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Infliximab in young paediatric IBD patients: it is all about the dosing

Infliximab (IFX) is administered intravenously using weight-based dosing (5 mg/kg) in inflammatory bowel disease (IBD) patients. Our hypothesis is that especially young children need a more intensive treatment regimen than the current weight-based dose administration. We aimed to assess IFX pharmaco...

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Autores principales: Jongsma, Maria M. E., Winter, Dwight A., Huynh, Hien Q., Norsa, Lorenzo, Hussey, Seamus, Kolho, Kaija-Leena, Bronsky, Jiri, Assa, Amit, Cohen, Shlomi, Lev-Tzion, Raffi, Van Biervliet, Stephanie, Rizopoulos, Dimitris, de Meij, Tim G. J., Shouval, Dror S., Wine, Eytan, Wolters, Victorien M., Martinez-Vinson, Christine, de Ridder, Lissy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666662/
https://www.ncbi.nlm.nih.gov/pubmed/32813123
http://dx.doi.org/10.1007/s00431-020-03750-0
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author Jongsma, Maria M. E.
Winter, Dwight A.
Huynh, Hien Q.
Norsa, Lorenzo
Hussey, Seamus
Kolho, Kaija-Leena
Bronsky, Jiri
Assa, Amit
Cohen, Shlomi
Lev-Tzion, Raffi
Van Biervliet, Stephanie
Rizopoulos, Dimitris
de Meij, Tim G. J.
Shouval, Dror S.
Wine, Eytan
Wolters, Victorien M.
Martinez-Vinson, Christine
de Ridder, Lissy
author_facet Jongsma, Maria M. E.
Winter, Dwight A.
Huynh, Hien Q.
Norsa, Lorenzo
Hussey, Seamus
Kolho, Kaija-Leena
Bronsky, Jiri
Assa, Amit
Cohen, Shlomi
Lev-Tzion, Raffi
Van Biervliet, Stephanie
Rizopoulos, Dimitris
de Meij, Tim G. J.
Shouval, Dror S.
Wine, Eytan
Wolters, Victorien M.
Martinez-Vinson, Christine
de Ridder, Lissy
author_sort Jongsma, Maria M. E.
collection PubMed
description Infliximab (IFX) is administered intravenously using weight-based dosing (5 mg/kg) in inflammatory bowel disease (IBD) patients. Our hypothesis is that especially young children need a more intensive treatment regimen than the current weight-based dose administration. We aimed to assess IFX pharmacokinetics (PK), based on existing therapeutic drug monitoring (TDM) data in IBD patients < 10 years. TDM data were collected retrospectively in 14 centres. Children treated with IFX were included if IFX was started as IBD treatment at age < 10 years (young patients, YP) and PK data were available. Older IBD patients aged 10–18 years were used as controls (older patients, OP). Two hundred and fifteen paediatric inflammatory bowel disease (PIBD) patients were eligible for the study (110 < 10 year; 105 ≥ 10 years). Median age was 8.3 years (IQR 6.9–8.9) in YP compared with 14.3 years (IQR 12.8–15.6) in OP at the start of IFX. At the start of maintenance treatment, 72% of YP had trough levels below therapeutic range (< 5.4 μg/mL). After 1 year of scheduled IFX maintenance treatment, YP required a significantly higher dose per 8 weeks compared with OP (YP; 9.0 mg/kg (IQR 5.0–12.9) vs. OP; 5.5 mg/kg (IQR 5.0–9.3); p < 0.001). The chance to develop antibodies to infliximab was relatively lower in OP than YP (0.329 (95% CI − 1.2 to − 1.01); p < 0.001), while the overall duration of response to IFX was not significantly different (after 2 years 53% (n = 29) in YP vs. 58% (n = 45) in OP; p = 0.56). Conclusion: Intensification of the induction scheme is suggested for PIBD patients aged < 10 years. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00431-020-03750-0) contains supplementary material, which is available to authorized users.
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spelling pubmed-76666622020-11-17 Infliximab in young paediatric IBD patients: it is all about the dosing Jongsma, Maria M. E. Winter, Dwight A. Huynh, Hien Q. Norsa, Lorenzo Hussey, Seamus Kolho, Kaija-Leena Bronsky, Jiri Assa, Amit Cohen, Shlomi Lev-Tzion, Raffi Van Biervliet, Stephanie Rizopoulos, Dimitris de Meij, Tim G. J. Shouval, Dror S. Wine, Eytan Wolters, Victorien M. Martinez-Vinson, Christine de Ridder, Lissy Eur J Pediatr Original Article Infliximab (IFX) is administered intravenously using weight-based dosing (5 mg/kg) in inflammatory bowel disease (IBD) patients. Our hypothesis is that especially young children need a more intensive treatment regimen than the current weight-based dose administration. We aimed to assess IFX pharmacokinetics (PK), based on existing therapeutic drug monitoring (TDM) data in IBD patients < 10 years. TDM data were collected retrospectively in 14 centres. Children treated with IFX were included if IFX was started as IBD treatment at age < 10 years (young patients, YP) and PK data were available. Older IBD patients aged 10–18 years were used as controls (older patients, OP). Two hundred and fifteen paediatric inflammatory bowel disease (PIBD) patients were eligible for the study (110 < 10 year; 105 ≥ 10 years). Median age was 8.3 years (IQR 6.9–8.9) in YP compared with 14.3 years (IQR 12.8–15.6) in OP at the start of IFX. At the start of maintenance treatment, 72% of YP had trough levels below therapeutic range (< 5.4 μg/mL). After 1 year of scheduled IFX maintenance treatment, YP required a significantly higher dose per 8 weeks compared with OP (YP; 9.0 mg/kg (IQR 5.0–12.9) vs. OP; 5.5 mg/kg (IQR 5.0–9.3); p < 0.001). The chance to develop antibodies to infliximab was relatively lower in OP than YP (0.329 (95% CI − 1.2 to − 1.01); p < 0.001), while the overall duration of response to IFX was not significantly different (after 2 years 53% (n = 29) in YP vs. 58% (n = 45) in OP; p = 0.56). Conclusion: Intensification of the induction scheme is suggested for PIBD patients aged < 10 years. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00431-020-03750-0) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2020-08-19 2020 /pmc/articles/PMC7666662/ /pubmed/32813123 http://dx.doi.org/10.1007/s00431-020-03750-0 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Original Article
Jongsma, Maria M. E.
Winter, Dwight A.
Huynh, Hien Q.
Norsa, Lorenzo
Hussey, Seamus
Kolho, Kaija-Leena
Bronsky, Jiri
Assa, Amit
Cohen, Shlomi
Lev-Tzion, Raffi
Van Biervliet, Stephanie
Rizopoulos, Dimitris
de Meij, Tim G. J.
Shouval, Dror S.
Wine, Eytan
Wolters, Victorien M.
Martinez-Vinson, Christine
de Ridder, Lissy
Infliximab in young paediatric IBD patients: it is all about the dosing
title Infliximab in young paediatric IBD patients: it is all about the dosing
title_full Infliximab in young paediatric IBD patients: it is all about the dosing
title_fullStr Infliximab in young paediatric IBD patients: it is all about the dosing
title_full_unstemmed Infliximab in young paediatric IBD patients: it is all about the dosing
title_short Infliximab in young paediatric IBD patients: it is all about the dosing
title_sort infliximab in young paediatric ibd patients: it is all about the dosing
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666662/
https://www.ncbi.nlm.nih.gov/pubmed/32813123
http://dx.doi.org/10.1007/s00431-020-03750-0
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