What is the recommended treatment for rheumatoid arthritis?

Treatment for Rheumatoid Arthritis

Methotrexate (MTX) should be initiated as the first-line disease-modifying antirheumatic drug (DMARD) for rheumatoid arthritis, with a high initial dose followed by rapid titration, combined with short-term glucocorticoids to achieve rapid disease control. 1

Initial Treatment Approach

• Therapy with DMARDs should be started immediately upon diagnosis of rheumatoid arthritis (RA) to prevent joint damage and disability 1
• Methotrexate is the anchor drug and should be the first DMARD used in most patients, 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 therapy to provide rapid symptomatic relief while waiting for DMARDs to take effect 1
• For patients with contraindications to MTX, leflunomide or sulfasalazine should be considered as alternative first-line agents 1, 4
• Folic acid supplementation should be given with MTX to reduce side effects 5, 3

Treatment Goals and Monitoring

• Treatment should aim for clinical remission (or at minimum low disease activity) as the primary target 1
• Disease activity should be monitored frequently (every 1-3 months) during active disease 1
• If no improvement is seen within 3 months or the target is not reached by 6 months, therapy should be adjusted 1
• Regular monitoring of laboratory parameters is essential: complete blood count, liver function, and renal function tests should be performed monthly initially, then every 1-2 months 2, 5

Treatment Escalation for Inadequate Response

If the treatment target is not achieved with first-line therapy:

For Patients with Poor Prognostic Factors:

• Poor prognostic factors include: presence of autoantibodies (RF/ACPA), high disease activity, early erosions, or failure of two csDMARDs 1
• Add a biological DMARD (bDMARD) or JAK inhibitor (JAKi) to MTX 1
• Options include TNF inhibitors (adalimumab, certolizumab, etanercept, golimumab, infliximab), IL-6 inhibitors (tocilizumab, sarilumab), T-cell co-stimulation modulator (abatacept), B-cell depleting therapy (rituximab), or JAK inhibitors (baricitinib, tofacitinib, upadacitinib, filgotinib) 1

For Patients without Poor Prognostic Factors:

• Consider triple therapy with MTX, hydroxychloroquine, and sulfasalazine 1
• Hydroxychloroquine can be added at 200-400mg daily 6, 4
• Sulfasalazine can be added and titrated to 2-3g daily 1

Treatment Failure Management

• If the first bDMARD or JAKi fails, switch to another bDMARD or JAKi from either the same or a different class 1
• For patients who fail TNF inhibitor therapy, consider switching to a different mechanism of action (abatacept, tocilizumab, rituximab, or JAK inhibitor) 1
• Rituximab may be particularly effective in seropositive patients (positive RF or ACPA) 1
• Each new treatment should be tried for at least 3-6 months to fully assess efficacy 1

Flare Management

• For isolated joint flares, consider intra-articular glucocorticoid injections 1, 7
• For systemic flares, short-term oral glucocorticoids (prednisolone 30-35mg/day for 3-5 days) may be used 7
• NSAIDs can help control pain and inflammation during flares but should be used with caution in patients with renal impairment or cardiovascular risk factors 7, 2

Treatment Tapering

• In patients who achieve sustained remission (typically ≥12 months), cautious tapering of DMARDs can be considered 1
• Typically, taper biologics first, then reduce conventional DMARDs 1
• Glucocorticoids should be tapered and discontinued as soon as clinically feasible 1, 7
• Complete drug-free remission is achievable in only 15-25% of patients; most will require some ongoing DMARD therapy 1

Important Considerations and Pitfalls

• Subcutaneous MTX should be considered if oral MTX is ineffective or poorly tolerated due to its superior bioavailability 3, 8
• When switching from oral to subcutaneous MTX, maintain the same dose rather than increasing it 3
• NSAIDs and salicylates may increase MTX toxicity by reducing its renal clearance 2
• Alcohol consumption should be limited (not necessarily eliminated completely) while taking MTX 8
• Patients should be educated about the weekly (not daily) dosing of MTX to avoid potentially fatal toxicity 2, 8
• Regular ophthalmologic screening is recommended for patients on hydroxychloroquine to monitor for retinal toxicity 6