Clinical response to lumacaftor-ivacaftor in patients with cystic fibrosis according to baseline lung function

Background: Phase 3 trials have demonstrated the safety and efficacy of lumacaftor-ivacaftor (LUMA-IVA) in patients with cystic fibrosis (CF) homozygous for the Phe508del CFTR mutation and percent predicted forced expiratory volume in 1 s (ppFEV(1)) between 40 and 90. Marketing authorizations have been granted for patients at all levels of ppFEV(1). Methods: To evaluate the safety and effectiveness of LUMA-IVA over the first year of treatment in patients with ppFEV(1) <40 or ppFEV(1) >= 90 in comparison with those with ppFEV(1) [40-90[. Analysis of data collected during a real world study, which included all patients aged >= 12 years who started LUMA-IVA in 2016 across all 47 French CF centers. Results: 827 patients were classified into 3 subgroups according to ppFEV(1) at treatment initiation (ppFEV(1) <40, n = 121; ppFEV(1) [40-90[, n = 609; ppFEV(1) >= 90, n = 97). Treatment discontinuation rate was higher in ppFEV(1) <40 patients (28.9%) than in those with ppFEV(1) [40-90[(16.4%) or ppFEV(1) >= 90 (17.5%). In patients with uninterrupted treatment, significant increase in ppFEV(1) occurred in the ppFEV(1) [40-90[subgroup (+2.9%, P<0.001), and in those ppFEV(1)<40 (+0.5%, P = 0.03) but not in those with ppFEV(1) >= 90 (P = 0.46). Compared with the year prior to initiation, the number of days of intravenous antibiotics were reduced in all subgroups, although 72% of patients with ppFEV(1) < 40 still experienced at least one exacerbation/year under LUMA-IVA. Comparable increase in body mass index was seen in the three subgroups. Conclusion: Phe508del homozygous CF patients benefit from LUMA-IVA at all levels of baseline lung function, but the characteristics and magnitude of the response vary depending on ppFEV(1) at baseline. (c) 2020 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.