The impact of elexacaftor/tezacaftor/ivacaftor on patient-reported outcomes in cystic fibrosis: a systematic review and meta-analysis

Background Elexacaftor/Tezacaftor/Ivacaftor (ETI) has transformed the clinical management of cystic fibrosis (CF), with marked improvements in clinical outcomes. However, its overall impact on patient-reported outcomes (PROs) has not been comprehensively synthesized. Objectives To systematically review and meta-analyze PROs following initiation of ETI in people with CF. Methods A systematic search of MEDLINE, EMBASE, SCOPUS, the Cochrane Library, and other online databases was conducted from January 2018 to May 2025. Eligible studies reporting PROs following ETI initiation were included. Risk of bias was assessed using appropriate appraisal tools. Narrative synthesis and meta-analyses with random-effects models were used to pool PRO changes, and meta-regression explored factors associated with observed effects. Results Sixty-seven studies met the inclusion criteria, including five randomized controlled trials and 62 observational studies. The majority of observational studies were prospective pre-post studies of fair quality, mostly biased due to small sample sizes. Health-related quality of life PROs, including meta-analyses of the Cystic Fibrosis Questionnaire-Revised, demonstrated consistent and substantial improvements following ETI initiation, especially for the respiratory (+ 13.6 points), physical (+ 16.8 points), weight (+ 12.5 points), and vitality (+ 12.5 points) domains. System-specific PROs showed clinically meaningful reductions in sinonasal symptoms (SNOT-22: -16.1 points), whereas gastrointestinal/abdominal outcomes demonstrated mixed results. Mental health-related PROs showed no evidence of overall worsening following ETI initiation. Conclusion This systematic review and meta-analysis suggests that ETI is associated with broad improvements in PROs, including quality of life and other multi-system benefits in people with CF. Findings are promising but would benefit from confirmation through additional studies, given the predominance of pre-post observational studies addressing non-respiratory PROs.