Methotrexate in rheumatoid arthritis.

Methotrexate is an established therapy for rheumatoid arthritis. It is also being utilized in a variety of other rheumatological conditions, autoimmune diseases, and inflammatory disorders. Several open studies over the past 20 years have reported efficacy and an acceptable tolerability profile with low-dose methotrexate in rheumatoid arthritis. These open studies report a moderate to marked improvement in selected clinical parameters [1–5]. The results from these uncontrolled trials have generated sufficient interest to initiate randomized placebo-controlled studies. Four randomized placebo controlled trials have been performed (Table 1), and all report efficacy with methotrexate [6–9]. In a 24-week double-blind cross-over study of low-dose weekly methotrexate versus placebo in 35 patients, an improvement in clinical parameters began as early as 3 weeks after initiation of methotrexate [7]. An improvement in the standard rheumatoid arthritis parameters was seen in this study in which the dose of methotrexate ranged from 7.5 to 15.0 mg per week. In this cross-over study an increase in disease activity occurred within 3 weeks after methotrexate discontinuation. A similar clinical response was observed in an 18-week randomized multicenter trial in which 189 patients were randomized to receive oral methotrexate (7.5–15.0 mg/week) or placebo [6].