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

Abstract

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 (ppFEV₁) between 40 and 90. Marketing authorizations have been granted for patients at all levels of ppFEV₁.

Methods: To evaluate the safety and effectiveness of LUMA-IVA over the first year of treatment in patients with ppFEV₁<40 or ppFEV₁≥90 in comparison with those with ppFEV₁ [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 ppFEV₁ at treatment initiation (ppFEV₁<40, n = 121; ppFEV₁ [40-90[, n = 609; ppFEV₁≥90, n = 97). Treatment discontinuation rate was higher in ppFEV₁<40 patients (28.9%) than in those with ppFEV₁ [40-90[(16.4%) or ppFEV₁≥90 (17.5%). In patients with uninterrupted treatment, significant increase in ppFEV₁ occurred in the ppFEV₁ [40-90[subgroup (+2.9%, P<0.001), and in those ppFEV₁<40 (+0.5%, P = 0.03) but not in those with ppFEV₁≥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 ppFEV₁<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 ppFEV₁ at baseline.