Elexacaftor-tezacaftor-ivacaftor for cystic fibrosis with Phe508del mutation: Evidence from randomized controlled trials.

ABSTRACT

Objective: This study aimed to conduct a systematic review and meta-analysis of randomized controlled trials to evaluate the effects of elexacaftor-tezacaftor-ivacaftor (ELX-TEZ-IVA) on patients with cystic fibrosis (CF). Methods: A systematic search was performed in PubMed, Embase, and the Cochrane Library from inception to August 1, 2022. Meta-analysis was conducted using Review Manager 5.3 software. Results: Six studies comprising seven reports involving a total of 1125 CF patients were included. The meta-analyses indicated that ELX-TEZ-IVA significantly improved the percentage predicted forced expiratory volume in 1 s (ppFEV1) by 10.29% (95% confidence interval (CI) (6.44, 14.14), p < 0.00001) and the CF questionnaire-revised respiratory domain (CFQ-R RD) by 14.59 points (95% CI (9.25, 19.94), p < 0.00001) compared to placebo, ivacaftor (IVA), or tezacaftor-ivacaftor (TEZ-IVA). In addition, the ELX-TEZ-IVA group showed significantly lower sweat chloride concentrations by 40.30 mmol/L (95% CI (-49.85, -30.74), p < 0.00001). However, the incidence of adverse events in the ELX-TEZ-IVA group was slightly higher than that in the placebo, IVA, or TEZ-IVA groups. Conclusion: ELX-TEZ-IVA demonstrated efficacy in improving ppFEV1, CFQ-R RD, and sweat chloride concentrations in patients with CF. However, caution should be exercised regarding the incidence of AEs, particularly mild and moderate ones.