Review: Methotrexate does not increase risk for lung disease in psoriasis, psoriatic arthritis, or IBD

Question In patients with psoriasis, psoriatic arthritis, or inflammatory bowel disease (IBD), does methotrexate increase risk for lung disease? Review scope Included studies compared methotrexate with placebo or another active agent in adults with psoriasis, psoriatic arthritis, or IBD, and reported respiratory side effects. Review methods MEDLINE, EMBASE/Excerpta Medica, and Cochrane Central Register of Controlled Trials (Jan 2014); and reference lists were searched for double-blind, randomized, controlled trials (RCTs) that had 50 patients, duration 12 weeks, and were published in English. 7 RCTs (n = {1630}*, mean age 33 to 49 y, 50% to 70% men), with 76 to 478 patients, met the selection criteria. Study durations were 16 to 52 weeks. The control group received placebo in 5 trials, briakinumab in 1 trial, and adalimumab/placebo in 1 trial. 4 RCTs had adequate randomization, and 4 had adequate allocation concealment. Main results Meta-analysis showed that methotrexate did not differ from control for overall adverse respiratory events, infectious adverse respiratory events, or noninfectious adverse respiratory events (Table). 1 patient in the methotrexate group had pneumonitis; no pulmonary deaths occurred in either group. Conclusion In patients with psoriasis, psoriatic arthritis, or inflammatory bowel disease, methotrexate does not increase risk for lung disease. Methotrexate vs control in psoriasis, psoriatic arthritis, or inflammatory bowel disease Outcomes Number of trials (n) Weighted event rates At 16 to 52 wk Methotrexate Control RRI (95% CI) All adverse respiratory events 7 (1630) 32% 31% 3% (10 to 17) Infectious adverse respiratory events 7 (1630) 29.0% 28.5% 2% (12 to 19) Noninfectious adverse respiratory events 7 (1630) 2.4% 2.2% 7% (42 to 96) Abbreviations defined in Glossary. RRI and CI calculated from control event rates and relative risks in article using a random-effects model. Commentary Methotrexate is a commonly used disease-modifying agent in inflammatory joint conditions and is usually well-tolerated, with few important adverse effects. Acute interstitial pneumonitis has been reported as a potential adverse effect in patients with rheumatoid arthritis (1) and usually results in permanent cessation of methotrexate treatment. It is unclear whether this complication occurs only in patients with rheumatoid arthritis and whether it relates to the potential complication of pulmonary fibrosis in such patients, unrelated to methotrexate treatment. Of the limited treatments available for psoriasis, psoriatic arthritis, and IBD, methotrexate is an important option. The meta-analysis by Conway and colleagues found no evidence of increased infectious or noninfectious lung disease in patients with these conditions treated with methotrexate, but the conclusions are based on 7 RCTs with just 1640 patients (946 patient-y of treatment), with the longest trial duration being 1 year. There are case reports of pneumonitis occurring in the setting of methotrexate treatment in both psoriatic arthritis (2) and Crohn disease (3). Although this review should give practitioners some confidence in the safety of methotrexate in these patient groups, long-term cohort studies with more patients and more potentially confounding comorbid conditions are needed to confirm the results.