A Retrospective, Longitudinal Registry Study on the Long-Term Durability of Ivacaftor Treatment in People with Cystic Fibrosis
Abstract Introduction Ivacaftor (IVA) has been shown to change the trajectory of cystic fibrosis (CF) disease progression by slowing the rate of lung function decline in clinical studies. Long-term real-world data help to confirm the durability of this response. Methods This non-interventional, long...
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Adis, Springer Healthcare
2024-09-01
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| Series: | Pulmonary Therapy |
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| Online Access: | https://doi.org/10.1007/s41030-024-00269-9 |
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| author | Christian Merlo Teja Thorat Lisa J. McGarry Christina V. Scirica Maral DerSarkissian Catherine Nguyen Yuqian M. Gu Aruna Muthukumar Joe Healy Jaime L. Rubin M. Alan Brookhart |
| author_facet | Christian Merlo Teja Thorat Lisa J. McGarry Christina V. Scirica Maral DerSarkissian Catherine Nguyen Yuqian M. Gu Aruna Muthukumar Joe Healy Jaime L. Rubin M. Alan Brookhart |
| author_sort | Christian Merlo |
| collection | DOAJ |
| description | Abstract Introduction Ivacaftor (IVA) has been shown to change the trajectory of cystic fibrosis (CF) disease progression by slowing the rate of lung function decline in clinical studies. Long-term real-world data help to confirm the durability of this response. Methods This non-interventional, longitudinal study used data from the US CF Foundation Patient Registry to describe the annualized rate of change in lung function in people with CF receiving IVA. The IVA-treated cohort included people with CF aged ≥ 6 years who had ≥ 1 CF transmembrane conductance regulator (CFTR)–gating mutation and initiated IVA between 31 January 2012 and 31 December 2018. An age-matched comparator cohort included people with CF heterozygous for the F508del-CFTR mutation and a minimal function mutation (R117H excluded) and had not received CFTR modulator therapy. Baseline characteristics were balanced using standardized mortality ratio (SMR) weights computed from estimated propensity scores. The annualized rate of change in percent predicted forced expiratory volume in 1 s (ppFEV1) was estimated over 5 years and used to calculate the relative annualized rate of change in lung function in the IVA-treated versus comparator cohorts. Results In the 5-year follow-up period, 548 people were in the IVA-treated and 541 in the comparator cohorts after SMR weighting. The annualized rate of change in ppFEV1 over 5 years was −1.23 (95% CI −1.45, −1.03) and −2.03 (−2.16, −1.90) percentage points in the IVA-treated and comparator cohorts, respectively. There was a 39% reduction (95% CI: 28, 50) in the rate of lung function decline in the IVA-treated versus comparator cohort over 5 years. Findings were generally consistent with those of shorter follow-up periods. Conclusion IVA showed a durable clinical benefit by slowing the rate of lung function decline over 5 years. Results support a sustained and consistent impact of IVA on lung function trajectory in people with CF. Word count: 300 (limit: 300 words). |
| format | Article |
| id | doaj-art-87a5f56fc12f4e5c98c0384be3eeadd6 |
| institution | OA Journals |
| issn | 2364-1754 2364-1746 |
| language | English |
| publishDate | 2024-09-01 |
| publisher | Adis, Springer Healthcare |
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| series | Pulmonary Therapy |
| spelling | doaj-art-87a5f56fc12f4e5c98c0384be3eeadd62025-08-20T02:33:05ZengAdis, Springer HealthcarePulmonary Therapy2364-17542364-17462024-09-0110448349410.1007/s41030-024-00269-9A Retrospective, Longitudinal Registry Study on the Long-Term Durability of Ivacaftor Treatment in People with Cystic FibrosisChristian Merlo0Teja Thorat1Lisa J. McGarry2Christina V. Scirica3Maral DerSarkissian4Catherine Nguyen5Yuqian M. Gu6Aruna Muthukumar7Joe Healy8Jaime L. Rubin9M. Alan Brookhart10Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of MedicineVertex Pharmaceuticals IncorporatedVertex Pharmaceuticals IncorporatedVertex Pharmaceuticals IncorporatedAnalysis Group, Inc.Analysis Group, Inc.Analysis Group, Inc.Analysis Group, Inc.Vertex Pharmaceuticals IncorporatedVertex Pharmaceuticals IncorporatedDuke UniversityAbstract Introduction Ivacaftor (IVA) has been shown to change the trajectory of cystic fibrosis (CF) disease progression by slowing the rate of lung function decline in clinical studies. Long-term real-world data help to confirm the durability of this response. Methods This non-interventional, longitudinal study used data from the US CF Foundation Patient Registry to describe the annualized rate of change in lung function in people with CF receiving IVA. The IVA-treated cohort included people with CF aged ≥ 6 years who had ≥ 1 CF transmembrane conductance regulator (CFTR)–gating mutation and initiated IVA between 31 January 2012 and 31 December 2018. An age-matched comparator cohort included people with CF heterozygous for the F508del-CFTR mutation and a minimal function mutation (R117H excluded) and had not received CFTR modulator therapy. Baseline characteristics were balanced using standardized mortality ratio (SMR) weights computed from estimated propensity scores. The annualized rate of change in percent predicted forced expiratory volume in 1 s (ppFEV1) was estimated over 5 years and used to calculate the relative annualized rate of change in lung function in the IVA-treated versus comparator cohorts. Results In the 5-year follow-up period, 548 people were in the IVA-treated and 541 in the comparator cohorts after SMR weighting. The annualized rate of change in ppFEV1 over 5 years was −1.23 (95% CI −1.45, −1.03) and −2.03 (−2.16, −1.90) percentage points in the IVA-treated and comparator cohorts, respectively. There was a 39% reduction (95% CI: 28, 50) in the rate of lung function decline in the IVA-treated versus comparator cohort over 5 years. Findings were generally consistent with those of shorter follow-up periods. Conclusion IVA showed a durable clinical benefit by slowing the rate of lung function decline over 5 years. Results support a sustained and consistent impact of IVA on lung function trajectory in people with CF. Word count: 300 (limit: 300 words).https://doi.org/10.1007/s41030-024-00269-9CFTR modulatorCystic fibrosisDisease trajectoryIvacaftorLongitudinal studyLung function decline |
| spellingShingle | Christian Merlo Teja Thorat Lisa J. McGarry Christina V. Scirica Maral DerSarkissian Catherine Nguyen Yuqian M. Gu Aruna Muthukumar Joe Healy Jaime L. Rubin M. Alan Brookhart A Retrospective, Longitudinal Registry Study on the Long-Term Durability of Ivacaftor Treatment in People with Cystic Fibrosis Pulmonary Therapy CFTR modulator Cystic fibrosis Disease trajectory Ivacaftor Longitudinal study Lung function decline |
| title | A Retrospective, Longitudinal Registry Study on the Long-Term Durability of Ivacaftor Treatment in People with Cystic Fibrosis |
| title_full | A Retrospective, Longitudinal Registry Study on the Long-Term Durability of Ivacaftor Treatment in People with Cystic Fibrosis |
| title_fullStr | A Retrospective, Longitudinal Registry Study on the Long-Term Durability of Ivacaftor Treatment in People with Cystic Fibrosis |
| title_full_unstemmed | A Retrospective, Longitudinal Registry Study on the Long-Term Durability of Ivacaftor Treatment in People with Cystic Fibrosis |
| title_short | A Retrospective, Longitudinal Registry Study on the Long-Term Durability of Ivacaftor Treatment in People with Cystic Fibrosis |
| title_sort | retrospective longitudinal registry study on the long term durability of ivacaftor treatment in people with cystic fibrosis |
| topic | CFTR modulator Cystic fibrosis Disease trajectory Ivacaftor Longitudinal study Lung function decline |
| url | https://doi.org/10.1007/s41030-024-00269-9 |
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