TY - JOUR T1 - Leflunomide Use and Risk of Lung Disease in Rheumatoid Arthritis: A Systematic Literature Review and Metaanalysis of Randomized Controlled Trials JF - The Journal of Rheumatology JO - J Rheumatol DO - 10.3899/jrheum.150674 SP - jrheum.150674 AU - Richard Conway AU - Candice Low AU - Robert J. Coughlan AU - Martin J. O'Donnell AU - John J. Carey Y1 - 2016/03/15 UR - http://www.jrheum.org/content/early/2016/03/09/jrheum.150674.abstract N2 - Objective To evaluate the relative risk (RR) of pulmonary disease among patients with rheumatoid arthritis (RA) treated with leflunomide (LEF). Methods We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials to April 15, 2014. We included double-blind randomized controlled trials (RCT) of LEF versus placebo or active comparator agents in adults with RA. Studies with fewer than 50 subjects or shorter than 12 weeks were excluded. Two investigators independently searched both databases. All authors reviewed selected studies. We compared RR differences using the Mantel-Haenszel random-effects method to assess total respiratory adverse events, infectious respiratory adverse events, noninfectious respiratory adverse events, interstitial lung disease, and death. Results Our literature search returned 5673 results. A total of 8 studies, 4 with placebo comparators, met our inclusion criteria. There were 708 respiratory adverse events documented in 4579 participants. Six cases of pneumonitis occurred, all in the comparator group. Four pulmonary deaths were reported, none in the LEF group. LEF was not associated with an increased risk of total adverse respiratory events (RR 0.99, 95% CI 0.56–1.78) or infectious respiratory adverse events (RR 1.02, 95% CI 0.58–1.82). LEF was associated with a decreased risk of noninfectious respiratory adverse events (RR 0.64, 95% CI 0.41–0.97). Conclusion Our study found no evidence of increased respiratory adverse events in RCT of LEF treatment. ER -