Effect of highly effective modulator therapy on quality of life in adults with cystic fibrosis.

BACKGROUND: Elexacaftor/tezacaftor/ivacaftor is a highly effective modulator that improves function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein, resulting in improved pulmonary function in patients with cystic fibrosis (CF). We hypothesize that improvements in lung function are associated with improvements in health-related quality of life and sinonasal health. The aim of this study is to measure the effect of elexacaftor/tezacaftor/ivacaftor on patient-reported sinonasal and overall quality of life, and to determine the relationship between changes in these 2 outcome measures. METHODS: A prospective cohort study was conducted at an accredited adult CF care center. Participants completed the 22-item Sino-Nasal Outcome Test (SNOT-22) and the Cystic Fibrosis Questionnaire-Revised (CFQ-R), a validated patient-reported outcome metric for CF patients, at baseline and at 3 months after initiation of elexacaftor/tezacaftor/ivacaftor. RESULTS: Forty-three individuals completed the study. There was significant improvement in nearly all domains of the SNOT-22 and CFQ-R after 3 months of therapy. SNOT-22 improved from 34.8 to 24.4 (p = 0.000003). Mean baseline FEV-1 improved from 65% to 76% predicted (p = 0.0000005). The greatest effect was seen in those participants previously taking modulator therapy. Linear regression between the change in SNOT-22 individual domains and the CFQ-R respiratory domain revealed the strongest correlation between the extranasal domain score and the respiratory domain of the CFQ-R (R2 = 0.24). CONCLUSION: CF patients taking elexacaftor/tezacaftor/ivacaftor experience a significant improvement in both sinonasal and health-related quality of life.

Effect of highly effective modulator treatment on sinonasal symptoms in cystic fibrosis.

BACKGROUND: Elexacaftor-tezacaftor-ivacaftor is a highly effective modulator for cystic fibrosis (CF) patients homozygous or heterozygous for F508del. Effects of the drug on sinonasal symptoms have not been studied. METHODS: Adult participants were prospectively evaluated at baseline and after three months of treatment using validated questionnaires assessing sinonasal symptoms (SNOT-22) and CF-related quality of life (CFQ-R). RESULTS: Forty-three participants completed the study; 23 were taking other CF transmembrane conductance (CFTR) modulators at the time of study participation. There was a significant improvement in mean SNOT-22 from 34.8 (29.4-40, 95% confidence interval) to 24.4 (19.9-29.0) (p = 0.000003) and in the Respiratory domain of the CFQR from 60.6 (57.1-64.1) to 83.3 (79.4-87.2) (p = 0.0000002), both achieving a minimal clinically important difference. Patients previously taking CFTR modulators experienced a greater benefit in sinonasal and respiratory symptoms. CONCLUSIONS: Elexacaftor-tezacaftor-ivacaftor is associated with significant improvement in sinonasal symptoms; previous use of CFTR modulators is associated with greater benefit.