What are the EULAR (European League Against Rheumatism) criteria for diagnosing and treating Rheumatoid Arthritis (RA)?

EULAR Criteria for Rheumatoid Arthritis

The 2010 ACR/EULAR classification criteria require a score of ≥6/10 points across four domains (joint involvement, serology, acute phase reactants, and symptom duration) to classify definite RA, and EULAR treatment recommendations emphasize immediate initiation of methotrexate with a treat-to-target strategy aiming for remission or low disease activity. 1, 2

Classification Criteria for Diagnosis

The 2010 ACR/EULAR classification criteria use a score-based algorithm that requires patients to have at least one joint with definite clinical synovitis not better explained by another disease. 1, 3 The scoring system includes four domains:

Joint Involvement Scoring

• 1 large joint = 0 points 3
• 2-10 large joints = 1 point 1, 3
• 1-3 small joints (with or without large joints) = 2 points 3
• 4-10 small joints (with or without large joints) = 3 points 3

• 10 joints (at least 1 small joint) = 5 points 3

Serology Scoring

• Negative RF and negative ACPA = 0 points 3
• Low positive RF or low positive ACPA (≤3× upper limit of normal) = 2 points 3
• High positive RF or high positive ACPA (>3× upper limit of normal) = 3 points 3

Acute Phase Reactants

• Normal CRP and normal ESR = 0 points 3
• Abnormal CRP or abnormal ESR = 1 point 3

Duration of Symptoms

• <6 weeks = 0 points 3
• ≥6 weeks = 1 point 3

A total score of ≥6/10 points classifies the patient as having definite RA. 1, 2 These criteria were developed to facilitate early diagnosis and enable prompt treatment intervention, which is critical for preventing joint destruction and disability. 4, 5

Disease Activity Assessment

EULAR recommends regular monitoring using validated composite measures to guide treatment decisions. 2 The disease activity states are defined as:

• Remission: DAS28 <2.6 (though ACR/EULAR Boolean remission criteria are preferred as DAS28<2.6 is not sufficiently stringent) 1
• Low disease activity: DAS28 ≤3.2 or CDAI ≤10 2
• Moderate disease activity: DAS28 >3.2 to ≤5.1 2
• High disease activity: DAS28 >5.1 2

The 2022 revision of ACR/EULAR remission criteria uses Boolean 2.0 criteria with a patient global assessment threshold of ≤2 cm (rather than ≤1 cm), which improves agreement with index-based criteria while maintaining predictive value for radiographic and functional outcomes. 6

EULAR Treatment Recommendations

First-Line Treatment Strategy

Treatment must begin immediately after RA diagnosis. 1, 2 The treatment target should be sustained remission or low disease activity in every patient. 1

• Methotrexate (15-30 mg/week) is the anchor drug and should be started as first-line therapy, combined with short-term low-dose glucocorticoids. 2
• If methotrexate is contraindicated, leflunomide or sulfasalazine should be used as alternatives. 1, 2
• Short-term glucocorticoids should be considered when initiating or changing conventional synthetic DMARDs, but must be tapered as rapidly as clinically feasible. 1

Monitoring and Treatment Adjustment

Disease activity must be monitored every 1-3 months in active disease. 1, 2 The treatment algorithm follows this timeline:

• If no improvement by 3 months: Therapy must be adjusted 1, 2
• If target not reached by 6 months: Therapy must be adjusted 1, 2

Methotrexate should be optimized to 25-30 mg weekly with folate supplementation and maintained for at least 8 weeks before assessing efficacy, as maximum effect may not be seen until 4-6 months. 2

Difficult-to-Treat RA Definition

EULAR defines difficult-to-treat RA when all three of the following criteria are present: 7, 2

1. Treatment failure: Failure of ≥2 biologic/targeted synthetic DMARDs with different mechanisms of action after failing conventional synthetic DMARD therapy (unless contraindicated) 7

2. Signs of active/progressive disease (≥1 of the following):

   • At least moderate disease activity (DAS28-ESR >3.2 or CDAI >10) 7
   • Signs/symptoms suggestive of active disease (joint-related or other) 7
   • Inability to taper glucocorticoids below 7.5 mg/day prednisone equivalent 7
   • Rapid radiographic progression (change in van der Heijde-Modified Sharp Score ≥5 points in 1 year) 7
   • Well-controlled disease but persistent RA symptoms causing reduced quality of life 7

3. Management perceived as problematic by the rheumatologist and/or patient 7

Critical Pitfalls to Avoid

• Do not delay treatment waiting for positive serology: Seronegative RA accounts for 20-30% of cases and has similar prognosis to seropositive disease. 3
• Do not dismiss diagnosis based on normal ESR/CRP: Acute phase reactants can be normal even in active disease and are poor predictors of RA. 3
• Do not make premature treatment changes: Maximum effect of most DMARDs may not be seen until 4-6 months of treatment. 2
• Do not use DAS28<2.6 as the sole remission criterion: ACR/EULAR Boolean remission criteria are preferred as they are more stringent. 1
• Do not forget to screen for comorbidities: Patients should be screened for hepatitis B, hepatitis C, and tuberculosis before starting biologic agents. 3