What is the first-line disease-modifying therapy for rheumatoid arthritis?

• A. Leflunomide
• B. Hydroxychloroquine
• C. Methotrexate
• D. Sulfasalazine

Answer: (C)

Starting disease-modifying therapy with methotrexate is favored because it provides the strongest, most consistent evidence for reducing joint inflammation and slowing radiographic damage in rheumatoid arthritis, which translates into better long-term function. It’s a conventional synthetic DMARD with robust trial data supporting its efficacy as both initial monotherapy and in combination, making it the standard first-line option. Dosing is typically weekly, with gradual escalation to a target range, and folic acid is added to lessen mucosal and hematologic toxicity. While relief may take several weeks, many patients achieve meaningful improvement by 3–6 months, and methotrexate can be continued with bridging low-dose steroids as needed. A careful monitoring plan is essential, including liver enzymes, blood counts, renal function, and consideration of pregnancy potential, since hepatotoxicity, bone marrow suppression, and teratogenicity are important risks. Because of its proven effectiveness, safety profile in the long term, and familiarity in practice, methotrexate remains the preferred starting DMARD. The other agents can be valuable in specific situations (e.g., intolerance to methotrexate or in combination therapy), but they do not consistently replace methotrexate as the initial first-line choice.