What is the best treatment for rheumatoid arthritis?

Best Treatment for Rheumatoid Arthritis

Start methotrexate 15-25 mg weekly with folic acid 1 mg daily immediately upon diagnosis, combined with short-term low-dose glucocorticoids, and escalate therapy rapidly using a treat-to-target strategy aiming for remission (CDAI ≤2.8) or low disease activity (CDAI ≤10). 1, 2, 3

Initial Treatment Algorithm

First-Line Therapy at Diagnosis

• Methotrexate monotherapy is the anchor drug, starting at 15 mg/week with folic acid supplementation 1, 2
• Escalate methotrexate to 20-25 mg/week within the first 3 months if needed 2
• Add short-term low-dose glucocorticoids for bridging therapy while DMARDs take effect 1, 2
• Alternative first-line csDMARDs include hydroxychloroquine, sulfasalazine, or leflunomide if methotrexate is contraindicated 4

Disease Activity Monitoring

• Measure disease activity every 1-3 months using validated composite measures (SDAI, CDAI, or DAS28) 1, 3
• Use SDAI for patients with elevated acute-phase reactants; use CDAI for all others 3
• Adjust treatment if no improvement at 3 months (defined as <50% reduction in disease activity) or target not met at 6 months 3

Treatment Escalation for Inadequate Response

Step 2: Add or Switch csDMARDs (3-6 months if no response)

• Add another csDMARD to methotrexate (combination therapy with hydroxychloroquine, sulfasalazine, or leflunomide) 4
• Consider double or triple therapy with conventional synthetic DMARDs before biologics 4

Step 3: Add Biologic or JAK Inhibitor (if poor prognostic factors present)

Poor prognostic factors include: 4, 1

• RF/ACPA positivity
• High disease activity
• Early erosions
• Failure of two csDMARDs

When these factors are present, add to methotrexate: 4, 2

• TNF inhibitors (adalimumab 40 mg every other week, etanercept 50 mg weekly, infliximab, golimumab, certolizumab) 5, 6
• Non-TNF biologics (abatacept, rituximab, tocilizumab, sarilumab) 4
• JAK inhibitors (tofacitinib, baricitinib, filgotinib, upadacitinib) 4

Step 4: Switch Biologics if Inadequate Response

• If anti-TNF fails, switch to another anti-TNF or non-TNF biologic (abatacept, rituximab, tocilizumab) 4
• Allow 12-24 weeks (3-6 months) for full therapeutic assessment of biologics 2

Treatment Strategy Principles

Treat-to-Target Approach

The treatment strategy is more important than the specific drug chosen 7, 8

• Establish clear remission or low disease activity targets with the patient 3, 7
• Use quantitative measurement with validated instruments every 1-3 months 3
• Rapidly adjust treatment if targets are not met 3, 8
• Shared decision-making between physician and patient is essential 3

Target Definitions

• Remission: CDAI ≤2.8 or SDAI ≤3.3 3
• Low disease activity: CDAI ≤10 or SDAI ≤11 3

Remission Management

Upon Achieving Sustained Remission

• Continue current DMARD regimen 1
• Taper or discontinue prednisone to minimize long-term risks (cataracts, osteoporosis, cardiovascular disease) 1
• DMARDs may be tapered but should not be stopped completely 4

Safety Considerations and Monitoring

Before Initiating Biologics

• Screen for latent tuberculosis before starting and periodically during therapy 5, 6
• Screen for hepatitis B and C 2
• Complete age-appropriate vaccinations 6

During Treatment

• Monitor for serious infections (tuberculosis reactivation, invasive fungal infections, opportunistic infections) 5, 6
• Regular monitoring for cytopenias, infections, and infusion reactions with biologics and DMARDs 1
• Discontinue therapy if serious infection or sepsis develops 5, 6

Malignancy Risk

• Lymphoma and other malignancies have been reported, particularly hepatosplenic T-cell lymphoma in young males receiving TNF blockers with azathioprine or 6-mercaptopurine 5, 6

Common Pitfalls to Avoid

• Never continue ineffective therapy beyond 6 months without escalating treatment 3
• Never use subjective assessment alone without validated composite instruments 3
• Never delay DMARD initiation—start immediately upon diagnosis 1, 8
• Never omit regular evaluation every 1-3 months during active disease 3
• Never use methotrexate without folic acid supplementation 2

Special Populations

Dose Adjustments

• Lower methotrexate doses may be required in elderly patients and those with chronic kidney disease 2

Concomitant Medications

• Methotrexate, other non-biologic DMARDs, glucocorticoids, NSAIDs, and analgesics may be continued during biologic therapy 5, 6