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.