S68 Effects of tezacaftor/ivacaftor (TEZ/IVA) treatment in patients with cystic fibrosis homozygous for F508del-CFTR: patient-reported outcomes in a phase 3 randomized, controlled trial (EVOLVE). (December 2018)

• Record Type: Journal Article
• Authors: Yang, Y; Rizio, AA; Chuang, C-C; Loop, B; You, X; Kosinski, M; Rendas-Baum, R; Lekstrom-Himes, J; Taylor-Cousar, J; Sole, A; Elborn, JS
• Is Part Of: Thorax. Volume 73(2018)Supplement 4
• Page Start: A42
• Page End: A42
• Publication Date: 2018-12
• Subjects: Chest -- Diseases -- Periodicals; Thorax; Chest -- Diseases; Periodicals; Periodicals; 617.54
• DOI: 10.1136/thorax-2018-212555.74
• Languages: English
• ISSNs: 0040-6376

Abstract

Abstract : Introduction and objectives: To examine the impact of TEZ/IVA on disease-related symptoms, functioning, and well-being as measured by Cystic Fibrosis Questionnaire–Revised (CFQ-R) in patients with cystic fibrosis (CF) homozygous for F508del-CFTR (F508del / F508del ). Improvement in the respiratory domain of CFQ-R, the only domain for which the minimal clinically important difference has been established, has been reported previously. Here, we report on the other health domains of CFQ-R. Methods: EVOLVE (NCT02347657 ), a Phase 3, randomized, double-blind, placebo-controlled trial, evaluated TEZ/IVA (100 mg QD/150 mg BID) in patients aged ≥12 years with CF homozygous for F508del -CFTR. CFQ-R consists of 12 domains, including respiratory symptoms (a key secondary endpoint in EVOLVE), and was assessed at baseline and weeks 4, 8, 12, 16, and 24. A mixed-effects model for repeated measures (MMRM) was used in the prespecified analysis of the absolute change in score from baseline through week 24. In a post hoc analysis, cumulative distribution functions (CDF) were used to compare the distribution of change in scores from baseline to week 24 across the two treatment groups. No multiplicity adjustment was used in the analyses. CDF differences were assessed using nominal P values obtained from the Anderson-Darling test. Results: Data from 504 patients with a baseline CFQ-R assessment were included in the analyses. A subset (n=481) with scores at baseline and week 24 were included in the post hoc analyses. An improvement was observed favoring TEZ/IVA over placebo on the following CFQ-R domains: physical functioning, treatment burden, health perceptions, vitality, and social functioning (table 1). In the post hoc CDF analyses, differences favoring TEZ/IVA were observed in a subset (5/12) of domains, including respiratory symptoms, as well as physical functioning, health perceptions, emotional functioning, and treatment burden (all p<0.05). The remaining domains (7/12) demonstrated no difference. Conclusion: The present analyses demonstrate TEZ/IVA treatment benefit across a broad range of patient-reported health outcomes beyond respiratory symptoms, including physical functioning. These findings further support the value of TEZ/IVA treatment in CF patients with F508del / F508del . Abstract previously submitted to the North American Cystic Fibrosis Conference, Denver, CO, 18–20 October, 2018 Sponsored by Vertex Pharmaceuticals Incorporated