Modeling long-term health outcomes of patients with cystic fibrosis homozygous for treated with lumacaftor/ivacaftor
Background: Lumacaftor/ivacaftor combination therapy is efficacious and generally safe for patients with cystic fibrosis (CF) homozygous for the F508del-CF transmembrane conductance regulator (CFTR) mutation. However, long-term survival benefits of lumacaftor/ivacaftor (LUM/IVA) cannot yet be quanti...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2019-02-01
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| Series: | Therapeutic Advances in Respiratory Disease |
| Online Access: | https://doi.org/10.1177/1753466618820186 |
| _version_ | 1828432666294222848 |
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| author | Jaime L. Rubin Lasair O’Callaghan Christopher Pelligra Michael W. Konstan Alexandra Ward Jack K. Ishak Conor Chandler Theodore G. Liou |
| author_facet | Jaime L. Rubin Lasair O’Callaghan Christopher Pelligra Michael W. Konstan Alexandra Ward Jack K. Ishak Conor Chandler Theodore G. Liou |
| author_sort | Jaime L. Rubin |
| collection | DOAJ |
| description | Background: Lumacaftor/ivacaftor combination therapy is efficacious and generally safe for patients with cystic fibrosis (CF) homozygous for the F508del-CF transmembrane conductance regulator (CFTR) mutation. However, long-term survival benefits of lumacaftor/ivacaftor (LUM/IVA) cannot yet be quantified. Simulation models can provide predictions about long-term health outcomes. In this study, we aimed to project long-term health outcomes of LUM/IVA plus standard care (SC) in patients with CF homozygous for F508del-CFTR . Methods: This modeling study was an individual patient simulation in US patients aged ⩾6 years with CF, homozygous for F508del-CFTR . The primary outcome was projected survival among (a) a cohort of patients who ever initiated LUM/IVA, accounting for treatment discontinuations, and (b) a cohort of patients who remain on continuous LUM/IVA. Patient characteristics and model parameters were derived from clinical trials: VX14-809-109, VX13-809-011B, TRAFFIC/TRANSPORT, and PROGRESS; published literature; and the US CF Foundation Patient Registry. Results: Lumacaftor/ivacaftor + SC is expected to increase median survival by 6.1 years versus SC alone, accounting for treatment discontinuations. The incremental median predicted survival versus SC assuming initiation of LUM/IVA at ages 6, 12, 18, and 25 years was 17.7, 12.6, 8.0, and 3.8 years, respectively. Assuming lifetime treatment with LUM/IVA, incremental median survival was predicted to be 7.8 years longer in the LUM/IVA + SC cohort. Initiating LUM/IVA at ages 6, 12, 18, and 25 years and assuming lifetime treatment resulted in incremental median predicted survival of 23.4, 18.2, 11.0, and 4.8 years, respectively. Conclusions: Lumacaftor/ivacaftor is projected to increase survival for patients with CF. Initiation at an early age and treatment persistence result in further increments in projected survival. |
| first_indexed | 2024-12-10T18:24:08Z |
| format | Article |
| id | doaj.art-ca5470f6683f4039843231b8785b87d8 |
| institution | Directory Open Access Journal |
| issn | 1753-4666 |
| language | English |
| last_indexed | 2024-12-10T18:24:08Z |
| publishDate | 2019-02-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Therapeutic Advances in Respiratory Disease |
| spelling | doaj.art-ca5470f6683f4039843231b8785b87d82022-12-22T01:38:08ZengSAGE PublishingTherapeutic Advances in Respiratory Disease1753-46662019-02-011310.1177/1753466618820186Modeling long-term health outcomes of patients with cystic fibrosis homozygous for treated with lumacaftor/ivacaftorJaime L. RubinLasair O’CallaghanChristopher PelligraMichael W. KonstanAlexandra WardJack K. IshakConor ChandlerTheodore G. LiouBackground: Lumacaftor/ivacaftor combination therapy is efficacious and generally safe for patients with cystic fibrosis (CF) homozygous for the F508del-CF transmembrane conductance regulator (CFTR) mutation. However, long-term survival benefits of lumacaftor/ivacaftor (LUM/IVA) cannot yet be quantified. Simulation models can provide predictions about long-term health outcomes. In this study, we aimed to project long-term health outcomes of LUM/IVA plus standard care (SC) in patients with CF homozygous for F508del-CFTR . Methods: This modeling study was an individual patient simulation in US patients aged ⩾6 years with CF, homozygous for F508del-CFTR . The primary outcome was projected survival among (a) a cohort of patients who ever initiated LUM/IVA, accounting for treatment discontinuations, and (b) a cohort of patients who remain on continuous LUM/IVA. Patient characteristics and model parameters were derived from clinical trials: VX14-809-109, VX13-809-011B, TRAFFIC/TRANSPORT, and PROGRESS; published literature; and the US CF Foundation Patient Registry. Results: Lumacaftor/ivacaftor + SC is expected to increase median survival by 6.1 years versus SC alone, accounting for treatment discontinuations. The incremental median predicted survival versus SC assuming initiation of LUM/IVA at ages 6, 12, 18, and 25 years was 17.7, 12.6, 8.0, and 3.8 years, respectively. Assuming lifetime treatment with LUM/IVA, incremental median survival was predicted to be 7.8 years longer in the LUM/IVA + SC cohort. Initiating LUM/IVA at ages 6, 12, 18, and 25 years and assuming lifetime treatment resulted in incremental median predicted survival of 23.4, 18.2, 11.0, and 4.8 years, respectively. Conclusions: Lumacaftor/ivacaftor is projected to increase survival for patients with CF. Initiation at an early age and treatment persistence result in further increments in projected survival.https://doi.org/10.1177/1753466618820186 |
| spellingShingle | Jaime L. Rubin Lasair O’Callaghan Christopher Pelligra Michael W. Konstan Alexandra Ward Jack K. Ishak Conor Chandler Theodore G. Liou Modeling long-term health outcomes of patients with cystic fibrosis homozygous for treated with lumacaftor/ivacaftor Therapeutic Advances in Respiratory Disease |
| title | Modeling long-term health outcomes of patients with cystic fibrosis homozygous for treated with lumacaftor/ivacaftor |
| title_full | Modeling long-term health outcomes of patients with cystic fibrosis homozygous for treated with lumacaftor/ivacaftor |
| title_fullStr | Modeling long-term health outcomes of patients with cystic fibrosis homozygous for treated with lumacaftor/ivacaftor |
| title_full_unstemmed | Modeling long-term health outcomes of patients with cystic fibrosis homozygous for treated with lumacaftor/ivacaftor |
| title_short | Modeling long-term health outcomes of patients with cystic fibrosis homozygous for treated with lumacaftor/ivacaftor |
| title_sort | modeling long term health outcomes of patients with cystic fibrosis homozygous for treated with lumacaftor ivacaftor |
| url | https://doi.org/10.1177/1753466618820186 |
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