Rheumatoid Arthritis (RA) Guidelines

Updated: Jan 31, 2022
  • Author: Howard R Smith, MD; Chief Editor: Herbert S Diamond, MD  more...
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Guidelines

Guidelines Summary

Disease Classification

The 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for RA are designed to identify patients with unexplained inflammatory arthritis in at least 1 peripheral joint and a short duration of symptoms who would benefit from early therapeutic intervention. They represents a paradigm shift from the 1987 ACR criteria, which lacked the sensitivity to detect early RA. [1]

According to the ACR/EULAR criteria, patients who should be tested are those with at least 1 joint with definite clinical synovitis that is not better explained by another disease (eg, lupus, psoriatic arthritis, or gout). [1]

The ACR/EULAR classification system is a score-based algorithm for RA that incorporates the following 4 factors:

  • Joint involvement
  • Serology test results
  • Acute-phase reactant test results
  • Patient self-reporting of the duration of signs and symptoms

The maximum number of points possible is 10. A classification of definitive RA requires a score of 6/10 or higher. Patients with a score lower than 6/10 should be reassessed over time. If patients already have erosive changes characteristic of RA, they meet the definition of RA, and application of this diagnostic algorithm is unnecessary. [1]

Disease Activity Measures

In 2012, the ACR published revised recommendations for the measurement of disease activity for clinical use at the point of care. The scales used included the following recommended measures [2] :

  • Patient-driven composite tools –  PAS (patient activity scale): scale, 0-10; PAS II: scale, 0-10; RAPID-3 (routine assessment of patient index data with 3 measures): scale, 0-10
  • Patient and provider composite tool – CDAI (clinical disease activity index): scale, 0-76
  • Patient, provider, and laboratory composite tools – DAS28 (28-joint disease activity score, using either the erythrocyte sedimentation rate [ESR] or C-reactive protein [CRP] level): scale, 0-9.4; SDAI (simplified disease activity index): scale, 0-86

The 6 measures above result in a single continuous index with defined ranges for low, moderate, or high disease activity or clinical remission. [2] See Table 3, below.

Table 3. Rheumatoid Arthritis Disease Activity Cutoffs (Open Table in a new window)

Tool Type

Tool

Low/Minimal Disease

Moderate Disease

High/Severe Disease

Patient-driven composite

PAS, PAS

0.26–3.70

3.71 to < 8.0

8.00–10.00

PASII

0.26–3.70

3.71 to < 8.0

8.00–10.00

Patient and provider composite

RAPID-3

>1.0–2.0

>2.0–4.0

>4.0–10

Patient, provider, and laboratory composite

CDAI

2.8–10.0

>10.0–22.0

>22.0

DAS28

2.6 to < 3.2

3.2–5.1

>5.1

SDAI

>3.3–11.0

>11.0 to 26

>26

PAS= Patient Activity Scale; RAPID-3 = Routine Assessment of Patient Index Data with 3 measures; CDAI = Clinical Disease Activity Index; DAS28 = 28-joint Disease Activity Score (with either erythrocyte sedimentation rate or C-reactive protein level); SDAI = Simplified Disease Activity Index

Measurement of disease remission

In the 2012 ACR-recommended RA disease activity measures, the following cutoffs indicate disease remission [2] :

  • PAS and PAS-II: 0.00-0.25

  • RAPID-3: 0-1.0

  • CDAI: ≤2.8

  • DAS28 (ESR or CRP): < 2.6

  • SDAI : ≤3.3

In 2011, the ACR and the EULAR jointly released two definitions for evaluating remission of RA in clinical trials, one a Boolean-based definition and the other based on a composite index of RA activity, the SDAI. The Boolean-based definition requires that the patient satisfy all of the following to be considered in remission [3] :

  • Tender joint count of 1 or less 
  • Swollen joint count of 1 or less 
  • CRP level of 1 mg/dL or lower
  • Patient global assessment of 1 or less (on a 0-10 scale)

To be considered in remission using the traditional index definition, the patient must have an SDAI score of less than 3.3. [3]

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Treating to Therapeutic Target

The following revised guidelines on treating RA to therapeutic target were issued in 2015 by an international task force of rheumatologists, patient representatives, and a rheumatology nurse [7, 8] :

  • The primary target for treatment of RA should be a state of clinical remission. (Level of evidence: Ib; grade of recommendation: A) which is defined as the absence of signs and symptoms of significant inflammatory disease activity.  (Level of evidence: IIc; grade of recommendation: B)
  • While remission should be a clear target, low-disease activity may be an acceptable alternative therapeutic goal, particularly in long-standing disease.  (Level of evidence: Ib; grade of recommendation: A)
  • The use of validated composite measures of disease activity, which include joint assessments, is needed in routine clinical practice to guide treatment decisions.  (Level of evidence: Ib; grade of recommendation: A)
  • The choice of the (composite) measure of disease activity and the target value should be influenced by comorbidities, patient factors, and drug-related risks.  (Level of evidence: IV; grade of recommendation: D)
  • Measures of disease activity must be obtained and documented regularly—as frequently as monthly for patients with high/moderate disease activity or less frequently (eg, every 6 mo) for patients in sustained low-disease activity or remission.  (Level of evidence: Ib; grade of recommendation: A)
  • Structural changes and functional impairment and comorbidity should be considered when making clinical decisions, in addition to assessing composite measures of disease activity.  (Level of evidence: IV; grade of recommendation: D)
  • Until the desired treatment target is reached, drug therapy should be adjusted at least every 3 mo.  (Level of evidence: Ib;  grade of recommendation: A)
  • The desired treatment target should be maintained throughout the remaining course of the disease.  (Level of evidence: IIc; grade of recommendation: B)
  • The rheumatologist should involve the patient in setting the treatment target and the strategy to reach this target.  (Level of evidence: IV; grade of recommendation: D)
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Management of Early RA

In 2016, the European League Against Rheumatism (EULAR) updated its 2007 guidelines for the management of early arthritis, which put renewed emphasis on early intervention, preventive lifestyle measures, and careful clinical examination rather than reliance on ultrasound or advanced imaging. Key recommendations, based on evidence and expert opinion, are as follows [163] :

  • Within 6 weeks of the onset of symptoms, patients presenting with joint swelling associated with pain or stiffness should be referred to a rheumatologist (Level of evidence: Ib; grade of recommendation: B)

  • Clinical examination is the method of choice for detecting arthritis, which may be confirmed by ultrasonography (Level of evidence: IIb; grade of recommendation: C)

  • Patients should be started on disease-modifying antirheumatic drugs (DMARDs) as early as possible (ideally within 3 months), even if they do not fulfill classification criteria for an inflammatory rheumatologic disease (Level of evidence: Ia; grade of recommendation: A)

  • Methotrexate (MTX) is the preferred DMARD, unless contraindicated, and should be first-line treatment (Level of evidence: Ia; grade of recommendation: A)

  • Systemic glucocorticoids should be used at the lowest dose necessary as temporary (< 6 months) adjunctive treatment to reduce pain, swelling, and structural progression. Intra-articular glucocorticoid injections should be considered for the treatment of local symptoms of inflammation (Level of evidence: Ia; grade of recommendation: A)

  • Regular monitoring of disease activity, adverse events and comorbidities should guide decisions on choice and changes in treatment strategies to reach clinical remission (Level of evidence: Ib; grade of recommendation: A)

  • Arthritis activity should be assessed at intervals of 1 to 3 months until clinical remission has been reached. Monitoring should include tender and swollen joint counts, patient and physician global assessments, erythrocyte sedimentation rate, and C-reactive protein; radiographic and patient-reported outcome measures, such as functional assessments, can be used as complementary monitors. (Level of evidence: Ia; grade of recommendation: A)

  • Nonpharmacological interventions, such as dynamic exercises and occupational therapy, should be considered as adjuncts to drug treatment (Level of evidence: Ia; grade of recommendation: B)

  • Smoking cessation, dental care, weight control, assessment of vaccination status, and management of comorbidities should be included in overall patient care (Level of evidence: IIb; grade of recommendation: C)

  • Education programs aimed at coping with pain, disability, maintenance of ability to work, and social participation may be used as adjunct interventions (Level of evidence: Ia; grade of recommendation: B)

In its 2015 revised guidelines for the management of RA, the American College of Rheumatology (ACR) included the following recommendations for treatment of early RA [4] :

  • A treat-to-target stategy should be used regardless of disease activity.  (Strong recommendation)
  • Low disease activity: DMARD monotherapy over double or triple therapy. MTCX is the preferred DMARD.  (Strong recommendation)
  • Moderate or high disease activity: DMARD monotherapy over double or triple therapy.  (Conditional recommendation)
  • Moderate /high disease activity despite DMARD monotherapy: Combination DMARDs  or  a  tumor necrosis factor (TNF) inhibitor  or  a non-TNF biologic agent (Strong recommendation)

A change from 2012 to 2015 guidelines is that the 2015 guidelines do not recommend initial combination DMARD therapy in early RA with moderate to high disease activity.

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Management of Established RA

Guidelines for pharmacologic therapy for RA have been issued by the following organizations:

  • American College of Rheumatology (ACR) [4, 75]
  • European League Against Rheumatism (EULAR) [5]

The 2019 update of the EULAR RA management guidelines includes the following key recommendations for pharmacologic therapy [5] :

  • Therapy with disease-modifying antirheumatic drugs (DMARDs) should be started as soon as the diagnosis of RA is made.
  • Treatment should be aimed at reaching a target of sustained remission or low disease activity in every patient.
  • Patients with active disease should have frequent monitoring (every 1–3 months); if there is no improvement by at most 3 months after the start of treatment or the target has not been reached by 6 months, therapy should be adjusted.
  • Methotrexate (MTX) should be part of the first treatment strategy.         
  • In patients with a contraindication to MTX (or early intolerance), leflunomide or sulfasalazine should be considered as part of the first-line treatment strategy.
  • Short-term glucocorticoids should be considered when initiating or changing the dose of a conventional synthetic DMARDs (csDMARD); different dose regimens and routes of administration may be used for glucocorticoids, but the drugs should be tapered as rapidly as clinically feasible.    
  • If the treatment target is not achieved with the first csDMARD strategy, in the absence of poor prognostic factors, other csDMARDs should be considered.
  • If the treatment target is not achieved with the first csDMARD strategy, when poor prognostic factors are present, a biologic DMARD or a targeted synthetic DMARDs (currently, Janus kinase inhibitors) should be added.
  • Biologic DMARDs or targeted synthetic DMARDs should be combined with a csDMARD; in patients who cannot use csDMARDs as comedication, interleukin-6 (IL-6) pathway inhibitors and targeted synthetic DMARDs may have some advantages compared with other biologic DMARDs.
  • If a biologic DMARD or targeted synthetic DMARD has failed, treatment with another biologic or targeted synthetic DMARD should be considered; if one tumor necrosis factor (TNF) inhibitor therapy has failed, patients may receive an agent with another mode of action or a second TNF inhibitor.
  • If a patient is in persistent remission after having tapered glucocorticoids, one can consider tapering biologic or targeted synthetic DMARDs, especially if this treatment is combined with a csDMARD.
  • If a patient is in persistent remission, tapering the csDMARD could be considered.                                                                                        

In its 2015 revised guidelines, the ACR included the following recommendations for treatment of patients with established RA [4] :

  • A treat-to-target stategy should be used regardless of disease activity.  (Strong recommendation)
  • Low disease activity: DMARD monotherapy over TNF inhibitor; MTX is the preferred DMARD.  (Strong recommendation)
  • Moderate or high disease activity: Combination DMARDs or  add a TNF inhibitor, or  non-TNF biologic or  tofacitinib  (Strong recommendation)
  • Moderate/high disease activity despite TNF inhibitor therapy: Switch to a non-TNF biologic with or without MTX over another TNF inhibitor or  tofacitinib  (Strong recommendation)

A change from 2012 to 2015 guidelines is that instead of switching from one anti-TNF biologic to another anti-TNF biologic because of continued activity, it is recommended to change first to a non-TNF biologic.

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