Safety evaluation of revefenacin at the approved dose in patients with chronic obstructive pulmonary disease: A meta-analysis.

Background: Revefenacin is the first once-daily long-acting muscarinic antagonist (LAMA) for nebulization use in maintenance therapy for patients with chronic obstructive pulmonary disease (COPD).

Objective: To investigate the safety and tolerability profile of revefenacin at the approved dose (175 μg), compared with placebo and a lower dose (88 μg), for the treatment of COPD.

Methods: Available randomized controlled trials (RCTs), both published and unpublished, were identified via databases. Risk differences (RDs) and risk ratios (RRs), with their corresponding 95% confidence intervals (CIs) were calculated as effect sizes.

Results: One unpublished RCT and four articles containing 5 RCTs were included. Combined results showed that there were no significant differences between COPD patients receiving 175 μg revefenacin and those receiving a placebo, concerning the risk of discontinuation due to adverse events (AEs), any all-grade AE, or any serious AE. 175 μg revefenacin also did not significantly increase the risk of antimuscarinic-related AEs, cardiovascular AEs, or 12 commonly reported AEs. Plus, a lower dose of 88 μg was shown to share a comparable safety profile with the 175 μg revefenacin. A non-significant trend towards a decrease in risks of AEs for 175 μg revefenacin was observed. The most frequently reported AE for each group was COPD worsening/exacerbation.

Conclusion: Revefenacin at the approved dose is generally well-tolerated and safe with minimal AEs, which supports its use as a once-daily nebulized LAMA for the treatment of moderate to severe stable COPD. Additional studies are needed to complete the safety and tolerability profile.