A multicentre, observational casecontrol study to determine the effect of lumacaftor/ivacaftor in patients with severe lung disease and cystic fibrosis

Abstract

Background: Lumacaftor/ivacaftor (LUM/IVA) has been shown to improve percent predicted FEV1 (ppFEV1) and reduce exacerbation frequency in patients with ppFEV1 40-90%. However, there is limited efficacy data on its use in patients with ppFEV1<40%. Aim: To determine the effect of LUM/IVA in patients >12 years old with cystic fibrosis (CF), homozygous for F508del CFTR mutation and with ppFEV1<40%. Methods: A retrospective cohort study on patients >12 years of age with CF, homozygous for F508del CFTR mutation and with ppFEV1<40% compared with data from age- and sex-matched controls with CFTR mutations ineligible for treatment with LUM/IVA and ppFEV1<40% was performed in 7 Australian CF centers. We assessed the mean rate of change in ppFEV1 using linear regression and the effect of LUM/IVA on lung function, exacerbation rate and adverse events. Results: Data were collected from 102 patients; 72 on LUM/IVA and 30 controls. LUM/IVA demonstrated a large reduction in exacerbations compared to controls; 0.485 (95% CI 0.318 to 0.740), p=0.001. Despite severe airflow obstruction at baseline, patients treated with LUM/IVA had reduced decline in FEV1 over 12 months; slope 0.34 (95% CI -0.2955 to 1.031) showing no significant decline, compared to -0.34 (-0.7170 to -0.03711) in controls. There were no differences in ppFEV1 at 4, 12, 24, 52 weeks when the 2 groups were compared. There was however a high rate of side effects and 43% discontinued treatment. Conclusions: Treatment with LUM/IVA in patients with severe lung disease appears to prevent decline in ppFEV1 over 12 months. It is associated with a large reduction in acute exacerbations. However, this group also suffer a higher rate of side effects.L6293882782019-09-26 <br />