What is the typical prescription for Rheumatoid arthritis?

Methotrexate as First-Line Treatment for Rheumatoid Arthritis

Methotrexate should be initiated as the first-line disease-modifying antirheumatic drug (DMARD) for rheumatoid arthritis, starting at 15 mg weekly with rapid escalation to 20-25 mg weekly (or 0.3 mg/kg) within 4-6 weeks, combined with folic acid supplementation. 1

Initial DMARD Selection

• Methotrexate is the anchor drug and preferred initial DMARD for most patients with rheumatoid arthritis, whether newly diagnosed or with established disease 1
• The European League Against Rheumatism (EULAR) and American College of Rheumatology (ACR) both prioritize methotrexate as first-line therapy due to its efficacy, extensive safety record, and role as the foundation for combination therapies 1
• Methotrexate can be used as monotherapy or in combination with other conventional synthetic DMARDs (csDMARDs) 1

Dosing Strategy

Optimal methotrexate dosing requires rapid escalation to therapeutic levels:

• Start at 15 mg weekly and escalate by 5 mg increments every 2-4 weeks 1
• Target dose is approximately 0.3 mg/kg weekly, which translates to 20-25 mg weekly for most Western patients 1
• Maximum dose typically reaches 25 mg weekly, though some protocols allow up to 30 mg 1
• Always prescribe folic acid supplementation to reduce gastrointestinal and hematologic adverse effects 1

Route of Administration

• Begin with oral administration 1
• Switch to subcutaneous methotrexate if inadequate response to oral therapy, as parenteral administration may improve bioavailability 1
• Subcutaneous administration can be considered when oral doses exceed 15-20 mg weekly 1

Glucocorticoid Bridge Therapy

Low-dose glucocorticoids should be added to methotrexate at treatment initiation for patients with moderate to high disease activity:

• Use prednisone ≤10 mg daily (or equivalent) 1
• Glucocorticoids serve as "bridge therapy" until methotrexate achieves full effect 1
• Taper glucocorticoids as rapidly as clinically feasible, ideally within 3 months and no longer than 6 months 1
• The risk-benefit ratio favors short-term, low-dose glucocorticoid use 1

Treatment Targets and Monitoring

Aim for remission or low disease activity as the treatment target:

• Assess response at 3 months; expect target achievement by 6 months 1
• Monitor disease activity every 1-3 months during active treatment 1, 2
• Use validated measures such as DAS28, SDAI, or CDAI to assess disease activity 1

Treatment Adjustment Algorithm

If target not achieved with methotrexate monotherapy at 3-6 months:

1. For patients WITHOUT poor prognostic factors: Switch to another csDMARD or add combination csDMARD therapy (sulfasalazine + hydroxychloroquine) 1

2. For patients WITH poor prognostic factors (high anti-CCP antibodies, rheumatoid factor positive, erosive disease): Add a biologic DMARD to methotrexate 1, 2

Biologic DMARD Addition

When methotrexate fails despite optimization, add a biologic DMARD while continuing methotrexate:

• TNF inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab) are first-line biologic options 1
• Alternative mechanisms include abatacept (T-cell costimulation blocker) or tocilizumab (IL-6 receptor antagonist) 1
• Rituximab (anti-CD20) is appropriate in certain circumstances, particularly for seropositive patients 1
• Always combine biologic DMARDs with methotrexate unless methotrexate is contraindicated, as combination therapy is more effective than biologic monotherapy 1, 2

Biologic Switching Strategy

• If first TNF inhibitor fails, either switch to another TNF inhibitor or change to a biologic with different mechanism of action 1, 2
• After failure of one biologic mechanism, switching to a different mechanism is recommended 2

Common Pitfalls to Avoid

Underdosing methotrexate is a frequent error:

• Many clinicians fail to escalate methotrexate rapidly enough or to adequate doses 1
• Starting at 7.5 mg weekly and slowly escalating delays therapeutic benefit 1
• Inadequate folic acid supplementation increases toxicity and treatment discontinuation 1

Premature addition of biologics:

• Biologic DMARDs should not be first-line therapy in DMARD-naive patients with early RA and low disease activity 1
• Methotrexate combined with glucocorticoids is as effective as methotrexate plus biologics in early disease 1

Prolonged glucocorticoid use:

• Continuing glucocorticoids beyond 3-6 months increases cardiovascular and mortality risks 1, 3
• Doses above 7.5 mg daily prednisone equivalent carry significantly higher risks 3

Special Considerations

For methotrexate contraindications or intolerance:

• Alternative csDMARDs include leflunomide, sulfasalazine, or hydroxychloroquine 1
• If csDMARDs fail or are contraindicated with poor prognostic factors present, proceed directly to biologic DMARD therapy 2

Patient education is critical:

• Address fears about methotrexate toxicity, which often stem from confusion with high-dose chemotherapy regimens 1
• Emphasize the importance of folic acid supplementation and regular monitoring 1
• Shared decision-making between patient and rheumatologist is essential 1