Salliot C, van der Heijde D. Ann Rheum Dis 2009;68:1100–4.
In the management of early and established rheumatoid arthritis, methotrexate is recommended as a first-line drug by the European League Against Rheumatism and the American College of Rheumatology. The long-term safety of methotrexate, including issues of liver toxicity, hypersensitivity pneumonitis, cytopenia, cardivascular diseases, serious infections, and malignancies, was investigated by the current systematic literature research.
In order to evaluate the safety of long-term methotrexate use, the Medline, Cochrane, and EMBASE databases, and the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) meetings abstracts from 2005–2007 were explored, with the input of relevant key words defining the exact population (adult patients with rheumatoid arthritis [RA]), intervention (methotrexate monotherapy for >2 years), control group (RA patients who had not received methotrexate but had received other disease-modifying antirheumatic drugs [DMARDs] or placebo), and outcomes (e.g. prevalence, incidence rate, and risk ratio). A total of 88 published studies were included in the analysis. The data revealed that the termination rates due to toxicity with methotrexate treatment were less than those for sulfasalazine, gold, d-penicillamine, but higher than those for hydroxychloroquine.