- Title
- Lumacaftor/ivacaftor reduces exacerbations in adults homozygous for Phe508del mutation with severe lung disease
- Creator
- Tong, Koliarne; Barker, Daniel; France, Megan; Burr, Lucy; Greville, Hugh; Visser, Simone; Middleton, Peter; Wainwright, Claire; Dorahy, Douglas; Wark, Peter
- Relation
- Journal of Cystic Fibrosis Vol. 19, Issue 3, p. 415-420
- Publisher Link
- http://dx.doi.org/10.1016/j.jcf.2019.12.006
- Publisher
- Elsevier
- Resource Type
- journal article
- Date
- 2020
- Description
- Background: Lumacaftor/ivacaftor (LUM/IVA) improves outcomes in cystic fibrosis (CF) patients homozygous for Phe508del with ppFEV1 > 40%. There is limited safety or efficacy data in patients with ppFEV1 < 40%. We determined whether LUM/IVA in patients with ppFEV1 < 40 would reduce the rate of pul- monary exacerbations. Methods: This was a case control study performed on patients > 12 years, homozygous for Phe508del CFTR mutation and with ppFEV1 < 40%. Control subjects were matched for age, sex and ppFEV1, and had mutations ineligible for LUM/IVA. We assessed the rate of pulmonary exacerbations requiring intravenous antibiotics, the mean rate of change in ppFEV1 over 12 months and all adverse events. Results: Data was collected from 7 Australian CF centres on 105 patients; 72 on LUM/IVA and 33 controls. LUM/IVA demonstrated a large reduction in exacerbations with an incident rate ratio of 0.455 (95%CI; 0.306 –0.676), p < 0.001 after adjusting for the number of exacerbations in the previous 12 months. LUM/IVA prolonged the time to first exacerbation and reduced the rate of decline in ppFEV1 over 12 months. Adverse events were common; chest tightness or dyspnoea was experienced by 55% and resulted in cessation of treatment in 32%. Conclusions: Treatment with LUM/IVA resulted in a substantially lower rate of pulmonary exacerbations, prolonged time to first exacerbation and slowed the rate of decline of ppFEV1 in participants with severe lung disease. Adverse reactions to LUM/IVA however were unacceptably frequent, and resulted in a very high discontinuation rate.
- Subject
- cystic fibrosis; exacerbations; CFTR modulator; lumacaftor; ivacaftor; adverse events; lung function; SDG 3; Sustainable Development Goals
- Identifier
- http://hdl.handle.net/1959.13/1436521
- Identifier
- uon:40051
- Identifier
- ISSN:1569-1993
- Language
- eng
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