Nataliya Volkova1, Kristin Moy2, Jennifer Evans3, Daniel Campbell4, Simon Tian5, Christopher Simard6, Mark Higgins7, Michael W Konstan8, Gregory S Sawicki9, Alexander Elbert10, Susan C Charman11, Bruce C Marshall12, Diana Bilton13. 1. Vertex Pharmaceuticals Incorporated, 50 Northern Avenue, Boston, MA, USA. Electronic address: Nataliya_Volkova@vrtx.com. 2. Vertex Pharmaceuticals Incorporated, 50 Northern Avenue, Boston, MA, USA. Electronic address: Kristin_Moy@vrtx.com. 3. Formerly of Vertex Pharmaceuticals Incorporated, 50 Northern Avenue, Boston, MA, USA. Electronic address: jevansdvm@gmail.com. 4. Vertex Pharmaceuticals Incorporated, 50 Northern Avenue, Boston, MA, USA. Electronic address: Daniel_Campbell@vrtx.com. 5. Vertex Pharmaceuticals Incorporated, 50 Northern Avenue, Boston, MA, USA. Electronic address: simon_tian@vrtx.com. 6. Vertex Pharmaceuticals Incorporated, 50 Northern Avenue, Boston, MA, USA. Electronic address: christopher_simard@vrtx.com. 7. Vertex Pharmaceuticals (Europe) Limited, 2 Kingdom Street, London W2 6BD, UK. Electronic address: Mark_Higgins@vrtx.com. 8. Case Western Reserve University School of Medicine, Rainbow Babies & Children's Hospital, 11100 Euclid Avenue, Cleveland, OH, USA. Electronic address: michael.konstan@uhhospitals.org. 9. Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, 482 Bedford Street, Lexington, MA, USA. Electronic address: Gregory.Sawicki@childrens.harvard.edu. 10. US Cystic Fibrosis Foundation, 4550 Montgomery Avenue, Suite 1100 N, Bethesda, MD, USA. Electronic address: aelbert@cff.org. 11. The Cystic Fibrosis Trust, 1 Aldgate, London, EC3N 1RE, UK. Electronic address: susan.charman@cysticfibrosis.org.uk. 12. US Cystic Fibrosis Foundation, 4550 Montgomery Avenue, Suite 1100 N, Bethesda, MD, USA. Electronic address: bmarshall@cff.org. 13. The Cystic Fibrosis Trust, 1 Aldgate, London, EC3N 1RE, UK; National Heart and Lung Institute, Imperial College London, & Hon Consultant, Royal Brompton Hospital, London, UK. Electronic address: d.bilton@rbht.nhs.uk.
Abstract
BACKGROUND: Ivacaftor is the first in a class of drugs, CFTR modulators, that target the underlying defect in cystic fibrosis (CF). This long-term observational safety study evaluated CF disease progression in patients treated with ivacaftor in a real-world setting for up to 5 years. METHODS: Data from existing US and UK CF patient registries were used to assess longitudinal patterns in lung function, nutritional status, pulmonary exacerbations and hospitalizations, CF-related diabetes (CFRD), and Pseudomonas aeruginosa in ivacaftor-treated vs untreated comparator cohorts matched by age, sex, and disease severity. RESULTS: US analyses included 635 ivacaftor-treated patients and 1874 comparators followed for 5 years from year 1 of market availability (2012-2016). Evaluation of outcome patterns from pretreatment baseline (2011) through year 5 (2016), showed that relative to comparators, ivacaftor-treated patients had better preserved lung function (mean change in percent predicted FEV1, -0.7 percentage points with ivacaftor vs -8.3 percentage points in comparators) and improved nutritional status (mean body mass index change +2.4 kg/m2 with ivacaftor vs +1.6 kg/m2 in comparators). US patients treated with ivacaftor had significantly lower frequencies of exacerbations and hospitalizations in each of the 5 years of follow-up relative to pretreatment baseline and comparators. Favorable trends in CFRD and P. aeruginosa prevalence were also observed. Findings from the smaller UK registry were directionally similar to and consistent with US findings. CONCLUSIONS: This observational study represents the largest longitudinal analysis of patients treated with ivacaftor in a real-world setting. The findings support disease modification by CFTR modulation with ivacaftor.
BACKGROUND:Ivacaftor is the first in a class of drugs, CFTR modulators, that target the underlying defect in cystic fibrosis (CF). This long-term observational safety study evaluated CF disease progression in patients treated with ivacaftor in a real-world setting for up to 5 years. METHODS: Data from existing US and UK CF patient registries were used to assess longitudinal patterns in lung function, nutritional status, pulmonary exacerbations and hospitalizations, CF-related diabetes (CFRD), and Pseudomonas aeruginosa in ivacaftor-treated vs untreated comparator cohorts matched by age, sex, and disease severity. RESULTS: US analyses included 635 ivacaftor-treated patients and 1874 comparators followed for 5 years from year 1 of market availability (2012-2016). Evaluation of outcome patterns from pretreatment baseline (2011) through year 5 (2016), showed that relative to comparators, ivacaftor-treated patients had better preserved lung function (mean change in percent predicted FEV1, -0.7 percentage points with ivacaftor vs -8.3 percentage points in comparators) and improved nutritional status (mean body mass index change +2.4 kg/m2 with ivacaftor vs +1.6 kg/m2 in comparators). US patients treated with ivacaftor had significantly lower frequencies of exacerbations and hospitalizations in each of the 5 years of follow-up relative to pretreatment baseline and comparators. Favorable trends in CFRD and P. aeruginosa prevalence were also observed. Findings from the smaller UK registry were directionally similar to and consistent with US findings. CONCLUSIONS: This observational study represents the largest longitudinal analysis of patients treated with ivacaftor in a real-world setting. The findings support disease modification by CFTR modulation with ivacaftor.
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