Abstract
IntroductionIn this long-term, postapproval, observational study, data from the US Cystic Fibrosis Foundation Patient Registry and the UK Cystic Fibrosis Registry were used to evaluate the impact of ivacaftor treatment on cystic fibrosis (CF) by comparing outcomes in ivacaftor-treated patients with those in matched untreated comparator patients. Registry data from up to 5 years of ivacaftor availability in the US and up to 4 years of availability in the UK were evaluated.MethodsStarting in the first year of ivacaftor availability, ivacaftor-treated patients in each registry were matched 1:5 to comparator patients who never received ivacaftor. Clinical endpoints were evaluated in annual cross-sectional safety analyses. The key endpoints were death, organ transplants, pulmonary exacerbation, and hospitalization. Relative risks and 95% CIs were calculated to compare the ivacaftor and comparator cohorts in each registry.ResultsHere, we report the complete and final results of the annual cross-sectional safety analyses across the duration of the study, with up to 5 years of follow-up. Data show a pattern of lower risk of death, transplant, pulmonary exacerbation, and hospitalization among ivacaftor-treated patients in both registries.ConclusionsIvacaftor-treated patients had consistently favorable clinical outcomes relative to untreated comparators, and no new safety concerns were identified. While general limitations of observational research apply, these findings support disease modification by CF transmembrane conductance regulator (CFTR) modulator therapy with ivacaftor. Future research of novel CFTR modulators will need to explore alternative methods for comparator selection for evaluation of clinical data given the evolving landscape of CF treatment.
Highlights
In this long-term, postapproval, observational study, data from the US Cystic Fibrosis Foundation Patient Registry and the UK Cystic Fibrosis Registry were used to evaluate the impact of ivacaftor treatment on cystic fibrosis (CF) by comparing outcomes in ivacaftor-treated patients with those in matched untreated comparator patients
In cystic fibrosis (CF), a life-shortening, rare genetic disease, researchers have the unique opportunity to evaluate data from the majority of patients in their respective regions collected by national CF registries, with the US Cystic Fibrosis Foundation Patient Registry (US CFFPR) and the UK Cystic Fibrosis Registry (UK CFR) being the largest
To evaluate disease progression and clinical outcomes in patients treated with ivacaftor, we conducted a long-term observational study comparing outcomes in patients in the US and UK registries who were treated with ivacaftor versus matched untreated comparator patients
Summary
Real-world data provide information about long-term safety and effectiveness of treatments outside of clinical trials; the value of such data is increasingly recognized as real-world analysis methodologies become more rigorous [1]. To evaluate disease progression and clinical outcomes in patients treated with the first approved CF transmembrane conductance regulator (CFTR) modulator targeting the underlying cause of CF, we conducted a long-term observational study comparing outcomes in patients in the US and UK registries who were treated with ivacaftor versus matched untreated comparator patients [7, 8] This postauthorization safety surveillance study was designed to fulfill a postmarketing commitment to the European Medicines Agency and is disclosed on the European Union electronic Register of PostAuthorization Studies (EUPAS4270) [7, 8]. Following previous reports, including the previously published disease progression analyses [7, 8], we report final results of the annual cross-sectional safety analyses across the duration of the study These data provide insights to address the aim of assessing patients’ long-term outcomes with highly effective CFTR modulation with ivacaftor in real-world clinical practice
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