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Evidence suggests that methotrexate causes adverse pulmonary events in patients with rheumatoid arthritis (RA). However, this evidence is confounded by the fact that RA itself has pulmonary manifestations. To assess risk for methotrexate-associated lung disease in patients with diseases that do not have pulmonary manifestations, investigators conducted a meta-analysis of seven randomized, controlled trials (duration range, 16–52 weeks) in which methotrexate (15–25 mg weekly) was compared with placebo or active comparator agents in 1640 patients with psoriasis, psoriatic arthritis, or inflammatory bowel disease.
A total of 504 adverse respiratory events occurred. Methotrexate was not associated with elevated risks for total adverse respiratory events, respiratory infections, or noninfectious adverse respiratory events. No pulmonary deaths occurred. Subgroup analyses showed no effects from study size, disease under study, comparator, folic acid use, study drop-out rate, or whether or not participants had used methotrexate previously.
Conway R et al. Methotrexate use and risk of lung disease in psoriasis, psoriatic arthritis, and inflammatory bowel disease: Systematic literature review and meta-analysis of randomised controlled trials. BMJ 2015 Mar 13; 350:h1269. (http://dx.doi.org/10.1136/bmj.h1269)
Comment
In this meta-analysis of randomized trials, methotrexate use was not associated with excess risk for adverse respiratory events in patients with psoriasis, psoriatic arthritis, or inflammatory bowel disease. This study has important limitations (e.g., uncertain generalizability, small number of trials, and relatively short duration of methotrexate use). Nonetheless, the authors believe that methotrexate-associated lung disease is rare and overly feared; indeed, they wonder if it exists at all.