What is the typical treatment for rheumatoid arthritis?

Treatment of Rheumatoid Arthritis

First-Line Therapy: Start Methotrexate Immediately

Begin methotrexate 15 mg weekly immediately upon diagnosis of rheumatoid arthritis, escalating to 20-25 mg/week as tolerated, as this is the most effective first-line disease-modifying antirheumatic drug (DMARD) that prevents irreversible joint damage. 1, 2

• Methotrexate is FDA-approved for reducing signs and symptoms, inducing major clinical response, inhibiting structural damage progression, and improving physical function in moderately to severely active RA 3
• Add folic acid supplementation to reduce gastrointestinal and hematological adverse effects 2
• If oral methotrexate at 20-25 mg/week is inadequate, switch to subcutaneous administration for better bioavailability before declaring treatment failure 4, 5

Bridging Therapy: Short-Term Glucocorticoids

• Add low-dose glucocorticoids (≤10 mg/day prednisone equivalent) for rapid symptom relief while methotrexate takes effect 6, 1
• Limit glucocorticoid use to less than 3 months duration—do not use beyond 1-2 years due to risks of cataracts, osteoporosis, fractures, and cardiovascular disease 6, 1
• For single-joint flares, use intra-articular glucocorticoid injection for targeted relief 4, 6

Combination Therapy for Poor Prognostic Factors

For patients with erosive disease, high rheumatoid factor levels, or high disease activity (SDAI >11 or CDAI >10), add hydroxychloroquine 400 mg daily immediately to methotrexate, with consideration of adding sulfasalazine for complete triple-DMARD therapy. 1

• Hydroxychloroquine is FDA-approved for treatment of acute and chronic rheumatoid arthritis 7
• Triple-DMARD therapy (methotrexate + sulfasalazine + hydroxychloroquine) is more effective than methotrexate monotherapy in patients with poor prognostic factors 4, 1
• Do not exceed methotrexate 5 mg/kg actual body weight daily to minimize retinopathy risk 7

Treatment Escalation Algorithm

If Inadequate Response at 3 Months:

1. Optimize methotrexate to 20-25 mg/week (or maximum tolerated dose) before declaring failure 4, 6
2. Add biologic DMARD or targeted synthetic DMARD rather than continuing to adjust conventional DMARDs 6

Biologic Selection:

• TNF inhibitors (adalimumab, etanercept) are first-line biologics, used alone or in combination with methotrexate 3
• Adalimumab dosing: 40 mg subcutaneously every other week; some patients not on concomitant methotrexate may benefit from 40 mg weekly or 80 mg every other week 3
• If TNF inhibitor fails, switch to a different mechanism of action (tocilizumab, abatacept, or rituximab) rather than trying another TNF inhibitor 4, 6

Critical Monitoring and Treatment Targets

• Target remission (SDAI ≤3.3, CDAI ≤2.8) or low disease activity (SDAI ≤11, CDAI ≤10) 6
• Reassess disease activity every 1-3 months during active disease 6, 1
• If no improvement by 3 months after treatment change, adjust therapy immediately—do not wait for 6-month maximal effect 6

Critical Pitfalls to Avoid

• Never delay DMARD initiation—this leads to irreversible joint damage 1
• Never use NSAIDs or corticosteroids alone—these provide only symptomatic relief without disease modification 1, 8
• Never underdose methotrexate—must reach 20-25 mg/week before concluding inadequate response 4, 6
• Never use long-term glucocorticoids (>1-2 years) as adverse effects outweigh benefits 6, 1

Serious Safety Considerations with Biologics

• Patients on TNF inhibitors like adalimumab are at increased risk for serious infections including tuberculosis reactivation, invasive fungal infections, and opportunistic infections 3
• Test for latent tuberculosis before initiating biologic therapy and initiate treatment for latent TB prior to biologic use 3
• Lymphoma and other malignancies, including fatal hepatosplenic T-cell lymphoma, have been reported with TNF blockers, particularly in adolescent and young adult males receiving concomitant azathioprine or 6-mercaptopurine 3
• Discontinue biologic if patient develops serious infection or sepsis 3