What is the recommended treatment for rheumatoid arthritis?

Treatment for Rheumatoid Arthritis

Start methotrexate immediately upon diagnosis at 15mg weekly, titrating to 20-25mg weekly, combined with short-term low-dose glucocorticoids for rapid symptom relief while awaiting DMARD effect. 1

Initial Treatment Strategy

First-Line Therapy

• Methotrexate is the anchor drug and should be initiated immediately upon diagnosis to prevent joint damage and disability 1
• Start at 15mg weekly and titrate up to 20-25mg weekly or maximum tolerated dose 1
• Administer with food or milk; do not crush or divide tablets 2
• Add folic acid supplementation to reduce methotrexate toxicity 3
• Combine with short-term low-dose glucocorticoids initially to provide rapid symptomatic relief while waiting for DMARDs to take effect (typically weeks to months for maximum therapeutic effect) 1

Alternative First-Line Agents

• If methotrexate is contraindicated, use leflunomide or sulfasalazine as alternative first-line agents 1
• Hydroxychloroquine can be used at 200-400mg daily (single or divided doses) for rheumatoid arthritis, though it is less commonly used as monotherapy 4

Treatment Goals and Monitoring Schedule

Target Outcomes

• Aim for clinical remission as the primary target, or at minimum low disease activity 1
• This treat-to-target approach improves long-term outcomes and slows joint damage 3

Monitoring Frequency

• Monitor disease activity every 1-3 months during active disease 1, 5
• Baseline assessment should include complete blood count with differential and platelet counts, hepatic enzymes, renal function tests, and chest X-ray 2
• During ongoing therapy: hematology at least monthly, renal function and liver function every 1-2 months 2
• If no improvement within 3 months or target not reached by 6 months, adjust therapy 1, 5

Treatment Escalation Algorithm

When to Escalate

Escalate therapy if patients have:

• Poor prognostic factors (autoantibodies, high disease activity, early erosions) 1
• Failure of two conventional synthetic DMARDs 1
• No improvement after 3 months of current therapy 1, 5

Escalation Options

Add a biological DMARD or JAK inhibitor to methotrexate 1:

• TNF inhibitors (etanercept, infliximab, adalimumab)
• IL-6 inhibitors (tocilizumab - can be given weekly for refractory cases) 5
• T-cell co-stimulation modulators (abatacept)
• B-cell depleting therapy (rituximab)
• JAK inhibitors 1

Managing Treatment Failure

First Biologic/JAK Inhibitor Failure

• Switch to another biological DMARD or JAK inhibitor from either the same or different class 1
• For patients who fail TNF inhibitor therapy specifically, consider switching to a different mechanism of action such as abatacept, tocilizumab, rituximab, or a JAK inhibitor 1

Combination Therapy Considerations

• NSAIDs and salicylates may be used concomitantly with methotrexate for symptom control 2
• Caution: NSAIDs can reduce tubular secretion of methotrexate and enhance toxicity, though studies in RA patients using 7.5-15mg/week methotrexate have not shown apparent problems 2
• Corticosteroids and other antirheumatic agents may be used concomitantly 4

Managing Disease Flares

• For isolated joint flares: use intra-articular glucocorticoid injections 1
• For systemic flares: short-term oral glucocorticoids may be used 1

Treatment Tapering in Remission

When to Consider Tapering

• Only in patients who achieve sustained remission 1
• Tapering should be cautious and systematic 1

Tapering Sequence

• Taper biologics first, then reduce conventional DMARDs 1
• Complete drug-free remission is achievable in only 15-25% of patients 1
• Most patients will require some ongoing DMARD therapy to maintain remission 1

Critical Safety Considerations

Methotrexate-Specific Warnings

• Weekly dosing only - mistaken daily use has led to fatal toxicity 2
• Prescriptions should not be written on a PRN basis 2
• Monitor for early signs of toxicity including dizziness, fatigue, and gastrointestinal symptoms 2
• Avoid high-dose NSAIDs prior to or concomitantly with methotrexate due to risk of severe hematologic and gastrointestinal toxicity 2

Drug Interactions to Avoid

• Penicillins may reduce renal clearance of methotrexate, increasing toxicity risk 2
• Probenecid diminishes renal tubular transport of methotrexate 2
• Salicylates, phenylbutazone, phenytoin, and sulfonamides may displace methotrexate from serum albumin, increasing toxicity 2

Special Populations

• Older patients: use relatively low doses due to diminished hepatic/renal function and decreased folate stores; monitor closely for early toxicity 2
• Renal impairment: aim for same treatment targets (remission or low disease activity) as patients without renal impairment 6