Update on methotrexate as the anchor drug for rheumatoid arthritis.

Methotrexate has become the "anchor drug" for rheumatoid arthritis (RA), taken by many more patients than any other disease modifying anti-rheumatic drug (DMARD) or biological agent. Methotrexate has greater efficacy and effectiveness than any other non-biologic DMARD, and greater tolerability and safety than other DMARDs. The efficacy of methotrexate is comparable to biologic agents in parallel clinical trials of DMARD-naïve patients. Adequate responses to methotrexate monotherapy or combinations with other non-biologic DMARDs are seen in about two- thirds of patients with RA in usual care. The most efficacious treatments for RA reported in the rheumatology literature are seen in strategy trials with methotrexate as the anchor drug, without any biologic agent. Interpretation of significantly lower radiographic progression between methotrexate and biologic agents in clinical trials is over- stated regarding clinic consequences. The admonition to patients to refrain entirely from consumption of alcohol while taking methotrexate may be unnecessary. Accurate information concerning methotrexate as the anchor drug for RA should lead to better understanding of optimal use and better to patient outcomes in usual clinical care.