Lumacaftor/ivacaftor-associated health stabilisation in adults with severe cystic fibrosis

Abstract

IntroductionLumacaftor-ivacaftor (LUM-IVA) has been shown to improve clinical outcomes in cystic fibrosis (CF) patients homozygous for Phe508del with ppFEV1>40%. We assessed the clinical utility of LUM-IVA in all eligible adult CF patients with ppFEV1<40% treated for at least 1 year under a single centre managed access program.MethodsFollowing clinical optimisation eligible patients (n=40) with ppFEV1<40% were commenced on LUM-IVA and monitored for tolerance and clinical outcomes including health service utilisation, pulmonary function, weight and body composition. Twenty-four patients reached 1 year of treatment by the time of evaluation. Six discontinued due to adverse events (five for increased airways reactivity) and 3 underwent lung transplantation.ResultsIn comparison to the year prior to LUM-IVA commencement, significant reductions (median/year) were observed in the treatment year in the number of pulmonary exacerbations requiring hospitalisation (3 to 1.5, p=0.002); hospitalisation days (27 to 17, p=0.0002) and intravenous antibiotic days (45 to 27, p=0.0007). Mean change in ppFEV1 was −2.10(se 1.18)% per year in the year prior, with the decline reversed in the year following (+1.45(se 1.13)% per year, p=0.035) although there was significant heterogeneity in individual responses. Mean 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 with severe underweight (BMI<18.5 kg·m−2) decreased from 33% at baseline to 13% at 1 year (p=0.003).ConclusionThis real-world evaluation study demonstrated benefits over several clinical domains (infective exacerbations requiring hospitalisation, intravenous antibiotics, pulmonary function decline and nutritional parameters) in CF patients with severe lung disease.

Long-term effectiveness of dual CFTR modulator treatment of cystic fibrosis

“…Real-world studies with a long-term follow-up are therefore important to provide additional post-approval data of the impact and sustainability of treatments on the entire heterogeneous population [12]. So far, seven studies have been published that assessed the effectiveness of LUM/IVA in a real-world setting [13][14][15][16][17][18][19]. Most of these studies were conducted in small populations, examining different subgroups and outcomes with a follow-up period of one year after LUM/IVA initiation and a limited observation period, not exceeding 845 patient-years.…”

Prediction of Real-World Long-Term Outcomes of People with CF Homozygous for the F508del Mutation Treated with CFTR Modulators

“…So far, few studies have focused on the differential effect of CFTR modulators between sexes on clinical outcomes. One study in a small group of pwCF with severe lung disease (ppFEV1 < 40%) described no differences in PEx rate between males and females one year after commencement with LUM/IVA [25]. However, a greater reduction in both SwCl and PEx rate was observed in females carrying CFTR-gating mutations after two years of treatment with IVA [26].…”

Cystic fibrosis year in review 2021

“…Continuing to work to understand the effect of LUM/IVA in populations that were not included in the original clinical trials were reported this year. One study evaluated adults over one year who had advanced lung disease ((ALD) defined as FEV1pp <40%) 14 . Of the 24 who reached the one-year time frame, a decrease in pulmonary exacerbations requiring hospitalization, days of hospitalization, IV antibiotic days, improvements in FEV1pp, and BMI were seen.…”