RELAPSE MANAGEMENT Pauline Shaw MS Nurse Specialist 25th June 2010 AIMS OF SESSION • • • • • Relapsing/Remitting MS Definition of relapse/relapse rate Relapse Management NICE Guidelines Regional Clinical Guidelines RRMS • • • • • 80 ‐ 85% of new cases will present with RRMS 40 ‐ 75% RRMS will go on to develop SPMS Most widely recognised type of MS RRMS varies greatly in severity in individuals Frequent relapses at the onset of disease are associated with poorer prognosis (Weinshenker 1995) Clinical course of RRMS • Variable, intermittent disease course – ‘Attacks’ or exacerbation of symptoms (relapses) – Followed by full or partial recovery (remission) • Disability accumulation due to incomplete recovery from relapses Relapse • Episode of acute or sub‐acute neurological symptoms of variable severity • Rapid appearance of new symptoms or reappearance of old over 1‐2 weeks • Relapse symptoms last more than 24 hours in the context of normal body temperature – Typically 2 ‐ 6 weeks – May persist for 6 months or longer • Annual relapse rate initially averages 2‐2.5 (Barnes 2000) gradually falling as the years progress Remission • Can last any length of time • Spontaneous recovery generally within 8 ‐ 12 weeks • Degree of recovery unpredictable and variable • May be complete (early in disease) or incomplete with residual disability Relapse trigger factors ? • Stress – Stress includes emotional stress, trauma, and medical interventions – NICE recommend that if a person with MS needs surgery for any reason then the surgery should go ahead • Injury / trauma ‐ Studies indicate that relapse is no more likely to happen (Thompson 2002) Relapse trigger factors? • Hormonal changes following child birth – No evidence that pregnancy itself influences the overall course of MS over time – Risk of relapse decreases during pregnancy, in the third trimester relapse is reduced by 60% (Thompson 2002) with same increase in relapse 3 months postpartum • Vaccinations A number of studies are inconclusive but Flu vaccine is now confirmed safe (NICE 2003) Confirmation of new relapse • Establish: – presence of new symptoms – re‐occurrence of old symptoms for longer than 24hours • Exclude pseudo‐exacerbating factors: – Infection – test urine – menstrual cycle – stress • Confirm a period of 30 days from end of any previous relapse Should You Treat if UTI Suspected? Steroids usually delayed if UTI suspected in local service UCL study • Study of 249 relapsing MS patients • If dipstick +ve abx started at same time as MP • If culture neg then abx stopped Results • UTI in 11% • 67 patients commenced on abx with negative culture • 7 patients negative dipstick but positive culture Should You Treat if UTI Suspected? Treatment of relapses • Assessment – Take history – Confirm relapse – Determine severity, functional disability / loss – Exclude infection • Medication • Supportive therapy – Physiotherapy; occupational therapy; counselling – Care package • Hospital admission for severe relapse Relapse Management Decision Aids NICE Guidelines / Scottish Guidelines / Cochrane Review / EFNS Guidelines/Local Guidelines http://www.pathways.scot.nhs.uk/Neurology/Neurol%20MS%2023Sep05.ht m Relapse management NICE Recommendations: • Any individual who experiences an acute episode sufficient to cause distressing symptoms or an increased limitation on activities should be offered a course of high‐dose corticosteroids – intravenous methylprednisolone 500mg – 1g for 3 to 5 days – high‐dose methylprednisolone 500mg – 2g daily for 3 to 5 days • An individual should be given a clear explanation of the risks and benefits involved in taking corticosteroids • Prolonged and frequent courses should not be used NICE MS Guidelines. 2004 National Clinical Guideline for Diagnosis and Management in Primary and Secondary Care Steroids for relapses • Anti‐inflammatory effect • Suppress immune system • Stabilise blood brain barrier • Thought to speed recovery • BUT do not influence degree of recovery or long‐term progression of disease • Side effects minor but include weight gain, acne, cataracts, osteoporosis and diabetes • The NICE Guideline recommends courses of steroids be limited to a maximum of three times a year NICE MS Guidelines. 2004 National Clinical Guideline for Diagnosis and Management in Primary and Secondary Care Anti‐inflammatory effect Reduce inflammatory responses by inducing several effects on the immune system – Inhibit lymphocyte proliferation and cell‐mediated immune response – Decrease circulating T‐helper cells, eosinophils & monocytes – Down‐regulate cytokine gene expression – Suppress synthesis of prostaglandins & leukotrienes – Block activation of T cells by IL‐1 – Inhibit expression of class II histocompatibility antigens on macrophage surface Corticosteroids – side‐effects • Common : • • • • • • • Oedema Raised glucose GI symptoms Metallic taste Anxiety / depression Reddening of face Altered sleep Usually well tolerated. Most SE transient • Less common – – – • • • • • – Infection HT Avascular necrosis Pancreatitis Herpes simplex Zoster Seizures Weight gain Anaphylaxis • Compared 1g MP iv with 1250mg prednisone orally (oral MP not available in Canada) • No difference in bioavailability between steroids administered either iv or orally (approx 80%) • Oral treatment is preferred by most patients, is cheaper, more convenient and has equivalent gastric safety profile Forty patients with MS randomized to receive either 1 g/day for 5 days of oMP (20 patients) or 1 g/day for 5 days of IV MP (20 patients) • Expanded Disability Status Scale (EDSS) and brain MRI (dual‐echo and postcontrast T1‐weighted scans) were assessed at baseline and at weeks 1 and 4 • The 2 groups showed a reduction of Gd‐enhancing lesions over time with a “non‐inferiority effect” between the 2 routes of administration at week 1. • Both groups showed an improvement of EDSS over time (p 0.001) without between group difference at week 4. • Both treatments were well‐tolerated and adverse events were minimal and occurred similarly in the 2 treatment arms. • MS Relapse Guidelines NICE Guidelines (2003) Innovation • Regional MS relapse guidelines developed (2005) – provide clear step‐by‐step guidance for treatment with oral steroids in a form that can be faxed to GP / pharmacy – Avoids need to admit patients to hospital for intravenous steroids in the majority of cases – PwMS receive treatment earlier and significant cost savings Current Guidelines • Treat only if relapse is distressing relapses or limiting activities • Check for UTI (Multistix for protein / nitrites) and delay treatment if present • Patient Information Sheet • Oral Prednisolone 500mg x 5/7 od (taken in the morning with food) • PPI if PUD / gastritis or concurrent aspirin / warfarin • Follow‐up after 6 weeks Ennis M et al. BJNN 2008;4(6):266-271 • Published December 2005 • Short‐term, high‐dose methylprednisolone treatment should be considered for the treatment of relapses of MS (level A recommendation) • Intravenous or oral methylprednisolone in a dose of at least 500 mg daily for 5 days should be considered for treatment of relapses (level A recommendation). Treatment with IV methylprednisolone (1 g once daily for 3 days) should be considered as an alternative treatment (good practice point; Multiple Sclerosis Therapy Consensus Group, 2004) • There is no evidence of major differences in the efficacy of methylprednisolone treatment given IV or orally in terms of clinical efficacy or side‐effects, but prolonged, oral treatment may possibly be associated with a higher prevalence of side‐effects EFNS MS Relapse Guidelines Treatment Failure • In patients who fail to respond to treatment with MP in the dose ranges used in placebo‐controlled trials higher doses should be considered (up to 2g / day for 5 days) (level C recommendation) [Multiple Sclerosis Therapy Consensus Group. J Neurol 2005;251:1329‐1339] • If patients do not respond to MP, one third may respond to PLEx • Intense, interdisciplinary rehabilitation programme should be considered after treatment with MP • No evidence to support ivIG or Natalizumab