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.

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.