What is the drug of choice for rheumatoid arthritis (RA) with positive European League Against Rheumatism (EULAR) criteria?

Drug of Choice for Rheumatoid Arthritis with Positive EULAR Criteria

Methotrexate (MTX) should be part of the first treatment strategy for patients with rheumatoid arthritis who meet EULAR criteria. 1

Initial Treatment Algorithm

First-Line Therapy

• MTX should be initiated as soon as the diagnosis of RA is made, with the highest level of evidence (1a) and strongest recommendation (A) 1
• Start with optimal dosing of MTX (25-30 mg weekly with folate supplementation) and maintain for at least 3 months to evaluate efficacy 1
• Short-term glucocorticoids should be added when initiating MTX to provide bridging therapy until MTX takes effect, but should be tapered as rapidly as clinically feasible (within about 3 months) 1

Alternative First-Line Options

• In patients with contraindications to MTX or early intolerance, leflunomide or sulfasalazine should be considered as part of the first treatment strategy 1
• Hydroxychloroquine has a limited place in RA treatment, mainly reserved for patients with mild disease 1

Treatment Monitoring and Adjustment

• Monitor disease activity frequently (every 1-3 months) in active disease 1
• If no improvement is seen by 3 months after treatment initiation or the target (remission or low disease activity) is not reached by 6 months, therapy should be adjusted 1

Second-Line Therapy

• If the treatment target is not achieved with the first csDMARD strategy and poor prognostic factors are absent, consider other csDMARDs 1
• If the treatment target is not achieved with the first csDMARD strategy and poor prognostic factors are present (autoantibodies, high disease activity, early erosions, or failure of two csDMARDs), add a biological DMARD (bDMARD) or targeted synthetic DMARD (tsDMARD) 1

Poor Prognostic Factors

• Presence of autoantibodies (especially at high levels)
• High disease activity
• Early joint damage/erosions
• Failure of two csDMARDs 1

Combination Therapy

• bDMARDs and tsDMARDs should be combined with a csDMARD for optimal efficacy 1
• In patients who cannot use csDMARDs as comedication, IL-6 pathway inhibitors and tsDMARDs may have some advantages compared to other bDMARDs 1

Treatment Failure Management

• If a bDMARD or tsDMARD fails, treatment with another bDMARD or tsDMARD should be considered 1
• If one TNF inhibitor therapy fails, patients may receive an agent with another mode of action or a second TNF inhibitor 1

Remission Management

• If a patient achieves persistent remission after tapering glucocorticoids, consider tapering bDMARDs or tsDMARDs, especially if combined with a csDMARD 1
• If persistent remission is maintained, tapering the csDMARD could be considered 1
• DMARDs should be tapered but not completely stopped in patients with sustained remission 2

Important Considerations

• Treatment should aim at reaching a target of sustained remission or low disease activity in every patient 1
• The treat-to-target strategy requires frequent monitoring and adjustment of therapy 3
• First DMARDs in new patients are generally more effective and retained longer than subsequent DMARDs 4
• Consider risks of major cardiovascular events, malignancies, and thromboembolic events when selecting therapy, particularly with JAK inhibitors 2

Common Pitfalls to Avoid

• Delaying DMARD initiation after diagnosis 1
• Inadequate dosing of MTX (optimal dose is 25-30 mg weekly) 1
• Failing to add glucocorticoids as bridging therapy when initiating or changing csDMARDs 1
• Not adjusting therapy if no improvement is seen by 3 months or target not reached by 6 months 1
• Completely stopping DMARDs in patients with remission rather than tapering 2