Long-term Impact of Ivacaftor on Mortality Rate and Health Outcomes in People with Cystic Fibrosis

Overview

Journal Thorax

Date 2024 Jun 27

PMID 38937105

Authors

Christian A Merlo

Teja Thorat

Maral DerSarkissian

Lisa J McGarry

Catherine Nguyen

Yuqian M Gu

Joe Healy

Jaime L Rubin

M Alan Brookhart

Affiliations

Soon will be listed here.

Abstract

Background: Ivacaftor (IVA) has been shown to improve lung function and other clinical outcomes in people with cystic fibrosis (CF). A decade of real-world IVA availability has enabled the examination of long-term outcomes with this treatment. This retrospective, longitudinal cohort study investigated the impact of IVA on mortality rate and health outcomes among people with CF in the US.

Methods: Data from the US CF Foundation Patient Registry from January 2010 to December 2019 were analysed. The IVA-treated cohort included people with a CF transmembrane conductance regulator () gating mutation (excluding ); age-matched comparator cohort included people with a and a minimal function mutation who had no prior CFTR modulator treatment. Baseline characteristics were balanced between cohorts using standardised mortality ratio weighting generated from propensity scores. Outcomes of interest were overall survival, lung transplant, percent predicted forced expiratory volume in 1 s (ppFEV), body mass index (BMI), pulmonary exacerbations (PEx), outpatient visits and hospitalisations.

Findings: Over a maximum follow-up of 7.9 years, the IVA-treated cohort (N=736) had lower rates of mortality (hazard ratio [HR] (95% CI): 0.22 (0.09 to 0.45)), lung transplant (HR: 0.11 (95% CI 0.02 to 0.28)), PEx (rate ratio: 0.49 (95% CI 0.42 to 0.55)) and all-cause hospitalisations (rate ratio: 0.50 (95% CI 0.43 to 0.56)) as well as better lung function (mean difference in ppFEV: 8.46 (95% CI 7.34 to 9.75)) and higher BMI/BMI -scores (mean difference 1.20 (95% CI 0.92 to 1.71) kg/m and 0.27 (95% CI 0.25 to 0.40), respectively) than the comparator cohort (N=733).

Interpretation: Our analysis suggests that IVA provides sustained clinical benefits in people with CF over a follow-up period of approximately 8 years. These findings reinforce the existing real-world evidence that IVA can slow disease progression and decrease the healthcare burden of CF over the long term.

Citing Articles

A Retrospective, Longitudinal Registry Study on the Long-Term Durability of Ivacaftor Treatment in People with Cystic Fibrosis.

Merlo C, Thorat T, McGarry L, Scirica C, DerSarkissian M, Nguyen C Pulm Ther. 2024; 10(4):483-494.

PMID: 39266929 PMC: 11573995. DOI: 10.1007/s41030-024-00269-9.

Impact of age at ivacaftor initiation on pulmonary outcomes among people with cystic fibrosis.

Merlo C, McGarry L, Thorat T, Nguyen C, DerSarkissian M, Muthukumar A Thorax. 2024; 79(10):915-924.

PMID: 38719441 PMC: 11503177. DOI: 10.1136/thorax-2023-220559.

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