Pancreatic enzyme prescription following ivacaftor licensing: A retrospective analysis of the US and UK cystic fibrosis registries.

Background: Relieving gastrointestinal symptoms is a research priority in cystic fibrosis. Emerging evidence highlights effects of cystic fibrosis transmembrane conductance regulator (CFTR) modulators on gastrointestinal function, including pancreatic sufficiency. This study explores ivacaftor licensing and treatment on recorded pancreatic enzyme replacement therapy (PERT) prescription in the US and UK CF registries.
Methods: Retrospective longitudinal registry study of recorded pancreatic PERT use between 2008 and 2017. Interrupted time series analysis in propensity-matched cohorts estimated annual change and step change according to ivacaftor eligibility before and after licensing year, 2012. Generalised estimating equations assessed adjusted risk of PERT use in individuals treated with ivacaftor after 2012 compared to untreated individuals.
Results: In the US CF registry, the difference in annual change in prevalence of PERT use post-2012 between eligible cases and ineligible controls was -5.0 per 1000 people/year (95 %CI -7.6; -2.3, p = 0.001). The step change and annual change in prevalence of PERT use in eligible cases was not significantly different to controls in the UK CF registry. Relative to the relationship in 2013, ivacaftor treatment in the US CF registry was associated with a lower adjusted risk ratio of PERT use compared to untreated individuals by 2016 (0.97, 95 %CI 0.96; 0.99), which was not observed in the UK CF registry.
Conclusions: Licensing of ivacaftor was followed by a lower prevalence of PERT use in the eligible US population compared to pre-licensing period, as well as lower risk of PERT use in those who received treatment. Inconsistencies in US and UK CF registries were observed.
Competing Interests: Declaration of competing interest A.R. Smyth has research grants (paid to the University of Nottingham) from Vertex Pharmaceuticals and payment for an advisory board (paid to the University of Nottingham) from Viatris Pharmaceuticals, all outside the current work. A.R. Smyth has patents issued (Camara M, Williams P, Barrett D, Halliday N, Knox A, Smyth A, Fogarty A, Barr H, Forrester D. Alkyl quinolones as biomarkers of Pseudomonas aeruginosa infection and uses thereof. US2016131648-A1; https://pubchem.ncbi.nlm.nih.gov/patent/US-2016131648-A1 Outside the current work, A.R. Smyth reports participation on a Data Safety Monitoring Board for the North American Cystic Fibrosis Foundation Therapeutic Development Network.
(Copyright © 2024. Published by Elsevier B.V.)