What is the management of Rheumatoid Arthritis (RA)?

Management of Rheumatoid Arthritis

The management of rheumatoid arthritis should begin with methotrexate (rapidly escalated to 25 mg/week) plus short-term glucocorticoids, aiming for clinical remission or low disease activity within 6 months. 1

Initial Treatment Approach

• Treatment with disease-modifying antirheumatic drugs (DMARDs) should be started immediately upon diagnosis of RA to prevent joint damage and disability 1, 2
• Methotrexate should be the anchor drug in the first treatment strategy for patients with active RA, starting with 15mg weekly and titrating up to 20-25mg weekly or maximum tolerated dose 1, 2, 3
• Short-term low-dose glucocorticoids should be added to initial DMARD therapy to provide rapid symptomatic relief while waiting for DMARDs to take effect, but should be tapered as rapidly as clinically feasible 1, 2
• For patients with contraindications or intolerance to methotrexate, alternative first-line agents include leflunomide, sulfasalazine, or injectable gold 1, 2

Treatment Goals and Monitoring

• Treatment should aim for clinical remission (defined by ACR-EULAR Boolean or index criteria) or at minimum low disease activity 1, 2
• Disease activity should be monitored frequently (every 1-3 months) during active disease with appropriate instruments 1, 2
• Treatment should be adjusted if no improvement is seen within 3 months or if the target is not reached by 6 months 1, 2
• The treat-to-target strategy requires strict monitoring and appropriate switching of treatments to achieve optimal outcomes 1, 2, 4

Treatment Escalation for Inadequate Response

• If the treatment target is not achieved with the first DMARD strategy, treatment should be stratified based on prognostic factors 1
• Without unfavorable prognostic markers, switching to or adding another conventional synthetic DMARD (plus short-term glucocorticoids) is recommended 1
• In the presence of unfavorable prognostic markers (autoantibodies, high disease activity, early erosions, failure of 2 csDMARDs), a biological DMARD or JAK inhibitor should be added to the conventional synthetic DMARD 1, 2
• Current practice for biological DMARDs would be to start with a TNF inhibitor (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab) combined with methotrexate 1

Management of Treatment Failure

• If the first biological DMARD or JAK inhibitor fails, another biological DMARD or JAK inhibitor should be used 1
• Options after TNF inhibitor failure include another TNF inhibitor, abatacept, rituximab, tocilizumab, or a JAK inhibitor 1, 5
• Rituximab is specifically indicated for patients with moderately to severely active RA who have had an inadequate response to one or more TNF antagonist therapies 5
• For refractory severe RA or contraindications to biological agents, alternative synthetic DMARDs might be considered, such as azathioprine or cyclosporine A 1

Optimizing Methotrexate Therapy

• Consider subcutaneous methotrexate administration for patients with inadequate response or intolerance to oral methotrexate, as it has improved bioavailability at higher doses 6
• Higher doses of methotrexate (≥20 mg weekly) may improve biologic retention in patients requiring combination therapy 7
• Folic acid supplementation should be used with methotrexate to reduce side effects 4

Treatment Tapering

• If a patient achieves sustained remission after tapering glucocorticoids, biological DMARDs can be tapered 1
• In cases of sustained long-term remission, cautious titration of synthetic DMARD dose could be considered 1
• Complete drug-free remission is achievable in only a minority of patients; most will require some ongoing DMARD therapy 2

Common Pitfalls and Caveats

• Delay in referral to rheumatologists is a common cause of delayed effective treatment; patients with suspected RA should be referred to rheumatologists as early as possible 1
• Inadequate methotrexate dosing is a common mistake; ensure proper dose escalation to 20-25mg weekly before declaring treatment failure 2, 6
• Premature discontinuation of conventional DMARDs when starting biologics may lead to reduced efficacy and increased immunogenicity of biological agents 8
• Regular monitoring for methotrexate toxicity and other DMARD side effects is essential, including complete blood counts, liver function tests, and renal function 3, 5