Pancreatic Enzyme Prescription Following Ivacaftor Licensing: A Retrospective Analysis of the US and UK Cystic Fibrosis Registries

Overview

Journal J Cyst Fibros

Publisher Elsevier

Specialty Pulmonary Medicine

Date 2024 Feb 11

PMID 38342635

Authors

Rebecca Calthorpe

Margaret Rosenfeld

Christopher H Goss

Nicole Green

Mark Derleth

Siobhan B Carr

Alan Smyth

Iain Stewart

Affiliations

Soon will be listed here.

Abstract

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.

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References

Smith H, Rayment J . Sustained recovery of exocrine pancreatic function in a teenager with cystic fibrosis treated with ivacaftor. Pediatr Pulmonol. 2020; 55(10):2493-2494. DOI: 10.1002/ppul.24952. View

Costa E, Girotti S, Pauro F, Leufkens H, Cipolli M . The impact of FDA and EMA regulatory decision-making process on the access to CFTR modulators for the treatment of cystic fibrosis. Orphanet J Rare Dis. 2022; 17(1):188. PMC: 9078013. DOI: 10.1186/s13023-022-02350-5. View

Bernal J, Cummins S, Gasparrini A . Interrupted time series regression for the evaluation of public health interventions: a tutorial. Int J Epidemiol. 2016; 46(1):348-355. PMC: 5407170. DOI: 10.1093/ije/dyw098. View

Megalaa R, Gopalareddy V, Champion E, Goralski J . Time for a gut check: Pancreatic sufficiency resulting from CFTR modulator use. Pediatr Pulmonol. 2019; 54(8):E16-E18. DOI: 10.1002/ppul.24353. View

Davies J, Cunningham S, Harris W, Lapey A, Regelmann W, Sawicki G . Safety, pharmacokinetics, and pharmacodynamics of ivacaftor in patients aged 2-5 years with cystic fibrosis and a CFTR gating mutation (KIWI): an open-label, single-arm study. Lancet Respir Med. 2016; 4(2):107-15. PMC: 6734927. DOI: 10.1016/S2213-2600(15)00545-7. View

Knapp E, Fink A, Goss C, Sewall A, Ostrenga J, Dowd C . The Cystic Fibrosis Foundation Patient Registry. Design and Methods of a National Observational Disease Registry. Ann Am Thorac Soc. 2016; 13(7):1173-9. DOI: 10.1513/AnnalsATS.201511-781OC. View

Munce D, Lim M, Akong K . Persistent recovery of pancreatic function in patients with cystic fibrosis after ivacaftor. Pediatr Pulmonol. 2020; 55(12):3381-3383. DOI: 10.1002/ppul.25065. View

Taylor-Robinson D, Archangelidi O, Carr S, Cosgriff R, Gunn E, Keogh R . Data Resource Profile: The UK Cystic Fibrosis Registry. Int J Epidemiol. 2017; 47(1):9-10e. PMC: 5837577. DOI: 10.1093/ije/dyx196. View

Grubb B, Livraghi-Butrico A . Animal models of cystic fibrosis in the era of highly effective modulator therapies. Curr Opin Pharmacol. 2022; 64:102235. PMC: 9386876. DOI: 10.1016/j.coph.2022.102235. View

10.

Cromwell E, Ostrenga J, Todd J, Elbert A, Brown A, Faro A . Cystic fibrosis prevalence in the United States and participation in the Cystic Fibrosis Foundation Patient Registry in 2020. J Cyst Fibros. 2023; 22(3):436-442. PMC: 11288252. DOI: 10.1016/j.jcf.2023.02.009. View

11.

Hutchinson I, McNally P . Appearance of Pancreatic Sufficiency and Discontinuation of Pancreatic Enzyme Replacement Therapy in Children with Cystic Fibrosis on Ivacaftor. Ann Am Thorac Soc. 2020; 18(1):182-183. DOI: 10.1513/AnnalsATS.202006-614RL. View

12.

Wright B, Cannon M, Ramsey L . Reversing the irreversible: Another potential benefit of CFTR modulators. Pediatr Pulmonol. 2020; 55(11):2844-2845. DOI: 10.1002/ppul.25047. View

13.

Ren C, Fink A, Petren K, Borowitz D, McColley S, Sanders D . Outcomes of infants with indeterminate diagnosis detected by cystic fibrosis newborn screening. Pediatrics. 2015; 135(6):e1386-92. DOI: 10.1542/peds.2014-3698. View

14.

Hamilton J, Zobell J, Robson J . Pancreatic insufficiency converted to pancreatic sufficiency with ivacaftor. Pediatr Pulmonol. 2019; 54(11):1654. DOI: 10.1002/ppul.24454. View

15.

Carroll W, Green J, Gilchrist F . Interventions for preventing distal intestinal obstruction syndrome (DIOS) in cystic fibrosis. Cochrane Database Syst Rev. 2021; 12:CD012619. PMC: 8693853. DOI: 10.1002/14651858.CD012619.pub3. View

16.

Nichols A, Davies J, Jones D, Carr S . Restoration of exocrine pancreatic function in older children with cystic fibrosis on ivacaftor. Paediatr Respir Rev. 2020; 35:99-102. DOI: 10.1016/j.prrv.2020.04.003. View

17.

Gelfond D, Heltshe S, Ma C, Rowe S, Frederick C, Uluer A . Impact of CFTR Modulation on Intestinal pH, Motility, and Clinical Outcomes in Patients With Cystic Fibrosis and the G551D Mutation. Clin Transl Gastroenterol. 2017; 8(3):e81. PMC: 5387753. DOI: 10.1038/ctg.2017.10. View

18.

Rosenfeld M, Cunningham S, Harris W, Lapey A, Regelmann W, Sawicki G . An open-label extension study of ivacaftor in children with CF and a CFTR gating mutation initiating treatment at age 2-5 years (KLIMB). J Cyst Fibros. 2019; 18(6):838-843. PMC: 6821553. DOI: 10.1016/j.jcf.2019.03.009. View

19.

Schwarzenberg S, Vu P, Skalland M, Hoffman L, Pope C, Gelfond D . Elexacaftor/tezacaftor/ivacaftor and gastrointestinal outcomes in cystic fibrosis: Report of promise-GI. J Cyst Fibros. 2022; 22(2):282-289. PMC: 10144072. DOI: 10.1016/j.jcf.2022.10.003. View

20.

Farrell P, White T, Ren C, Hempstead S, Accurso F, Derichs N . Diagnosis of Cystic Fibrosis: Consensus Guidelines from the Cystic Fibrosis Foundation. J Pediatr. 2017; 181S:S4-S15.e1. DOI: 10.1016/j.jpeds.2016.09.064. View