VOCAL: An observational study of ivacaftor for people with cystic fibrosis and selected non-G551D-CFTR gating mutations.

Background: VOCAL was an observational study of the effect of long-term ivacaftor on real-world clinical outcomes and healthcare resource utilization (HCRU) in people with cystic fibrosis (pwCF) in Italy, the Netherlands, and the UK.
Methods: pwCF aged ≥6 years with non-G551D-CFTR gating mutations were eligible. Prospective data were collected up to 48 months after enrollment; retrospective data were collected to ensure that 12 months of pre-ivacaftor data were available. Endpoints included absolute change from baseline in percent predicted forced expiratory volume in 1 second (ppFEV ₁ ) and measures of nutritional status. Pulmonary exacerbation (PEx) rates, HCRU, and respiratory microbiology during ivacaftor treatment were compared with data from the 12-month period before initiation.
Results: Seventy-three eligible pwCF were enrolled and received ivacaftor; 65 (89.0%) completed the study (48 [65.8%] completed ≥48 months of ivacaftor). During the first 6 months of ivacaftor, ppFEV ₁ , body mass index (BMI), and BMI-for-age z-score showed least-squares mean absolute improvements of 10.8 percentage points, 0.79 kg/m ² , and 0.54, respectively; improvements were maintained through 48 months. Rates of PEx, antibiotic use due to PEx, and hospitalization decreased by >50% during ivacaftor treatment compared with before ivacaftor. The number of respiratory cultures and sputum was lower post-ivacaftor, as was the percentage of pwCF with positive respiratory cultures for 3 of 9 pathogens evaluated (Pseudomonas aeruginosa, Aspergillus fumigatus, Stenotrophomonas maltophilia). Reported safety results were consistent with CF and ivacaftor's known safety profile.
Conclusions: These results demonstrate the positive long-term effectiveness of ivacaftor on clinical outcomes and HCRU in pwCF with non-G551D-CFTR gating mutations in real-world settings.
Competing Interests: Declaration of Competing Interest All authors received nonfinancial support (assistance with manuscript preparation) from ArticulateScience, LLC, which received funding from Vertex Pharmaceuticals Incorporated. Additional disclosures are as follows: CCa reports consulting fees from Vertex, Chiesi, and Mylan in the past 36 months. CCo reports steering committee fees from Vertex during the conduct of the present study and participation in advisory boards for Vertex and Mylan in the past 36 months. CD, MLC, and NK are former employees of Vertex and may own stock in Vertex. KC and TT are employees of Vertex and may own stock or stock options in Vertex. CKvdE has nothing further to disclose. MLC owns stock or stock options in Pfizer Inc, in the past 36 months. NJS reports steering committee fees from Vertex since the initial planning of the work; honoraria for lectures from Vertex, Chiesi, and Zambon in the past 36 months; honoraria for lectures and speakers bureau from Gilead in the past 36 months; and participation on an advisory board for Vertex, Gilead, Chiesi, and Menarini in the past 36 months.
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