Introduction: 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. 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.
Methods: Starting 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.
Results: Here, 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.
Conclusions: Ivacaftor-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.
Keywords: Cystic fibrosis; Ivacaftor; Long-term safety; Real-world data; Registry.
We performed a study to better understand the long-term impact of treatment with a drug called ivacaftor for patients with cystic fibrosis (CF). Our study used data from CF patient registries in the United Kingdom and the United States. These registries collect information about patients with CF, their health, and the treatments they receive. Using data from these registries, we compared patients treated with ivacaftor with a similar group of patients (similar age, sex, and disease severity) who did not receive ivacaftor. We looked at the clinical outcomes of each group every year for up to 5 years. In the final analysis from our study, we found no new safety concerns associated with ivacaftor treatment. Additionally, we found that patients treated with ivacaftor tended to have lower risks of death, organ transplant, pulmonary exacerbations, and hospitalizations. Overall, these results demonstrate the favorable impact of ivacaftor treatment on long-term outcomes of patients with CF.