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

Susannah J King; Dominic Keating; Elyssa Williams; Eldho Paul; Brigitte M Borg; Felicity Finlayson; Brenda M Button; John W Wilson; Tom Kotsimbos

doi:10.1183/23120541.00203-2020

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

ERJ Open Res. 2021 Feb 1;7(1):00203-2020. doi: 10.1183/23120541.00203-2020. eCollection 2021 Jan.

Authors

Susannah J King^{1

2

3}, Dominic Keating^{2

4}, Elyssa Williams², Eldho Paul⁵, Brigitte M Borg⁶, Felicity Finlayson², Brenda M Button^{2

4

7}, John W Wilson^{2

4}, Tom Kotsimbos^{2

4}

Affiliations

¹ Nutrition Dept, Alfred Hospital, Melbourne, Australia.
² Cystic Fibrosis Service, Dept of Respiratory Medicine, Alfred Hospital, Melbourne, Australia.
³ Dept of Dietetics, Nutrition and Sport, LaTrobe University, Bundoora, Australia.
⁴ Dept of Medicine, Monash University, Melbourne, Australia.
⁵ School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.
⁶ Physiology Service, Dept of Respiratory Medicine, Alfred Hospital, Melbourne, Australia.
⁷ Physiotherapy Dept, Alfred Hospital, Melbourne, Australia.

Abstract

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.