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

Nicholas J. Simmonds*, C. Kors van der Ent, Carla Colombo, Nils Kinnman, Cynthia DeSouza, Teja Thorat, Marci L. Chew, Keval Chandarana, Carlo Castellani

*Corresponding author for this work

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Abstract

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 (ppFEV1) 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, ppFEV1, body mass index (BMI), and BMI-for-age z-score showed least-squares mean absolute improvements of 10.8 percentage points, 0.79 kg/m2, 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.

Original languageEnglish
Pages (from-to)124-131
Number of pages8
JournalJournal of Cystic Fibrosis
Volume22
Issue number1
DOIs
Publication statusPublished - Jan 2023

Keywords

  • CFTR gating mutation
  • Cystic fibrosis
  • Healthcare resource utilization
  • Ivacaftor
  • Lung function
  • Real-world experience

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