The Efficacy and Toxicity of Methotrexate Monotherapy versus Methotrexate Combination Therapy with Non-biologic Disease-modifying Anti-rheumatic Drugs in Rheumatoid Arthritis: A Systematic Review and Meta-analysis

Objective to systematically review randomized trials that compared methotrexate (MTX) monotherapy to MTX in combination with other non-biologic disease-modifying anti-rheumatic Drugs (DMARD) and to compare the performances of PubMed versus MEDLINE (Ovid®) and EMBASE. Methods We performed a systematic review of randomized trials comparing MTX alone and MTX in combination with other non-biologic DMARDs. Heterogeneity was investigated and explored. The performances of Pubmed and MEDLINE were evaluated. The EMBASE unique trials were identified and investigated. Results A total of 19 trials were included and grouped by the type of patients randomized. Trials in DMARD naive patients showed no significant advantage of the MTX combination versus monotherapy. The recall was 85% vs. 90% for Ovid and PubMed, respectively, while the precision and number-needed-to read of Ovid and Pubmed were comparable. Only 23% of trials were EMBASE unique trials Conclusions In DMARD naive patients, the balance of efficacy/toxicity favours MTX monotherapy.MAS