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Pharmacokinetics, Safety and Efficacy of Intravenous Vedolizumab in Paediatric Patients with Ulcerative Colitis or Crohn’s Disease: Results from the Phase 2 HUBBLE Study
BACKGROUND AND AIMS: To date, there are no systematic pharmacokinetic [PK] data on vedolizumab in paediatric inflammatory bowel disease [IBD]. We report results from HUBBLE, a dose-ranging, phase 2 trial evaluating the PK, safety and efficacy of intravenous vedolizumab for paediatric IBD. METHODS: E...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9426668/ https://www.ncbi.nlm.nih.gov/pubmed/35301512 http://dx.doi.org/10.1093/ecco-jcc/jjac036 |
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author | Hyams, Jeffrey S Turner, Dan Cohen, Stanley A Szakos, Erzsébet Kowalska-Duplaga, Kinga Ruemmele, Frank Croft, Nicholas M Korczowski, Bartosz Lawrence, Promise Bhatia, Siddharth Kadali, Harisha Chen, Chunlin Sun, Wan Rosario, Maria Kabilan, Senthil Treem, William Rossiter, Guillermo Lirio, Richard A |
author_facet | Hyams, Jeffrey S Turner, Dan Cohen, Stanley A Szakos, Erzsébet Kowalska-Duplaga, Kinga Ruemmele, Frank Croft, Nicholas M Korczowski, Bartosz Lawrence, Promise Bhatia, Siddharth Kadali, Harisha Chen, Chunlin Sun, Wan Rosario, Maria Kabilan, Senthil Treem, William Rossiter, Guillermo Lirio, Richard A |
author_sort | Hyams, Jeffrey S |
collection | PubMed |
description | BACKGROUND AND AIMS: To date, there are no systematic pharmacokinetic [PK] data on vedolizumab in paediatric inflammatory bowel disease [IBD]. We report results from HUBBLE, a dose-ranging, phase 2 trial evaluating the PK, safety and efficacy of intravenous vedolizumab for paediatric IBD. METHODS: Enrolled patients [aged 2–17 years] with moderate to severe ulcerative colitis [UC] or Crohn’s disease [CD] and body weight ≥10 kg were randomized by weight to receive low- or high-dose vedolizumab [≥30 kg, 150 or 300 mg; <30 kg, 100 or 200 mg] on Day 1 and Weeks 2, 6 and 14. Week 14 assessments included PK, clinical response and exposure–response relationship. Safety and immunogenicity were assessed. RESULTS: Randomized patients weighing ≥30 kg [UC, n = 25; CD, n = 24] and <30 kg [UC, n = 19; CD, n = 21] had a baseline mean [standard deviation] age of 13.5 [2.5] and 7.6 [3.2] years, respectively. In almost all indication and weight groups, area under the concentration curve and average concentration increased ~2-fold from low to high dose; the trough concentration was higher in each high-dose arm compared with the low-dose arms. At Week 14, clinical response occurred in 40.0–69.2% of patients with UC and 33.3–63.6% with CD in both weight groups. Clinical responders with UC generally had higher trough concentration vs non-responders, while this trend was not observed in CD. Fourteen per cent [12/88] of patients had treatment-related adverse events and 6.8% [6/88] had anti-drug antibodies. CONCLUSIONS: Vedolizumab exposure increased in an approximate dose-proportional manner. No clear dose–response relationship was observed in this limited cohort. No new safety signals were identified. |
format | Online Article Text |
id | pubmed-9426668 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-94266682022-08-31 Pharmacokinetics, Safety and Efficacy of Intravenous Vedolizumab in Paediatric Patients with Ulcerative Colitis or Crohn’s Disease: Results from the Phase 2 HUBBLE Study Hyams, Jeffrey S Turner, Dan Cohen, Stanley A Szakos, Erzsébet Kowalska-Duplaga, Kinga Ruemmele, Frank Croft, Nicholas M Korczowski, Bartosz Lawrence, Promise Bhatia, Siddharth Kadali, Harisha Chen, Chunlin Sun, Wan Rosario, Maria Kabilan, Senthil Treem, William Rossiter, Guillermo Lirio, Richard A J Crohns Colitis Original Articles BACKGROUND AND AIMS: To date, there are no systematic pharmacokinetic [PK] data on vedolizumab in paediatric inflammatory bowel disease [IBD]. We report results from HUBBLE, a dose-ranging, phase 2 trial evaluating the PK, safety and efficacy of intravenous vedolizumab for paediatric IBD. METHODS: Enrolled patients [aged 2–17 years] with moderate to severe ulcerative colitis [UC] or Crohn’s disease [CD] and body weight ≥10 kg were randomized by weight to receive low- or high-dose vedolizumab [≥30 kg, 150 or 300 mg; <30 kg, 100 or 200 mg] on Day 1 and Weeks 2, 6 and 14. Week 14 assessments included PK, clinical response and exposure–response relationship. Safety and immunogenicity were assessed. RESULTS: Randomized patients weighing ≥30 kg [UC, n = 25; CD, n = 24] and <30 kg [UC, n = 19; CD, n = 21] had a baseline mean [standard deviation] age of 13.5 [2.5] and 7.6 [3.2] years, respectively. In almost all indication and weight groups, area under the concentration curve and average concentration increased ~2-fold from low to high dose; the trough concentration was higher in each high-dose arm compared with the low-dose arms. At Week 14, clinical response occurred in 40.0–69.2% of patients with UC and 33.3–63.6% with CD in both weight groups. Clinical responders with UC generally had higher trough concentration vs non-responders, while this trend was not observed in CD. Fourteen per cent [12/88] of patients had treatment-related adverse events and 6.8% [6/88] had anti-drug antibodies. CONCLUSIONS: Vedolizumab exposure increased in an approximate dose-proportional manner. No clear dose–response relationship was observed in this limited cohort. No new safety signals were identified. Oxford University Press 2022-03-17 /pmc/articles/PMC9426668/ /pubmed/35301512 http://dx.doi.org/10.1093/ecco-jcc/jjac036 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Hyams, Jeffrey S Turner, Dan Cohen, Stanley A Szakos, Erzsébet Kowalska-Duplaga, Kinga Ruemmele, Frank Croft, Nicholas M Korczowski, Bartosz Lawrence, Promise Bhatia, Siddharth Kadali, Harisha Chen, Chunlin Sun, Wan Rosario, Maria Kabilan, Senthil Treem, William Rossiter, Guillermo Lirio, Richard A Pharmacokinetics, Safety and Efficacy of Intravenous Vedolizumab in Paediatric Patients with Ulcerative Colitis or Crohn’s Disease: Results from the Phase 2 HUBBLE Study |
title | Pharmacokinetics, Safety and Efficacy of Intravenous Vedolizumab in Paediatric Patients with Ulcerative Colitis or Crohn’s Disease: Results from the Phase 2 HUBBLE Study |
title_full | Pharmacokinetics, Safety and Efficacy of Intravenous Vedolizumab in Paediatric Patients with Ulcerative Colitis or Crohn’s Disease: Results from the Phase 2 HUBBLE Study |
title_fullStr | Pharmacokinetics, Safety and Efficacy of Intravenous Vedolizumab in Paediatric Patients with Ulcerative Colitis or Crohn’s Disease: Results from the Phase 2 HUBBLE Study |
title_full_unstemmed | Pharmacokinetics, Safety and Efficacy of Intravenous Vedolizumab in Paediatric Patients with Ulcerative Colitis or Crohn’s Disease: Results from the Phase 2 HUBBLE Study |
title_short | Pharmacokinetics, Safety and Efficacy of Intravenous Vedolizumab in Paediatric Patients with Ulcerative Colitis or Crohn’s Disease: Results from the Phase 2 HUBBLE Study |
title_sort | pharmacokinetics, safety and efficacy of intravenous vedolizumab in paediatric patients with ulcerative colitis or crohn’s disease: results from the phase 2 hubble study |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9426668/ https://www.ncbi.nlm.nih.gov/pubmed/35301512 http://dx.doi.org/10.1093/ecco-jcc/jjac036 |
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