Lumacaftor/Ivacaftor reduces pulmonary exacerbations in patients irrespective of initial changes in FEV1

Abstract

Background: Improved lung function and fewer pulmonary exacerbations (PEx) were observed with lumacaftor/ivacaftor (LUM/IVA) in patients with cystic fibrosis homozygous for F508del. It is unknown whether PEx reduction extends to patients without early lung function improvement.

Methods: Post hoc analyses of pooled phase 3 data (NCT01807923, NCT01807949) categorized LUM/IVA-treated patients by percent predicted forced expiratory volume in 1 s (ppFEV1) change from baseline to day 15 into threshold categories (absolute change ≤0 vs >0; relative change <5% vs ≥5%) and compared PEx rates vs placebo.

Results: LUM (400 mg q12h)/IVA (250 mg q12h)-treated patients (n = 369) experienced significantly fewer PEx vs placebo, regardless of threshold category. With LUM/IVA, PEx rate per patient per year was 0.60 for those with absolute change in ppFEV1 > 0 and 0.85 for those with absolute change ≤0 (respective rate ratios vs placebo [95% CI]: 0.53 [0.40-0.69; P < .0001], 0.74 [0.55-0.99; P = .04]).

Conclusions: LUM/IVA significantly reduced PEx, even in patients without early lung function improvement.

Keywords: Cystic fibrosis; Ivacaftor; Lumacaftor; Percent predicted forced expiratory volume in 1 s; Pulmonary exacerbations.

Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.

Figures

Figure 1.

Subgroup analysis of PEx rate ratio for LUM/IVA vs placebo at week 24. Data shown are rate ratio vs placebo from the pooled TRAFFIC and TRANSPORT studies for patients treated with LUM 400 mg q12h/IVA 250 mg q12h. Error bars represent 95% CIs. IVA, ivacaftor; LUM, lumacaftor; P aeruginosa, Pseudomonas aeruginosa; PEx, pulmonary exacerbation; ppFEV1, percent predicted forced expiratory volume in 1 second.

Figure 2.

PEx rates and rate ratios by treatment with LUM 400 mg q12h/IVA 250 mg q12h or placebo and early change in ppFEV1 threshold category. Event rates are described per year by treatment group and ppFEV1 threshold category of the relative change from baseline to day 15 in ppFEV1 of (A) ≤0 vs >0 and (B) <5% vs ≥5%. Forty-eight weeks was considered equivalent to 1 year for the analysis. Tables show rate ratios (95% CI) for the treatment group vs placebo by ppFEV1 threshold category. Abs Δ, absolute change; IV, intravenous; IVA, ivacaftor; LUM, lumacaftor; PEx, pulmonary exacerbation; ppFEV1, percent predicted forced expiratory volume in 1 second; q12h, every 12 hours; Rel Δ, relative change.