What is the first-line disease-modifying antirheumatic drug (DMARD) for rheumatoid arthritis and what monitoring is required?

• A. Hydroxychloroquine; monitor retinal exams
• B. Methotrexate; monitor CBC and LFTs; give folic acid; avoid in pregnancy
• C. Sulfasalazine; monitor CBC
• D. Leflunomide; monitor LFTs

Answer: (B)

Methotrexate is the first-line DMARD for rheumatoid arthritis because it provides robust overall improvement, slows radiographic progression, and has a long track record of use with acceptable safety when monitored properly. The key is balancing efficacy with safety through targeted monitoring and supportive measures.

Because methotrexate can cause bone marrow suppression and hepatotoxicity (and its clearance depends in part on kidney function), baseline and periodic laboratory tests are essential. Start with a full CBC, liver function tests, and renal function, and consider hepatitis B and C screening since immunosuppression can uncover latent infections. The monitoring plan typically includes checking CBC and LFTs (and renal function) every 1–3 months early in therapy, then less frequently once stable. To reduce mucosal and hepatic toxicity, give folic acid supplementation (commonly daily on non-methotrexate days, with a weekly higher-dose strategy used in some protocols). Methotrexate is teratogenic, so it should be avoided in pregnancy; women of childbearing potential should use effective contraception and discontinue methotrexate well before conception.

Other DMARDs like hydroxychloroquine, sulfasalazine, or leflunomide have useful roles but generally are not started first-line when methotrexate is suitable, due to differences in efficacy, onset of action, and safety considerations.