In treatment-naive patients with moderately to high disease activity RA, which DMARD is preferred?

• A. Leflunomide (LEF)
• B. Methotrexate (MTX)
• C. Hydroxychloroquine (HCQ)
• D. Sulfasalazine (SSZ)

Answer: (B)

Methotrexate is favored because it has the strongest, most consistent evidence for both reducing joint symptoms and slowing radiographic progression when starting treatment in RA with moderate to high disease activity. Its efficacy as a disease-modifying therapy is well established in numerous trials, and it serves as the backbone of initial RA management. Clinically, MTX works well as a monotherapy and also integrates smoothly into combination approaches (for example with short-term steroids for rapid control) if needed. With proper monitoring and folic acid supplementation to lessen side effects, MTX tends to offer a favorable balance of effectiveness and tolerability, making it the first-line choice in treatment-naive patients who have active disease.

Leflunomide, hydroxychloroquine, and sulfasalazine can be useful in certain contexts or as part of combination regimens, but they generally do not match MTX for initial control of high disease activity when used alone. Leflunomide has similar efficacy but carries a risk of hepatotoxicity and a slower onset in some patients; hydroxychloroquine is typically less potent for high activity RA; sulfasalazine can be effective but often has more GI and other tolerability issues and may be less robust in preventing radiographic progression when used alone.