Lumacaftor/Ivacaftor-Associated Health Stabilisation In Adults With Severe Cystic Fibrosis

Introduction: Lumacaftor/ivacaftor (LUM/IVA) has been shown to improve clinical outcomes in cystic fibrosis (CF) patients homozygous for Phe508del with forced expiratory volume in 1 s (FEV1) % pred >40%. We assessed the clinical utility of LUM/IVA in all eligible adult CF patients with FEV1 % pred <40% treated for at least 1 year under a single-centre managed access programme.Methods: Following clinical optimisation, eligible patients (n=40) with FEV1 % pred <40% were commenced on LUM/IVA and monitored for tolerance and clinical outcomes, including health service utilisation, pulmonary function, weight and body composition. 24 patients reached 1 year of treatment by the time of evaluation. Six patients discontinued due to adverse events (five for increased airways reactivity) and three underwent lung transplantation.Results: In comparison with the year prior to LUM/IVA commencement, significant reductions (median per year) were observed in the treatment year in the number of pulmonary exacerbations requiring hospitalisation (from 3 to 1.5; p=0.0002), hospitalisation days (from 27 to 17; p=0.0002) and intravenous antibiotic (IVAB) usage days (from 45 to 27; p=0.0007). Mean +/- SD change in FEV1 % pred was -2.10 +/- 1.18% per year in the year prior, with the decline reversed in the year following (+1.45 +/- 1.13% per year; p=0.035), although there was significant heterogeneity in individual responses. Mean +/- SD weight gain at 1 year was 2.5 +/- 4.1 kg (p=0.0007), comprising mainly fat mass (mean 2.2 kg). The proportion of patients severely underweight (body mass index <18.5 kg.m(-2)) decreased from 33% at baseline to 13% at 1 year (p=0.003).Conclusion: This real-world evaluation study demonstrated benefits over several clinical domains (infective exacerbations requiring hospitalisation, IVABs, pulmonary function decline and nutritional parameters) in CF patients with severe lung disease.