Longitudinal trends in real-world outcomes after initiation of ivacaftor: A cohort study from the cystic fibrosis registry of Ireland

Rationale: Patient registries have the potential to collect and analyze high-quality postauthorization data on new medicines. Objectives: We used cystic fibrosis (CF) registry data to assess outcomes after the initiation of ivacaftor, a CF transmembrane conductance regulator (CFTR) potentiator approved for the treatment of CF with a defective gating CFTR mutation. Methods: Longitudinal trends were examined using mixed-effects regression analysis in 80 ivacaftor-treated patients with CF aged 6 to 56 years registered with the CF Registry of Ireland with at least 36 months of before and after commencement data. The effects of ivacaftor treatment on forced expiratory volume in 1 second (FEV ₁ ) % predicted, body mass index (BMI), hospitalization for pulmonary exacerbation, and oral and intravenous antibiotic use were assessed. Results: In the 36 months after ivacaftor initiation, FEV ₁ % predicted improved by 2.26% per annum (95% confidence interval [CI], 0.2 to 4.3) for patients aged younger than 12 years, remained unchanged for 12- to younger than 18-year-olds (95% CI, 21.9 to 2.9), and declined in adults by 1.74% per annum (95% CI, 23.1 to 20.4). BMI in adults increased 0.28 kg/m ² per annum (95% CI, 0.03 to 0.5), and there was no significant change in BMI z-score in children (95% CI, 20.01 to 0.1). In the year after ivacaftor initiation, intravenous antibiotic treatment reduced by 46% (95% CI, 262.5% to 223.3%, oral antibiotic treatment reduced by 49% (95% CI, 261.1% to 232.1%), and there was no significant reduction in hospitalization (95% CI, 259.2% to 9.7%). Conclusions: In this study of real-world CF registry data, clinical outcomes improved and healthcare resource utilization decreased after commencing ivacaftor.