What is the treatment for rheumatoid arthritis?

Treatment for Rheumatoid Arthritis

Methotrexate (MTX) should be the first-line therapy for rheumatoid arthritis, starting at 15 mg weekly with escalation to 20-25 mg weekly or maximum tolerated dose, with subsequent switch to subcutaneous administration if needed for better efficacy. 1

Initial Treatment Approach

The treatment of rheumatoid arthritis follows a structured algorithm aimed at reducing inflammation, preventing joint damage, and improving quality of life:

1. First-line therapy: Methotrexate

   • Start at 15 mg weekly orally
   • Escalate dose to 20-25 mg weekly or maximum tolerated dose
   • Switch to subcutaneous administration if oral therapy shows inadequate response 1, 2
   • Add folic acid supplementation to reduce side effects

2. For patients with single isolated joint inflammation

   • Consider intra-articular glucocorticoid injections 1

3. For patients with inadequate response to MTX monotherapy

   • Add sulfasalazine (SSZ) and hydroxychloroquine (HCQ) to create triple therapy 1
   • Alternative: Add leflunomide if unable to tolerate SSZ or HCQ 3

Disease Activity Assessment and Treatment Targets

Treatment should follow a treat-to-target approach with regular assessment using validated measures:

• Target: Remission (SDAI ≤3.3 or CDAI ≤2.8) or Low Disease Activity (SDAI ≤11 or CDAI ≤10) 1
• Assess disease activity every 1-3 months using standardized measures
• Adjust therapy if target is not achieved within 3-6 months

Biologic and Targeted Synthetic DMARDs

For patients with moderate to high disease activity despite conventional DMARDs:

1. TNF inhibitors (e.g., adalimumab) 4

   • 40 mg subcutaneously every other week
   • Can be used alone or in combination with MTX

2. Alternative biologics after inadequate response to TNF inhibitors:

   • Abatacept (CTLA4-Ig)
   • Tocilizumab (anti-IL-6R)
   • Rituximab (anti-CD20) - particularly effective in seropositive patients 1
   • IL-1 receptor antagonists (anakinra)

Important Clinical Considerations

• Biomarker guidance: Patients positive for rheumatoid factor or anti-citrullinated protein antibodies may respond better to rituximab 1
• Route of administration matters: Subcutaneous MTX has better bioavailability than oral MTX at higher doses (>15 mg/week) 2, 5
• Duration of therapy assessment: Any new treatment should be tried for at least 3-6 months to fully assess efficacy 1
• Corticosteroid use: Consider short-term use for flares, but avoid long-term use beyond 1-2 years due to risks of cataracts, osteoporosis, fractures, and cardiovascular disease 1

Potential Pitfalls and Caveats

• MTX administration: Nausea is more common with higher starting doses (15 mg vs. 7.5 mg), but efficacy outcomes may be similar with rapid dose escalation from either starting point 6
• Monitoring requirements: Regular laboratory monitoring for hepatotoxicity, bone marrow suppression, and pulmonary toxicity with MTX
• Infection risk: Biologic therapies increase risk of serious infections; screen for tuberculosis before initiating 4
• Remission considerations: In patients with sustained remission for ≥1 year, consider cautious de-escalation of therapy, though only 15-25% achieve sustained drug-free remission 1

Special Situations

• Fibromyalgia overlap: Patients may have high disease activity scores due to tender joints and patient global assessment without objective inflammation; avoid inappropriate escalation to biologics 1
• Seronegative patients: Consider abatacept or tocilizumab rather than rituximab if inadequate response to TNF inhibitors 1
• Isolated joint inflammation: Use intra-articular glucocorticoid injections 1

The goal of treatment is to achieve remission or low disease activity as quickly as possible to prevent joint damage and disability, with MTX as the cornerstone of therapy and biologics reserved for those with inadequate response to conventional DMARDs.