningar som finns på behandlingsresultat. Hur ser du på kliniken idag och de möjligheter som finns för framtiden? – Jag kom till kliniken i ett läge då flera av de seniora specialisterna var på väg mot pensionsålder. Nu finns det än så länge resurser för att klara utbildningsbehovet, men fler läkare måste rekryteras och det är så klart ett orosmoment. Vilka styrkor ser du hos Sara Bucher? – Hon är driven och entusiastisk och har ett stort stöd hos vårdpersonalen. Jag upplever Sara som ambitiös, engagerad och lyhörd. Hon drivs av en stark vilja att skapa förändring och vidta förbättringsåtgärder. Det känns tryggt. Jag tror att hon kan åstadkomma något väldigt bra. I dag bedrivs ingen forskning vid kliniken, skulle du själv vilja forska om möjligheten fanns? – Sara försöker driva kliniken mot forskning och utveckling och det är väldigt bra. I dag är jag inte i så mycket kontakt med forskning, men det finns en önskan hos mig att det på sikt ska kunna ingå i min tjänst. Förutsättningen är dock att vi blir fler, i dag har vi en alltför hög arbetsbelastning för att också kunna klara av forskning. Hur vill du beskriva stämningen på kliniken? – Den är väldigt familjär. Det finns en stark positiv känsla på kliniken. Det är korta beslutsvägar och det finns en anda av att ”ingenting är omöjligt”. Vi arbetar nära varandra, på både mottagningen och vårdavdelningen. Det är högt i tak att pröva olika saker, diskutera och omvärdera och det värdesätter jag mycket. Maria Berglund ReumaBulletinen Nr 96 · 2/2014 7 SRF´s STYRELSE 2014 Ralph Nisell Ordförande Reumatologiska Kliniken Karolinska Universitetssjukhuset 171 76 Stockholm Tel 08-517 760 93 [email protected] Utrota barncancer. Boel Mörck Vice ordförande Reumatologiska kliniken SU/Sahlgrenska 413 45 Göteborg Tel 031-342 10 00 [email protected] Din gåva gör skillnad. Gerd-Marie Alenius Facklig sekreterare Reumatologiska Kliniken Västerbotten Norrlands Universitetssjukhus 901 85 Umeå Tel: 090-785 16 76 [email protected] Britt-Marie Nyhäll-Wåhlin Kassör Kliniken för reumatologi Falu lasarett 791 82 Falun Tel 023-49 27 22 [email protected] Christopher Sjöwall Vetenskaplig sekreterare Universitetsöverläkare IKE, avd f Reumatologi, Hälsouniversitetet 581 85 Linköping Tel: 010-1032416 [email protected] Ann Knight Utbildningsansvarig Verksamhetsområde Reumatologi Verksamhetsområde Hudoch Könssjukdomar Akademiska Sjukhuset 751 85 Uppsala Tel 018-611 92 29 [email protected] Yulia Stennikova Ledamot, representant för läkare under utbildning Östersunds sjukhus Östersunds rehabcentrum Remonthagen Reumatologmottagningen 831 83 Östersund Tel: 063-153000 [email protected] 6 BCF_plugg_115x297.indd ReumaBulletinen 3 Nr 96 · 2/2014 2013-04-26 10:33 REUMATOLOGKLINIKEN I ÖREBRO · Eva Nordin Intervju med Awat Jalal Awat Jalal tog sin läkarexamen i Irak. Han gjorde sin AT och ST i Norrköping och har en dubbelspecialistexamen i internmedicin och reumatologi. H an är överläkare och har arbetat på Reumatologiska kliniken i över 20 år. Då han började var kliniken välfungerande med god klinisk verksamhet och hade en god bemanning med erkänt duktiga kliniker. Hur ser du på kliniken idag och de möjligheter som finns för framtiden? – Vi har en självständig klinik med duktig och trevlig personal. Jag trivs bra på kliniken. Det är olyckligt att antalet läkare minskat under många år. Samtidigt växer vårt uppdrag, då har det tillkommit potenta antireumatiska mediciner som kräver läkarinsatser. Jag skulle nog säga att vi inte hunnit tillräckligt långt med vårt uppdrag. I dag klarar vi till exempel inte av att erbjuda våra patienter rimliga återbesökstider. Som läkare kan jag ofta känna mig otillräcklig och detta har konsekvenser för patienterna. Vi har fått en ny verksamhetschef och jag tror att det finns goda förutsättningar att vi ska kunna bli fler specialister, och då får vi också större möjligheter och mer tid att satsa på forskning och utveckling. Vilka styrkor ser du hos Sara Bucher? – Hon tillsattes på ett demokratiskt sätt. Samtliga fackföreningar har varit med i chefsrekryteringsprocessen och vi föreslog henne till sjukhusledningen. Sara Bucher har klara ledarförmågor, hon är tydlig och ärlig som person. Den mest akuta åtgärden är att rekrytera fler läkare. I dag har vi två läkare som redan har fyllt 65 år, och två seniora läkare som inom kort ska gå i pension. De ska ensam klara ett stort utbildningsbehov. Jag har stort förtroende för henne och att hon tillsammans med klinikens anställda ska klara de problem och utmaningar som vi brottas med. EVA NORDIN Awat Jalal Hjälp oss att rädda dig. Vi är en ideell förening utan bidrag från staten. Ditt stöd behövs för att vi ska kunna rädda liv till sjöss. Ge ett bidrag eller bli medlem på sjoraddning.se. Du kan också ringa 077-579 00 90. Dina pengar kommer fram! Vi har 90-konto och kontrolleras av Svensk Insamlingskontroll. ReumaBulletinen Nr 96 · 2/2014 9 MÖTESPROGRAM · Reumadagarna i Örebro Mötesprogram Time Tisdag 1 april 10:00-12:00 Tid för Grupper 12:00-13:00Registrering/Lunch 13:00-13:10Introduktion 13:10-14:10Introföreläsning Konsten att njuta av kemi Lokal: Hjalmar Bergman Ulf Ellervik Bengt Wahlin: Prediction of coronary artery calcification and relation to inflammation in rheumatoid arthritis: A fol- low-up study. Mitra Nadali: Transcriptional activity of adipose tissue may be an early marker of cardio- vascular risk in rheumatoid arthritis. Anders Bengtsson: Type I interferon-mediated decrease of serotonin synthesis in sys- temic lupus erythematosus – a possible relation to cardio- vascular disease? Anna Ighe: Application of the 2012 Systemic Lupus Internanational Collaborating Clinics Classification criteria on a regional Swedish systemic lupus erythematosus register. Nanna Svartz-föreläsning 2013 Lokal: Hjalmar Bergman Carol Langford, Cleveland Clinic, OH, Moderator: Anna Rudin Anna Tjärnlund: Progress report on the development of new classification criteria for adult and juvenile idiopathic inflammatory myopathies. 17:00-18:00 Nanna Svartz-föreläsning 2014 Lokal: Hjalmar Bergman teatern. Betty Diamond, Manhasset, NY Moderator: Christopher Sjöwall 18:00 Time Mingelkväll, konferenscentrum Lennart Jacobsson: Patients witn non-AS axial SPA and AS have similar prevalence and levels of patient reported out comes measures. Results from a population based study. 10:00-12:00 Postervandring abstracts/ fika 08:30- Utvalda abstract inom reumatologisk forskning Moderator: Agneta Zickert, Björn Löfström 14:10-14:30Kaffe/Te 14:30-16:00Värdarrangörssymposium Dagens pedagogiska utma- ning: Allt ljus på den infor- merade patienten och den självständiga studenten? Lokal: Hjalmar Bergman Moderator: Marie Vallgårda Marie Lidskog, Helen Setterud Elisabet Welin Henriksson Ulrika Bergsten 16:00-17:00 Onsdag 2 april 12:00-13:00Lunch 13:00-13:30 Pris och föredrag bästa abstracts 10:00 Pauline Raaschou: TNF in- hibitor therapy and risk of breast cancer recurrence in patients with rheumatoid arthritis – a nationwide cohort study. 13:30-14:15 Utdelning och föredrag Pfizers stora forskningsstipendium 15:00-16:30 10 Lotta Ljung: Good response on tumour necrosis factor inhibitors are associated with a decreased risk of acute coronary syndromes in patients with rheumatoid arthritis. ReumaBulletinen Nr 96 · 2/2014 14:15-15:00Kaffe/Te Speakers corner företag Axplock avhandlingar Niklas Hagberg, Uppsala Kristofer Andréasson, Lund Karin Hellgren, Stockholm Annelie Bilberg, Göteborg Emma Haglund, Lund 16:30-17:30 SRF föreningsmöte 19:00 Vårmötesmiddag St. Hotellet Time Torsdag 3 april 08:30-10:00Temasymposium Tyrosinkinas-hämmare Moderator: Anna Rudin Catharina Lindholm Ronald van Vollenhoven Johan Richter 10:00-10:30Kaffe/Te 10:30-12:00 Temasymposium PMR/TA Moderator: Ann Knight Elisabeth Nordborg Johan Fredén-Lindqvist, Augustinas Sakinis Carl Turesson 12:00-13:00Lunch 13:00-14:30Temasymposium Behandling vid SLE Moderator: Christopher Sjöwall Iva Gunnarsson Ioannis Parodis Anders Bengtsson 14:30-15:00Kaffe/Te Speakers corner företag 15:00-16:00 Utdelning och föredrag Pfizers stipendium för yngre forskare 2013 & 2014, Pfizers stipendium för samarbets- projekt, MSD Reumatologi stipendium samt Abbvies sti- pendium för yngre forskare 16:00-18:00 Tid för grupper 18:00 Guidning och middag Örebro slott Time Fredag 4 april 08:30-09:30 Interaktiva seminarier: Hyper IgG4-syndrom - i teori och praktik Moderator: Lilian Vasaitis Interaktiva seminarier: SLE - finns det en ”modern” behandling? Moderator: Lars Rönnblom 09:30-09:50Kaffe/Te MÖTESPROGRAM · Reumadagarna i Örebro 09:50-10:50 Interaktiva seminarier Nya biologiska terapier vad kan vi vänta oss? Moderator: Ronald van Vollenhoven Interaktiva seminarier Rituximab vid behandling av systemiska vaskuliter Moderator: Per Eriksson 10:50-11:00 Nästa punkt startar 11:00 11:00-12:00 Biosimilarer - vad är det och hur ska vi hantera dem? Helena Møllby, Ann Johnsson 12:00-12:30 Summering av mötet Värdarrangör 12:30-13:30Lunch 13:30-15:30 Studiebesök lokal klinik Parallellt program SveReFo, FRS, RF Time Onsdag 2 april 12:00-13:00Lunch Mathilda Björk, Petra Wagman 09:30-10:00 Kost vid reumatisk sjukdom Ann-Charlotte Elkan 10:00-10:30Kaffe/Te 10:30-11:00 Rök-avvänjning inom reumatologi Marie-Louise Karlsson 11:00-12:00 Avslutning arrangörerna 12:00-12:15 Avslutning arrangörerna 12:15-13:00Lunch Hitta till Conventum Olof Palmes Torg 1 · 702 22 Örebro, Sverige Med tåg Centralstationen ligger centralt och många av tågen stannar till vid Örebro Södra, en liten station som ligger endast tvåhundra meter från Conventum! Med bil WGS 84 (lat, lon): N 59° 16.098’, E 15° 12.490’ WGS 84 decimal (lat, lon): 59.26830, 15.20817 RT90: 6572079, 1465955 SWEREF99: 6569946, 511867 Med flyg Örebro har dagliga direktförbindelser med Malmö/Sturup och Köpenhamn/Kastrup. 13:00-13:30 Välkommen- arrangörerna Icke-farmakologiska åtgärder vid reumatisk sjukdom – vad säger Socialstyrelsens riktlinjer? Christina Opava 13:30-14:15Levnadsvanor Matthias Lidin 14:15-15:00Kaffe/Te Speakers corner företag 15:00-16:00Avhandlingar Personcentrerad vård i reu- matologisk omvårdnad Ingrid Larsson 16:30-18:00 SveReFo, FRS föreningsmöte 19:00Vårmötesmiddag Stora Hotellet Parallellt program SveReFo, FRS, RF Time Torsdag 3 april 08:30-09:30 Balans och viktiga aktiviteter i vardagen ReumaBulletinen Nr 96 · 2/2014 11 12 ReumaBulletinen Nr 96 · 2/2014 Folkets Hus, stockholm / 20–23 september 2014 Scandinavian Congress of Rheumatology Den 35:e Skandinaviska kongressen i reumatologi 20–23 sept 2014 i Stockholm Välkomna till den 35:e Skandinaviska kongressen i reumatologi som kommer att äga rum den 2023 september, 2014 i Folkets hus, City konferenscenter vid Norra Bantorget i centrala Stockholm. Som vi tidigare har meddelat kommer den skandinaviska kongressen 2014 att ha ett fokus på områden som är av gemensamt intresse i de skandinaviska länderna. Ett viktigt mål med kongressen 2014 är att ge unga forskare som arbetar med vetenskap inom reumatologi möjlighet att presentera sig och sin forskning. Ett annat viktigt mål är att lyfta fram tvärprofessionell forskning inom Skandinavien. Kongressen sker i samarrangemang mellan Scandinavian Society for Rheumatology, Svensk Reumatologisk Förening, Nordiskt Reumaråd som representerar de nordiska patientföreningarna, nordiska Health Professionals och barnläkare från Skandinavien. Det är nu möjligt att börja lägga in abstracts. Sista dagen att skicka in abstrakt är den 15 april, 2014. Nedan följer de områden som kommer att finnas med på programmet som vetenskapliga sessioner: • • • • • • • • • • • • • How to apply current knowledge comparing the effectiveness of treatments for rheumatic diseases Treatment strategies for RA- Today and tomorrow The pre-clinical and very early phases of RA: disease mechanisms and opportunities for prevention Pain in rheumatic diseases- clinical and molecular aspects Spondyloarthritis (ankylosing spondylitis and psoriatic arthritis) with modern management of psoriatic arthritis and ankylosing spondylitis Modern imaging – clinical and molecular Osteoarthritis – Molecular and Clinical aspects Fatigue and cognitive dysfunction in rheumatic diseases Life style factors and intervention in rheumatic diseases Modern anti-rheumatic treatment and current strategies for prevention of infections Immunological mechanisms and clinical phenotypes in inflammatory systemic diseases Autoinflammatory diseases Adolescent rheumatology Därutöver kommer vi att ha workshops kring olika teman och några s.k. keynote lectures, varav en om ANCA–associerad vaskulit, där professor David Jayne från Cambridge har tackat ja. Följ utvecklingen av programmet på www.scr2014.se Varmt välkomna! Ingrid LundbergRalph Nisell Scandinavian Society for RheumatologySvensk Reumatologisk Förening ReumaBulletinen Nr 96 · 2/2014 13 ABSTRACTS Reumadagarna 2014 - Abstracts Premiärdags! Välkommen till Reumadagarna i Örebro! I år är det premiär för vår nya mötesordning. Därför är det fantastiskt roligt att kunna konstatera att den vetenskapliga aktiviteten är fortsatt hög inom svensk reumatologi. De vetenskapliga bidragen har aldrig varit fler än i år (jämfört med tidigare Riksstämmor). Hela 95 stycken abstractbidrag har inkommit och accepterats för presentation under Reumadagarna. 83 av dessa inkom till SRF och har kvalitetsgranskats av SRFs professorskollegium, medan 12 granskats av FRS/SveReFo. Posters kommer att hänga uppe i Conventums foajé under hela onsdagen den 2 april. Mellan kl 10-12 kommer författarna finnas vid sina respektive posters. 8 bidrag har av SRFs professorskollegium utvalts för muntlig presentation, dessa framförs på morgonen samma dag i sal Tunnbindaren med start 08:30. På följande sidor finner Ni samtliga abstractbidrag. För några av bidragen visas endast titel, författare och hemvist. Detta är inte något redaktionellt misstag utan svarar mot ett önskemål från flera av forskarna. Genom att bidragen inte publiceras i sin helhet finns inga formella hinder för att de presenteras vid internationella möten som tidsmässigt ligger efter Reumadagarna. På detta sätt kan vi bjudas på nyheter innan de når större reumatologikretsar på t.ex. Eular eller ACR. Än en gång, varmt välkomna! Christopher Sjöwall, Vetenskaplig sekreterare ABSTRACTNUMMER: 1 1 Kvalitetsregister med kvalitet Lotta Ljung1,2, Johan Askling1 Institutionen för medicin, enheten för klinisk epidemiologi, Karolinska Institutet, Stockholm 2 Institutionen för folkhälsa och klinisk medicin/Reumatologi, Umeå Universitet, Umeå sponsdata ökade med i genomsnitt 14/år, men minskade procentuellt från 86 % 1999 till 62 % 2010. Individer som startade med ett icke-anti-TNF-preparat (5 %) hade tillgängliga EULAR-responsdata i lägre utsträckning (55 % jämfört med 71 % för anti-TNF), vilket endast delvis förklaras av en lägre registreringsgrad under senare år. 1 Täckningsgraden i Svensk Reumatologis Kvalitetsregister (SRQ) för förskriven TNF-hämmarbehandling vid reumatoid artrit (RA) har beräknats vara omkring 90 %. Syftet med denna undersökning var att ge en överblick över tillgängliga uppföljningsdata i registret. Metod Individer (n=19631) som påbörjat ett första biologiskt läkemedel 1999-2010 identifierades i SRQ. Vid RA-diagnos beräknades andelen där registreringen möjliggjorde beräkning av EULAR- respons (samtliga DAS 28-variabler registrerade vid start och vid besök efter 2-12 månader). Vid psoriasisartrit (PsoA), spondartrit (SpA) eller ankyloserande spondylit (AS) beräknades andelen med minst en aktivitetsvariabel (SR, 28-ledstatus, global VAS, läkarbedömning, DAS28 och/eller BASDAI) från behandlingsstart och vid uppföljning efter 2-12 månader. Konklusion Besöksregistreringarna i SRQ för patienter med en första bio-behandling håller en hög kvalitet. Bortfallet avseende uppföljningsdata förklaras delvis av avslutade behandlingar men huvudsakligen av ofullständiga registreringar eller saknade/oregistrerade besök. Om SRQ ska kunna användas för uppföljning av behandlingseffekt bör registreringsfrekvensen bibehållas på en hög nivå. ABSTRACTNUMMER: 2 2 Hur stor andel av alla patienter med reumatoidartrit som behandlas med biologiska eller ickebiologiska dmards idag täcks av SRQ? Kristin Waldenlind2, Hjalmar Wadström1, Martin Neovius1, Johan Askling1,2 Enheten för klinisk epidemiologi, Institutionen för medicin, Karolinska Institutet, Stockholm 2 Enheten för reumatologi, Institutionen för medicin, Karolinska Institutet, Stockholm 1 Resultat För individer med RA-diagnos (n=12037) fanns totalt 34649 registrerade besök under året efter behandlingsstart, varav 88 % med samtliga DAS28-variabler. Vid PsoA (n=2306) och AS (n=1485)/SpA (n=1305) noterades 6152 respektive 6986 besök, med minst en aktivitetsvariabel registrerad i nära 100 % av besöken. BASDAI-registrering vid SpA/AS ökade från 1 % 2004 till 40 % av besöken 2010. EULAR-responsdata vid RA fanns för 69 % och aktivitetsdata vid start och uppföljning vid PsoA och AS/SpA för 78 respektive 74 % av individerna. I 10-13 % hade behandlingen avslutats och data saknades. Registrering saknades eller var ofullständig för 12-18 %. Antalet individer med RA och tillgängliga EULAR-re- 14 ReumaBulletinen Nr 96 · 2/2014 Bakgrund Svensk reumatologis kvalitetsregister (SRQ) är unikt och har gett upphov till flertalet studier för främst biobehandlade patienter med reumatoid artrit (RA), där täckningsgraden har beräknats till 87%, medan täckningsgradsiffror för totala patientgruppen med RA har redovisats i öppna jämförelser. Här påvisas möjligheter och utmaningar med täckningsgradsberäkningar för patienter med RA i SRQ. ABSTRACTS Material och metod Via patientregistret och läkemedelsregistret definierades prevalent RA med aktiv anti-reumatisk behandling: individer ≥18 år, bosatta i Sverige 2012-12-31, ≥2 besök med RA-diagnos i öppenvårdsregistret varav ≥1 besök vid reumatologi/intern-medicinsk avdelning, och ≥1 uthämtning av DMARD under 2012. Individer som även haft diagnos AS/PsA/SpA/JIA exkluderades. Registeridentifierad incident RA definierades som individer ≥18 år med ett återbesök med RA-diagnos inom 1 år efter det första besöket, varav ≥1 besök vid reumatologi/internmedicinsk avdelning, samt ≥1 uthämtning av DMARD under 2012. Patienter med diagnoserna AS/PsA/SpA/JIA, samt patienter med uthämtning av DMARD >6 månader före det första besöket med RA, exkluderades. För vardera av dessa två patientgrupper (nämnarna), identifierades de som också fanns i SRQ (täljaren). Resultat 26,058 prevalenta DMARD-behandlade patienter (prevalens= 0.34%) identifierades från patientregistret under 2012, av vilka 19,501 (75%) var inkluderade i SRQ. Högst täckningsgrad (>90%) hade Dalarna, Östergötland, Gävleborg och Gotland, medan Västernorrland, Jönköping och Kronoberg hade de lägsta (<50%). Stockholm och Västra Götaland hade liknande täckningsgrad (≈80%), medan Skåne hade 60%. För incident DMARD-behandlad RA identifierades 2043 patienter (27 per 100,000) under 2011, varav 1507 var inkluderade i SRQ (74%), med en liknande variation för täckningsgrad över landsting som för prevalenta patienter. Patientregistret har använts med antagandet att alla patienter med diagnosen RA är korrekt, dock visar en preliminär valideringsstudie att 10% är felaktiga, vilket innebär att våra beräkningar bör ge en motsvarande underskattning av den sanna täckningsgraden. Slutsats Av aktivt behandlade prevalenta och incidenta patienter med RA, är minst tre fjärdedelar inkluderade i SRQ. ABSTRACTNUMMER: 3 3 Validitet av RA serostatus i Patientregistret och SRQ Thomas Frisell1, Karin Hellgren1,2, Camilla Bengtsson3, Johan Askling1,2 Enheten för Klinisk epidemiologi, Inst för Medicin, Solna, Karolinska Institutet 2 Reumatologienheten, Inst för Medicin, Solna, Karolinska Institutet 3 Institutet för Miljömedicin, Karolinska Institutet 1 Bakgrund Det finns ett ökande intresse för forskning som studerar likheter och skillnader mellan seropositiv och seronegativ RA avseende etiologiska faktorer, prognostiska markörer och behandlingssvar. Det är därför viktigt att bedöma i vilken utsträckning vi i storskaliga registerstudier kan särskilja dessa underformer från varandra. Material och metod Samtliga individer diagnosticerade med RA i det svenska Patientregistret (från 2001) länkades till diagnoser och reumatoid faktor (RF) i SRQ, samt till RF och antikroppar mot citrullinerade peptider (ACPA) uppmätt i fall-kontrollstudien EIRA. Serostatus kodades från patientregistrets diagnoser med två metoder. A: Patienten tilldelades den serostatus av vilken den fått flest diagnoser; B: Vi krävde 2+ diagnoser, varav minst en hos specialist i reumatologi eller internmedicin. Om patienten då uppfyllde kriterier för både seropositiv och seronegativ RA an- sågs den seropositiv. I EIRA mättes RF med nefelometri och ACPA med anti-CCP2 ELISA. Resultat Med metod A/B kunde 69151/60991 individer från Patientregistret kategoriseras som seropositiv eller seronegativ RA. Av de som även fanns i SRQ klassificerade metod A 89% korrekt som RF-positiva, jämfört med 82% för metod B. Motsvarande siffror för RFnegativa RA var 94% respektive 93%. RF-status i SRQ och i EIRA stämde överens till mer än 95%. RF-status och diagnos i SRQ stämde överens till 96%. För de som var RF-positiva enligt metod A/B och även fanns i EIRA var 83%/77% också ACPA-positiva, medan RF-negativa oftast var ACPA-negativa (80%/84%). Slutsats Metod A kunde klassificera fler patienter, och visade något bättre prediktivt värde än Metod B. Diagnos i SRQ överensstämmer väl med RF-status i såväl SRQ som i EIRA. RF och ACPA är tydligt korrelerade, men cirka 25 % av RF-negativa är ACPA-positiva och vice versa. Det är möjligt att göra en relativt korrekt klassificering av RF-status baserad på RA diagnos i Patientregistret, men om möjligt bör man använda information från SRQ och/eller kompletterande analyser. 4 ABSTRACTNUMMER: 4 En gemensam biobanksmodul kopplad till svensk reumatologisk valitetsregister Thomas Bergman1, Eva Baecklund4,5, Inger Gjertsson4,6, Solbritt Rantapää Dahlqvist2,4, Thomas Skogh4,7, Carl Turesson4,8, Johan Askling3,4 Karolinska Institutet, enheten för reumatologi, inst. för medicin 2 Norrlands Universitetssjukhhus, reumatologiska kliniken 3 Karolinska Universitetssjukhuset, reumatologiska kliniken 4 SRF arbetsgrupp för biobanker 5 Akademiska sjukhuset Uppsala, reumatologmottagningen 6 Sahlgrenska Universitetssjukhuset, reumatologiska kliniken 7 Linköpings Universitetssjukhus, reumatologiska kliniken 8 Skånes Universitetssjukhus, reumatologiska kliniken 1 Bakgrund Individualiserad terapi vid RA kräver kunskap om prediktorer för respons på behandling, liksom prediktorer för bieffekter av behandling. För att möjliggöra detta krävs därför inte bara tillgång till data från SRQ (tex respons) och eventuellt från andra register (tex bieffekter) utan också tillgång till information om serologiska och genetiska markörer. Vi tror därför att utvecklingen av kliniska behandlingsriktlinjer, och vår förståelse för sjukdomsprogress och förlopp vid RA, avsevärt kan förbättras genom att systematiskt samla in inte bara kliniska data utan även biobanksprov som möjliggör analys av genetik och serologi på våra patienter. Vårt syfte har därför varit att skapa en enkel, transparent, robust, och kostnadseffektiv storskalig biobanksmodul kopplad till svensk reumatologis kvalitetsregister (SRQ). Metoder De primära inklusionskriterierna i SRQ biobank är patienter som nyligen har insjuknat i RA och därför inkluderas i SRQ, samt befintliga RA patienter i SRQ vilka startat biologisk behandling efter 1 januari 2010. För att underlätta rekryteringen av patienter till biobanken har vi implementerat ett beslutsstöd, integrerat i SRQ, som påminner om att patienten kan tillfrågas att lämna fyra blodprov. Proven (två EDTA plasma rör, ett serumrör och ett helblodsrör för DNA extraktion) skickas till BBMRI.se biobank för bered- ReumaBulletinen Nr 96 · 2/2014 15 ABSTRACTS ning och långtidsförvaring i frysar. Resultat Reumatologkliniken på Karolinska Universitetssjukhuset påbörjade insamling av biobanksprov under senvåren 2013. Därefter har de åtta följande reumatologiska klinikerna och enheterna anslutit sig och samlar in prov till biobanken; Sahlgrenska, Eskilstuna, Farsta Lars Kanerud, Falun, Danderyds sjukhus, Kalmar, Karlskrona/Karlshamn och Akademiska sjukhuset Uppsala. Flera ytterligare kliniker planerar och förbereder biobanking via denna modul. Vid årsskiftet 2013/14 hade totalt 536 patienter lämnat prov via SRQ biobanksmodul. Med nuvarande takt beräknas 1000 patienter ha provtagits via denna modul någon gång under andra kvartalet 2014. Slutsats Arbetet med gemensam biobanksmodul har kommit igång och har hög potential för att ytterligare förbättra utbytet av SRQ. ABSTRACTNUMMER: 5 5 How good is the coverage and how accurate are data in the swedish biologics register (artis) Hjalmar Wadström, Jonas Eriksson, Martin Neovius, Johan Askling Enheten för klinisk epidemiologi, institutionen för medicin, Solna 2 Enheten för reumatologi, institutionen för medicin, Solna 1 Background The usefulness of biologics registers and the interpretation of results from analyses based on such data both hinge upon an understanding of the coverage of eligible patients, and on the accuracy and validity of the data entered. Sweden with its virtually complete national registers that can be linked together offers the possibility to compare clinical register data against a “gold standard”. The purpose of this study was to assess the coverage of the Swedish biologics register (ARTIS) across indications, and the accuracy of the registered information on biologics treatment. Methods Through cross-reference of ARTIS national heath registers on prescriptions (adalimumab and etanercept), outpatient visits, and death/residency during 2008-2010, we assessed: the coverage of ARTIS, per treatment indication, the validity of the registered start- and stop dates, ARTIS treatments with no dispensations, and the accuracy of the registered information on concomitant antirheumatic therapies. Results 3945 individuals with a spondylarthropathy and 8032 patients with rheumatoid arthritis had at least one adalimumab or etanercept prescription filled during the study period. Of these, 86% of those with spondyloarthropathies, and 95% of patients with rheumatoid arthritis were also found in ARTIS with the corresponding treatment. 95% of patients had filled their anti-TNF prescriptions between the ARTIS’ start and stop dates (allowing a 90-day window). 5% of patients had their first filling of their anti-TNF prescription >60 days prior to, and 4% >60 days after, the registered start date in ARTIS. 8% of patients had anti-TNF prescriptions filled >90 days after the registered stop date in ARTIS. Conclusions We observed a high coverage and accuracy of ARTIS data on biologics exposure, both for spondyloarthropathies and for rheumatoid 16 ReumaBulletinen Nr 96 · 2/2014 arthritis. The combination of data from clinical registers such as ARTIS with data from national health registers offers a high quality measurement of de facto treatment. ABSTRACTNUMMER: 6 6 The inhibitor therapy and risk of breast cancer recurrence in patients with rheumatoid arthritis - a nationwide cohort study Pauline Raaschou1,2,3, Thomas Frisell1,2,3, Johan Askling1,2,3 Karolinska Institutet 2 Institutionen för Medicin 3 Avd. för klinisk epidemiologi 1 Background Tumor necrosis factor (TNF) has diverse and incompletely understood effects in tumor biology. Cancer recurrence in RA-patients treated with TNF-inhibitors (TNFi) remains a clinically important, yet unresolved, concern. Based on limited evidence, most clinical guidelines advice against the use of TNFi in patients with a malignancy within five or ten years. We investigated the risk of breast cancer recurrence in RA-patients with a history of breast cancer starting treatment with TNFi. RA, breast cancer, and co-morbidity-related factors were taken into account. Material and methods Population-based matched cohort study based on prospectively recorded data in Sweden.120 TNFi-treated (1999-2010) and 120 matched biologics-naïve individuals with RA and a history of equally recent/distant breast cancer were followed through chart reviews for breast cancer recurrence, through 2011. Hazard ratios (HRs) for recurrence were calculated using Cox regression. Results The median time from breast cancer diagnosis until TNFi treatment/start of follow-up was 9.4 years. Discrete differences were noted in breast cancer characteristics and/or treatment, at time of breast cancer diagnosis. Mean follow-up was 4.9 years from TNFi start (4.6 years among biologics-naïve). Among the TNFi-treated, 9 developed a breast cancer recurrence (crude incidence rate 15/1000 person-years) during follow-up, compared to 9 among the matched biologics-naïve (16/1000 person-years). The corresponding HR was 0.8 (95% CI 0.3-2.1). Adjusting for the observed differences in breast cancer characteristics, the HR was 1.1 (95% CI 0.4-2.8). The HR for recurrence was similar among patients who started TNFi within five years, and more than five years, from their breast cancer diagnosis. Conclusions Among patients with RA and a history of breast cancer, those who started TNFi treatment did not experience more breast cancer recurrences than RA patients treated otherwise. The generalizability of our findings to women with a recent or a poor prognosis breast cancer remains unknown. Abstractnummer: 7 7 ARE PATIENTS WITH RHEUMATOID ARTHRITIS STILL AT AN INCREASED RISK OF TUBERCULOSIS AND WHAT IS THE ROLE OF BIOLOGICAL TREATMENTS? Elizabeth Arkema1, Jerker Jonsson2,3, Eva Baecklund4, Judith Bruchfeld3, Nils Feltelius5,6, Johan Askling1,6 ABSTRACTS Karolinska Institutet, Clinical Epidemiology Unit 2 Swedish Institute for Infectous Disease Control 3 Karolinska Institutet, Infectious Diseases Unit 4 Uppsala University, Unit of Rheumatology 5 Medical Products Agency 6 Karolinska Institutet, Rheumatology Unit. 1 Background The extent to which increased awareness and pre-treatment screening have reduced tuberculosis (TB) risk with biologicals is not clear. Our aim was to estimate the risk of TB in patients with rheumatoid arthritis (RA) both with and without exposure to biological therapy and to directly compare the risks between therapies. Methods Data from the Swedish National Population Registers, Tuberculosis Register and the Swedish Biologics Register were used to conduct a prospective population-based national cohort study (2002-2011). We estimated the rate of incident TB in the general population, and in a cohort of biological-naïve and biological-exposed patients diagnosed with RA. Cox models were used to estimate Hazard Ratios (HR) with particular attention to risks by calendar and follow-up time and individual biologics. Results Compared to the general population, RA patients not exposed to biologicals had a 4-fold increased risk of TB (HR 4.2; 95% CI 2.7 to 6.7), which did not decline over calendar time. In contrast, the rate of TB in the biological-exposed RA population decreased since 2002 compared to biological-naïve; from HR=8.0 (95%CI 3.4 to 18.9) in 2002-2006 to HR=2.4 (95%CI 0.9 to 6.1) in 2007-2011. The HRs for most recent exposure to adalimumab and infliximab compared to etanercept were 3.1 (95%CI 0.8 to 12.5) and 2.7 (95%CI 0.7, 10.9), respectively and the HR for etanercept compared to biological-naïve RA was 1.7 (95%CI 0.6 to 4.6). Conclusions In the past decade, the risk of TB has decreased among biological-exposed RA patients but remains higher than in biological-naïve RA patients. Most cases of TB in RA occur in biological-naïve RA patients underscoring the elevated risk also in these patients. Abstractnummer: 8 8 IS THERE AN ASSOCIATION BETWEEN RHEUMATOID ARTHRITIS, AMYOTROPHIC LATERAL SCLEROSIS AND TUMOR NECROSIS FACTOR INHIBITOR TREATMENT? Elizabeth Arkema, Tomas Olsson, Johan Askling Karolinska Institutet, Institutionen för klinisk neurovetenskap 2 Karolinska Institutet, Department of Medicine, Rheumatology Unit 3 Karolinska Institutet, Clinical Epidemiology Unit 1 Background A recent signal of an unusual number of cases of amyotrophic lateral sclerosis (ALS) was reported in patients with rheumatoid arthritis (RA) treated with tumor necrosis factor inhibitors (TNFi). Our objective was to investigate this signal using a national population-based cohort study design. Methods Patients with RA, exposure to TNFi and ALS diagnosis were identified using national Swedish registers from 2001 to 2011. General population comparators were selected from the national population register matched on age, sex and county to the RA population. We calculated crude and age- and sex-standardized incidence rates (IR) of ALS per 100,000 person-years using the overall RA population as the standard. Results Over 293,220 person-years of follow-up in the overall RA population, we observed 23 ALS cases (IR 7.8; 95%CI 5.0 to 11.8). Eighteen were TNFi-naïve and 5 were TNFi-exposed. The age- and sex-standardized IR for TNFi-naïve RA and TNFi-exposed RA was 7.1 (95%CI 4.2 to 11.5) and 7.8 (95%CI 2.5 to 41.1) per 100,000 person-years, respectively. The standardized IR in the general population was 8.6 (95%CI 7.1 to 10.3). Conclusion Incidence rates of ALS were similar in the TNFi-exposed and TNFi-naïve RA populations. We found no evidence that TNFi exposure is associated with an increased risk of ALS. 9 Abstractnummer: 9 LÄKEMEDELSÖVERLEVNAD VID METOT-REXATBEHANDLING UTAN UPPTRAPPNING Bakgrund Mellan 2006-2011 minskade praxis av upptrappning vid nyinsättning av metotrexat kraftigt i Falun. Vanligast blev att inleda behandling direkt med 20 mg per vecka. Syftet med studien var att kartlägga hur detta fallit ut avseende läkemedelsöverlevnad och sjukdomskontroll. Material och metod Från SRQ identifierades alla patienter som fick diagnos RA i Falun år 2006-2011 och fick metotrexat, N=281. Vid journalgenomgång registrerades ordinerad dos, DAS28 och ALAT vid metotrexat-start samt vid uppföljande 3 återbesök (åb1, åb2, åb3). Orsaker till eventuell dosminskning/utsättning registrerades. Data analyserades i JMP med ANOVA, chi-square, Wilcoxon och Tukey-KramerHSD. Resultat 141 patienter började med 20 mg metotrexat (“20mg-gruppen”), 53 patienter fick successivt stigande dos (“Upptrappningsgruppen”), 87 patienter började med <20 mg utan att det fanns avsikt att dosöka (“Lågdosgruppen”). Frånsett att lågdosgruppen var äldre fanns inga skillnader avseende ålder, kön, seropositivitet eller DAS28 vid baseline mellan grupperna. Medeluppföljningstiden vid åb1 var 96 dagar utan skillnad mellan grupperna. Medeluppföljningstid vid åb3 var 438 dagar, upptrappningsgruppen hade något kortare uppföljningstid vid åb3. 2006 inleddes 20% av metotrexatbehandlingarna med 20 mg utan upptrappning, 2011 var andelen 76%. Behandlingar som inleddes med upptrappning minskade från 45% till 3%. Vid åb3 var 33 metotrexatbehandlingar utsatta. Utsättning pga biverkningar/toxicitet var signifikant vanligast i upptrappningsgruppen, N=9 (15%). Motsvarande siffra i 20mg-gruppen var N=6 (4%) och i lågdosgruppen N=7 (8%). Utsättningsfrekvensen var stabil över tid och påverkades inte av vilket år behandlingen inletts. DAS28 vid åb1 var i 20mg-gruppen 2,62±1,34, lågdosgruppen 3,11±1,21, upptrappningsgruppen 3,10±1,16, skillnaden var signifikant till 20mg-gruppens fördel. Slutsats Att inleda metotrexatbehandling med 20 mg fungerade bra när behandlande läkare bedömt detta lämpligt, denna grupp uppnådde lägst DAS28 vid åb1. Utsättningar pga biverkningar/toxicitet var vanligast förekommande när man valt att ge metotrexat i upptrappning. ReumaBulletinen Nr 96 · 2/2014 17 ABSTRACTS Under perioden slutade man nästan helt praktisera upptrappning, men utsättningar pga intolerans/toxicitet ökade inte. Resultaten talar för att upptrappning inte skyddar mot utsättning pga biverkningar/toxicitet. Abstractnummer: 10 10 PREVIOUS BIOLOGICAL THERAPIES INFLUENCE DRUG SURVIVAL IN RHEUMATOID ARTHRITIS PATIENTS STARTING ABATACEPT TREATMENT 2006-2012. Saedis Saevarsdottir1, Leszek Stawiarz1, Carl Turesson2, Staffan Lindblad1 1 Karolinska Institutet 2 Lund University Background Abatacept (Orencia®) is a biological antirheumatic drug used in rheumatoid arthritis (RA). Our aim was to evaluate drug survival probability of abatacept in clinical practice, using the nationwide Swedish Rheumatology Quality registry (SRQ). Methods Observational data from the SRQ were collected for the period from April 1st, 2006 to June 30th, 2012. True retention rates and survival analysis (Kaplan Meier) with right censoring and logrank test of equality across strata were performed and Šidák multiple-comparison adjustments applied. Results 815 RA patients (637 females, 78.2%) started abatacept between April 2006 and June 2012 (77.5% of total 1051 patients treated with abatacept). The median (IQR) age at start of abatacept was 61 years (52-67) and the median duration of RA was 11.4 years (6.0-19.8). In patients with previous biological treatment, median time since first biological treatment to abatacept start was 3.4 years (IQR 2.4-7.9). Median follow-up on abatacept was 0.9 years (IQR 0.4-1.9). Abatacept was prescribed as the first biological in 12.1%, after one biological drug in 26.9%, and after two or more biologicals drugs in 61%. Bio-naïve patients had significantly better drug survival than patients with two or more previous biologicals (p=0.02). From 1 to 5 years, drug survival was respectively 72%, 55%, 49%, 49% and 49% in bio-naïve patients, 57%, 41%, 38%, 34% and 25% in those with 1 previous biological drugs and 57%, 41%, 32%, 28% and 24% in those with 2+ previous biologicals. A longer drug survival was found in men compared to women (p=0.0008). Conclusions In this nationwide cohort of RA patients starting abatacept treatment, drug survival time was longer for bionaïve patients compared to patients previously treated with ≥2 biological drugs. Furthermore, a gender difference in favour of men was seen. Abstractnummer: 11 11 DRUG SURVIVAL IN PATIENTS RECEIVING GOLIMUMAB TREATMENT 2010-2013. RESULTS FROM THE SWEDISH RHEUMATOLOGY QUALITY REGISTER. Saedis Saevarsdottir1, Michele Santacatterina1, Leszek Stawiarz1, Carl Turesson2, Helena Forsblad d’Elia3, Lennart Jacobsson3, Staffan Lindblad1 1 Karolinska Institutet 2 Lund University 3 University of Gothenburg 18 ReumaBulletinen Nr 96 · 2/2014 Background Golimumab (Simponi®) is a TNF inhibiting biological drug that was approved in Sweden in 2010 for the treatment of Rheumatoid Arthritis (RA), Psoriatic Arthritis (PsA) and Ankylosing Spondylitis (AS). In observational studies, the 24-month adhesion to therapy of TNF inhibitors in bio-naïve patients has ranged from 50-70%. The aim of the current study was to evaluate cumulative survival probability of golimumab in clinical practice for patient with RA, PsA, AS as well as other spondyloarthritidies (SpA). Methods Data were retrieved for all patients initiating golimumab treatment from 2010 until April 30th 2013 from the nationwide Swedish Rheumatology Quality register (SRQ). Survival analysis (Kaplan Meier) was performed with right censoring and log-rank test of equality across strata. Results Of 1681 patients initiating golimumab treatment during the study period, 678 (40%) had RA, 364 (22%) PsA, 240 (14%) AS, 194 (12%) SpA and 205 (12%) had other diagnoses. The proportions of women in RA/PsA/AS/SpA patient groups were 80%/50% /28%/52%, respectively; and their median age at baseline was 58/50/45/43 years. In patients with RA/PsA/AS/SpA, the proportions receiving golimumab as the first biological treatment were 47%/45%/41%/37%; and the proportions receiving concurrent diseasemodifying anti-rheumatic drugs (DMARDs) were 70%/58%/22%/38%. When stratified by previous exposure to biological treatment (0/12/3+ biologicals), the 24-month cumulative survival probability of golimumab in patients with RA was 56%/52%/32%, PsA 56%/51%/53%, AS 65%/57%/40% and SpA 60%/49%/47%. In RA, significant difference was observed between bio-naïve patients and those who had previously received 1+ biological drugs (p=0.0018), a similar trend was observed in AS patients (p=0.069), but not in PsA (p=0.6). Conclusion The 24-month adhesion rates to golimumab in clinical practice appear to be comparable to other TNF inhibitors, whereas further studies are necessary to evaluate the long term performance. Abstractnummer: 12 12 DIETARY IMPACT ON METHOTREXATE IN RHEUMATOID ARTHRITIS Cecilia Lourdudoss1, Alicja Wolk2, Camilla Bengtsson2, Lars Alfredsson2, Ronald van Vollenhoven1 1 MedS, Karolinska institutet 2 IMM, Karolinska institutet Abstractnummer: 13 13 Tät kontroll av RA gav hög andel patienter i remisSion Annika Teleman, Stefan Bergman 1 Axess Medica Spenshult Sjukhus 2 FoU Spenshult Bakgrund Täta kontroller, framför allt tidigt i sjukdomsförloppet, ger en möjlighet till förbättrad sjukdomskontroll vid RA. Syfte Att studera andelen patienter i remission vid 12 månader efter införandet av tät kontroll vid nydebuterad RA i vanlig klinisk praxis. ABSTRACTS Metod Klinisk studie inkluderande 65 patienter med nydebuterad RA på Spenshults reumatologiska mottagning. Läkarbesök varje månad under det första året. Registrering i Svensk Reumatologis Kvalitetsregister (SRQ). Läkemedelsbehandlingen utifrån Svensk Reumatologisk Förenings riktlinjer. Svullna leder injicerades. Sjukdomsaktivitet bedömdes med DAS28 (≤2,6 remission, ≤3,2 lågaktiv sjukdom och >5,1 högaktiv sjukdom). Resultat 38 patienter kunde följas upp vid 12 månader. Förutom bortfall på tre patienter hade övriga ännu inte uppnått 12 månaders behandling. För 95 % framgår att de uppfyller kriterier för RA (1987 och/ eller 2010). Vid inklusion var 29 % högaktiva, 49 % medelaktiva, 14 % lågaktiva och 6 % i remission. Vid 6 månader var 74 % i remission och ytterligare 8 % lågaktiva. Vid 12 månader var 74 % i remission och 16 % lågaktiva. DAS28 vid inklusion i medeltal 4,5 och vid 12 månader 2,0. Vid 12 månader behandlades 33 (87 %) med metotrexat varav 8 i kombination med DMARD och 3 i kombination med biologiskt läkemedel. Tre patienter behandlades med salazopyrin och 1 med antimalaria. 27 patienter hade prednisolon (2,5-7,5 mg). En patient hade ingen rapporterad behandling alls. Slutsats Täta kontroller gav i hög grad remisson eller låg sjukdomsaktivitet (74 resp 16 %) med ett ringa behov av biologiska läkemedel. Patienterna förbättrades som förväntat ganska snabbt och efter 6 månader kan kontrollerna troligen glesas ut, vilket vi numera gör på vår mottagning. Tät kontroll är en genomförbar behandlingsstrategi i vanlig klinisk praxis och kan bidra till en ökad adherence till behandlingen och i slutänden god inflammationskontroll. Abstractnummer: 14 14 TUMOUR NECROSIS FACTOR INHIBITORS AND THE RISK OF ACUTE CORONARY SYNDROME IN RHEUMATOID ARTHRITIS – A NATIONAL COHORT STUDY Lotta Ljung1,2, Johan Askling1, Solbritt Rantapää-Dahlqvist2, Lennart Jacobsson3 Institutionen för medicin, enhet för klinisk epidemiologi, Karolinska Institutet, Stockholm 2 Institutionen för folkhälsa och klinisk medicin/reumatologi, Umeå Universitet, Umeå 3 Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning, Sahlgrenska Academin, Göteborgs Universitet, Göteborg 1 Background The objective of the study was to evaluate the risk of acute coronary syndromes (ACS) in patients treated with tumour necrosis factor inhibitors (TNFi) for rheumatoid arthritis (RA) compared with the risk in bio-naïve RA patients and in the general population. Methods From the underlying national cohort of all individuals with two or more outpatient diagnoses of RA we identified: 1) A cohort of patients with RA starting their first TNFi 2001-2010 as registered in the Swedish Biologics Register (n=7,704, mean age 57.1 years, 75.9% women) and 2) A matched bio-naïve RA comparator (3:1, n=23,112). Furthermore, a matched comparator cohort (5:1, n=38,520) was randomly selected from the Population Register. The outcome, incident ACS, was defined as a primary discharge diagnosis of myocardial infarction, or unstable angina, or myocardial infarction as the underlying cause of death. Using three defined exposure windows, incidence rates were calculated and relative risks analysed using Cox Proportional Hazards Regression models. Results Among patients ever exposed to TNFi 221 ACS were identified (crude incidence rate 6.8 (5.9-7.7)/1,000 person-years). The fully adjusted hazard ratios, HR (95%CI), for ever TNFi exposed compared with bio-naïve RA patients were 0.82 (0.70-0.95), comparing bio-naïve RA with the general population 2.03 (1.80-2.29), and for the TNFi cohort compared with the general population 1.61 (1.361.92) for the risk of ACS. Similar risk patterns were observed also when the risk window was limited to time on treatment or the first two years of treatment. Conclusion Treatment with TNFi was associated with a lower risk of ACS in patients with RA. Compared with the general population the risk of ACS in RA was increased, although less pronounced among the TNFi exposed patients. This could be attributable to the TNFi per se, or correspond to a higher degree of inflammatory control in the treatment group. Abstractnummer: 15 15 GOOD RESPONSE ON TUMOUR NECROSIS FACTOR INHIBITORS ARE ASSOCIATED WITH A DECREASED RISK OF ACUTE CORONARY SYNDROMES IN PATIENTS WITH RHEUMATOID ARTHRITIS Lotta Ljung1,2, Lennart Jacobsson3, Solbritt Rantapää-Dahlqvist2, Johan Askling1 Institutionen för medicin, enheten för klinisk epidemiologi, Karolinska Institutet, Stockholm 2 Institutionen för folkhälsa och klinisk medicin, Umeå Universitet, Umeå 3 Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning, Sahlgrenska akademin, Göteborgs Universitet, Göteborg 1 Background Inflammatory activity, as well as traditional cardiovascular risk factors, has been suggested to underlie the increased risk of coronary disease in patients with rheumatoid arthritis (RA). We therefore wanted to evaluate whether level of response to tumour necrosis factor inhibitors (TNFi) in RA are associated with the risk of acute coronary syndrome (ACS). Methods All patients with RA and no previous ischemic heart disease who started treatment with a first TNFi 2001-2010 as registered in the Swedish Biologics Register were identified. Of the patients (n=6,615) at risk for the exposure, i.e. EULAR response at 5+/-3 months, response data was available for 75% (n=4,938). For each patient 5 matched referents were randomly selected from the Population Register. Follow-up was maximized to 1 and 2 years, respectively. The outcome, incident ACS, was defined as a primary discharge diagnosis of myocardial infarction or unstable angina, or myocardial infarction as the underlying cause of death. Incidence rates were calculated and adjusted Cox Proportional Hazard Regression models were utilized for risk estimations. Results During the 1st year of follow-up 33 ACS occurred among the patients. The risk (HR 95%CI) of ACS for good responders compared with none responders, fully adjusted, was 0.26 (0.08-0.83), and for moderate responders compared with none responders 0.81 (0.36- ReumaBulletinen Nr 96 · 2/2014 19 ABSTRACTS 1.79). Compared with the general population no increase in the risk of ACS was observed among good responders, HR 0.74 (0.27-2.06). The lower risk of ACS among good responders was noted also during 2 years of follow-up. Conclusion Good EULAR response after 5 months of treatment with TNFi in RA patients was associated with a significantly decreased risk of ACS. In patients with good response on therapy no significant increase in the risk of ACS was detectable in comparison with the risk in general population during the 2 years after the evaluation. Abstractnummer: 16 16 Rheumatoid Arthritis, a more severe disease than Psoriatic Arthritis? A comparison of diseAse activity in patients with Psoriatic Arthritis and Rheumatoid Arthritis from the Swedish Early Psoriatic Arthritis registry (SwePsA) and the Swedish Rheumatology Quality Registry for early RA (SRQ). Gerd-Marie Alenius1, Tomas Husmark2, Elke Theander3, Per Larsson4, Mats Geijer5, Annika Teleman6, Ulla Lindqvist7 Umeå University, Department of Public Health and Clincal Medicin, Rheumatology, Umeå 2 Falu Hospital, Department of Rheumatology, Falun 3 Skåne University Hospital, Lund University, Department of Rheumatology, Malmö 4 Karolinska University Hospital Huddinge, Department of Rheumatology, Stockholm 5 Skåne University Hospital, Lund, Center for Medical Imaging and Physiology, Lund 6 Spenshult AB , Oskarström 7 Uppsala University, Department of Medical Sciences, Rheumatology, Uppsala 1 Objectives To compare the disease activity between psoriatic arthritis (PsA) and rheumatoid arthritis (RA) in patients with early disease, and at five year follow-up. Methods 208 PsA patients included in SwePsA were compared with 381 RA patients included in SRQ. The patients were matched (1:1-2) for age, gender, year of inclusion in the registries and region of residence. Inflammatory parameters such a DAS28, its components, CRP, HAQ, pain VAS and treatment, were measured at inclusion and at 5 year follow-up. Single and multiple regression analyses were performed and the stratified proportional hazards model has been used to model the 1-2 or 1-1 matching designs depending on the number of controls available for a case. Results At inclusion, patients with RA had higher DAS28, ESR, CRP, HAQ, tender joint count (p<0.001, respectively), swollen joint count (p=0.009), painVAS (p=0.003) and patient globalVAS (p=0.008) compared to patients with PsA. After 5 years all parameters had decreased. ESR was slightly higher in RA-patients (15.22 vs 12.36, p=0.046), while tender joint count now was higher in patients with PsA (3.58 vs 1.95, p< 0.000). DMARDs, steroids and biologics were less common among PsA-patients than RA-patients at inclusion ( 40.9 % vs 84.7%, 9.1 vs 39.6 and 0.5 vs 2.8% respectively), and at 5-year-follow up (46.2% vs 80%, 8.2% vs 18.7%, and 13% vs 37.7% respectively). Conclusion In this study, the disease activity at inclusion was higher in patients with RA compared to PsA. At 5-year-follow up the disease activity had decreased in both patient groups with significant differences 20 ReumaBulletinen Nr 96 · 2/2014 in only two of the parameters, ESR that was slightly higher in the RA-patients and TJC that was higher in the PsA-patients. The patients in the RA-group were more often aggressively treated with steroids, DMARDs and biologics indicating that RA may be a more severe disease. Abstractnummer: 17 17 VALIDITY OF ANKYLOSING SPONDYLITIS AND SPONDYLOARTHRITIS DIAGNOSES IN THE SWEDISH NATIONAL PATIENT REGISTER. U Lindström1, S Exarchou2, V Sigurdardottir3, B Sundström4, J Askling5, JK Eriksson5, H Forsblad-d’Elia1, C Turesson2, LE Kristensen2, L Jacobsson1 Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden 2 Section of Rheumatology, Department of Clinical Sciences, Malmö, Lund University, Malmö, Sweden 3 Department of Rheumatology, Falun hospital, Falun, Sweden 4 Department of Public Health and Clinical Medicine, Rheumatology, Umeå University, Umeå, Sweden 5 Clinical Epidemiology Unit, Rheumatology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden 1 Background Epidemiological studies of spondyloarthritis (SpA) are scarce. Using ICD-codes from the Swedish National Patient Register (NPR) offers unique possibilities for such studies. For this purpose, the validity of these ICD-codes needs to be determined. Objectives To validate the ICD-codes for ankylosing spondylitis (AS) and SpA in the NPR against established classification criteria (modified New York (mNY), ASAS, Amor and ESSG criteria). Methods All patients with an ICD-code of AS or SpA in the NPR 1966-2009 at a visit to a specialist in rheumatology or internal medicine, or corresponding hospitalization, were identified (n=20074). Following a structured procedure to achieve geographical representativeness, 500 random patients with a registered diagnosis of AS or SpA in 2007-2009 were selected. A structured review of clinical records, with extraction of necessary information for the established classification criteria was performed and positive predictive values (PPV) were calculated. Results In this cohort 11472 (34% women) patients had received an AS diagnosis and 11004 (56% women) a SpA diagnosis. The overlap group having received both types of diagnoses constituted 11% of the population, and had similar frequencies for fulfillment of mNY criteria, symptoms and signs of back disease as the group having been coded as AS only. Of those being coded as AS only, the PPV for fulfilling the mNY, any criteria set and any of the included criteria elements were 70%, 89% and 96% respectively. Of those with SpA (without AS ever) the corresponding PPV values were 20%, 79% and 99% respectively. Conclusion A diagnosis of AS or SpA (without AS) had a high validity, suggesting that case identification based on ICD-codes in the Swedish NPR can be used for epidemiological studies of these diseases. ABSTRACTS Abstractnummer: 18 18 Use of Biologics in Poly- and Dermatomyositis - A National Register Study John Svensson1, Anna Tjärnlund1, Maryam Dastmalchi1, Johan Askling1, Balsam Hanna2, Sara Magnusson Bucher3, Ingrid E Lundberg1 Karolinska Institutet Universitetssjukhus 1 2 Sahlgrenska Universitetssjukhus 3 Örebro Background/Purpose Biologics have been used off-label in treatment of refractory polymyositis (PM) and dermatomyositis (DM). In this study we aimed to describe the use of biologics in patients with PM and DM based on national registries in Sweden. Methods Patients were identified by linking the national patient care registers, the prescribed drug register, the Swedish Rheumatology Quality register (SRQ) and the Swedish Myositis Network (SWEMYONET). Effectiveness was based on an overall assessment of clinical outcome in the medical records, serum levels of creatine phosphokinase (CPK) and prednisolone dose. Results 63 patients treated with at least one biologic (36 PM, 27 DM, mean age 60 (12) years, 45 women, 18 men) were identified at 11 different centers between 2001 and 2011. Rituximab (Mabthera®) was the most often used biological agent: rituximab =42, abatacept (Orencia®)=13, anakinra (Kineret®)=15, TNF-inhibitors (infliximab (Remicade®), etanercept (Enbrel®)) =13 No new treatment with anakinra (ANA) had been started after 2009 and no new treatment with TNF-inhibitors (TNFi) had been started after 2003. In this population we found an overall favorable response to rituximab and abatacept in 2/3 of patients but less often to anakinra and TNF-inhibitors (1/3 and 1/5 respectively). A statistically significant decrease in CPK levels was found for RTX treated patients. All other changes in CPK and prednisolone dose was non-significant. Less than 15% of rituximab and abatacept treated patients stopped treatment due to side effect while being more common for TNFinhibitors (30%) and anakinra (45%). Conclusion We found an increasing use of RTX and ABA in patients with PM and DM. In this population, abatacept and rituximab was reported as favorable more often than anakinra and TNF-inhibitors. Abstractnummer: 19 19 Kontrollprovtagning vid metotrexatbehandling av RA patienter Johanna Karlsson Sundbaum1,2, Johan Back2, Niklas Lehto1, Irene Vikman1, Eva Baecklund2 Inst för Hälsovetenskap Luleå Tekniska Universitet 2 Inst för medicinska vetenskaper Uppsala universitet 1 Bakgrund Metotrexat (MTX) står för en stor del av den kontrollprovtagning med dithörande uppföljning och åtgärder som görs inom reumatologin. För att eventuellt kunna förbättra dessa rutiner ville vi undersöka förekomsten av stegrade ALAT-värden, patientkaraktäristika hos dem med och utan avvikelser, följsamhet till provtagningsruti- ner och vilka åtgärder labavvikelser leder till hos MTX-behandlade RA patienter på vår enhet. Metod RA patienter med MTX insatt jan 2005-april 2013 på reumatologen, Akademiska sjukhuset, Uppsala ingick i studien. Information om klinik och provtagning inhämtades från journal kompletterat med telefonenkät om alkoholintag och BMI. För jämförelser mellan grupperna användes oberoende T-test och chi2-test. Resultat Totalt 214 patienter ingick i studien. Medelbehandlingstiden med MTX var 225 veckor (8-456). ALAT-stegring (> övre referensvärde) sågs hos 85 (36 %) patienter efter i medel 82 veckor (1-379) vid en medeldos MTX på 15 mg (7,5–25). ALAT > 2x övre referensvärdet uppmättes hos 33 (39 %). Totalt avbröt 8 (9 %) behandlingen pga. ALAT-stegring. ALAT-stegring var signifikant kopplad till kvinnligt kön, högre BMI och tidigare känd ALAT-stegring. Följsamheten till provtagning var sämst under år 1,64 % av patienterna följde rutin, men bra under år 2 och 3 (90 % följde rutin). Efter förhöjt värde genomfördes ett antal åtgärder (uppehåll, sänkt dos, höjd Folacindos, utsättande av annat läkemedel, utredning) eller ingen åtgärd alls, utan struktur eller konsekvent koppling till uppmätt ALAT-värde. Konklusion Med dagens behandlingsregim är ALAT-stegring vanlig (36 %) men leder sällan till utsättning av MTX (9 %). Stor spridning i tid för ALAT-stegring motiverar långtidsuppföljning. Behov finns för strukturering av åtgärder efter avvikande labsvar. Ytterligare analys av detta material kan ge underlag för detta. Abstractnummer: 20 20 HIGH SERUM CHOLESTEROL PREDICTS RHEUMATOID ARTHRITIS IN WOMEN Carl Turesson1,2, Ulf Bergström1,2, Mitra Pikwer2,3, Jan-Åke Nilsson1,2, Lennart Jacobsson2,4 Reumatologiska kliniken, Skånes Universitetssjukhus 2 Sektionen för Reumatologi, Institutionen för Kliniska Vetenskaper, Malmö, Lunds Universitet 3 Reumatologkliniken, Mälarsjukhuset, Eskilstuna 4 Avdelningen för Reumatologi och Inflammationsforskning, Sahlgrenska Akademin, Göteborgs Universitet 1 Background Lipid metabolism and hormonal factors may contribute to the development of rheumatoid arthritis (RA). The purpose of this study was to examine sex-specific effects of serum cholesterol on the future risk of RA. Methods Between 1974 and 1992, 33346 subjects (22444 men and 10902 women) were included in the Malmö Preventive Medicine Program (MPMP). Serum cholesterol was assessed using fasting blood samples. Individuals who developed RA after inclusion in the MPMP were identified by linkage to several RA registers and a structured review of the medical records. Four controls for each validated case, matched for sex, year of birth and year of screening, who were alive and free of RA when the index person was diagnosed with RA, were selected from the MPMP register. The impact of serum cholesterol on the risk of RA was examined in conditional logistic regression models, stratified by sex. ReumaBulletinen Nr 96 · 2/2014 21 ABSTRACTS Results There were 290 incident cases of RA [151 men and 139 women; median time from inclusion to RA diagnosis 12 years (range 1-28); mean age at diagnosis 60 years . Cholesterol levels did not differ between men who subsequently developed RA and controls (mean 5.66 vs.5.64 mmol/l). By contrast, women with a diagnosis of RA during the follow-up had higher cholesterol levels at baseline compared to controls mean 6.04 vs. 5.71 mmol/l; OR 1.54 per standard deviation (95 % CI 1.22-1.94)]. The association between higher cholesterol and subsequent development of RA in women remained significant in multivariate analyses adjusted for smoking (p=0.001) or early menopause (at age <46 years) (p=0.01). Conclusions A higher serum cholesterol was associated with increased risk of RA in women, but not in men. This suggests that sexspecific exposures modify the impact of lipids on the risk of RA, and implicates early metabolic pathways in the etiology of RA. Abstractnummer: 21 21 Interaktion mellan saltintag och rökning ökar risken för reumatoid artrit Björn Sundström1, Ingegerd Johansson2, Solbritt RantapääDahlqvist1 Umeå Universitet, Inst. f. Folkhälsa och klinisk medicin/reumatologi 2 Umeå Universitet, Inst.f.Kariologi 1 Bakgrund Studier på mänskliga celler och djurmodeller har påvisat att natriumklorid kan initiera patogena Th17 celler genom ett saltkänsligt kinas (SGK1). Därför är det av intresse att studera huruvida natriumintag påverkar risken för att insjukna i reumatoid artrit (RA). Material och metod En nestlad fall-kontrollstudie genomfördes på basis av prospektiva data insamlade inom Västerbottensprojektet (VIP) mellan år 1991 och 2011. I studien ingick 386 fall som tidigare hade uppgivit sina kostvanor inom VIP före debut av första symtom på RA. Dessa jämfördes med 1886 matchade kontroller ifrån samma databas. Resultat Vid analys av alla fallen som homogen grupp sågs inga signifikanta samband mellan saltintag och risk för att utveckla RA. I analyser stratifierade för rökvanor (rökare och icke-rökare) vid tidpunkten för undersökningen så mer än fördubblade saltintaget risken att insjukna i RA bland rökare (OR = 2,26, 95% CI 1,06-4,81). Detta sågs inte hos icke-rökare. Vid interaktionsanalys av rökning och den tredjedel av fallen som hade högst saltintag sågs att 54% av den ökade risken för att utveckla RA kunde hänföras till en interaktion mellan rökning och saltintag (Attributable proportion of risk due to interaction, AP: 0,54 95% CI 0,26-0,82). Motsvarande överskjutande relativ risk av interaktion (RERI) var också signifikant (1.34, 95% CI 0.37-2.32). Dessa andelar av riskerna ökade ytterligare vid avgränsning av analyserna till de fall som var positiva för anti-CCP och/eller HLA-SE. Slutsats Ett högre saltintag bland rökare var associerat med en ökad risk för att utveckla RA. Denna interaktion mellan saltintag och rökning kan ge nya insikter i patogenesen för RA. Eftersom saltintaget i hög grad är korrelerat till konsumption av livsmedel som till exempel kött, frukt och grönsaker så kan dessa resultat även ha betydelse för 22 ReumaBulletinen Nr 96 · 2/2014 analyser av kostens betydelse för att utveckla RA. Abstractnummer: 22 22 Reduced sick leave in today’s early RA patients compared to 10 years ago, The Swedish TIRA project Mathilda Björk1, Thomas Skogh2, Magnus Husberg3, Ingrid Thyberg4 Rehabenheten, HMC, Universitetssjukhuset i Linköping, Landstinget i Östergötland 2 Avdelningen för reumatologi/AIR, IKE, Hälsouniversitetet i Linköping 3 CMT, Hälsouniversitetet i Linköping 4 Reumatologkliniken, HMC, Universitetssjukhuset i Linköping, Landstinget i Östergötland 1 Background Ten years ago rheumatoid arthritis (RA) was associated to extensive sick leave during the years after diagnosis despite early instituted disease modifying anti rheumatic drugs (DMARD:s). Since then the treatment strategies have undergone big changes and biological agents have been introduced. Objectives To compare sick leave in early RA today compared to10 years ago. Methods 320 patients were included in the Swedish early RA cohort (TIRA1) during 1996-1998 and 522 patients were included 2005-2008 in the TIRA2 cohort. The prescription of traditional DMARD:s was more frequent in TIRA2 already at inclusion but there were no differences in DAS28 between two cohorts that timepoint. The 120 patients (76% women) that were still participating in TIRA1 at 3-year follow-up and that were ≤ 64 years were included in the present study together with the corresponding 275 patients (74% women) in TIRA2. Sick leave data (sickness benefit and disability pension) were obtained for patients three years before until three years after inclusion (diagnosis). Results The proportion of patients on sick leave started to increase during the year before diagnosis to 40% in TIRA1 and 44% in TIRA2. During the year after diagnosis this number increased to 56% in TIRA1 and 50% in TIRA2. In TIRA2 the number decreased during the second (36%) and third year (30%), in contrast to TIRA1 where sick leave remained rather stable (54-52%). Conclusions The far lower sick leave rate seen today after a diagnosis of RA, compared to the situation 10 years ago, cannot be explained by differences in sick leave during the year before diagnosis. Although sick leave is lower today, the sick leave rate in TIRA2 is still high compared to the general population. This highlights a need to develop efficient multiprofessional intervention strategies in addition to modern anti-rheumatic pharmacotherapy regimens. Abstractnummer: 23 23 COMORBIDITY IN EARLY RHEUMATOID ARTHRITIS. DOES INFLAMMATION MATTER? Solveig Wållberg Jonsson, Lena Innala, Clara Sjöberg, Anna Södergren, Bozena Möller, Torgny Smedby, Staffan Magnusson, Solbritt Rantapää Dahqvist 1 Inst. för Folkhälsa och klinisk medicin/Reumatologi, Umeå Universitet, ABSTRACTS Umeå 2 Reumatologkliniken, Sunderby sjukhus, Luleå 3 Reumatologkliniken, Östersunds sjukhus 4 REumtologkliniken, Sundsvalls sjukhus Background Patients with rheumatoid arthritis (RA) suffer from comorbidities that contribute to a shortened lifespan. Inflammation is of importance for the development of cardiovascular disease, but little is known on its relationship with other comorbidities in RA. We examined the prevalence of comorbidities in early RA and the role of inflammation in this context. Material and methods All patients with early RA (symptom duration <12 months) in Northern Sweden are since 1995 included in a prospective study on co-morbidities. By now 950 patients have been included. At the time of this compilation, 715 patients were followed-up of whom 498 had been ill for ≥ 5 years. Data on comorbidities, disease activity, x-ray (hands/feet), laboratory samples (autoantibodies, inflammatory variables) and pharmacological therapy were collected in record studies and further validated using a questionnaire at RA onset (T0) and after 5 years of disease (T5). Results 53% had one or more comorbidities at RA onset. After 5 years, 41% developed at least one new comorbidity. At T0, the most common comorbidities were: hypertension (26.7%), obstructive pulmonary disease (13.4%), diabetes (7.1%), hypothyroidism (7.0%) and malignancy (5.2%). At T5, the most common new comorbidities were: hypertension (14.3%), malignancy (7.6%), stroke/TIA (5.0%), myocardial infarction (4.8%) and osteoporosis (4.4%). Univariate regression analyses showed that age (p< 0.001), ESR (p<0.01), extra-articular disease (p<0.01), corticosteroids (p<0.001) were associated with a new comorbidity during 5 years. Female gender and biologics reduced this risk (p<0.01 for both). In a multiple regression model adjusted for sex, age, corticosteroid treatment and smoking, ESR was associated with new endocrine disease during 5 years. Conclusion There was substantial comorbidity among RA patients already at disease onset and considerable new comorbidity during the first five years of disease. Measures of disease activity were associted with occurrence of comorbidity. Abstractnummer: 24 24 ASSOCIATIONS OF ANTIBODIES AGAINST CITRULLINATED PEPTIDES WITH HLA SHARED EPITOPE, PTPN22 1858T VARIANT, AND SMOKING IN INDIVIDUALS PRIOR TO THE DEVELOPMENT OF RHEUMATOID ARTHRITIS Heidi Kokkonen1, Mikael Brink1, Monika Hansson2, Linda Mathsson3, Ewa Lassen4, Johan Rönnelid3, Lars Klareskog2, Solbritt Rantapää Dahlqvist1 Institution of Public Health and Clinical Medicine/Rheumatology, Umeå University, Umeå 2 Rheumatology Unit, Karolinska University Hospital, Stockholm 3 Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala 4 Transfusional Medicin, University Hospital, Umeå. 1 Abstractnummer: 25 25 IgG anti-CCP SUBCLASS DISTRIBUTION AND ISOTYPE USAGE IN EARLY RHEUMATOID ARTHRITIS 1 Hälsouniversitetet Linköping, AIR / Reumatologi Introduction In this study we investigate patterns of IgG-subclass utilization regarding antibodies against cyclic citrullinated peptides (anti-CCP) among patients with rheumatoid arthritis (RA). The patients were sub-grouped based on smoking-habits, ‘shared epitope’ (SE) genotype and immunoglobulin (Ig)A anti-CCP status. Materials & Methods Serum samples were obtained from 498 patients with recent-onset RA (<12 months) at the time of inclusion in the Swedish TIRA-2 cohort (‘Early Intervention in Rheumatoid Arthritis’). IgG antiCCP subclasses were measured by enzyme-linked immunosorbent assay. Presence of the different IgG anti-CCP subclasses was then compared with smoking habits, SE genotype and IgA anti-CCP status. Results The proportions of patients testing positive for the respective IgG anti-CCP subclass (1-4) were: 72, 31, 43, 55%. The corresponding results among ever-smokers were: 74, 39, 49, 56%; never-smokers: 64, 25, 39, 46%; SE+: 82, 33, 49, 62%; SE−: 45, 18, 30, 34%; IgA antiCCP+: 100, 70, 86, 95%; IgA anti-CCP−: 62, 17, 27, 41%. No significant differences were seen between ever and never-smokers. The proportion of patients positive for IgG1, IgG3 and IgG4 anti-CCP were significantly higher among SE+ compared to SE−. The IgA anti-CCP+ subgroup showed significantly higher proportions of IgG1-4 anti-CCP as well as higher IgG subclass usage compared to the IgA anti-CCP− subgroup. Conclusion Our results indicate that smoking per se does not exert a significant impact on the IgG anti-CCP subclass repertoire. IgG2 anti-CCP was unaffected by SE whereas the other subclasses were, especially IgG1 and IgG4. IgA anti-CCP strongly associated with a wide IgG anti-CCP repertoire, reflected by the high isotype utilization. However, due to the relatively small study groups, additional studies on larger patient materials should be performed before definite conclusion can be made. Abstractnummer: 26 26 PREDICTIVE POTENTIAL OF SURVIVIN MEASURED IN UNSELECTED SERUM SAMPLES REFFERED TO THE CLINICAL IMMUNOLOGY LABORATORY FOR DETECTION OF RF AND/ OR ANTI-CCP ANTIBODIES – ONE YEAR EXPERIENCE FROM THE VÄSTRA GÖTALAND REGION Minna Turkkila1, Malin Erlandsson1, Rille Pullerits1, Maria Bokarewa1 Department of Rheumatology and Inflammation Research, Sahlgrenska University Hospital, University of Gothenburg 1 Abstractnummer: 27 27 Serum survivin in early rheumatoid arthritis – results from the SWEFOT trial Adrian Levitsky1, Malin Erlandsson2, Ronald van Vollenhoven1, Maria Bokarewa2 1 ClinTRID, Karolinska Institutet 2 Sahlgrenska University Hospital Anders Johansson1, Thomas Skogh1, Klara Martinsson1 ReumaBulletinen Nr 96 · 2/2014 23 ABSTRACTS Abstractnummer: 28 28 INTRACELLULAR SURVIVIN IS DECREASED IN CD4+ T-CELLS OF RHEUMATOID ARHTRITIS PATIENTS WITH HIGH SERUM SURVIVIN Nicola Filluelo Cavallini1, Minna Turkkila1, Mikael Brisslert1, Karin Andersson1, Maria Bokarewa1 Department of Rheumatology and Inflammation Research, University of Gothenburg 1 Background Survivin has recently emerged as a specific and sensitive biomarker in RA. We have recently shown that serum survivin (sS) is associated with severity of the disease and with joint destruction. Objective We studied intracellular expression of survivin on the peripheral T-cell populations and its relation to serum levels of survivin. Methods Serum and intracellular expression of survivin was analysed in 144 RA patients (age 21-71 years, disease duration 1-49 years) using ELISA and qPCR respectively. Patients were grouped according to sS levels (cut-off >0.45 ng/mL). In 18 RA patients the intracellular protein expression of survivin was studied on CD4+ and CD8+ T-cells using flow cytometry. Gating strategy defined Survivin+ or survivinhi populations, and also effector and memory T-cell populations. Results Intracellular mRNA levels of survivin were similar in sS- (n=68) and sS+ (n=76) patients. Intracellular survivin was present in 88 % CD4+ T-cells and in 85 % CD8+ T-cells. The survivinhi subset comprised 0.5-11 % of the T-cells and was enriched in the CD4+ effector (CD62Lneg) population compared to central memory and naïve CD4+ T-cells. Survivinhi cells are mostly found in CD4+ Tcells, which also have a significantly larger population than CD8+ T-cells. The survivin+ subset within the effector CD4+ T-cells was characterised by a selective expression of Bcl6, a transcriptional regulator of follicular T-cells. The survivin+CD4+ subset were smaller in sS+ patients compared to sS- patients, and were inversely correlated to sS levels of the patients. The sS+ patients had lower Bcl6 mRNA levels compared to sS- patients. Conclusions CD4+ effector T-cells are distinguished by the enhanced expression of survivin in RA patients. Patients with high serum levels of survivin had a smaller fraction of Surv+Bcl6+ effector T-cells, which may potentially indicate a cytolytic origin of the extracellular survivin. Abstractnummer: 29 29 SURVIVIN BUT NOT FMS-LIKE TYROSINE KINASE LIGAND (FLT3L) IS UP-REGULATED BEFORE ONSET OF RHEUMATOID ARTHRITIS Maria Bokarewa2, Mikael Brink1, Malin Erlandsson2, Solbritt Rantapää Dahlqvist1 Institutionen för Folkhälsa och Klinisk Medicin, Umeå Universitet 2 Avdelningen för reumatologi och inflammationsforskning, Göteborgs Universitet 1 Background Antibodies against citrullinated peptides (anti-CCP) and incre24 ReumaBulletinen Nr 96 · 2/2014 ased levels of cytokines precede the development of rheumatoid arthritis (RA) by several years. Recently, the proteins survivin and Fms-like tyrosine kinase 3 ligand (Flt3L) have been identified as biomarkers of RA associated with joint destruction. The aim was to investigate the potential of survivin and Flt3L as predictors of RA in samples from patients prior to onset of symptoms. Methods This study included 47 individuals sampled before onset of RA (median 2.5 years (IQR 4.5) and 155 matched controls, all were donors to the Medical Biobank of Northern Sweden, and 36 RA patients. Levels of anti-CCP, survivin and Flt3L were measured using ELISAs and 29 cytokines/chemokines by multiplex detection. Results Levels of survivin were increased in presymptomatic individuals compared with controls (p=0.003), whilst the levels of Flt- 3L were similar. The frequency of survivin positivity in the pre-symptomatic individuals was increased compared with the controls (36.2 vs.14.2%, p=0.001) and predicted disease development (OR=3.4[95%CI 1.6-7.2]). The frequency of survivin and Flt3L in RA patients was increased compared with the controls (both, p<0.0001, OR=12.1[95%CI, 5.3-27.6] and OR=11.0 [3.9-30.9], respectively). Anti-CCP positive pre-symptomatic individuals and patients had significantly higher levels of survivin compared with anti-CCP2 negative individuals. In pre-symptomatic individuals, survivin correlated with IL-12, IL-1Beta and IL-9 whereas Flt3L correlated to a significantly broader spectrum of cytokines in RA patients. Conclusion Proto-oncogene survivin was increased in individuals prior to onset of symptoms of RA and was correlated to cytokines suggesting its role at pre-clinical stages of the disease. Abstractnummer: 30 30 IN EARLY RHEUMATOID ARTHRITIS, THE 12 INDIVIDUAL BIOMARKERS THAT COMPRISE THE MULTIPLEBIOMARKER DISEASE ACTIVITY SCORE RELATE DIFFERENTIALLY TO CLINICAL RESPONSE AND RADIOGRAPHIC PROGRESSION: RESULTS FROM A RANDOMIZED TRIAL Karen Hambardzumyan1, Saedis Saevarsdottir 1, Rebecca Bolce2, Kristina Forslind3, Sofia Ernestam4, Ingemar Petersson5, Pierre Geborek5, Ronald van Vollenhoven1 Karolinska Institutet 2 Crescendo Bioscience Inc. 3 Section of Rheumatology, Department of Medicine, Helsingborg General Hospital 4 Karolinska University Hospital 5 Lund University 1 Background In early rheumatoid arthritis (eRA), clinical and radiographic predictors would be very useful for optimizing available therapies. For these purposes, individual biomarkers and their combination in the multi-biomarker disease activity (MBDA, Vectra DA) test, was evaluated using serum from the eRA patients from the SWEFOT trial. The objective of this study was to assess the 12 individual biomarkers that comprise the MBDA score at baseline (BL) as predictors of clinical response at 3 months and radiographic progression at 1 year in eRA. Methods Analyses were performed for patients from the SWEFOT trial who had BL and 3-month data of DAS28-ESR), the MBDA score and the 12 individual biomarkers at BL; and for a subset of patients who ABSTRACTS also had radiographs at BL and 1 year (assessed using the Van der Heijde modified Sharp score [SHS]). Patients with DAS28 > 3.2 at 3 months were considered clinical non-responders, and patients with a change in SHS > 0 as radiographic progressors. Group comparisons of biomarkers were performed by Mann-Whitney U test. Results Clinical non-responders had significantly higher BL values for CRP and IL-6 compared to responders. TNF-R1 and VCAM-1 were significantly lower for non-responders, while other biomarkers and the MBDA did not differ. The patients who progressed radiographically had, at BL, significantly higher MBDA scores, inflammatory biomarkers (CRP, SSA and IL-6), MMP-1, MMP-3 and TNF-R1, as well as a trend towards higher VEGF. Conclusion In eRA patients treated with MTX, some individual biomarkers at BL may help in predicting clinical non-responsds after 3 months of MTX therapy. Other biomarkers, as well as the MBDA score, may identify patients at higher risk for radiographic progression during the first year of therapy. Thus biomarkers can differentially predict aspects of disease course in eRA. Abstractnummer: 31 31 A MULTI-BIOMARKER DISEASE ACTIVITY SCORE CORRELATES WITH RADIOGRAPHIC PROGRESSION IN EARLY RHEUMATOID ARTHRITIS: RESULTS FROM A RANDOMIZED TRIAL Karen Hambardzumyan1, Rebecca Bolce2, Kristina Forslind3, Saedis Saevarsdottir1, Ingemar Petersson4, Pierre Geborek4, Sofia Ernestam5, Ronald van Vollenhoven1 Karolinska Institutet 2 Crescendo Bioscience Inc. 3 Section of Rheumatology, Department of Medicine, Helsingborg General Hospital 4 Lund University 5 Karolinska University Hospital 1 Background In early rheumatoid arthritis (eRA), predictors of radiographic damage are needed for optimal targeting of therapy. It has been suggested that combining various biomarkers may improve this prediction. Objective To assess the baseline MBDA score as a predictor of radiographic progression over one year in eRA patients from the SWEFOT trial. Methods Analyses were performed for 235 patients from SWEFOT with baseline, month 3 (n=220) and week 52 (n=235) assessments of DAS28, DAS28-CRP, CRP, MBDA score, and radiographs at baseline and 1 year (using the Van der Heijde modified Sharp score [SHS]). Associations between disease activity indices and radiographic progression at one year were evaluated using Wald’s chisquare test. Spearman’s correlation coefficients (r) were determined for the BL disease index scores versus radiographic progression (deltaSHS >5) over 1 year. Results Baseline MBDA score correlated with deltaSHS from baseline to 1 year: r = 0.271 (p<0.001); correlations of DAS28, DAS28-CRP, and CRP with deltaSHS were weaker: r = 0.063, 0.014, and 0.178, respectively (p=NS, p=NS, p=0.006). In bivariate analyses adjusting for DAS28 or CRP, MBDA had a significant additive value to prediction of radiographic progression at one year (p<0.01). Of the 43 patients with deltaSHS > 5, 98% had a high baseline MBDA score, 77% a high DAS28 (>5.1) and 49% a high CRP (>3mg/dL). Of patients with a high MBDA score at baseline, 21% had SHS progression, versus 3% and 0% for moderate and low MBDA, respectively (p<0.04). Conclusion The association of a high MBDA score at baseline with higher risk of radiographic progression in eRA patients, and low and moderate MBDA score with lower risk was stronger than that of CRP or DAS28. Thus, in untreated eRA, MBDA may help identify patients at low versus high risk of radiographic progression and thereby support rational treatment choices. Abstractnummer: 32 32 SIGNIFICANT DIFFERENCES IN DISPENSED DOSES WERE OBSERVED BETWEEN SELF-ADMINISTERED TNFINHIBITORS Esbjörn Larsson1,2, Mats Ekelund2, Anders Berglund2 1 Reumatologkliniken, Karolinska Sjukhuset 2 Pfizer AB Sverige Background Neutralizing anti-bodies have been observed with self-administered TNF-inhibitors, adalimumab, golimumab and cerolizumab pegol but not with etanercept. Neutralizing anti-bodies may cause loss of efficacy and subsequent increases of dose. Dose increases may be initiated by the doctor or occur as the patient shortens the interval between self-injections. We aimed to study a combined measure of dose increase that captures both prescribed increases in dose and patient initiated increases in dose. Materials and methods This retrospective study retrieved information from the Swedish Prescribed Drugs Register among adult patients for the first time prescribed with etanercept, adalimumab, golimumab or certolizumab pegol by a rheumatologist between May 2010 and Mars 2013. The ratio between the observed and the expected dispensed dose based on the recommended dose according to the SMPC by TNF blockers were evaluated during follow up. Results Data from 2,137 patients on etanercept, 2,181 on adalimumab, 1,102 on golimumab and 1,161 certolizumabpegol were analyzed. During follow up the ratio between the observed versus the expected dose in relation to time was 0.96 (CI 95% 0.95-0.97) for etanercept, 0.99 (CI 95% 0.94-1.03) for certolizumab pegol, 1.013 (CI 95% 1.00-1.03) for adalimumab, and 1.05 (CI 95% 1.04-1.07), respectively. The ratio between the TNF blockers were significant between etanercept and adalimumab (p<0.001), golimumab (p<0.001) but not for certolizumab pegol (p=0.189) Conclusions New and continuing patients on etanercept had a significantly lower observed versus expected dose ratio in comparison with patients on golimumab and adalimumab. Cost comparisons based on actual doses may be more relevant to payers than cost comparisons based on labelled doses. Abstractnummer: 33 33 Reduced relative risk of serious pneumococcal infections after immunisation with heptavalent pneumococcal conjugate vaccine in arthritis patients on different treatments including methotrexate and TNF-inhibitors. ReumaBulletinen Nr 96 · 2/2014 25 ABSTRACTS Johanna Nagel1, Pierre Geborek1, Tore Saxne1, Göran Jönsson2, Martin Englund3,4, Ingemar Petersson3, Jan-Åke Nilsson1, Meliha Crnkic Kapetanovic1 Department of Clinical Sciences, Lund, Section of Rheumatology, Skåne University Hospital, Kioskgatan 3, Lund, SE-221 85 Sweden 2 Dept of Clinical Sciences Lund, Section of Infectious Diseases, Lund University, Sweden 3 EpiCentrum Skåne, Skane University Hospital, Department of Orthopedics, Clinical Sciences Lund, Lund University, Sweden 4 Clinical Epidemiology Research & Training Unit, Boston University School of Medicine, Boston, MA, USA 1 Abstractnummer: 34 34 EARLY DEXAMETHASONE TREATMENT IMPROVES SURVIVAL IN ENDOTOXEMIC SHOCK Maria Bergquist1,2, Merja Nurkkula1, Christian Rylander3, Göran Hedenstierna2, Catharina Lindholm1 Avd för Reumatologi och Inflammationsforskning, Göteborgs Universitet 2 The Hedenstierna Laboratory, Uppsala Universitet 3 Department of Anaesthesia & Intensive Care, Sahlgrenska Universitetssjukhuset 1 Introduction Severe sepsis is associated with high mortality despite antibiotic treatment. The role of glucocorticoid treatment in severe sepsis and septic shock remains controversial. The reasons for the contradictory outcomes of glucocorticoid treatment in clinical trials are unknown. A possible mechanism behind glucocorticoid resistance could be decreased expression and/or function of glucocorticoid receptors (GR). Objectives To study the expression and function of GR in endotoxemic shock and to investigate the relation between GR expression and function with the response to glucocorticoid therapy. Methods Male C57BL/6J mice were given LPS intraperitoneally. Blood and spleen cells were collected for analyses of GR expression in T cells (CD4+ and CD8+), B cells, monocytes, and neutrophils by flow cytometry. GR function was assessed by in vitro binding of FITC-labelled dexamethasone and nuclear translocation by ImageStream. The effect of dexamethasone treatment on mortality was studied. Results Blood and spleen B cells and neutrophils had increased GR expression in contrast to the decreased expression in CD4+ T lymphocytes and monocytes (p<0.05). The dexamethasone binding capacity was increased in B cells in blood and spleen (p≤0.02). Interestingly, spleen neutrophils bound less dexamethasone (p=0.01) in spite of higher GR expression. On day 1 after LPS administration, the translocation ability was increased compared to healthy controls but reduced on day 2 compared to day 1 in all cells (p<0.0001). Dexamethasone administered 2 hours after LPS administration resulted in reduced mortality compared to when dexamethasone treatment was started at 12 hours (p=0.02) and when no dexamethasone treatment was given (p=0.02). Conclusion Steroid treatment in endotoxemic shock is only effective when given early. Neutrophils have reduced ability to bind dexamethasone during endotoxemic shock despite their increased GR expression. This, in combination with the increased numbers of neutrophils 26 ReumaBulletinen Nr 96 · 2/2014 seen in sepsis, may explain why steroid treatment is only beneficial when administered early. Abstractnummer: 35 35 BAZEDOXIFENE AND ESTROGEN IN COMBINATION EFFICIENTLY INHIBITS EXPERIMENTAL ARTHRITIS WITH MINIMAL UTERINE STIMULATION Annica Andersson1, Angelina Bernardi1, Alexandra Stubelius1, Merja Nurkkala-Karlsson1, Louise Grahnemo1, Hans Carlsten1, Ulrika Islander1 Centre for Bone and Arthritis Research, Department of Rheumatology and Inflammation Research, The Sahlgrenska Academy, University of Gothenburg, Sweden 1 Background Estrogen treatment, as in hormone-replacement therapy, has been reported to be beneficial in postmenopausal RA, however, is associated with certain side effects. Bazedoxifene (BZA), a selective estrogen-receptor modulator, combined with estrogens, is used as a tissue selective estrogen complex (TSEC) to treat menopausal symptoms and prevent bone loss without stimulating the breast or endometrium. The aim of this study was to investigate effects of TSEC in experimental arthritis. Methods Female ovariectomized DBA/1 mice were subjected to collagen-induced arthritis (CIA) and therapeutically treated with s.c. injections of 17beta-estradiol only (E2; 0.1 and 0.5 microg/day), BZA only (24 microg/day), BZA + E2 (24 + 0.1 microg/day), BZA + E2 (24 + 0.5 microg/day) or vehicle. Arthritis development was macroscopically assessed days 17-42 after first immunization anduteri were weighed at termination. Results Mice treated with BZA + E2, or E2 only, displayed dramatically reduced arthritis severity (AUC day 17-42; p< 0.001) and decreased incidence of arthritis (p< 0.01 day 28-31, p< 0.001 day 33-42), compared to vehicle controls. Importantly, mice treated with BZA + E2 showed minimal uterine growth, with significant reductions in mean uterine weights by 79% for BZA + E2 0.1 microg compared to E2 only, and 69% for BZA + E2 0.5 microg vs. E2 only. Conclusions TSEC (bazedoxifene and estrogen) is efficiently inhibiting experimental autoimmune arthritis and diminishes estradiolmediated uterine side effects. The findings in this study are of importance regarding the treatment regimen of women with RA experiencing concurrent menopausal symptoms and increased risk for osteoporosis. Abstractnummer: 36 36 CHEMOKINE-MEDIATED REGULTION OF TH17-CELL MIGRATION AS A NOVEL MECHANISM FOR ESTROGEN-INDUCED AMELIORATION OF EXPERIMENTAL ARTHRITIS Annica Andersson1, Alexandra Stubelius1, Merja Nurkkala-Karlsson1, Cecilia Engdahl1,2, Malin Erlandsson1, Louise Grahnemo1, Marie K Lagerquist2, Hans Carlsten1, Ulrika Islander1 Centre for Bone and Arthritis Research, Department of Rheumatology and Inflammation Research, The Sahlgrenska Academy, University of Gothenburg, Sweden 2 Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, The Sahl- 1 ABSTRACTS grenska Academy, University of Gothenburg, Sweden Background The incidence and progression of many autoimmune diseases are gender-biased, which partly might be explained by the immune-modulating properties of endocrine hormones. Estrogen treatment, as in hormone-replacement therapy, has been shown to be beneficial in rheumatoid arthritis (RA), although the mechanisms involved are mostly unknown. Pro-inflammatory T helper 17 (Th17) cells have emerged as key players in driving RA, although it has not been studied if estrogen modulates Th17 cells in this disease. Therefore, the aim of this study was to investigate effects of estrogen on Th17 cells in experimental arthritis. Methods Female ovariectomized DBA/1 mice, treated with 17beta-estradiol (E2; 0.83mikrog/day) or placebo, were subjected to collagen-induced arthritis (CIA) and Th17 cells in joints and lymph nodes were studied at several time points, with flow cytometry and IL-17 ELISPOT. Results E2-treated mice with established CIA showed reduced severity and incidence of arthritis and fewer Th17 cells in joints compared to placebo controls. Interestingly, mice treated with E2 displayed accumulation of Th17 cells in lymph nodes during the induction phase of CIA, which was associated with an up-regulation of chemokine receptor 6 (CCR6) on lymph node Th17 cells as well as increased expression of the corresponding chemokine CCL20 within lymph nodes. Conclusions The E2-induced retention of Th17 cells within the lymph nodes in CIA, caused by interference with the CCR6-CCL20 pathway, suggests a novel mechanism in estrogen-mediated inhibition of arthritis. Our study presents new important perspectives on the effects of estrogen on the immune system, and the CCR6-CCL20-induced retention of Th17 cells in lymph nodes per se could be implicated in development of new treatment strategies in RA. Abstractnummer: 37 37 with las, bza, ral, 17β-estradiol (E2) or vehicle. Bone marrow and spleen cells were phenotyped by flow cytometry and antibody-producing cells were quantified using ELISPOT assay. Results As expected, treatment with E2 caused a decrease of B cells at all developmental stages from pro-B cells (in bone marrow) to transitional 1 B cells (in spleen). However, treatment with las and bza only led to a significant decrease in two distinct B cell populations; immature B cells in bone marrow and transitional 1 B cells in spleen. Also, in contrast to E2, treatment with las and bza did not result in increased numbers of antibody-producing cells. Conclusion LasandbzadifferfromE2byretainingnormalnumberofcellsatmostBcell stages during B lymphopoesis. Also, las and bza do not cause the increase in antibody production observed after treatment with E2. Abstractnummer: 38 38 B-REGULATORY CELLS ARE FUNCTIONALLY IMPAIRED IN PATIENTS WITH RHEUMATOID ARTHRITIS AND IN THEIR FIRST DEGREE RELATIVES COMPARED WITH CONTROLS Mikael Brink1, Lisbeth Ärlestig1, Solbritt Rantapää Dahlqvist1, Kristina Lejon2 Institutionen för Folkhälsa och Klinisk Medicin, Umeå Universitet 2 Institutionen för Klinisk Mikrobiologi, Umeå Universitet 1 Abstractnummer: 39 39 Does evaluation of hand bone loss by Digital x-ray radiogrammetry within the first 3 months after diagnosis of rheumatoid arthritis identify patients at risk for radiological progression? Ewa Berglin1, Katrine Åhlström Riklund2, Solbritt Rantapää Dahlqvist1 ROLE OF LASOFOXIFENE AND BAZEDOXIFENE IN B CELL DEVELOPMENT AND FUNCTION 1 Inst. för folkhälsa och klinisk medicin/Reumatologi 2 Inst. för strålningsvetenskaper/Diagnostisk radiologi Angelina Bernardi1, Annica Andersson1, Louise Grahnemo 1, Merja Nurkkala-Karlsson1, Hans Carlsten1, Ulrika Islander1 Abstractnummer: 40 1 Göteborgs Universitet Background/Aim Lasofoxifene (las) and bazedoxifene (bza) are selective estrogen receptor modulators (SERM) approved for the prevention and treatment of postmenopausal osteoporosis. 17β-estradiol (E2) and the traditional SERM raloxifene (ral) both have antiarthritic and bone protective properties in experimental postmenopausal arthritis. Preliminary data from our ongoing studies show that treatment with las and bza significantly inhibits experimental arthritis and inflammation-induced bone loss. In order to understand the mechanism for the beneficial effect of las and bza on arthritis it is necessary to clarify how they affect the healthy immune system. The inhibitory effect of E2 on B lymphopoesis and stimulatory effect on antibody production are well documented. However the impact of las and bza on B cell development and function has never previously been studied. Materials/Methods Healthy mice were ovariectomized (ovx). Mice received treatment 40 The Diagnostic Utility of Fluore-scence Optical Imaging in the Identification of Synovial Inflammation in Hand and Wrist Joints. Yogan Kisten, Noémi Győri MD, Ronald van Vollenhoven MD PhD, Hamed Rezaei MD, Erik af Klint MD PhD, Carolina Romanus, Anna Karlsson Background Fluorescence optical imaging (FOI, “Rheumascan”) is a novel modality that allows imaging of inflammation in the hands using a fluorescent dye. Here, the utility of FOI in identifying synovitis was compared to clinical examination and ultrasound (US). Methods A total of 748 joints of the bilateral hands and wrists, including 3 wrist joints, 5 MCPs, 5 PIPs, and 4 DIPs in 22 patients with inflammatory arthritis were examined clinically, by US and FOI. Results 71 out of 748 joints (9%) were considered inflamed clinically, 139 ReumaBulletinen Nr 96 · 2/2014 27 ABSTRACTS (19%) by US, and 123 (17%) by FOI. Of the clinically inflamed joints, 49 (69%) were inflamed by ultrasound, and 30/65 (46%) of these joints were inflamed by FOI. 593/683 (87%) of joints that were clinically negative were negative by ultrasound and 590 (86%) were negative by FOI. The agreement between clinical examination and US was fair (kappa 0.39+0.05) and somewhat stronger than the agreement between clinical examination and FOI (kappa 0.23+0.05). 98/142 (69%) joints that were inflamed by US showed inflammation by FOI, while 576/606 (95%) non-inflamed joints by US were non-inflamed by FOI. The agreement between US and FOI was good (kappa 0.67+0.04). 27/30 (90%) joints that were inflamed both by clinical examination and by US were inflamed by FOI. Conclusions The sensitivity of FOI for inflammation is 46-90%, and the specificity 86-95%, suggesting that it has lower sensitivity but similar specificity compared to US. These findings suggest that FOI may be used in practice as a complement to clinical examination, in particular when US is not available, in order to identify synovitis earlier and with greater confidence. Abstractnummer: 41 41 The Utility of Fluorescence Optical Imaging for Detecting Clinically Silent Synovitis of the Hands and Wrists. Yogan Kisten, Noémi Győri MD, Ronald van Vollenhoven MD PhD, Erik af Klint MD PhD, Hamed Rezaei MD, Anna Karlsson, Carolina Romanus Background Fluorescence optical imaging (FOI, “Rheumascan”) is a novel modality that allows imaging of inflammation in the hands and wrists using a fluorescent dye. Here, we investigated whether FOI could be used for ascertaining subclinical synovitis. Methods A total of 748 joints of the bilateral hands and wrists, including 3 wrist joints, 5 MCPs, 5 PIPs, and 4 DIPs in 22 patients with inflammatory arthritis (RA: 9; JIA, gout, psoriatic arthritis, SLE, and other diagnoses, 1-2 each) were examined clinically, by ultrasound (US) and FOI. Joints were considered clinically inflamed when both swollen and tender, and non-inflamed otherwise. Ultrasound was considered positive for synovitis if both thickening on grey scale and Doppler signal were present. FOI was considered positive by visual inspection of the images. Results Out of 748 joints, 71 (9%) were considered inflamed by clinical examination and 677 were not. Of the clinically noninflamed joints, 100 were inflamed by US. Of these joints, 80 were inflamed by FOI and 20 were not. Thus, the sensitivity of FOI for detecting sub-clinical synovitis when defined as a positive US in the absence of clinical inflammation was 80%. Out of the 577 joints that were non-inflamed clinically and non-inflamed by ultrasound, 26 had inflammation by FOI, yielding a specificity of 95%. Conclusion Under the assumption that US can correctly identify sub-clinical synovitis in clinically non-inflamed joints the sensitivity of FOI for detecting subclinical synovitis in the hands and wrists is 80% and the specificity 95%. These metrics suggest that it may be a useful tool in the setting of identifying patients with very early synovial inflammation of the hands/wrists. 28 ReumaBulletinen Nr 96 · 2/2014 Abstractnummer: 42 42 HÖFTFRAKTURER OCH INFLAMMATORISK REUMATISK SJUKDOM DALARNA 2001 -2011 Britt-Marie Nyhäll-Wåhlin Bakgrund Under de senaste 20 åren har patienter med höftfraktur alltmer uppmärksammats. Bakomliggande orsaker till frakturerna är främst ålder och osteoporos. Ytterligare en bidragande orsak kan vara inflammatorisk reumatisk sjukdom. Samtidigt har man under denna tid börjat använda potenta läkemedel för såväl osteoporos som inflammatorisk reumatisk sjukdom. Syfte Beskriva förekomsten av höftfrakturer och höftfrakturer + inflammatorisk reumatisk sjukdom under 11 år (2001-2011) i Dalarna. Material och metod Patienter boende i Dalarna med höftfraktur, som vårdats inneliggande på ortopedkliniken (ortopeden Falun och Mora) under diagnoserna (förstagångsdiagnos) 720, 721 och 722 under åren 2001 – 2011 identifierades. Därefter adderades diagnoser för inflammatorisk reumatisk sjukdom från reumatologklinikens besöksregister. Patienterna subgrupperades i frakturår, dvs 11 grupper och jämfördes med avseende på frakturantal, medelålder, kön och förekomst av diagnos för inflammatorisk reumatisk sjukdom. Resultat 5 907 patienter med förstagångshöftfraktur kunde identifieras; 1 842 män och 4 065 kvinnor (31% vs 69%). Äldsta patienten var 106 år, den yngsta 46 år. Medelåldern var 82 år (män 80 år, kvinnor 82 år). 209 höftfrakturpatienter (3,5%) hade en diagnos förenlig med inflammatorisk reumatisk sjukdom (182 artritsjukdom, 27 systemsjukdom). I de 11 subgrupperna baserade på frakturår sågs en minskning av antalet höftfrakturer (2001:572, 2006:540, 2011:524). Antalet patienter med inflammatorisk artritdiagnos var få (2001:18, 2006:19, 2011:13). Slutsats En trend till minskat antal höftfrakturer kan ses, men ingen skillnad i könsfördelning eller ålder vid fraktur. Även en viss trend till färre patienter med inflammatorisk ledsjukdom kan anas, men det krävs betydligt större patientmaterial med inflammatorisk ledsjukdom för att undersöka detta liksom för att se om höftfraktur är vanligare i denna grupp. Abstractnummer: 43 43 VITAMIN D INSUFFISCIENCY OBSERVED IN 50-75% OF HEALTHY SWEDISH ADULTS Eva Klingberg1, Göran Oleröd2, Ola Hammarsten2 1 Department of Rheumatology and Inflammation Research, University of Gothenburg, Sweden 2 Department of Clinical Chemistry and Transfusion Medicine University of Gothenburg, Sweden Background Numerous observational studies associate vitamin-D insufficiency (VDI) with chronic illnesses, including rheumatic diseases. There are two definitions of VDI; serum 25-hydroxy vitamin-D (S-25OHD) <50nmol/L or <75nmol/L. We aimed to study the inter- and intra-individual variations in S-25-OHD during different seasons of the year and to explore demographic and lifestyle related para- ABSTRACTS meters associated with S-25-OHD in healthy Swedish adults. Methods Blood donor serum was collected during 12 months and analyzed for 25-OHD and parathyroid hormone (S-iPTH). The blood donors answered questionnaires concerning vitamin-D supplements, smoking, physical activity, solarium use and sun holidays. To study the intra-individual variations in S-25-OHD repeated samples were also collected from thrombocyte donors during a period from April to November. Results 540 blood donors (60% men; mean age 41±13 years) and 75 thrombocyte donors (92% men, aged 46±11 years) were included. S-25OHD varied greatly over the year correlating with the UV-B iirradiation intensity (rS=0.326;p<0.001).The mean S-25-OHD was 73% higher in July (81.9±26.2 nmol/L) than in February (47.4±20.7 nmol/L;p<0.001) During Jan-Mars S-25-OHD below the thresholds of 50 and 75 nmol/L was observed in 58% and 88% respectively and during July-September in 11% and 50% (p<0.001). S-25-OHD correlated negatively with BMI and S-iPTH, but was significantly higher in sun-holiday travellers, solarium-users, nonsmokers and in the physically active. The intra-individual analyses showed a mean increase in S-25-OHD of 8nmol/L/month between April to August and that 27% of the subjects with a S-25-OHD <50nmol/L in late spring remained at this level during the whole summer. Conclusions Vitamin-D insufficiency is common in the Swedish healthy adult population. Approximately 75% had serum 25-OHD values <75 nmol/L during the whole year and 50% had serum 25-OHD values <50 nmol/L during 50% of the year. Serum 25-OHD was strongly associated with parameters related to sun exposure, but only weakly with intake of vitamin-D supplements. Abstractnummer: 44 44 GLUCOCORTICOIDS PROTECT AGAINST TRABECULAR BONE LOSS IN OVARIEC-TOMIZED MICE Louise Grahnemo1, Caroline Jochems1,3, Annica Andersson1, Cecilia Engdahl2, Marie K Lagerquist2, Claes Ohlsson2, Ulrika Islander1, Hans Carlsten1 Centre for Bone and Arthritis Research (CBAR), Department of Rheumatology and Inflammation research, The Sahlgrenska Academy, University of Gothenburg, Sweden. 2 Centre for Bone and Arthritis Research (CBAR), Department of Internal Medicine and Clinical Nutrition, The Sahlgrenska Academy,University of Gothenburg, Sweden. 3 Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA 1 Abstractnummer: 45 45 HEPATOCYTE GROWTH FACTOR, A NEW BIOMARKER FOR OSTEOPROLIFERATION IN MALE AS PATIENTS? Eva Klingberg, Merja Nurkkala, Hans Carlsten, Helena Forsblad-d’Elia Institution of Medicine, Center for Bone and Arthritis Research 2 Department of Rheumatology and Inflammation Research, University of Gothenburg, Sweden Background Ankylosing spondylitis (AS) is characterized by osteoproliferation, which can be seen as an enhanced reparative response to inflammation, mechanical stress or micro-damage. Male sex is a risk factor for the disease and for the osteoproliferation. Hepatocyte growth factor (HGF), initially known as a mitogen for hepatocytes, is an important factor for regeneration and repair in many tissues. HGF is produced by osteoblasts, has receptors on osteoblasts and osteoclasts and stimulates both cell types. The aims of this study were to compare the serum HGF levels in AS patients with healthy controls and to explore the association with disease activity, osteoproliferation and bone density. Methods Serum from AS patients (modified NY-criteria) and healthy controls was analyzed for HGF with ELISA (Quantikine R&DSystems). Disease activity was assessed by BASDAI, ASDAS, ESR and CRP, back-mobility with BASMI, syndesmophyte formation with mSASSS and BMD with DXA of femoral neck. Results 204 AS patients (87 women/117 men; age 50±13 years; symptom duration 24±13 years; BASDAI 3.6±2.1; ASDAS-CRP 2.4±0.9) and 80 sex and age-matched controls were included. HGF was significantly higher in the AS patients compared with the controls (1556±452 vs. 1450±527 pg/ml p=0.024). HGF correlated with age in the male AS patients (rS=0.316;p=0.001) but not in the female patients nor in controls of both sexes. In the AS men HGF also correlated with ESR(rS=0.380;p<0.001), CRP(rS=0.304;p=0.001), BASMI(rS=0.323;p <0.001), mSASSS (rS=0.302;p=0.001) and femoral neck BMD(rS=-0.211;p=0.022), but in the female patients only with ESR. HGF was significantly higher in male smokers (p=0.005), although there was no age-difference in male smokers and non-smokers. In multiple linear regression age, CRP, and smoking were all independently associated with HGF. Conclusion Known risk factors for osteoproliferation in AS were independently associated with serum HGF. HGF could be a negative prognostic biomarker, especially for the male AS patients. Further prospective studies are warranted. Abstractnummer: 46 46 Reactive oxygen species are diSpensable for ovariectomy-induced bone loss Alexandra Stubelius1, Annica Andersson1, Rikard Holmdahl2, Claes Ohlsson 1, Ulrika Islander1, Hans Carlsten1 Centre for Bone and Arthritis Research, Sahlgrenska Academy, Gothenburg University 2 Medical Inflammation Research, Karolinska Institute 1 Abstractnummer: 47 47 S-CALPROTECTIN – A POTENTIAL MARKER OF INFLAMMATION IN PATIENTS WITH PSORIATIC ARTHRITIS? Claes Hansson, Med. stud1 Catharina Eriksson, MD, PhD2 GerdMarie Alenius, MD, PhD1 1 Department of Public Health and Clinical Medicine, Rheumatology, Umeå University, Umeå, Sweden 2 Department of Clinical Microbiology/Clinical Immunology, Umeå University, Umeå, Sweden 1 ReumaBulletinen Nr 96 · 2/2014 29 ABSTRACTS Abstractnummer: 48 48 FAECAL LEVELS OF CALPROTECTIN IN SYSTEMIC SCLEROSIS, PRIMARY SJÖGREN’S SYNDROME AND RHEUMATOID ARTHRITIS Kristofer Andréasson1, Tore Saxne1, Agneta Scheja1, Izabela Bartosik1, Thomas Mandl2, Roger Hesselstrand1 Institutionen för kliniska vetenskaper Lund, Avdelning för Reumatologi, Lunds Universitet 2 Institutionen för kliniska vetenskaper Malmö, Avdelning för Reumatologi, Lunds Universitet 1 Abstractnummer: 49 49 THE INFANTILE GUT BACTERIAL COLONIZATION PATTERN IS ASSOCIATED WITH HIGHER CYTOKINE RESPONSES BUT NOT WITH THE PROPORTIONS OF REGULATORY T CELLS IN CHILDHOOD Anna Rudin1, Hardis Rabe1, Anna Strömbeck1, Annica Ljung2, Anna-Carin Lundell1, Kerstin Andersson1, Agnes Wold2, Ingegerd Adlerberth2 Avd för Reumatologi och Inflammationsforskning, Sahlgrenska Akademin 2 Avd för infektionssjukdomar, Sahlgrenska Akademin Results In total, we identified 394 singleton deliveries among women with a history of a diagnosis of AS, and 1201 deliveries among the matched general population controls. Caesarean section and epidural analgesia was more common and pregnancies tended to be of shorter gestational age. Adjustment for maternal age, smoking habits, BMI and educational level did not change point estimates of relative risk. Sensitivity analyses restricted to those with a diagnoses before start of gestation and exploring effects in different calendar time periods resulted in similar point estimates. Conclusion Women with AS had increased risk of being delivered with and caesarean section, both planned and acute. Abstractnummer: 51 51 PATIENTS WITH NON-AS AXIAL SPA AND AS HAVE SIMILAR PREVALENCE AND LEVELS OF PATIENT REPORTED OUTCOME MEASURES. RESULTS FROM A POPULATION BASED STUDY. U Lindström1, A Bremander2, S Bergman2, E Haglund2, IF Petersson3, LTH Jacobsson1 1 Abstractnummer: 50 50 PREGNANCY OUTCOME IN PATIENTS WITH ANKYLOSING SPONDYLITIS – A NATIONAL REGISTER STUDY Gustav Jakobsson1, Olof Stephansson2, Johan Askling3,4, Lennart Jacobsson1 Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden 2 Department of Women and Child Health, Division of Obstetrics and Gynecology, Karolinska Institutet, Stockholm, Sweden 3 Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden 4 Dept of Rheumatology, Karolinska University Hospital, Stockholm, Sweden Dpt. Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg, Sweden 2 Clinical Sciences Lund, Section of Rheumatology, Lund University, Sweden 3 Orthopedics, Clinical Sciences, Lund University, Lund, Sweden 1 Background Non-radiographic axial spondyloarthritis (nrax-SpA) is emerging as a treatable disease comparable to ankylosing spondylitis (AS). The aim of this study was to estimate the prevalence of nrax-SpA and compare the patient reported outcome measures (PROMS) to that of AS. 1 Background and aim AS often starts in fertile age and is characterized by back pain, local and systemic inflammation, and may require systemic treatment. Other chronic inflammatory diseases, such as inflammatory bowel disease and rheumatoid arthritis affect pregnancy and birth outcomes, but for AS this has not been studied, which was the aim of this study. Methods We performed a, nationwide, registry- and population-based care-control study. Cases were identified by diagnosis of an ICD code for AS in the Swedish national patient register at a visit to a specialist in rheumatology or internal medicine. For each index case 5 controls were identified matched for birth year, time and county at first AS diagnosis. Data on cases and controls were linked to the Medical Birth Register (MBR) for identification of pregnancy and birth outcomes and to Statistics Sweden (educational level). Cases and matched controls were included in the present analyses if they had their first singleton birth after inclusion, i.e after diagnoses of AS for cases. Relative risks were assessed using conditional logistic regression models. 30 ReumaBulletinen Nr 96 · 2/2014 Methods All health care seeking individuals, ≥18 years, given a SpA-diagnosis, according to ICD-10, (N = 5771), 2003 - 2007, were identified through the regional health care register in Skåne. 2009 they were sent a questionnaire (response rate 48%), including questions concerning the SpA-features constituting the ASAS-criteria, PROMS and medication. Review of clinical records support the notion of using AS as a substitute for radiographic changes. Non-AS axial SpA was defined as having an ICD10 code of SPA without having one of AS, and > 3 months of Back Pain (BP) the last year and ≥2 SpA-features. Assuming similar answers from the nonresponders, prevalence rates were estimated for non-AS axial SpA and AS. Results 742 responders had an AS-diagnosis (60.5% men) and 640 fulfilled the study criteria for non-AS axial SpA (29.5% men). The prevalence of AS was 0.13% (95% CI; 0.115-0.148) and of non-AS axial SpA 0.11% (95% CI; 0.096-0.130). Mean values for PROMs and frequency of comorbidities were higher in the non-AS axial SpA vs both the AS, and the subgroup of AS individuals reporting BP > 3months during the last year. Self-reported present use of TNF-inhibitors was similar between the groups (Table 1). Conclusion The results suggest that at a population level the prevalence for non-AS axial SpA almost equals that for AS, but with a reverse gender distribution. The non-AS axial SpA group report similar frequencies of SpA- comorbidities (except psoriasis) and treatment with TNF-inhibitors, but worse levels of perceived health. ABSTRACTS Abstractnummer: 52 52 Patienter med tidig axial spondylartrit inkluderade i SPACE i Sverige har en hög förekomst av inflammation enligt MRI och kliniskt aktiv sjukdom Sofia Exarchou 3, Christopher Schaufelberger1, Tomas Husmark 2, Joaquin Lopis 4, Per Larsson 5, Milad Rizk 6, Åke Thörner 7, Käth Nilsson 3, Carl Turesson 3, Lennart Jacobsson1 Avdelningen för reumatologi och inflammationsforskning, Sahlgrenska Akademin, Göteborgs Universitet, Göteborg 2 Reumatologiska kliniken, Falu lasarett, Falun 3 Reumatologiska kliniken, SUS, Malmö 4 Sektionen för reumatologi, Skövde sjukhus 5 Reumatologiska kliniken, Karolinska sjukhuset, Stockholm 6 Reumatologiska kliniken, Västmanlands sjukhus, Västerås 7 Reumatologiska kliniken, Eskilstuna sjukhus, Eskilstuna 1 Bakgrund Relativt litet är känt om långtidsförlopp och prognostiska faktorer för patienter med tidig axial Spondylartrit (ax-SPA). Syfte Att belysa långtidsförlopp och prognostiska faktorer för kronisk sjukdom samt strukturella förändringar (ankyloserande spondylit (AS) enligt New York kriterierna) vid ax-SPA. Metod Internationell multiccenter kohortstudie (SPondylArthitis Caught Early (SPACE)) med centra i Holland, Norge och Italien. Patienter identifierade i rutinsjukvård med följande inklusionskriterier; 1) ryggsmärta under 2 års duration, 2) 16 – 45 års ålder vid smärtdebut, 3) andra tecken talande för ax-SPA; minst 1 av tungt vägande indikatorer (HLA-B27, MRI (ödem)/röntgen (bilateralt sakroiliit), hereditet, uveit) eller minst 2 av andra mindre tungt vägande indikatorer (se figur nedan). Patienterna följs kliniskt (vid inklusion, efter 3 mån och därefter årligen) med frågeformulär, klinisk undersökning och provtagning, samt med bilddiagnostik (röntgen och MRI av bäckenleder och kotpelare) vartannat år. Resultat I december 2013 hade över 300 patienter inkluderats internationellt, varav 47 i Sverige . Bland de svenska patienterna (56% män) var medelåldern vid symptomdebut 26 år, och medeldurationen av ryggsmärta var 13 månader. Vid inklusion hade patienterna en hög förekomst av HLA-B27 (94%) positivitet och inflammation av bäckenleder enligt MRI (63%) (figur). PLATS FÖR FIGUR! Vid inklusion behandlades 80% med NSAID, 10% med kortison och 3% med TNF-hämmare. Genomsnittsliga värden (SD) för BASDAI respektive BASFI var 4,4 (1,9) och 2,2 (1,9). Konklusion Patienterna med tidig ax-SPA i svenska delen av SPACE har vid inklusion en hög förekomst av inflammation enligt MRI samt sjukdomsaktivitet (BASDAI) som är jämförbara med studier av etablerad AS från t.ex. den Skånska kohorten SPAScania1. Studier av tidig SPA har hög potential för att bidra till framtida kvalitetsförbättring och forskning. 1. Haglund E, Bremander AB, Petersson IF et al. Prevalence of spondyloarthritis and its subtypes in southern Sweden. Referens: Ann Rheum. Dis. 2011 Jun; 70(6):943-8. Abstractnummer: 53 53 DIFFERENCES IN SPINAL MOBILITY MEASURES IN RELATION TO DISEASE DURATION AND BETWEEN SUBGROUPS WITH AXIAL SPONDYLOARTHRITIS Elisabeth Mogard2, Elisabet Lindqvist1, Stefan Bergman1,Ann Bremander2 1 SRF 2 SWEREFO Introduction Spinal mobility is a core domain for research and clinical practice in Ankylosing Spondylitis (AS) but less studied in undifferentiated SpA (USpA). Our objective was to study the change of commonly used spinal mobility measures stratified on disease duration in patients with AS and differences in these measures in AS vs. USpA. Methods Patients with AS or USpA were identified from a cohort attending a specialist clinic. A cross sectional study, were the first measures of spinal mobility for each patient recorded during 1999 to 2012 were analyzed. Disease duration was split into tertiles, (<17 years (G1), 18-30 years (G2) and >31 years (G3)). Differences between AS G1/ G2/G3 were calculated with Kruskal-Wallis. Differences between AS and USpA were controlled for sex and disease duration (ANCOVA). Results 126 patients with AS vs. 57 with USpA were included in the study, mean (SD) age 48.4 (13.7) vs. 41.6 (11.4) years and 23% vs. 46% were women. In AS, lumbar, and thoracic measures, vital capacity and the BASMI composite score were the first measures to deteriorate in relation to disease duration (G1 vs. G2, p<0.035). Late in the disease all measures had deteriorated (G1 vs. G3, p<0.036). Patients with USpA presented better scores in lumbar, hip and thoracic spinal measures (p<0.05), data controlled for sex and disease duration. In early disease (<17 years) also cervical measures (p<0.05) were less affected compared to patients with AS. Conclusion The first measures to significantly change during the disease course in AS were the lumbar and thoracic mobility measures and the BASMI score. As expected, patients with USpA were less affected in mobility than patients with AS. Keywords Ankylosing spondylitis (AS), physical therapy, range of motion and Spondyloarthritis Abstractnummer: 54 54 Inflammatory Bowel Disease associated Arthritis (IBD-aA): validity of diagnoses based on ICD-coding and characteristics of the disease. Panagiota Drivelegka1, Nikolaos Papachrysos2, Ingemar Petersson3, Ann Bremander4, Lennart Jacobsson1 Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden 2 Department of Gastroenterology, Sahlgrenska University Hospital/ Östra, Gothenburg, Sweden 3 Department of Orthopedics, Department of Clinical Sciences, Lund, Lund University, Lund, Sweden 4 Research and Development Centre, Spenshult Hospital for Rheumatic Diseases, Halmstad, Sweden 1 Abstractnummer: 55 55 TRANSCRIPTIONAL ACTIVITY OF ADIPOSE TISSUE MAY BE AN EARLY MARKER OF CARDIOVASCULAR RISK IN RHEUMATOID ARHTRITIS ReumaBulletinen Nr 96 · 2/2014 31 ABSTRACTS Mitra Nadali 1, Rille Pullerits1, Karin Andersson1, Sofia Töyrä Silfverswärd1, Maria Bokarewa1 FIVE YEARS IN PATIENTS WITH EARLY RHEUMATOID ARTHRITIS Department of Rheumatology and Inflammation Research, Sahlgrenska University Hospital, University of Gothenburg Anna Södergren1, Kjell Karp2, Elisabet Lundström2, Torgny Smedby3, Bozena Möller4, Solbritt Rantapää-Dahlqvist1, Solveig Wållberg-Jonsson1 1 Abstractnummer: 56 56 PREDICTION OF CORONARY ARTERY CALCIFICATION AND RELATION TO INFLAMMATION IN RHEUMATOiD ARTHRITIS: A FOLLOW-UP STUDY Bengt Wahlin1, Thomas Meedt1, Fredrik Jonsson2, Michael Henein2, Kjell Karp3, Solveig Wållberg Jonsson1 Enheten för folkhälsa och klinisk medicin, reumatologi, Umeå universitet 2 Enheten för folkhälsa och klinisk medicin, Umeå universitet 3 Enheten för kirurgisk och perioperativ vetenskap, klinisk fysiologi, Umeå universitet 1 Background We previously reported increased prevalence of coronary atherosclerosis in patients with RA. In this follow-up, we evaluated the relation between measures of atherosclerosis, inflammatory markers and potential biomarkers of atherosclerosis at baseline and the presence of coronary artery calcification (CAC) 12 years later. Methods Twenty-two RA patients (4m, 18f, mean age 65 years, RA-duration 30-36 years) from an original (baseline; n=39) ultrasound study of atherosclerosis (intima-media-thickness (IMT) and plaque) were included in this follow-up study 12 years after baseline. CAC was assessed by CT and quantified according to Agatston. At the same time, inflammatory markers (ESR, CRP, haptoglobin), clinical disease activity ( joint counts, DAS28, HAQ, VAS-scales) and lipids (cholesterol, HDL, LDL, triglycerides) were measured. The effect on CAC of cytokines (IL-6, IL2sR), adhesion molecules (ICAM-1, sE-selectine), hemostatic factors (PAI-1, tPA-ag, vWF, fibrinogen, D-dimer, cardiolipin antibodies), circulating immune complexes and antibodies against modified LDL, all collected at baseline, was also evaluated. Statistical analysis of factors explaining presence of CAC was done by orthogonal projection to latent structures (OPLS) with repeated exclusion of variables without explanatory information. Results Eight patients had no detectable CAC, 2 patients had CAC 1-10 and 12 had >10 (range 18-1700). The final OPLS model discriminated well between groups with low (0-10) and high CAC (>10), predicting 68% and explaining 88% of the variation. ROC analysis showed 89% sensitivity and 92% specificity distinguishing high CAC from low. The most important variables in the OPLS model were baseline values of plaque, IMT, HDL, age, hypertension, tPA and current DAS28. Patients with high CAC differed from those with low regarding ESR (24,3 vs 9,9 mm/h; p<0.01) and swollen joint count (2 vs 0; p<0,05). Conclusion In patients with long term RA, CAC was predicted by markers of endothelial activation and traditional cardiovascular risk factors, but also current disease activity. These findings highlight the importance of inflammation in the process of atherosclerosis. Abstractnummer: 57 57 PROGRESSION OF SUBCLINICAL ATHEROSCLEROSIS OVER 32 ReumaBulletinen Nr 96 · 2/2014 Inst för folkhälsa och klinisk medicin, enh för reumatologi, Umeå universitet 2 Inst för kirurgi och perioperativ vetenskap, klinisk fysiologi, Umeå universitet 3 Enh för reumatologi, Östersunds sjukhus 4 Enh för reumatologi, Sunderby sjukhus 1 Background In patients with rheumatoid arthritis (RA) of recent onset, we have found intima media thickness (IMT) and flowmediated dilation (FMD) to be similar as in controls. In this prospective 5-year follow up, we investigated the progression of atherosclerosis, in relation with traditional cardiovascular disease (CVD) risk factors and inflammation, in patients with early RA compared to controls. Methods Patients from northern Sweden diagnosed with early RA are consecutively recruited into an ongoing prospective study. From these, a subgroup aged ≤60 years (n=71) was consecutively included for ultrasound measurements of IMT of a. carotis communis and FMD of a. brachialis at inclusion (T0) and after 5 years (T5). 40 age-sex-matched controls were included. The patients were clinically assessed and DAS28 was calculated as a composite measure of RA disease activity. Blood was analysed for lipids, ESR and CRP. Results Patients with RA had a significant aggravation in both IMT (0.52 at T0 and 0.58 at T5, p<0.001) and FMD (109.2% at T0 and 107.0 at T5, p<0.001). In controls the increase was only significant for IMT (0.55 at T0 and 0.60 at T5, p<0.001). In simple linear regression analyses among RA-patients, the IMT at T5 was significantly associated with several variables at T0: systolic blood pressure, cholesterol, triglycerides, SCORE and Reynolds Risk Score. In the corresponding analyses of FMD at T5, it was significantly inversely associated with age, smoking, SCORE as well as Reynolds Risk Score at T0 and area under the curve (AUC) for DAS28 over 60 months. Conclusions After five years, the increase in subclinical atherosclerosis tended to be more evident among patients with early RA compared to the controls. Both traditional CVD risk factors as well as inflammatory load over time seems to contribute to this increased atherosclerotic findings among patients with RA. Abstractnummer: 58 58 HJÄRT-KÄRLSJUKDOM VID PRIMÄRT SJÖGRENS SYNDROM EN PILOTSTUDIE Linnea Signér1, Lilian Vasaitis1, Dag Leonard1, Lars Rönnblom1, Elisabet Svenungsson, Gunnel Nordmark1 Reumatologsektionen, Institutionen för medicinska vetenskaper, Uppsala Universitet, Uppsala 2 Reumatologsektionen, Institutionen för medicin, Karolinska Sjukhuset och Karolinska Institutet, Stockholm 1 Bakgrund Förekomsten av hjärt-kärlsjukdom vid primärt Sjögrens syndrom (pSS) är ofullständigt studerad. Patienter med systemisk lupus erythematosus (SLE) har en ökad risk för hjärt-kärlsjukdom där en ABSTRACTS singelnukleotidpolymorfi (SNP) i signal transducer and activator of transcription 4 (STAT4) är associerad med stroke (1). Syftet med denna studie var att undersöka frekvensen hjärtkärlsjukdom hos patienter med pSS, jämföra med SLE, analysera sambandet med hög sjukdomsaktivitet vid diagnos mätt med European League Against Rheumatism Sjögren´s syndrome disease activity index (ESSDAI) samt studera associationen mellan hjärtkärlsjukdom och STAT4. ligast där genen NFKB1 kodar för p50 subenheten. Associationen mellan en NFKB1 singelnukleotidpolymorfi (SNP) och patienter med pSS positiva för SSA/SSB-antikroppar har beskrivits (2). En 4 baspar insertion/deletion (ins/del) -94ATTG, i promoterregionen av NFKB1, har associerats till ulcerös kolit och försämrad överlevnad vid kolorektal cancer (3). Målet med denna studie var att analysera associationen mellan NFKB1 -94ATTG ins/del och pSS samt anti-SSA/SSB-positivitet och kliniska manifestationer. Material och metod Totalt 114 patienter med pSS (90 % kvinnor, medelålder 60 år) ingick i studien. Kliniska data insamlades från journalerna. Data fanns tillgängliga för 170 patienter med SLE (88 % kvinnor, medelålder 51 år). STAT4 fanns genotypad hos 93 pSS patienter. Frekvenser jämfördes med Fishers exakta test, kontinuerliga variabler med t-test eller Mann-Whitney U test och allelfrekvensen med associationsanalys. Material och metod Totalt 684 patienter med pSS (92,8 % kvinnor, medelålder 58 år, 73,8 % anti-SSA och/eller -SSB-positiva) från Sverige (n=488) och Norge (n=196) och 1601 friska kontroller (Sverige n=1383, Norge n=218) ingick i studien. NFKB1 -94ATTG ins/del genotypades med TaqMan PCR (3). Insertionen (ins, 2xATTG) är vildtyp, deletionen (del, 1xATTG) den mindre vanliga allelen. Associationsanalyser utfördes i PLINK. Kliniska data hämtades från journalerna. Resultat Tjugofem pSS patienter (21,9 %) hade haft en eller flera manifestationer av hjärt-kärlsjukdom (cerebrovaskulär sjukdom (CVS) 2,6 %, ischemisk hjärtsjukdom (IHS) 6,1 %, ischemisk perifer vaskulär sjukdom 0 %, venös tromboembolism 8,8 % och engagemang av hjärtklaffar 8,8 %). Frekvensen cerebrovaskulär sjukdom var lägre än i SLE-gruppen (11,8 %, p=0,007). Det fanns ingen skillnad i sjukdomsaktivitet mätt med ESSDAI vid diagnos mellan pSS patienter med och utan hjärt-kärlsjukdom. Patienter med arteriell hjärt-kärlsjukdom (CVS+IHS) var äldre och hade oftare antihypertensiv behandling jämfört med pSS utan arteriell hjärtkärlsjukdom (p<0,01). En STAT4 SNP, rs7582694, var associerad med arteriell hjärt-kärlsjukdom (p=0.03, odds ratio 3.0). Resultat Vi fann en association mellan NFKB1 -94ATTG del allelen och pSS (allelfrekvens pSS 0,42, kontroller 0,38), p=0,01, OR 1,18. Genotypen associerade i en dominant modell (del/del+del/ins versus ins/ins) med p=0,02, OR 1,25. Samtliga patienter och 979 kontroller var tidigare genotypade för NFKB1 SNP rs4648022 (2). En haplotyp av NFKB1 -94ATTG del och SNP rs4648022 associerade med pSS, p=0,03, OR 1,35. Vi fann ingen association mellan NFKB1 -94ATTG del och förekomsten av SSA/SSB, Raynaud, artrit, hudvaskulit, spottkörtelsvullnad, lymfadenopati, lymfom, hypotyreos, leukopeni, hypergammaglobulinemi eller germinalcentra i läppspottkörtelbiopsin. Slutsats Patienter med pSS har, trots högre medelålder, en lägre frekvens cerebrovaskulär sjukdom än patienter med SLE. Sjukdomsaktiviteten vid diagnos tycks inte bidra till hjärt-kärlsjukdom medan det kan finnas en genetisk bakgrund till arteriell hjärtkärlsjukdom vid pSS. Referens 1. Svenungsson E et al. Ann Rheum Dis 2010; 69: 834-840. Abstractnummer: 59 59 ASSOCIATION MELLAN NFKB1 -94ATTG INS/DEL PROMOTER POLYMORFI OCH PRIMÄRT SJÖGRENS SYNDROM Gunnel Nordmark1, Lilian Vasaitis1, Elke Theander2, Marika Kvarnström3, Christopher Sjöwall4, Helena Forsblad-d´Elia5, Helmi Jazebi3,6, Marie Wahren-Herlenius3, Maija-Leena Eloranta1, Per Eriksson4 Reumatologsektionen, Institutionen för medicinska vetenskaper, Uppsala universitet, Uppsala 2 Reumatologsektionen, Skånes universitetssjukhus Malmö, Lunds universitet, Malmö 3 Reumatologsektionen, Institutionen för medicin, Karolinska Institutet, Stockholm 4 Reumatologsektionen, Institutionen för klinisk och experimentell medicin, Linköpings universitet, Linköping 5 Avdelningen för reumatologi och inflammationsforskning, Sahlgrenska akademin, Göteborgs universitet, Göteborg 6 Reumatologsektionen, Universitetssjukhuset Örebro, Örebro 1 Bakgrund Aktivering av NF-kappaB resulterar i inflammation och autoimmunitet och har visats i salivkörtelepitelceller från patienter med primärt Sjögrens syndrom (pSS) (1). Heterodimeren p50/p65 är van- Slutsats Genetisk variation i NFKB1 -94ATTG ins/del visas här för första gången associerad med pSS. Hur denna genvariant påverkar aktiveringen av NF-kappaB vid pSS är okänt och mål för framtida studier. Referenser 1 Lisi S et al. Laboratory investigation 2012 2 Nordmark G et al. Scand J Immunol 2013 3 Ungerback J et al. Carcinogenesis 2012 Abstractnummer: 60 60 SERUM MEDIATED PHAGOCYTOSIS OF NECROTIC MATERIAL BY POLYMORPHONUCLEAR LEUKOCYTES IN SYSTEMIC LUPUS ERYTHEMATOSUS (SLE). Michele Compagno1, Birgitta Gullstrand2, Andreas Jönsen1, Lennart Truedsson2, Gunnar Sturfelt1, Anders A. Bengtsson1 Institutionen för kliniska vetenskaper i Lund, Avdelningen för Reumatologi, Lunds Universitet 2 Institutionen för laboratoriemedicin i Lund, Avdelningen för Mikrobiologi, Immunologi och Glykobiologi, Lunds Universitet 1 Background Polymorphonuclear (PMNs) leukocytes with engulfed necrotic cell material (NCM), as formerly used in the LE-cell test, are frequently seen in SLE and associated to severe clinical manifestations. The aim of this study was to investigate if phagocytosis of NCM could predict or was associated with specific clinical phenotypes and/or disease activity in patients affected by SLE. Methods Sixty-nine SLE-patients were followed longitudinally for a median time of 2.1 years. A total of 1074 serum samples were taken approxReumaBulletinen Nr 96 · 2/2014 33 ABSTRACTS imately every 60 days together with registration of an extensive set of clinical and laboratory variables. NCM was generated by heat treatment of mononuclear cells from healthy donors, and PMNs from healthy donors were isolated by density gradient centrifugation. Sera from SLE-patients were incubated with PMNs and NCM, and phagocytosis was assessed by flow cytometry. Association and prediction of relevant clinical phenotypes and disease activity (measured by SLEDAI) were evaluated with mixed model and odds ratio (OR) and 95% confidence intervals (CI) were calculated. Results In serum samples from 46 of the 69 SLE patients, phagocytosis of NCM by PMNs was seen at least once and totally 417 times. Significant association between phagocytosis of NCM by PMNs was found with clinical phenotypes such as lupus nephritis (OR=1.7, CI=1.2-2.5), mucocutaneous involvement (OR=1.45, CI=1.11.9), arthritis (OR=0.51, CI=0.3-0.8) and also with increased SLEDAI (OR=1.41, CI=1.0-2.0). Furthermore, phagocytosis of NCM by PMNs could predict alopecia (OR=2.22, CI=1.3-3.7) and was inversely related to arthritis (OR=0.38, CI=0.1-1). Conclusion In SLE, high capacity of serum mediated phagocytosis of NCM by PMNs may be associated with certain clinical features (mucocutaneous and renal involvement) and disease activity. It may be a predictor for alopecia. It is inversely related to a milder disease course (arthritis). Thus, its assessment may be used as a complementary laboratory tool in SLE-patients. Abstractnummer: 61 61 LOW PRODUCTION OF REACTIVE OXYGEN SPECIES IN GRANULOCYTES IS ASSOCIATED WITH ORGAN DAMAGE IN SYSTEMIC LUPUS ERYTHEMATOSUS Anders Bengtsson1, Åsa Pettersson2, Stina Wichert3, Birgitta Gullstrand, Markus Hansson3, Thomas Hellmark2, Åsa Johansson3 Department of Clinical Sciences, Section of Rheumatology, Lund University and Skåne University Hospital, Sweden 2 Department of Nephrology, Clinical Sciences, Lund University, Lund, Sweden 3 Department of Haematology, Lund University and Skåne University Hospital, Sweden 4 Department of Laboratory medicine Lund. Section of Microbiology, immunology and Glycobiology, Lund University, Lund, Sweden 5 Clinical Immunology and Transfusion Medicine, University and Regional Laboratories Region Skåne, Lund, Sweden 2014 1 Abstractnummer: 62 62 ly been detected in SLE patients, their role in SLE pathogenesis still remains elusive. The aim of this study was to evaluate levels of anti-HMGB1 antibodies in relation to other autoantibodies and to disease activity in a Swedish cohort of SLE patients. Subjects and methods Serum from 205 patients with SLE (92% female; mean age 50.5 years/range 18-80; mean duration 11 years/range 0-45) and from 112 healthy donors (91% female; mean age 46.5 years/range 19-84). Levels of anti-HMGB1 antibodies were detected by ELISA. Briefly, plates were coated with recombinant HIS-tagged HMGB1, blocked with milk and incubated with serum samples diluted 1:500. HRP-conjugated anti-human IgG was added and after development, the absorbance was measured. Arbitrary units (AU) were calculated by normalization against a positive control sample. Cut-off value 300 AU was calculated as mean value of the healthy controls + 2 standard deviations. Results 22% of the SLE patients were anti-HMGB1 antibody positive compared to 4% of the healthy controls. The levels of anti-HMGB1 antibodies were significantly higher in the patients compared to the healthy controls. The levels of anti-HMGB1 antibodies correlated significantly with the levels of anti-dsDNA antibodies, SLE Disease Activity Index (SLEDAI) and erythrocyte sedimentation rate, whereas albuminuria, complement function (classical pathway) and complement protein C4 were inversely correlated with anti-HMGB1. Conclusion The correlation of anti-HMGB1 antibodies with SLE disease activity scores and serological measures of disease activity indicates that these antibodies may be involved in the pathogenesis of SLE. Our findings also suggest that anti-HMGB1 antibodies may serve as a useful diagnostic and prognostic tool in SLE. Abstractnummer: 63 63 PLATELET ACTIVATION AND ANTIPHOSPHOLIPID ANTIBODIES COLLABORATE IN THE ACTIVATION OF THE COMPLEMENT SYSTEM ON PLATELETS IN SYSTEMIC LUPUS ERYTHEMATOSUS Christian Lood1, Helena Tydén1, Birgitta Gullstrand2, Gunnar Sturfelt1, Andreas Jönsen1, Lennart Truedsson2, Anders Bengtsson1 Department of Clinical Sciences Lund, Section of Rheumatology, Lund University and Skåne University Hospital, Lund, Sweden 2 Department of Laboratory Medicine Lund, Section of Microbiology, Immunology and Glycobiology, Lund University, Lund 1 64 EVALUATION OF AUTOANTIBODIES AGAINST HIGH MOBILITY GROUP BOX PROTEIN 1 (HMGB1) IN SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) Abstractnummer: 64 Hanna Schierbeck1, Lina Wirestam2, Marie Fischer1, Lars Ottosson1, Ann-Charlotte Aveberger1, Christopher Sjöwall2, Jonas Wetterö2, Erik Sundberg1, Thomas Skogh2, Helena Erlandsson Harris1 EFFECT OF SINGLE-NUCLEOTIDE POLYMORPHISMS ON TYPE I INTERFERON PRODUCTION BY PLASMACYTOID DENDRITIC CELLS STIMULATED WITH SLE-ASSOCIATED IMMUNE COMPLEXES 1 Karolinska Institutet 2 Linköping University Introduction HMGB1 has been implicated in the pathogenesis of SLE since HMGB1 is required in the DNA-containing immune complexes that stimulate production of anti-dsDNA antibodies, which is a hallmark of SLE. Although anti-HMGB1 antibodies have previous34 ReumaBulletinen Nr 96 · 2/2014 Olof Berggren1, Andrei Alexsson1, Karolina Tandre1, AnnChristine Syvänen2, Lars Rönnblom1, Maija-Leena Eloranta1 Uppsala University, Dept. of Medical Sciences, Rheumatology and Science for Life Laboratory, Uppsala, Sweden. 2 Uppsala University, Dept. of Medical Sciences, Molecular Medicine and Science for Life Laboratory, Uppsala, Sweden. 1 ABSTRACTS Introduction Systemic lupus erythematosus (SLE) and many other systemic autoimmune diseases have a persistently activated type I interferon (IFN) system, displayed as elevated serum levels of IFN-alpha and increased expression of type I IFN inducible genes (an IFN signature). Lately, studies have shown an association between the susceptibility to SLE and several gene variants within the type I IFN system, and we have showed that IFN-alpha production by the plasmacytoid dendritic cell (pDC) was enhanced by crosstalk with natural killer (NK) cells and B cells. Laboratory, Uppsala University 2 Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences Aim We investigated whether single nucleotide polymorphisms (SNPs) associated with SLE and other autoimmune diseases have an impact on the IFN-alpha production by pDC. Methods: pDC, B and NK cells were isolated from peripheral blood obtained from healthy individuals, and stimulated with RNA-containing immune complexes (IC), herpes simplex virus (HSV) or the oligonucleotide ODN2216. IFN-alpha production was measured in the cell cultures by an immunoassay. All blood donors were genotyped with 200K ImmunoChip and a 5bp CGGGG length polymorphism in the IFN regulatory factor 5 gene (IRF5) by PCR. Methods Human T cells were activated by anti-CD3/CD28 antibodies or in a mixed leukocyte reaction (MLR). T cells or supernatant from T cell cultures were co-cultured with pDCs stimulated with immune complexes containing U1 snRNP particles and SLE-IgG (RNA-IC). Cells were analyzed by flow cytometry and cytokines in co-culture supernatants were depleted or blocked by monoclonal antibodies. Culture supernatants were analyzed after 20h for IFNα and other cytokines. Results We found associations between IFN-alpha production and 28-107 SNPs (p<0.001) depending on the combination of stimulated cell types. However, only three of these associated SNPs were shared between the cell type combinations. Several of the SNPs have not been associated with type I IFN production previously, while some loci have been described earlier for their genetic association with SLE. Furthermore, we found that the SLE-risk variant of the 5 bp IRF5 CGGGG-indel was associated with a lower IFN-alpha production. Conclusion We found a large number of genetic variants affecting the IC-mediated type I IFN production that highlight the intricate regulation of the type I IFN system and can reveal new therapeutic targets for SLE. Abstractnummer: 65 65 TYPE I INTERFERON-MEDIATED DECREASE OF THE SEROTONIN SYNTHESIS IN SYSTEMIC LUPUS ERYTHEMATOSUS – A POSSIBLE RELATION TO CARDIVASCULAR DISEASE? Christian Lood1, Helena Tydén1, Birgitta Gullstrand, Cecilia Klint, Christina Wenglén, Christoffer Nielsen, Niels Heegaard, Andreas Jönsen1, Anders Bengtsson1 Department of Clinical Sciences Lund, Section of Rheumatology, Lund University and Skåne University Hospital, Lund, Sweden 2 Department of Laboratory Medicine Lund, Section of Microbiology, Immunology and Glycobiology, Lund University, Lund, Sweden 3 Anamar AB, Lund, Sweden 4 Department of Clinical Biochemistry, Immunology and Genetics, Statens Serum Institut, Copenhagen, Denmark 1 Abstractnummer: 66 66 Activated T-cells Enhance the Interferon-α Production by RNA-IC stimulated Plasmacytoid Dendritic Cells Dag Leonard1, Maija-Leena Eloranta1, Niklas Hagberg1, Olof Berggren1, Karolina Tandre1, Gunnar Alm2, Lars Rönnblom1 1 Department of Medical Sciences, Rheumatology, Science for Life Background A prominent interferon-α (IFNα) signature is seen in several autoimmune diseases, including systemic lupus erythematosus (SLE). We asked if T cells can promote the IFNα production by plasmacytoid dendritic cells (pDCs) stimulated with RNA containing immune complexes. Results Activated T cells or supernatants from activated T cells increased the IFNα production >20-fold. After addition of cytokines to RNAIC stimulated pDCs, GM-CSF and IL-3 was demonstrated to increase the IFNα production. This stimulatory effect was reduced after depletion of GM-CSF in supernatants from activated T cells (81%), blocking of GM-CSF (78%) or its receptor subunits CD131 and CD116 (70-75%). Supernatant from activated T cells also increased the frequency of CD80 and CD86 expressing RNA-IC stimulated pDC from 7% to 37% and 8% to 21%, respectively. Activated SLE-T cells enhanced the IFNα production in RNA-IC stimulated pDC to the same extent as activated T cells from healthy individuals. Elevated levels of serum-GM-CSF (4.2-128 pg/ml) was found in 30% of SLE patients, all characterized by increased levels of serum-IFNα (3.0-29 U/ml). Conclusions Activated T cells enhance the IFNα production by RNA-IC stimulated pDCs via GM-CSF and IL-3 and induces maturation of the pDCs. The observation that all SLE patients with measurable serum levels of GM-CSF had elevated serum levels of IFNα indicates that activated T cells may be important for the ongoing IFNα production in this disease. Abstractnummer: 67 67 AUTOANTIBODIES TO THE CD94/NKG2A AND CD94/NKG2C RECEPTORS IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS Niklas Hagberg1, Jakob Theorell2, Karin Hjorton1, Maija-Leena Eloranta1, Yenan Bryceson2,3, Lars Rönnblom1 Department of Medical Sciences, Section of Rheumatology, Science for Life Laboratories, Uppsala University 2 Center for Infectious Medicine, Department of Medicine, Karolinska Institute, Karolinska University Hospital Huddinge 3 Broegelmann Research Laboratory, Institute for Clinical Sciences, University of Bergen 1 Introduction Recently, we serendipitously identified a patient with SLE harboring autoantibodies to CD94/NKG2A. CD94/NKG2A is a NK cell receptor that binds HLA-E and regulates cytotoxicity. In the present study, we investigated the occurrence and function of autoantibodies targeting the CD94/NKG2A, ReumaBulletinen Nr 96 · 2/2014 35 30 ReumaBulletinen Nr 95 · 1/2014 ABSTRACTS CD94/NKG2C or NKG2D receptors in patients with SLE. Method Sera from 203 SLE patients and 90 healthy individuals were analyzed for Ig-binding to murine Ba/F3 cells transfected with CD94/ NKG2A, CD94/NKG2C or NKG2D, using flow cytometry. Identified autoantibodies were characterized for interference with HLA-E-binding, effect on NK cell degranulation in response to HLA-E-transfected K562 cells, and their capacity to mediate antibody-dependent cellular cytotoxicity (ADCC). The exons encoding NKG2A (KLRC1), NKG2C (KLRC2), and CD94 (KLRD1) were sequenced. The titers of anti-CD94/NKG2A and anti-CD94/NKG2C autoantibodies were determined in longitudinally sampled sera and correlated to disease activity (SLEDAI) and severity (SLICC/ACR damage index). Results Anti-CD94/NKG2A autoantibodies were detected in sera from seven patients. Six sera inhibited HLA-E-binding to CD94/NKG2A, whereas one increased this binding. Two of these sera also contained Ig that bound CD94/NKG2C, with one inhibiting, and one augmenting, HLA-E-binding to CD94/NKG2C. Anti-CD94/ NKG2A and anti-CD94/NKG2C autoantibodies abrogated the HLA-E-mediated inhibition of CD94/NKG2A+ and activation of CD94/NKG2C+ NK cells, respectively. Furthermore, these autoantibodies facilitated elimination of CD94/NKG2A- and CD94/NKG2C-expressing cells through ADCC. No unique nonsynonymous sequence variations were found in KLRC1, KLRC2, or KLRCD1. The titers of anti-CD94/NKG2A autoantibodies were associated to disease activity. Conclusions Autoantibodies targeting the CD94/NKG2A or the CD94/NKG2C receptor are found in a subset of patients with SLE. Their titers are associated to the disease activity and a more severe SLE phenotype. Mechanistically, the autoantibodies can affect NK cell cytotoxicity and mediate ADCC. Consequently, anti-CD94/NKG2A and anti-CD94/NKG2C autoantibodies may contribute to the pathogenesis of SLE and our findings highlight the possible importance of NK cells in the SLE disease process. Abstractnummer: 68 68 INTRATHECAL LEVELS OF SOLUBLE RECEPTOR FOR ADVANCED GLYCATION END PRODUCTS (SRAGE) IN PATIENTS WITH SUSPECT NEUROPSYCHIATRIC MANIFESTATIONS OF SYSTEMIC LUPUS ERYTHEMATOSUS Estelle Trysberg1, Sara Haghighi2, Rille Pullerits 1 Department of Rheumatology and Inflammation Research, Institute of Medicine, The Sahlgrenska Academy at the University of Gothenburg 2 Department of Neuroscience and Physiology, Institute of Clinical Neuroscience, The Sahlgrenska Academy at the University of Gothenburg 1 Abstractnummer: 69 69 Pro-inflammatory S100 proteins are associated with glomerulonephritis and anti-dsDNA antibodies in systemic lupus erythematosus Helena Tydén1, Christian Lood1,2, Birgitta Gullstrand2, Andreas Jönsen1, Fredrik Ivars3, Tomas Leanderson3, Anders A Bengtsson1 Department of Clinical Sciences, Division of Rheumatology, Lund University and Skane University Hospital, Lund 2 Department of Laboratory Medicine, Division of Microbiology, Immunology and Glycobiology, Lund University, Lund 3 Department of Experimental Medical Science, Immunology Group, Lund University, Lund 1 Background Phagocytosis of autoantibody-coated necrotic cell material (NC) by polymorphonuclear neutrophils (PMNs) is commonly seen in SLE patients but downstream events such as PMN-mediated activation and release of proinflammatory S100 proteins are less investigated. We specifically wanted to know if S100A8/A9 and S100A12 serum levels could be related to phagocytosis of NC by PMNs in vitro, disease activity, as well as to the clinical phenotype in SLE. Methods Serum levels of S100A8/A9 and S100A12 from 100 SLE patients were measured with ELISA. Phagocytosis of NC by PMNs from healthy donors in the presence of SLE serum from the 100 SLE patients was analysed by flow cytometry. Disease manifestations and autoantibody profile at the time point of blood sampling were also recorded. Results Serum levels of S100A8/A9 and S100A12 were increased in SLE patients with active disease as compared to healthy controls (p<0.0001 and p=0.0001, respectively). S100A8/A9 serum levels were particularly increased in SLE patients with anti-dsDNA antibodies (p=0.01), as well as in patients with serum with high ability to support phagocytosis of NC by PMNs (p=0.01). Furthermore, increased serum levels of S100A8/A9 were seen in SLE patients with active glomerulonephritis who had not started treatment with immunosuppressive drugs (p=0.04) compared to patients at flare without this manifestation. Conclusions Elevated serum levels of S100A8/A9 and S100A12 were seen in active SLE. The elevated serum levels of S100A8/A9 were associated with glomerulonephritis, presence of anti-dsDNA antibodies and a high capacity to promote phagocytosis of NC by PMNs. Serum levels of S100A8/A9 and S100A12 may be useful markers of disease activity in SLE patients. Abstractnummer: 70 70 Comparison of three assays to assess antibodies against double-stranded DNA in systemic lupus erythematosus Helena Enocsson1, Lina Wirestam1, Charlotte Dahle2, Johan Rönnelid3, Alf Kastbom1, Jonas Wetterö1, Christopher Sjöwall1, Thomas Skogh1 Rheumatology/AIR, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden 2 Clinical Immunology & Transfusion Medicine, County Council of Östergötland, Linköping Sweden 3 Genetics & Pathology, Department of Immunology, Rudbeck Laboratory C5, Uppsala University, Sweden 1 Background Analysis of antibodies against double-stranded DNA (anti-dsDNA) is a diagnostic tool in systemic lupus erythematosus (SLE). Generally, anti-dsDNA analyses by conventional enzyme-immunoassays have lower diagnostic accuracy than the Crithidia luciliae immunofluorescence test (CLIFT) and Farr. Herein, CLIFT was used ReumaBulletinen Nr 96 · 2/2014 37 ABSTRACTS as reference to compare the PhaDia enzyme immunoassay and the fluorescent microspehere immunodetection system (FIDIS). Subjects and methods Sera from 192 SLE patients were analyzed for IgG anti-dsDNA by CLIFT (cut-off >99th percentile among 100 healthy female blood donors), PhaDia (Thermo Fisher Scientific/Phadia AB) and FIDIS (Theradiag) with the cut-off limits suggested by the manufacturers. The patients were from the KLURING project (Kliniskt Lupusregister i nordöstra Götaland) and fulfilled the 1982 ACR criteria (81%) or the Fries’ criteria. For CLIFT and PhaDia, the following disease controls were included: 100 blood donors (50 women, 50 men), 97 with rheumatoid arthritis and 54 patients with primary Sjögren’s syndrome. Results Phadia captured a higher number of SLE patients (34%) than CLIFT (25%) but did also detect a higher number of disease controls. Fisher’s exact test revealed that all anti-dsDNA tests showed significant positive associations to ACR criterion 7 (renal disease) and 10 (immunologic disorder). CLIFT and FIDIS, but not PhaDia, showed significant negative associations to criterion 3 (photosensitivity), whereas PhaDia alone showed a negative association to criterion 4 (oral ulcers). Anti-dsDNA measured by CLIFT correlated more strongly to FIDIS (rho=0.631) than to PhaDia (rho=0.475). The correlation coefficient between PhaDia and FIDIS was 0.607. Conclusion When CLIFT is chosen as ‘the gold standard’ for anti-dsDNA measurement in SLE, the present study indicates that FIDIS performs better than PhaDia. This applies both to the associations with disease manifestations, and to correlation with CLIFT anti-dsDNA. As regards diagnostic specificities, we found that a positive CLIFT was more SLE-specific than PhaDia. Abstractnummer: 71 71 Associations between antinuclear antibody staining patterns and clinical features of systemic lupus erythematosus Martina Frodlund1, Örjan Dahlström2, Alf Kastbom1, Thomas Skogh1, Christopher Sjöwall1 Rheumatology/AIR, Department of Clinical and Experimental Medicine, Linköping University, Linköping 2 Swedish Institute for Disability Research, Department of Behavioural Sciences and Learning, Linköping University, Linköping 1 An abnormal antinuclear antibody (ANA) titer evaluated by immunofluorescence (IF) microscopy is a cornerstone in the 1982 American College of Rheumatology (ACR-82) classification criteria of systemic lupus erythematosus (SLE) as well as in the new Systemic Lupus International Collaborating Clinics (SLICC) criteria. Several studies have addressed the clinical value of ANA finespecificities in SLE but, to our knowledge, has none evaluated how distinct ANA staining patterns are related to clinical features of SLE. Thus, we aimed at comparing indirect IF microscopy patterns with SLE phenotypes in a local Swedish SLE-register. 222 SLE patients taking part in the prospective control programme at Linköping university Hospital. 178 patients (80%) met the ACR-82, whereas 44 (20%) had a clinical SLE based on abnormal ANA titer and ≥two typical manifestations (Fries criteria). ANA was analyzed by IF microscopy using multispot slides with fixed HEp-2 cells, anti-dsDNA by Crithidia luciliae and autoantibodies to extracta- 38 ReumaBulletinen Nr 96 · 2/2014 ble nuclear antigens by double radial immunodiffusion and/or line-blot. Differences in the proportions of patients with homogenous, speckled, homogenous/speckled and nucleolar±combination with other patterns were calculated. 54% SLE patients displayed homogenous staining, 22% speckled, 11% homogenous/speckled, 9% nucleolar±other patterns. Homogenous staining pattern was associated with immunologic disorder (p<0.001). Speckled pattern was inversely associated with arthritis (p=0.02), immunologic disorder (p<0.001) and SLICC/ ACR damage index ≥1 (p=0.007). Positive anti-SSA antibody test was associated with photosensitivity (p=0.023) and inversely associated with arthritis (p=0.016). This cohort of well-characterized patients confirmed that homogenous nuclear staining is the most common IF-ANA pattern in Caucasian SLE patients. The inverse relation between speckled pattern and arthritis was strengthened by the corresponding relation between anti-SSA and arthritis. The previously described association between anti-SSA and photosensitivity was confirmed. The inverse relationship between speckled staining and SLICC/ ACR damage index could indicate a milder disease with a better prognosis for individuals with this ANA pattern. Abstractnummer: 72 72 Quality of life and organ damage are strongly related to activity limitations in patients with systemic lupus erythematosus Mathilda Björk1, Örjan Dahlström2, Jonas Wetterö3, Christopher Sjöwall3 Rehabenheten HMC, Linköpings universitetssjukhus, Landstinget i Östergötland 2 Institutionen för beteendevetenskap och lärande, Linköpings universitet 3 Avdelningen för reumatologi/AIR, IKE, Hälsouniversitetet i Linköping 1 Objective Systemic lupus erythematosus (SLE) is an autoimmune multi-organ disease, characterized by episodes of disease flares and remissions over time, which may restrain affected patients’ ability to perform daily activities. The aims of the present study were to describe the variation in activity limitation among well-defined SLE patients, and to identify the influence of disease phenotypes on activity limitation and patient self-reported health. Methods The disease phenotypes were organized into 4 different clusters and logistic regression analyses were used to identify how an elevated health assessment questionnaire (HAQ) score was related to the phenotypes. Correlation and multiple linear regression analyses were used to examine the association between each group of variables – demographics, disease variables and self-reported measurements – and the degree of elevated HAQ. Results We found a higher proportion of activity limitation in SLE patients with skin and joint manifestations compared to others. The presence of activity limitation, as detected by the HAQ instrument, was significantly associated with quality of life (EuroQol–5D) and irreversible organ damage (SLE international collaborative clinics/ ACR damage index). Conclusions The findings highlight the differing requirements of the multi-professional rehabilitation interventions for the various SLE phenoty- ABSTRACTS pes in order to optimize the clinical care of the patients. Abstractnummer: 73 73 SF-36 in SLE of Various Disease Durations: A comparison with RA and controls Christine Bengtsson1, Elias Jönsson2, Elisabet West3, Solveig Wållberg-Jonsson4 Inst för Folkhälsa och Klinisk medicin, UMU. Reumatologenheten, Östersunds sjukhus 2 Läkarstudent, T10, UMU 3 Reumatolokliniken, NUS 4 Inst för Folkhälsa och Klinisk medicin, UMU 1 Objective The aim of this study was to evaluate the self-experienced health in patients with systemic lupus erythematosus (SLE) in relation to patients with rheumatoid arthritis (RA) and controls. A further aim was to compare the self-experienced health over time and between sexes. Method Patients from the Northern region of Sweden with SLE; short (2 years) (n=17), medium (6 years) (n=46) and long (20 years) (n=47) disease duration (DD), were compared with RA-patients (n=51, respectively 51 and 39) and healthy age- and sex matched controls (n=36). Quality of life was measured using SF-36 health survey consisting of eight domains; Physical Function (PF), Role Physical (RP), Role Emotional (RE), Social Function (SF), Bodily Pain (BP), Mental Health (MH), Vitality (VT), Global Health (GH) but is also summarized into: physical (PCS)- and mental (MCS) component summary. Results Lower quality of life was seen in all groups of DD in SLE compared with RA. This was noted at 2 year regarding SF (p=0.04), 6 year regarding SF (p=0.01), MH (p=0.002), VT (p=0.02) and MCS (0.002) and at 20 year regarding SF (p=0.003), VT (p=0.006), GH (p=0.012) and MCS (p<0.001). The only domain where SLE- patients estimated their health higher than RA- patients was PF (p=0.019) at 20 years DD. Patients with SLE estimated their health significantly lower regarding all domains compared with controls. This was also noted regarding RA all DDs and controls except mental component (p>0.17). In SLE men generally estimated their health higher compared with women in contrast with RA. Conclusion We found that the SLE-patients generally experienced lower quality of life than RA-patients. Especially noted in 20 years DD, where the SLE-patients scored significantly lower than RA-patients in three domains and one dimension. Lower quality of life was noted among women compared with men in SLE, at contrast with the results in RA. Abstractnummer: 74 74 UTILITY OF SWEDISH REGISTER DATA IN CLASSIFYING SYSTEMIC LUPUS Elizabeth Arkema1, Andreas Jönsen2, Lars Rönnblom3, Christopher Sjöwall4, Elisabet Svenungsson, Julia Simard1,6,7 Karolinska Institutet, Department of Medicine, Clinical Epidemiology Unit 2 Lund University Hospital, Department of Rheumatology 3 Uppsala University, Department of Medical Sciences, Rheumatology 1 Unit 4 Linköping University, Dpeartment of Clinical and Experimental Medicine 5 Karolinska University Hospital, Department of Medicine, Rheumatology Unit 6 Stanford School of Medicine, Department of Health Research and Policy, Division of Epidemiology 7 Stanford School of Medicine, Department of Medicine, Division of Rheumatology and Immunology Background Systemic Lupus Erythematosis (SLE) is a rare disease, making it a challenge to achieve an adequate sample size for many research questions. Our aim was to use data mining techniques to identify a classification algorithm using national register data in Sweden. Methods Clinically confirmed SLE cases were pooled from four major clinical centers in Sweden (Linköping, Lund, Stockholm and Uppsala), we excluded cases with <4 ACR criteria. We identified a population of non-SLE comparators by randomly selecting individuals from the National Population Register matched on age, sex and county to individuals with SLE from the national registers. Both cases (N=940) and comparators (N=24,370) were restricted to adults (>16y) living in Sweden January 1, 2010. Covariates on demographics, comorbid conditions, prescriptions and family history of autoimmune disease were obtained from multiple registers and linked to the case and non-case populations. We applied 2 different methods (classification tree analysis and penalized least absolute shrinkage and selection operator (LASSO) regression) to generate an algorithm to identify cases from non-cases in men and women separately. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated to measure the algorithm’s accuracy. Sensitivity analyses investigated the influence of SLE prevalence on predictive values. Results Both the classification tree method and LASSO regression identified only one variable as the best single discriminator between cases and non-cases: at least one SLE ICD code listed in a specialized clinic. This resulted in a sensitivity of 0.99 and a PPV of 0.98 in women. Results in men were similar. Discussion The use of an SLE ICD code in a specialized clinic to distinguish between cases and non-cases performed well. It is possible to identify individuals with SLE among thousands of people in Sweden, however validation studies are necessary to assess the magnitude of potential misclassification. Abstractnummer: 75 75 TWO YEAR FOLLOW-UP ON BIOLOGICS USE IN 13 CENTERS DATA FROM THE INTERNATIONAL REGISTRY FOR BIOLOGICS IN SLE (IRBIS) Melinda Mild, Ronald van Vollenhoven, Sören Jacobsen2, Daniel Wallace3, Manel Ramos-Casals4, and for the SLICC group Karolinska Institutet, ClinTRID, Stockholm, Sverige 2 Köpenhamns Universitetssjukhus, Köpenmand, Danmark 3 Cedars-Sinai Medical Center, West Hollywood, United States 4 Hospital Clinic, Barcelona, Spain 1 Background Only one biologic agent has been approved for use in SLE, but some are used off-label. To obtain systematic information regarding this, the SLICC group initiated the International Registry for Biologics ReumaBulletinen Nr 96 · 2/2014 39 ABSTRACTS in SLE (IRBIS). Here, data are presented from 13 (of 28) centers for which two-year-follow-up were available. Methods IRBIS investigators provided retrospective data on all patients treated with a biologic at their center in 2010-2011. Demographic-, disease-specific and treatment-data at biologic initiation and at yearly follow-ups were collected in standardized CRFs. Results In the entire cohort of 455 patients, 84% were treated with rituximab, belimumab 10%, epratuzumab 5% and the remaining with anti-TNF agents (each <1%). The major organ manifestation leading to biologic treatment was lupus nephritis (LN, 44%); reason for choosing the biologic was mainly disease-control (73%). At biologic initiation, mean disease duration (±SD) was 9.5±7.9 years; mean age was 42.2±12.5. Most patients (91%) were female. Prior to biologic treatment, most patients (91%) had been treated with ≥1 immunosuppressives. At two-year follow-up (n=120), SLE disease activity (SLEDAI) and corticosteroid (CS) dose were significantly lower versus baseline (SLEDAI: 9.4±5.3 to 3.1±2.5; CS: 10.7±13.9 to 4.8±5.9 mg; mean±SD paired analyses, p<0.0001 for both comparisons). At baseline, concomitant CS was used in 91% of patients compared to 61% at follow-up. SLICC damage-index remained unchanged. There were six deaths, none attributed to the biologic. In 48% of patients there was at least one adverse event reported over the follow-up period, of which 5% were attributed to the biologic agent. Serious adverse events included 6 infections, 4 opportunistic infections, 3 posterior reversible encephalopathy syndrome and 4 allergic reactions. Conclusion Rituximab was the biologic used most commonly in this international cohort of SLE patients. At two-year-follow-up lupus activity and concomitant corticosteroid dosage decreased significantly and corticosteroids were discontinued in 30% of patients. Abstractnummer: 76 73 OFF-LABEL USE OF RITUXIMAB FOR SLE IN EUROPE: LIMITED USE MOSTLY IN REFRACTORY PATIENTS Melinda Mild1, Ronald van Vollenhoven1, Sören Jacobsen2, and for the SLICC group Karolinska Institutet, ClinTRID, Stockholm, Sverige 2 Köpenhamns Universitetssjukhus, Köpenhamn, Danmark 1 Background Rituximab (RTX) is not approved for use in SLE but has been used off-label in European countries with efficacy in some patients. We previously reported, based on the International Registry for Biologics in SLE (IRBIS) and data from investigators, that 0.5-1.3% of European SLE patients have been treated with RTX. Here, we compared the characteristics of SLE patients treated with RTX to those treated with conventional non-biologic immunosuppressives (ISs). Methods Investigators participating in IRBIS, initiated by the SLICC group, provided data for this study. Data submitted to the IRBIS registry by 28 centers in 11 European countries were complemented with additional information from the participating sites. Comparators were patients started on any conventional IS, not necessarily naïve for this. 40 ReumaBulletinen Nr 96 · 2/2014 Results One-hundred-and-seventy-five patients were analysed; 103 were treated off-label with RTX and 72 with IS. Most frequently used ISs were mycophenolate mofetil (43%) and azathioprine (33%). For both groups, about 90% were female, 90% caucasians and 85% non-smokers. Organ manifestations leading to treatment with RTX or ISs were mainly lupus nephritis (LN, 58% and 53%, respectively). Reason for treatment initiation with RTX was mainly disease control while steroid sparing was frequently the main reason for ISs. At treatment initiation mean disease duration (±SD) was 9.1±7.0 for RTX-treated patients and 4.1±6.6 for patients on ISs (p<0.0001); mean ages were 41.2±12.5 and 36.1±11.3, respectively (p=0.007). There were significant differences between the groups for SLEDAI (12.2±7.0 vs. 9.4±7.0; p=0.001) and SLICC damage index (1.6±3.4 vs. 0.57±1.0, p=0.014). Conclusion Both RTX and conventional ISs are mostly used for LN. However, patients started on RTX were somewhat older, had significantly longer disease duration, higher disease activity and more damage compared to patients started on conventional ISs only. These data support the view that RTX is used for selected patients with later-stage, more severe SLE. Abstractnummer: 77 75 Application of the 2012 Systemic Lupus International Collaborating Clinics Classification Criteria On a Regional Swedish Systemic Lupus Erythematosus Register Anna Ighe1, Örjan Dahlström2, Th mas Skogh1, Christopher Sjöwall1 Rheumatology/AIR, Department of Clinical and Experimental Medicine, Linköping University, Linköping 2 Swedish Institute for Disability Research, Department of Behavioural Sciences and Learning, Linköping University, Linköping 1 In addition to the 1982 American College of Rheumatology criteria (ACR-82) for scientific classification of systemic lupus erythematosus (SLE), many clinicians find the ’Fries criteria’ (requiring an abnormal ANA titer plus ≥two typical organ manifestations) helpful for diagnostic purposes. Last year, the Systemic Lupus International Collaborating Clinics group proposed a new set of validated classification criteria (SLICC-12), claimed to being more sensitive. The aim of the present study was to analyze the performance of SLICC-12 compared to Fries criteria and ACR-82 among well-characterized SLE cases and controls in a regional Swedish register. The study population consisted of 231 SLE cases (93% Caucasians; 203 women, 28 men; mean age 38.8 years) confirmed by Fries criteria and/or ACR-82. 53 controls (46 women, 7 men; 40.8 years) were enrolled on the basis of referral to a rheumatology specialist based on at least one criterion regarding ’immunologic disorder’ according to ACR-82 and a clinical suspicion of SLE. Sensitivity and specificity figures for SLE were calculated. All confirmed SLE cases took part in a prospective follow-up programme at Linköping University hospital. Of the confirmed SLE cases, 98% fulfilled Fries criteria, 81% ACR82 and 91% SLICC-12. The combinations of Fries and/or SLICC-12 identified 99%, compared to 93% of all confirmed SLE cases identified by ACR-82 and/or SLICC-12. The sensitivity was high for Fries (97%) and SLICC-12 (91%), but lower for ACR-82 (79%), whereas the specificity was superior for ACR-82 (98%) compared to Fries (83%) and SLICC-12 (75%). We confirm that the ACR-82 criteria set offers a very high diagnostic specificity, but fail to reveal >20% ABSTRACTS of the SLE cases as defined here. The SLICC-12 criteria provide important additional sensitivity, whereas the specificity was mediocre in this comparison. To increase sensitivity and specificity figures, we advice a combination of the ACR-82 and SLICC-12 criteria for future studies. Abstractnummer: 78 73 CUMULATIVE INCIDENCE OF LARGE VESSEL INVOLVEMENT IN BIOPSY-PROVEN GIANT CELL ARTERITIS Aladdin Mohammad1,2,3, Carl Turesson2,4 Department of Renal Medicine, Vasculitis and Lupus Clinic, Addenbrooke’s Hospital, Cambridge, UK 2 Reumatologiska kliniken, Skånes Universitetssjukhus 3 Sektionen för Reumatologi, Institutionen för Kliniska Vetenskaper, Lund, Lunds Universitet 4 Sektionen för Reumatologi, Institutionen för Kliniska Vetenskaper, Malmö, Lunds Universitet 1 Abstractnummer: 79 73 Progress Report on the Development of New Classification Criteria for Adult and Juvenile Idiopathic Inflammatory Myopathies Anna Tjärnlund, Matteo Bottai, Lisa G Rider, Victoria P Werth, Clarissa Pilkington, Marianne de Visser, Lars Alfredsson, Anthony Amato, Richard J Barohn, Matthew Liang, Jasvinder A Jasvinder A Singh, Frederick W Miller, Ingrid E Lundberg1 Rheumatology Unit, Department of Medicine, Karolinska University Hospital, Solna, Karolinska Institutet, Stockholm, Sweden 2 Institute for Environmental Medicine, Karolinska Institutet, Stockholm, Sweden 3 Environmental Autoimmunity Group, Program of Clinical Research, National Institute of Environmental Health Sciences, National Institutes of Health, US Department of Health and Human Services, Bethesda, USA 4 Department of Dermatology, Philadelphia VAMC and Hospital of the University of Pennsylvania, Philadelphia, USA 5 Department of Rheumatology, Great Ormond Street Hospital for Children NHS Trust, London, United Kingdom 6 Department of Neurology, Academic Medical Centre, Amsterdam, Netherlands 7 Department of Neurology, Brigham and Women’s Hospital, Harvard Medical School, Boston, USA 8 Department of Neurology, University of Kansas Medical Center, Kansas City, USA 9 Division of Rheumatology, Immunology and Allergy, Brigham and Women´s Hospital, Boston, USA 1 Background Inadequate classification criteria for IIM are a fundamental limitation in clinical studies. An international, multidisciplinary collaboration, the International Myositis Classification Criteria Project (IMCCP), was established to address this problem. Methods Candidate variables for classification criteria were assembled from published criteria and inclusion criteria in controlled myositis trials. Comparator groups confused with IIM were defined. Clinical and laboratory data from IIM and comparator patients were collected from 47 rheumatology, dermatology, neurology and pediatrics clinics worldwide from 2008-2011. Crude pair-wise associations among all variables measured and between each variable and clinician’s diagnosis were assessed. Approaches for derivation of criteria were: 1. Traditional: case defined by specified number of items from a set 2. Risk score: patient assigned a probability risk score by summing score-points associated with the variables (Probability models 1 and 2) 3. Classification tree: case defined by a decision tree A random forest algorithm explored the most important variables. Internal validation using bootstrap methods was performed. External validation using data from the Euromyositis register and an UK juvenile myositis register was performed. Results Data from 973 IIM patients, representing subgroups of IIM, and 629 comparators were obtained. Comparators include other myopathies and systemic rheumatic diseases. Two probability score models were developed: Model 1 comprised clinical variables on muscles, skin, and laboratory measures; Model 2 additionally comprised muscle biopsy variables. Model 1 performed nearly as well as Model 2 and both models performed as well as and often better than, the classification tree developed and published criteria. External validation using data on 2363 myositis patients in the Euromyositis register and 332 juvenile myositis cases resulted in >99% and 100% sensitivity respectively for both probability models. Conclusion New classification criteria for IIM with readily clinically assessable measurements and symptoms have been developed. They generally show superior performance compared with existing criteria. 75 Abstractnummer: 80 Inklusionskroppsmyosit - en eller två sjukdomar? Ingrid Lundberg1,2, Inger Nennesmo1,2, Snjolaug Arnardottir1,2, Anna Tjärnlund1,2 1 Karolinska Institutet 2 Karolinska Universitetssjukhuset Bakgrund Inklusionskroppsmyosit (IBM) tillhör de inflammatoriska myopatierna. Sjukdomens patogenes är idag omdiskuterad och till stor del okänd. IBM förekommer både ensam och tillsammans med autoimmuna systemsjukdomar varav Sjögrens syndrom (SS) är vanligast. Sambandet mellan IBM och SS är i dag till stor del outforskat. Denna studie syftade till att jämföra IBM-patienter utan SS med IBM-patienter som hade samtidig SS-diagnos för att undersöka om det finns betydelsefulla skillnader mellan grupperna som skulle kunna leda till en indelning av IBM i olika subgrupper. Material och metoder: 51 patienter med IBM, varav 10 även hade SS, som mellan 2003–2013 behandlats på Reumatologiska och Neurologiska klinikerna vid Karolinska Universitetssjukhuset i Solna inkluderades. Grupperna jämfördes utifrån demografiska, kliniska och laboratoriemässiga variabler. Patientdata inhämtades från journaler och kvalitetsregister. Resultat Skillnader som påvisades var att patientgruppen med både IBM och SS bestod övervägande av kvinnor (p=0,036) med en tidigare sjukdomsdebut (p=0,098). En mer uttalad muskelsvaghet sågs också i denna grupp, även om den var svårtolkad. Laboratoriemässigt sågs en förhöjd sänkereaktion (p=0,0015) och vanligare förekomst av antinukleära antikroppar (p=0,0083). Slutsatser De demografiska, laboratoriemässiga och kliniska skillnaderna utgör preliminära resultat som tyder på att en distinktion mellan grupperna kan göras. Mer forskning krävs dock för att klinisk til�lämpning ska kunna ske. ReumaBulletinen Nr 96 · 2/2014 41 ABSTRACTS Abstractnummer: 81 81 CD28NULL T-CELLER DÖDAR AUTOLOGA MUSKELCELLER FRÅN PATIENTER MED POLYMYOSIT IN VITRO Jayesh Pandya1, Paulius Venalis1, Lubna Al-Khalili, Mohammad Shahadat Hossain1, Vanessa Stache1, Ingrid Lundberg1, Vivianne Malmström1, Andreas Fasth1 Enheten för reumatologi, Karolinska univesrsitetssjukhuset Solna, Karolinska Institutet, Stockholm 2 Sektionen för integrativ fysiologi, Institutionen för molekylär medicin och kirurgi, K.I, Stockholm 1 Bakgrund Inflammatory infiltrates of muscles in polymyositis are dominated by CD4+CD28null and CD8+CD28null T-cells. In contrast to conventional CD28+ T-cells, these cells rapidly release large amounts of IFN-gamma and TNF and can kill tissue cells by granzyme B and perforin upon activation. Syfte To in a fully autologous system investigate the myotoxic effect of CD28null T-cells on muscle-cells from polymyositis patients. Material och metod Muscle stem cells were extracted from biopsies from 5 patients with polymyositis, and differentiated into myotubes. T-cell subsets from the same patients were isolated from peripheral blood by flow-cytometry. Co-cultures of autologous muscle-cells and unstimulated or pre-activated (anti-CD3-antibodies) T-cells were performed for 24 hours. Dead myotubes were quantified by calcein release or by flow-cytometry. Blocking experiments were performed by adding indicated antibodies to the cultures. Resultat CD4+CD28null and CD8+CD28null T-cells caused spontaneous death of 13-60% (n=2 patients) of the muscle-cells. No or low muscle-cell death was detected in cultures with conventional CD4+ and CD8+ T-cells. By blocking perforin the myotoxicity was reduced by 33-62% with CD4+CD28null T-cells and by 42-56% in cultures with CD8+CD28null T-cells (n=3). TNF or IFN-gamma did not induce death of muscle-cells in the absence of T-cells, but did upregulate MHC class I and II on musclecells (n=3-5). Blockade of IFN-gamma and TNF in co-cultures with T-cells reduced the level of dead muscle-cells by 42-70% (CD4+CD28null) and 10-78% (CD8+CD28null) (n=3). The reduced myotoxicity is likely attributed to reduced MHC expression, as MHC blockade resulted in a comparable reduction in myotoxicity, 56-70% (CD4+CD28null) and 38-95% (CD8+CD28null) (n=5). Slutsats The myotoxic effect by CD28null T-cells in polymyositis is mediated by directed perforin-dependent killing and regulated by IFN-induced MHC expression by muscle-cells. Together this suggests that CD28null T-cells are key effector cells directly contributing to the muscle-cell damage in polymyositis, hence represent target candidates for future therapies. Abstractnummer: 82 82 Autophagy May Contribute to Glu- cocorticoid Resistance in Patients with Myositis by Maintaining T Lymphocytes Homeostasis in the Muscles Mei Zong1, John Jörholt1, Julia Winter1, Eva Lindroos1, Helena E Harris1, Ingrid E Lundberg1 42 ReumaBulletinen Nr 96 · 2/2014 1 Enheten av reumatologi, Karolinska Universitetssjukhuset Background Infiltrating T cells is a typical histopathologic feature in muscles of myositis patients and they play important roles in disease development. In contrast to macrophages that can be reduced after glucocorticoid (GC) treatment, T cells often persist. Autophagy helps cells to survive under cellular stresses. In this context endogenous, cytosolic high mobility group box 1 (HMGB1) is interesting as HMGB1 can induce autophagy by binding Beclin1 (an upstream protein initiating autophagy) and thereby contribute to cell survival. Here we investigated whether autophagy initiated by HMGB1-Beclin1 binding contributes to T cell survival and whether this homeostatic T cells contribute to the GC resistance. Methods Muscle biopsies were obtained from poly- and dermatomyositis patients with no or limited clinical response to GC and from patients with good response. Clinical response was evaluated by functional index (FI) and serum creatine kinase (CK). Biopsies were investigated by immunohistochemistry for macrophages (CD163, CD68), T cells (CD3), HMGB1 and Beclin1. Computer image analysis was performed. Co-localization of HMGB1, Beclin1 and T cells was done by consecutive section staining and double immunofluorescence. Results HMGB1 and Beclin1 was detected in muscle tissue of patients and co-localized to the infiltrating T cells. Beclin1 correlated well with HMGB1, T cells positively and muscle function negatively. In nice GC responders HMGB1 and Beclin1 expression was decreased after treatment, so was the trend for T cells. Analyses are ongoing on the non-responders. According to our hypothesis in these patients T cells will not be reduced as many as in responders after treatment, and HMGB1 and Beclin1 expression will maintain at high levels. Conclusion Autophagy is present in the invading T cells in muscle tissue of myositis patients. Autophagy initiated by HMGB1- Beclin1 binding may contribute to T cell survival. These homeostatic T cells could be a factor contributing to the GC resistance. Abstractnummer: 83 83 PROFILE OF CIRCULATINING MICRORNAS IN FIBROMYALGIA AND THEIR RELATION TO SYMPTOM SEVERITY Jan Bjersing1, Maria Bokarewa1, Kaisa Mannerkorpi2 Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg 2 University of Gothenburg Centre for Person-centred Care (GPCC), Sahlgrenska Academy 1 Abstractnummer: 84 84 DILEMMAS OF PARTICIPATION IN EVERYDAY LIFE IN EARLY RHEUMATOID ARTHRITIS (RA), A QUALITATIVE INTERVIEW STUDY (The Swedish TIRA study). Annette Sverker1, Gunnel Östlund, Mikael Thyberg, Eva Waltersson1, Mathilda Björk, Ingrid Thyberg 1 Rehabgruppen NSC Universitetssjukhuset i Linköping, Landsting- ABSTRACTS et i Östergötland 2 Avdelning för socialt arbete, Akademin för hälsa, vård och välfärd, Mälardalens högskola. 3 Institutionen för klinisk och experimentell medicin, Linköpings universitet, Länskliniken för reumatologi, Landstinget i Östergötland. 4 Rehabiliteringsmedicin, Institutionen för Medicin och Hälsa, Linköpings Universitet, 5 Avdelningen för socialt arbete; Institutionen för samhälls och välfärdsstudier, Linköpings Universitet Background An important perspective in research is the patients´ own experiences of how it is to live with RA, in terms of dilemmas and consequences in everyday life. Although there have been improvements in the outcomes due to the pharmacological treatment, RA still has an impact on functioning. The aim was to explore dilemmas of participation experienced in everyday life in early RA. Material and methods We interviewed 48 patients, age 20 – 63, with early RA about participation dilemmas in everyday life, with Critical Incident Technique. Transcribed interviews were condensed into meaningful units describing situations. In next step, these descriptions were linked to ICF activity/participation codes according to ICF linking rules. Dilemmas related to ICF activity/participation according to domestic life, interpersonal interactions/relationships, community, social and civic lives are reported here. Results Regarding domestic life dilemmas were linked to acquisition of goods and services, preparing meals, doing housework, caring for household objects and assisting others. Regarding interpersonal interactions and relationships the dilemmas were linked to basic interpersonal interactions, complex interpersonal interactions, relating with strangers, informal social relationships, family relationships and intimate relationships. About community, social and civic life dilemmas were linked to community life, recreation and leisure, and religion and spirituality. The described ICF-linked dilemmas were also linked to each other. For instance dilemmas related to community life are combined with dilemmas within mobility such as lifting and carrying objects and moving objects with lower extremities when being active in an association. Other combined dilemmas concern interpersonal interactions and relationships such as refraining from attending a wedding party due to fear of shaking hands with people or not engaging in association activities when not having the energy to engage in other people. Conclusion The results illustrate patterns of participation restrictions in early RA. Awareness about described patterns is relevant to comprehensive multidisciplinary assesements. Abstractnummer: 85 85 Emotions related to participation restrictions experienced by patients with early rheumatoid arthritis: A qualitative interview study (The Swedish TIRA study) Gunnel Östlund1, Mathilda Björk2,3,4, Ingrid Thyberg2,4, Mikael Thyberg4, Eva Valtersson2, Birgitta Stenström5, Annette Sverker2 1 Division of Social Work, School of Health, Care and Social Welfare, Mälardalen University 2 County Council of Östergötland 3 Jönköping University 4 Linköping University 5 The Swedish Rheumatism Association Background Psychological distress is a well-known complication in rheumatoid arthritis (RA). It is usually studied by questionnaires with predefined items related to mental functions, and the knowledge regarding the full spectrum of emotions and their relations to practical participation restrictions is still scarce. Objectives The aim was to explore emotions related to participation restrictions. Method This study is part of the Swedish TIRA-project. 48 patients with early RA, age 20 – 63, were interviewed about participation restrictions with Critical Incident Technique. Transcribed interviews were synthesized into dilemmas and linked to ICF activity/participation codes. The emotions described by the patients have been condensed and categorized. Results Sadness, fear, anger, and shame were expressed in relation to RA participation restrictions. Sadness was described when trying to perform daily activities such as getting up in the mornings, getting dressed, or at work when not being able to perform duties. Sadness was also experienced in relation to not being able to continue leisure activities or in caring for children. Examples of fear descriptions were found in relation to the deteriorating health and fumble fear made the individual withdraw from activities when mistrusting the body. Anger was described in relation to domestic and employed work, but also in social relations when the individual felt hindered to continue valued activities. Shame or embarrassments were described when participation restrictions became visible in public. Conclusions Sadness, anger, fear and shame are closely related to practical participation restrictions and may be addressed by corresponding multiprofessional interventions that facilitate participation. 86 Abstractnummer: 86 The GOT-NET Study – A randomized study evaluating the efficacy of nurse-led clinic compared to patients receiving regular care, a study protocol description. Ulrika Bergsten, Lennart Jacobsson1 Göteborgs Universitet, Avdelningen för Reumatologi och inflammationsforskning 1 Purpose To compare a nurse-led clinic including person-centered care and tight control with “care as usual” in patients with rheumatoid arthritis (RA) and moderate/ high disease activity. Project description Study population: Patients with RA, 18-80 years old, with moderate/ high Disease Activity Score of 28 joints (DAS28 > 3.8) and disease duration > 2 years in a 6-month randomized controlled study with a 6 month open follow-up. Intervention group (N=60): Nurse-led visits every 6th week, with structured person-centered care and evaluation of disease activity. If disease remission is not reached, pharmacological treatment including both shortterm (intra-articular and oral steroids) and long-term alterations (DMARDs and biologics) is modified according to a predefined algorithm. The control group (N=60) is treated according to “care as usual” with visits to physician every 6th month. ReumaBulletinen Nr 96 · 2/2014 43 ABSTRACTS Outcome measures Primary outcome measure is change in Diseases Activity Score (DAS) at week 26. Secondary outcomes are; compare the proportion of patients with low diseases activity and proportions of remission and EULAR response, quality of life, self-efficacy, disability, emotional well-being, pain, fatigue, sleep and satisfaction at week 26 and 50. The study starts in January 2014 and will be ongoing for at least 2 years. Expected outcomes Based on “regular care” data from 2012, only 30 % of out-patient care of RA patients with the above inclusion criteria will reach the low disease activity (DAS28 < 3,2) at follow-up. The present study aim to compare this “regular care” with a model based on nurse-led clinics with person-centered care and tight disease control. If effective, this model could easily be implemented in the health care system. Abstractnummer: 87 87 SAMBAND MELLAN FATIGUE, NEDSTÄMDHET OCH LIVSKVALITET VID PRIMÄRT SJÖGRENS SYNDROM Rezvan Kiani1, Lilian Vasaitis2, Gunnel Nordmark2 Reumatologsektionen, Institutionen för folkhälso- och vårdvetenskap, Uppsala Universitet 2 Reumatologsektionen, Institutionen för medicinska vetenskaper, Uppsala Universitet 1 Bakgrund Vid primärt Sjögrens syndrom (pSS) är en förlamande trötthet, fatigue, ofta ett dominerande symptom. Orsakerna är inte klarlagda men behandlingsbara tillstånd såsom nedstämdhet kan bidra. Syftet med denna studie var att identifiera förekomsten av fatigue hos patienter med pSS, studera sambandet med nedstämdhet, ångest och livskvalitet samt med autoantikroppar, extraglandulära manifestationer, inflammationsparametrar och blodvärde. Material och metod Åttiotvå patienter med pSS inbjöds att delta i studien varav 62 (75,6 %) tackade ja. Fyra instrument besvarades; VAS fatigue, Eular Sjögren’s Syndrome Patient Reported index (ESSPRI), Hospital Anxiety and Depression Scale (HADS) och Short Form-36 (SF-36). Förekomst av SSA/SSB-antikroppar och extraglandulära manifestationer hämtades ur journalerna. SR, CRP och Hb togs vid besöket. Resultat Totalt 45/62 patienter (72,6 %) skattade hög VAS fatigue (≥50 mm) vilket korrelerade med ESSPRI fatigue (r2=0,8). Det var ingen skillnad i autoantikroppar eller extraglandulära manifestationer mellan patienter med hög (≥50 mm) respektive låg (<50 mm) fatigue. Totalt 19 % av patienterna erhöll >8/21 poäng för depression och 26 % fick >8/21 poäng för ångest, indikerande sjuklighet. VAS fatigue korrelerade starkt med poängen för nedstämdhet (HADS D) och ångest (HADS-A), (r2=0,24-0,26, p<0,0001). Patienterna skattade sin livskvalitet i SF 36 som låg jämfört med publicerade åldersmatchade friska kontroller1. VAS fatigue korrelerade med samtliga domäner i SF-36, (r2=0,1-0,4, p<0,01). Det fanns inte något samband mellan fatigue och SR, CRP eller Hb. Slutsats Hög fatigue förekommer hos cirka tre fjärdedelar av patienterna med pSS vid vår mottagning och korrelerar till nedstämdhet, ångest och nedsatt livskvalitet. Det finns inget samband mellan fatigue och autoantikroppar, extraglandulära manifestationer, SR, CRP eller Hb. Identifiering och behandling av nedstämdhet och ångest 44 ReumaBulletinen Nr 96 · 2/2014 kan möjligen minska tröttheten hos en grupp av patienter med pSS. Referens (1) Segal B et al. Health and quality of life outcomes, 2009; 7: 46. Abstractnummer: 88 88 Valued life activities: Swedish version (VLA-swe) with cultural adaption, ICF linkage, psychometric testing Mathilda Björk1, Mikael Thyberg2, Eva Valtersson3, Patricia Katz4 Rehabenheten, HMC, Universitetssjukhuset i Linköping 2 Avdelningen för rehabiliteringsmedicin, Hälsouniversitetet i Linköping 3 NSC, Universitetssjukhuset i Linköping 4 Department of Rheumatology, University of California, San Fransisco 1 Background Disability is an important outcome in rheumatoid arthritis (RA). The Valued Life Activity scale (VLA) comprises a wide range of life activities deemed to be important by the individual. Objectives Translation, cultural adaptation including linkage to the International Classification of Functioning, Disability and Health (ICF) and psychometric testing of the VLA scale in Swedish patients with RA. Methods The VLA was translated and culturally adapted to a Swedish version, the VLA- swe. Both the VLA and VLA-swe were linked to the ICF according to linking rules. 737 RA patients(73% women)aged 18 - 80 (mean age 62 years) were recruited from the Swedish Rheumatology Quality Registry (SRQ). The average disease duration was 16 years. Data for disease activity (DAS28), activity limitations (HAQ) and life satisfaction (LiSat11) were registered and patients completed the VLA-swe. Internal consistency was assessed with Cronbach’s alpha and item statistics. To establish construct validity VLA-swe was correlated to DAS28, HAQ and LiSat11. Results: The conceptual similarity between the VLA-swe and the original VLA was high when linked to the ICF. Each of the 9 ICF activity/participation domains was represented in one or more items. The internal consistency was excellent for the VLA- swe (0.97) and alpha coefficients did not improve after omitting any of the 33 items. The correlations between the single items and the total VLA-swe score varied between r=0.57 and r=0.84. Scores of the VLA-swe correlated strongly with the HAQ (r=0.87), moderately with the LiSat11 (r=-0.61) and weakly with the DAS28 (r=0.38), as expected. Conclusions The VLA-swe is culturally adapted and validated, and addresses a broad range of ICF activity/participation domains. Since both the patients ́ preferences and ICF concepts of disability are taken into account, it is a useful complement to traditional measures, such as the HAQ, which measure activity limitations only. Abstractnummer: 89 89 THE EXERCISE BENEFITS/BARRIERS SCALE - TEST-RETEST RELIABILITET OCH SAMBAND MED FYSISK AKTIVITETSNIVÅ OCH UPPLEVD HÄLSA Maria Svedling1, Nina Brodin2 Hälsopoolen Rehabklinik, Södermalm, Stockholm 2 Karolinska Institutet Institutionen för Neurobiologi, Vårdvetenskap och samhälle, Sektionen för Sjukgymnastik 1 ABSTRACTS Bakgrund Ankyloserande spondylit (AS) leder till stora begränsningar i individens funktion och aktivitetsnivå. Fysisk aktivitet är en av hörnstenarna i behandlingen av individer med AS. Trots det är knappt hälften av individer med AS regelbundet fysiskt aktiva. Exercise benefits/barrier scale (EBBS) är ett frågeformulär som används för att bedöma fördelar och hinder med fysisk aktivitet. Det har tidigare inte funnits tillgängligt på svenska och inte använts på individer med AS i Sverige. Syfte Att beskriva test-retest reliabilitet hos den svenska versionen av EBBS samt att studera samband mellan EBBS och fysisk aktivitetsnivå respektive upplevd hälsa hos individer med AS. Material och metod Trettiotvå individer med AS deltog i studien. Test-retest reliabilitet av EBBS undersöktes med en veckas mellanrum. För att beskriva samband med fysisk aktivitetsnivå och upplevd hälsa användes The International Physical Activity Questionnaire (IPAQ) och delskalor i The short form-36 (SF-36). Resultat Test-retest reliabilitet var god för de tre kategorierna EBBS totalsumma (ICC 0.818, 95% CI 0.659 – 0.907), EBBS benefits (ICC 0.806, 95% CI 0.639-0.900) samt EBBS barriers (ICC 0.820, 95% CI 0.662-0.908). De 14 frågorna om barriers visade måttlig till god överensstämmelse enligt viktad Kappa (Kw) (Kw 0.526-0.860) utan systematiska skillnader (p > 0.05). Av de 29 frågorna om benefits visade 11 svag överensstämmelse (Kw 0.200-0.389) och övriga 18 måttlig till god överensstämmelse (Kw 0.422-0.813) utan systematiska skillnader (p > 0.05). Spearman korrelationer mellan EBBS och fysisk aktivitetsnivå eller upplevd hälsa var alla mycket låga till låga (rs 0.05-0.34). Slutsats EBBS är ett reliabelt instrument hos individer med AS. Vissa av de inkluderade frågorna visade dock låg överensstämmelse vid upprepat test. Detta sammantaget med att endast mycket låga samband mellan EBBS och fysisk aktivitetsnivå respektive upplevd hälsa sågs kan indikera att instrumentet har bristande validitet för att bedöma hinder och fördelar med fysisk aktivitet hos individer med AS. Abstractnummer: 90 90 LOW LEVELS OF PAIN IMPACT ON VALUED LIFE ACTIVITIES IN WOMEN AND MEN WITH RHEUMATOID ARTHRITIS Inger Ahlstrand1, Mathilda Björk1,2,3, Ingrid Thyberg2,3, Torbjörn Falkmer1,3,4,5 Hälsohögskolan, Högskolan i Jönköping 2 Reumatologkliniken, Universitetssjukhuset i Linköping 3 Linköpings universitet 4 School of Occupational Therapy & Social Work, CHIRI, Curtin University, Perth, WA 5 School of Occupational Therapy, La Trobe University, Melbourne, Australia 1 Background Disability in Rheumatoid Arthritis (RA) is more pronounced in women than in men and pain is strongly related to activity limitation and participation. The Valued life activity scale (VLA) is a questionnaire in which patient’s first report if the activities are valued or not to perform and secondly difficulties to perform these activities. To measure disability with VLA includes the patient’s perspective in a unique way compared to traditional disability measurements (e.g., HAQ). Objective To examine difficulties to perform valued life activities and how these difficulties were related to pain in women and men with RA. Methods In total, 737 persons with RA (73% women) from three rheumatology’ units in Sweden responded to a questionnaire measuring performance of 33 valued life activities and pain. The relationship between performance of valued life activities and pain were analysed based on gender and pain intensity. Multiple linear regression analyses were carried out with the total VLA score as dependent variable. Results Women reported more pain and difficulties in performing valued life activities than men. Across genders, 85% reported at least one valued life activity affected by RA. Significantly more women than men encountered difficulties in performing some activities such as cooking, gardening and meeting new people. Women reported higher pain intensity (35 mm VAS) than men (31 mm VAS). Almost all 33 difficulty ratings for valued life activities were higher among persons with high pain (VAS>40 mm) than persons with lower pain. Difficulty ratings for valued life activities correlated positively with pain in persons with lower pain, but not among those with high pain. Conclusions The results highlight the importance of addressing pain especially among women with RA as they reported pain to impact on their valued life activities. Interestingly, this was evident also in women with lower levels of pain. Abstractnummer: 91 91 COST-EFFECTIVENESS OF A ONE-YEAR COACHING PROGRAM FOR HEALTHY PHYSICAL ACTIVITY IN EARLY RHEUMATOID ARTHRITIS Nina Brodin1,2, Malin Lohela-Karlsson3, Emma Swärdh1, Christina H Opava1,4 Karolinska Institutet, Institutionen för Neurobiologi, Vårdvetenskap och Samhälle, Sektionen för sjukgymnastik 2 Danderyds Sjukhus, Oprtopedkliniken, Paramedicinska sektionen 3 Karolinska Institutet, Institutet för miljömedicin, Institutionen för Interventions- och implementeringsforskning 4 Karolinska Universitetssjukhuset, Reumatologiska kliniken 1 Background Economic evaluations of interventions, as a complement to the effect evaluation, intend to inform decision makers about whether the intervention provides good value for the money. Since resources in healthcare are scarce, there is an increased demand from decision makers for economic evaluations. Economic evaluations of non-pharmacologic care in RA are still not as commonly presented as evaluations of the costs related to medications. Purpose To describe cost-effectiveness of the Physical Activity in Rheumatoid Arthritis study intervention overall and for different subgroups. At the CARE VI meeting, the importance of such evaluations was acknowledged. Method Costs were collected and estimated retrospectively. Cost-effectiveness was calculated based on the intervention cost per patient ReumaBulletinen Nr 96 · 2/2014 45 ABSTRACTS with respect to change in health status (EuroQol global visual analog scale, EQ-VAS, and EuroQol, EQ-5D) and activity limitation (Health assessment questionnaire, HAQ) using cost-effectiveness-, and cost-minimization analyses. Results Total cost of the one-year intervention program was estimated to €67317 or €716 per participant. Estimated difference in total societal cost between the intervention (IG) and control (CG) was €580 per participant. Incremental cost-effectiveness ratio (ICER) for one point (1/100) of improvement in EQ-VAS was estimated to €116. By offering the intervention to more affected participants (MO) in the IG compared to less affected participants (LE), 15.5 extra points of improvement in EQ-VAS and 0.13 points of improvement on HAQ were gained at the same cost. ‘Ordinary physiotherapy’ was most cost-effective with regard to EQ-5D. re ansåg att FA är ett viktigt hälsomål för patienter och rekommenderade regelbundet FA till sina patienter. 70 %, 89 % respektive 96 % ansåg att folkhälsorekommendationer avseende måttligt ansträngande FA var lämpliga för patienter med RA och de användes av 36 %, 90 % respektive 91 % i Holland, Italien och Sverige. I medeltal skattade deltagare sin kompetens för att främja FA som 6.3, 7.1 och 5.6 av 10, och 69 %, 89 % respektive 71 % uttryckte ett behov av ytterligare utbildning inom området. Konklusion FA enligt folkhälsorekommendationer för personer med RA anses lämpligt, men rekommenderas hälften så ofta i Holland som i Italien och Sverige. Den upplevda kompetensen för att främja FA var lägst i Sverige och högst i Italien avseende samtliga frågor. Abstractnummer: 93 93 Conclusions The intervention resulted in improved effect in health status for the IG with a cost of €116 per extra point in VAS. The intervention was cost-effective if targeted towards a subgroup of more affected patients when evaluating the effect using VAS and HAQ. Reliabilitet och validitet hos modifierad Fear- Avoidance Beliefs Questionnaire i en poulation med reumatoid artrit Abstractnummer: 92 1 92 ATT FRÄMJA FYSISK AKTIVITET - EN JÄMFÖRANDE STUDIE MELLAN HOLLAND, ITALIEN OCH SVERIGE OM ATTITYDER OCH KUNSKAP HOS VÅRDPERSONAL Nina Brodin1, Emalie Hurkmans, Luigi Di Matteo, Tiziana Nava, Thea Vliet Vlieland, Christina H Opava1 Karolinska Institutet, Institutionen för Neurobiologi, Vårdvetenskap och Samhälle, Sektionen för sjukgymnastik 2 Danderyds sjukhus, Ortopedkliniken, Paramedicinska sektionen 3 University of Applied Sciences, Vienna, Austria 4 Local Hospital, ASL, Pescara, Italy 5 University of Milan, Italy 6 Leiden University Medicla Center, the Netherlands 7 Karolinska Universitetssjukhuset, Reumatologiska kliniken 1 Bakgrund Personer med reumatoid artrit (RA) är i många fall fysiskt inaktiva, trots att bevis finns för många hälsovinster av en fysiskt aktiv livsstil. Effektiva metoder för att främja fysisk aktivitet (FA) har utvecklats, men kunskap saknas kring i vilken utsträckning vårdpersonal inom reumatologi (reumatologer, sjuksköterskor, sjukgymnaster) använder sig av dessa. Syfte Att beskriva och jämföra attityder hos vårdpersonal i Holland, Italien och Sverige avseende FA, i vilken utsträckning FA rekommenderas, upplevd kompetens avseende främjande av FA samt eventuellt utbildningsbehov inom området. Metod Frågeformulär distribuerades till 700 Holländska, 1402 Italienska och 837 Svenska reumatologer, sjuksköterskor och sjukgymnaster inom reumatologi. Frågeformuläret innehöll 23 frågor om främjande av FA och utvecklades för den ursprungliga holländska studien och översattes till italienska och svenska enligt gängse standardiserade procedur. Resultat Svarsfrekvensen var 53 % i Holland, 25 % I Italien och 29 % I Sverige. Medelålder var 45.8, 41.3 och 52.6 år i respektive land och klinisk erfarenhet inom reumatologi var 13.3, 16.6 respektive 24.7 år. 98 % av holländska, 96 % av italienska och 99 % av svenska deltaga46 ReumaBulletinen Nr 96 · 2/2014 Anna Dahlgren, MSc, Ingrid Demmelmaier, PhD Abstract Karolinska Institutet, Institutionen för neurobiologi, vårdvetenskap och samhälle, sektionen för sjukgymnastik Bakgrund Syftet var att undersöka reliabilitet och validitet hos mätinstrumentet modifierad Fear- Avoidance Beliefs Questionnaire (mFABQ) i en population med reumatoid artrit (RA). Material och metod Studien är en psykometrisk studie med upprepad mätning för bestämning av test-retestreliabilitet och tvärsnittsanalyser för bestämning av inre överensstämmelse och begreppsvaliditet. Datainsamlingen gjordes inom en större studie (PARA 2010) för individer med RA. Test-retestreliabilitet analyserades med viktad Kappa (n=179). Inre överensstämmelse analyserades med item-to-total correlation (n=216) och begreppsvaliditet med korrelationsanalyser (n=216). mFABQ ingick i ett formulär som fylldes i av deltagarna vid två tillfällen med 4-6 månaders mellanrum före interventionen i PARA 2010. Resultat Enligt beräkning av kappavärden var test-retestreliabiliteten låg till måttlig (0.28-0.42) i varje enskilt item, liksom korrelationen för totalsumman (rs= 0.53, p<0.001). Den inre överensstämmelsen mätt med item-to-total correlation var låg till måttlig (0.22-0.63, p<0.001). Begreppsvaliditeten stärktes i fem av de sex i förväg uppställda hypoteserna vad gällde korrelationer med förväntningar på fysisk aktivitet (rs= -0.17, p<0.05; rs= -0.02, p<0.01), smärta (rs= 0.36, p<0.001), ålder och kön (inga signifikanta korrelationer). Slutsats Reliabiliteten och validiteten behöver undersökas vidare för att säkra den kliniska användbarheten av mFABQ för individer med RA. Resultatet för test-retestreliabiliteten i studien förklaras sannolikt till stor del av att tiden mellan de två mättillfällena var för lång. Fortsatt psykometrisk testning bör göras i studier med detta som primärt syfte, och validera instrumentet gentemot t.ex. aktivitetsbegränsning och nedstämdhet, som ingår i fear-avoidancemodellen. Abstractnummer: 94 94 HAND PAINS IN WOMEN AND MEN IN EARLY RA, A ONE YEAR FOLLOW UP AFTER DIAGNOSIS IN THE TIRA-2 COHORT ABSTRACTS Ingrid Thyberg1, Örjan Dahlström2, Mathilda Björk3,4,5, Birgitta Stenström1, Jo Adams6 Rheumatology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Department of Rheumatology in Östergötland, County Council of Östergötland, Linköping, Sweden 2 Swedish Institute for Disability Research, Department of Behavioural Sciences and Learning, Linköping University, Sweden 3 Rehabilitation section, County Council of Östergötland, Linköping, Sweden 4 Department of Rehabilitation, School of Health Sciences, Jönköping University, Sweden 5 Division of Community Medicine, Rehabilitation medicine, Faculty of Health Sciences, Linköping University 6 Centre for Innovation and Leadership, Faculty of Health Sciences University of Southampton 1 Objectives To analyze general pain intensity, hand pain at rest and hand pain during activity in women and men in early RA. Methods Out of the 454 patients that were recruited into the Swedish early RA project “TIRA” the 373 patients (67% women) that remained at 12 months follow up are reported here. Disease activity (DAS-28) and pain (VAS) was registered at inclusion and at 3 (M3), 6 (M6), and 12 (M12) months. General pain, hand pain during rest, hand pain during test of grip force by Grippit , prescribed diseasemodifying anti-inflammatory drugs (DMARDs) and hand dominance was registered. Results Women had somewhat higher DAS and somewhat more prescribed DMARD:s than men. The difference was significant regarding DMARD:s at M3. All pain types were significant higher at inclusion than at the follow-ups and women reported significant higher pain than men at the follow-ups but not at inclusion. The pain types were significantly different, general pain was highest and hand pain at rest was lowest. A significant interaction between pain-type and follow-up showed that the three pain types differed at each follow-up but for general pain and hand pain during activity at M3. There were no significant differences in hand pain related to hand dominance or between right and left hand. ded. At admission and discharge the patients were evaluated with measures on functioning (HAQ), self-efficacy (ASES), psychological health (HSCL-25), pain and fatigue and on health related quality of life (HRQoL) as captured by the EQ-5D and the SF-36. The patients set individual goals for their rehabilitation. At discharge the patients reported if the goals were achieved completely, partially or not at all. Results 108/146 patients reported level of goalachievement, and were included in further analyses, 76% were females and 55% had RA. At baseline median age was 54 years (IQR 17), median HAQ 0.88 (IQR 0.88), median HRQoL as captured by EQ-5D 0.62 (IQR 0.57), median psychological wellbeing according to HSCL-25 1.62 (IQR 0.68), median fatigue 6.0 (IQR 4.0) and pain 5.0 (IQR 3.0). The rehabilitation program lasted for median 18 days (IQR 2). 58/108 patients (54%) rated their goal to be completely achieved, 40 patients (37%) reported partial goal achievement while 10 (9%) patients had not achieved their goal. Positive reporting of compliance during the rehabilitation was obtained from 100 (93%) of the patients. Change after intervention and compliance did not affect reports of goal achievement after rehabilitation. Females reported goal achievement more often than men did (p=0.019). Those not achieving their goals reported less psychological wellbeing (HSCL25, p=0.011) at admission together with reports of worse pain (SF36bp, p=0.011). Conclusion 54% of the included patients reported complete goal achievement after arthritis team rehabilitation. Neither change after intervention nor compliance affected patients’ reports of goal achievement. Female patients were more prone to achieve their goals. Patients experiencing less psychological wellbeing or more pain at baseline were less prone to report goal achievement. Conclusions Overall women reported higher pain than men at the follow-ups. Hand pain in activity was higher than pain during rest, strongly indicating that hand pain is closely related to hand related activities. Abstractnummer: 95 95 WHO WILL ACHIEVE INDIVIDUALLY SET GOALS AFTER ARTHRITIS TEAM REHABILITATION? Sofia Hagel1, Elisabet Lindqvist1, Ann Bremander2,3 Institutionen för Kliniska Vetenskaper Lund, avdelningen för Reumatologi. Lunds Universitet och Skånes Universitetssjukvård 2 FoU-centrum Spenshult, Halmstad, 3 Institutionen för Kliniska Vetenskaper Lund, avdelningen för Reumatologi, Lunds Universitet 1 Background/Purpose To study goal achievement among patients with chronic inflammatory arthritis after arthritis team rehabilitation. Materials and methods 146 consecutive patients with rheumatoid arthritis (RA) and spondyloarthritis, completing team rehabilitation program, were inclu- ReumaBulletinen Nr 96 · 2/2014 47 ReumaKalender 2014 Reumadagarna 1 april 1–4 april, Örebro www.reumadagarna2014.se 1 maj The Extracellular matrix The legacy of Dick Heinegård. Center for Biochemistry, University of Cologne, Germany. May 1-3, 2014 12 maj Kroniska artritsjukdomar – diagnostik, patogenes och behandling SK-kurs, Stockholm 12-16/5 19 maj Nationella ST-dagar i reumatologi 19–20 maj, Umeå Tema: Infektioner som orsak till och komplikation vid reumatisk sjukdom. 12 sept Farmakoterapikurs SK-kurs, 8-12 september, Lund 21 sept Scandinavian Congress of Rheumatology 21-23 september, Stockholm 16 okt Cutting Edge Rheumatology Symposium 16 oktober, Lund 14 nov ACR/ARHP Annual Meeting 14-19 november, Boston 24 nov SK-Kurs Reumatologisk immunologi 24-28 november, Göteborg 11 juni EULAR Congress 2014 11–14 juni, Paris www.eular.org Information/program/inbjudan återfinnes i Reumakalendern på www.svenskreumatologi.se Pottholtz funderingar enligt Tomas Weitoft 48 ReumaBulletinen Nr 96 · 2/2014
© Copyright 2024