Efficacy and safety of gefapixant for chronic cough: a meta-analysis of randomised controlled trials

Background The efficacy and safety of gefapixant in adults with chronic cough remain unclear. Our objective was to assess the efficacy and safety of gefapixant using updated evidence. Methods MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL) and Embase databases were searched from inception through September 2022. Subgroup analysis based on dose of gefapixant (i.e. <= 20, 45-50 and >100 mg twice daily for low, moderate and high doses, respectively) was performed to explore a potential dose-dependent effect. Results Five studies involving seven trials showed the efficacy of moderate-or high-dose gefapixant for reducing objective 24-h cough frequency (estimated relative reduction 30.9% and 58.5%, respectively) (i.e. primary outcome) and awake cough frequency (estimated relative reduction 47.3% and 62.8%, respectively). Night-time cough frequency was only reduced with high-dose gefapixant. Consistently, the use of moderate-or high-dose gefapixant significantly alleviated cough severity and improved cough -related quality of life, but increased the risk of all-cause adverse events (AEs), treatment-related AEs and ageusia/dysgeusia/hypogeusia. Subgroup analysis showed dose dependency in both efficacy and AEs with a cut-off dose being >45 mg twice daily. Conclusions This meta-analysis revealed dose-dependent efficacy and adverse effects of gefapixant against chronic cough. Further studies are required to investigate the feasibility of moderate-dose (i.e. 45-50 mg twice daily) gefapixant in clinical practice.