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

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 safety or efficacy data on its use in patients with ppFEV1 < 40. Aim: To determine the safety and efficacy of LUM/IVA in patients > 12 years of age with cystic fibrosis (CF), homozygous for F508del CFTR mutation and with ppFEV1 < 40. Methods: A retrospective cohort design was used. Data was collected from patients > 12 years of age with CF, homozygous for F508del CFTR mutation and with ppFEV1 < 40, and compared with data from age- and sex-matched controls with CFTR mutations leading to severe CFTR dysfunction and ppFEV1 < 40. Seven Australian CF centres contributed patient data. The primary outcome was the rate of pulmonary exacerbations requiring the use of intravenous antibiotics over a 12-month period. Secondary outcomes included: mean rate of change in ppFEV1; time to first exacerbation; death; lung transplantation; treatment-emergent adverse events, and discontinuation of LUM/IVA. Results: Data was collected from 132 patients; 72 patients on LUM/IVA and 60 matched controls. The rate of pulmonary exacerbations in patients on LUM/IVA was 40% lower than in the control group. Chest tightness or dyspnoea was experienced in 54% of patients on LUM/IVA, and treatment was discontinued in 43%. Conclusion: In this cohort of patients with CF and ppFEV1 < 40, LUM/IVA reduced the frequency of pulmonary exacerbations when compared to matched controls. However, there was a high discontinuation rate due to adverse events.