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Rheumatoid Arthritis (RA) — Summary of Medical Guidelines
Rheumatoid arthritis is a chronic inflammatory disease characterized by uncontrolled proliferation of synovial tissue and a wide array of multisystem comorbidities.
Prevalence is estimated to be 0.8 percent worldwide, with women twice as likely to develop the disease as men. Untreated, 20 to 30 percent of persons with
rheumatoid arthritis become permanently work-disabled within two to three years of diagnosis.
Key Recommendations for Practice:
Clinical recommendation
Evidence rating
Patients with inflammatory joint disease should be referred to a rheumatology subspecialist, especially if symptoms last more than six weeks.
In persons with RA, combination therapy with two or more disease-modifying antirheumatic drugs is more effective than monotherapy. However, more than one
biologic agent should not be used at one time (e.g., adalimumab [Humira] with abatacept [Orencia]) because of the high risk of adverse effects.
A guided exercise program can improve quality of life and muscle strength in patients with RA.
Cardiovascular disease is the main cause of mortality in persons with RA; therefore, risk factors for coronary artery disease should be addressed in these
patients.
C
A
B
C
RA = rheumatoid arthritis.
A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case
series.
Recommended Disease Activity Measures:
The ACR recommends the following instruments for the systematic measurement of disease activity to facilitate clinical decision making in RA. They are accurate reflections of
disease activity; are sensitive to change; discriminate well between low, moderate, and high disease activity states; have remission criteria; and are feasible to perform in clinical
settings. Incorporation of these validated RA disease activity measures into a practice’s workflow will facilitate adherence to the ACR guidelines for the treatment of RA and provide
the necessary tools for treating to target.
Disease activity cutoffs for each American College of Rheumatology–recommended disease activity measure*
Disease activity measure
Patient-driven composite tools
PAS
PAS-II
RAPID-3
Patient and provider composite tool
CDAI
Patient, provider, and laboratory
composite tools
DAS28 (ESR or CRP)
SDAI
Scale
Remission
Low/minimal
Moderate
High/severe
0–10
0–10
0–10
0.00–0.25
0.00–0.25
0–1.0
0.26–3.70
0.26–3.70
>1.0 to 2.0
3.71 to <8.0
3.71 to <8.0
>2.0 to 4.0
8.00–10.00
8.00–10.00
>4.0 to 10
0–76
≤2.8
>2.8 to 10.0
>10.0 to 22.0
>22.0
0–9.4
0–86
<2.6
≤3.3
≥2.6 to <3.2
>3.3 to ≤11.0
≥3.2 to ≤5.1
>11.0 to ≤26
>5.1
>26
* PAS = Patient Activity Scale; RAPID-3 = Routine Assessment of Patient Index Data with 3 measures; CDAI = Clinical Disease Activity Index; DAS28 = Disease Activity Score with 28-joint counts;
ESR = erythrocyte sedimentation rate; CRP = C-reactive protein; SDAI = Simplified Disease Activity Index.
Treatment
After RA has been diagnosed and an initial evaluation performed, treatment should begin. Recent guidelines have addressed the management of RA but patient
preference also plays an important role. There are special considerations for women of childbearing age because many medications have deleterious effects on
pregnancy. Goals of therapy include minimizing joint pain and swelling, preventing deformity (such as ulnar deviation) and radiographic damage (such as
erosions), maintaining quality of life (personal and work), and controlling extra-articular manifestations. Disease modifying antirheumatic drugs (DMARDs) are the
mainstay of RA therapy.
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RA 1212
Rheumatoid Arthritis (RA) — Summary of Medical Guidelines
Considerations for Treatment and Limitations of Recommendations
Topic
Recommendation
The goal for each RA patient should be low disease activity or remission, but in others,
low disease activity may be an acceptable target.
The decision about what the target should be for each patient is appropriately left to the
clinician caring for each RA patient, in the context of patient preferences, comorbidities,
and other individual considerations.
More aggressive treatment in patients with early RA is recommended.
Expectations: 1) the earlier the treatment the better the outcome, 2) the thought that
joint damage is largely irreversible so prevention of damage is an important goal, and
3) the data that early intensive therapy may provide the best opportunity to preserve
physical function and health-related quality of life and reduce work-related disability.
Indications for starting or resuming DMARDs and biologic agents
Switching between therapies
Use of biologic agents in high-risk patients (those with hepatitis,
congestive heart failure, and malignancy)
TB screening for patients starting/ receiving biologic agents*
Vaccinations in patients starting/ receiving DMARDs or biologic agents based on age
and risk*
See the following figures and legends for early and established RA
See the following figures and legends for early and established RA .
Comorbidity/clinical circumstance
Hepatitis C
Untreated chronic hepatitis B or with treated
chronic hepatitis B with Child-Pugh class B and
higher†
Treated solid malignancy _5 years ago or
treated nonmelanoma skin cancer _5 years ago
Treated solid malignancy within the last 5 years
or treated nonmelanoma skin cancer within the
last 5 years
Treated skin melanoma‡
Treated lymphoproliferative malignancy
Congestive heart failure: NYHA class III/IV and
with an ejection fraction of _50%
Recommended
Etanercept
Not recommended
Any biologic agent
Any biologic agent
Rituximab
Rituximab
Rituximab
Anti-TNF biologic
Screening to identify LTBI in all RA patients being considered for therapy with biologic
agents, regardless of the presence of risk factors
Before DMARD or biologic
agent
Patients
already taking a DMARD or
a biologic agent, if not
previously done
RA patients already taking a
DMARD
all killed (pneumococcal,
pneumococcal (killed),
herpes zoster
influenza intramuscular,
influenza intramuscular
vaccine
and hepatitis B),
(killed), hepatitis B (killed),
recombinant (human
and HPV vaccine
papillomavirus [HPV], and
(recombinant)
live attenuated (herpes
zoster) vaccinations
Recommendations regarding the use of other antiinflammatory medications, such as nonsteroidal antiinflammatory drugs and intraarticular and oral corticosteroids, and
nonpharmacologic therapies (such as physical and occupational therapies), although these may be important components of RA treatment, are not discussed
New classification criteria for RA (ACR/European League Against Rheumatism collaborative initiative) were published in September 2010 but the literature review these
recommendations were based on preceded the publication of the new criteria.
*Concordant with CDC guidelines
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RA 1212
Rheumatoid Arthritis (RA) — Summary of Medical Guidelines
Treatment Approach for Early Rheumatoid Arthritis
DMARD diseasemodifying antirheumatic drug (includes
hydroxychloroquine [HCQ], leflunomide [LEF], methotrexate
[MTX], minocycline, and sulfasalazine); anti-TNF _ anti–tumor
necrosis factor.
* Disease activity was categorized as low, moderate, or high.
† Patients were categorized based on the presence or absence of
1 or more of the following poor prognostic features: functional
limitation (e.g., Health Assessment Questionnaire score or similar
valid tools), extraarticular disease (e.g., presence of rheumatoid
nodules, RA vasculitis, Felty’s syndrome), positive rheumatoid
factor or anti– cyclic citrullinated peptide antibodies, and bony
erosions by radiograph.
‡ Combination DMARD therapy with 2 DMARDs, which is most
commonly MTX based, with some exceptions (e.g., MTX + HCQ,
MTX + LEF, MTX + sulfasalazine, and sulfasalazine + HCQ), and
triple therapy (MTX + HCQ + sulfasalazine)
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RA 1212
Rheumatoid Arthritis (RA) — Summary of Medical Guidelines
Treatment Approach for Established Rheumatoid Arthritis
Depending on a patient’s current medication regimen, the management algorithm may begin at an appropriate
rectangle in the figure, rather than only at the top of the figure.
-Disease-modifying antirheumatic drugs (DMARDs) include hydroxychloroquine (HCQ), leflunomide (LEF),
methotrexate (MTX), minocycline, and sulfasalazine (therapies are listed alphabetically; azathioprine and
cyclosporine were considered but not included).
-DMARD monotherapy refers to treatment in most instances with HCQ, LEF, MTX, or sulfasalazine; in few
instances, where appropriate, minocycline may also be used.
-Anti–tumor necrosis factor (anti-TNF) biologics include adalimumab, certolizumab pegol, etanercept, infliximab,
and golimumab.
-Non-TNF biologics include abatacept, rituximab, or tocilizumab (therapies are listed alphabetically).
* Disease activity was categorized as low, moderate, or high.
† Features of poor prognosis included the presence of 1 or more of the following: functional limitation (e.g.,
Health Assessment Questionnaire score or similar valid tools), extraarticular disease (e.g., presence of
rheumatoid nodules, RA vasculitis, Felty’s syndrome), positive rheumatoid factor or anti– cyclic citrullinated
peptide antibodies (33–37), and bony erosions by radiograph.
‡ Combination DMARD therapy with 2 DMARDs, which is most commonly MTX based, with few exceptions
(e.g., MTX + HCQ, MTX + LEF, MTX + sulfasalazine, sulfasalazine _ HCQ), and triple therapy (MTX + HCQ _
sulfasalazine). § Reassess after 3 months and proceed with escalating therapy if moderate or high disease
activity in all instances except after treatment with a non-TNF biologic (rectangle D), where reassessment is
recommended at 6 months due to a longer anticipated time for peak effect.
¶ LEF can be added in patients with low disease activity after 3–6 months of minocycline, HCQ, MTX, or
sulfasalazine.
# If after 3 months of intensified DMARD combination therapy or after a second DMARD has failed, the option is
to add or switch to an anti-TNF biologic.
** Serious adverse events were defined per the US Food and Drug Administration; all other adverse events
were considered nonserious adverse events.
†† Reassessment after treatment with a non-TNF biologic is recommended at 6 months due to anticipation that
a longer time to peak effect is needed for non-TNF compared to anti-TNF biologics.
‡‡ Any adverse event was defined as per the US FDA as any undesirable experience associated with the use
of a medical product in a patient. The FDA definition of serious adverse event includes death, life-threatening
event, initial or prolonged hospitalization, disability, congenital anomaly, or an adverse event requiring
intervention to prevent permanent impairment or damage.
Source: AAFP. Wasserman, 2011: Diagnosis and Management of Rheumatoid Arthritis.
ACR Recommendations for the Use of Disease-Modifying Antirheumatic Drugs and Biologic Agents in the Treatment of Rheumatoid Arthritis, May 2012. Available online: http://www.rheumatology.org/practice/clinical/guidelines/Singh%20et%20alACR%20RA%20GL-May%202012%20AC&R.PDF#toolbar=1
ACR: Rheumatoid Arthritis Disease Activity Measures, May 2012. Available online: http://www.rheumatology.org/practice/clinical/forms/RADAM-May%202012-AC&R.pdf#toolbar=1
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RA 1212