Effectiveness of strategies to suppress antibodies to infliximab in pediatric inflammatory bowel disease

Author:

Jagt Jasmijn Z.12ORCID,Holleman Koen W.3,Benninga Marc A.4,Van Limbergen Johan E.4,de Boer Nanne K. H.5,de Meij Tim G. J.14

Affiliation:

1. Department of Pediatric Gastroenterology, Emma Children's Hospital, Amsterdam UMC Vrije Universiteit Amsterdam Amsterdam The Netherlands

2. Pediatric Gastroenterology, Amsterdam Gastroenterology Endocrinology Metabolism, De Boelelaan Amsterdam UMC, Vrije Universiteit Amsterdam Amsterdam Netherlands

3. Faculty of Medicine Amsterdam UMC, Academic Medical Centre Amsterdam The Netherlands

4. Department of Pediatric Gastroenterology Emma Children's Hospital, Amsterdam UMC, Academic Medical Centre Amsterdam The Netherlands

5. Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism (AGEM) Research Institute Amsterdam University Medical Centre, VU University Amsterdam Amsterdam The Netherlands

Abstract

AbstractObjectivesAntibodies to infliximab (ATIs) are associated with loss of response in children with inflammatory bowel disease (IBD). We aimed to describe the effectiveness of strategies for treatment modification following ATI development in pediatric IBD: (1) treatment escalation; and (2) switching to another anti‐TNF agent.MethodsThis multicenter retrospective study included children with IBD (4–18 years) on infliximab. Therapeutic drug monitoring (TDM) < 6 months and corticosteroid‐free remission following each strategy were evaluated for low ATI titers (≤30 AU/mL) and high ATI titers (>30 AU/mL).ResultsAnti‐infliximab antibodies were detected in 52/288 patients (18%) after a median of 15.3 months. Three of 52 ATI‐positive patients were excluded due to alternative treatments. Of the remaining 49 patients, 19 had low titers and 30 had high titers. Of 19 low‐ATIs, 16 (84%) underwent treatment escalation with infliximab (IFX). Of 13 patients with TDM available, seven (54%) achieved ATI suppression at subsequent TDM and 12 (92%) at any time point. Among 30 patients with high‐ATIs, 17 (57%) continued with IFX; immunomodulators were started in seven patients. Of 14 patients with TDM, seven (50%) achieved ATI suppression at subsequent TDM and 10 (71%) at any time point. At 24 months of follow‐up, 73% of low‐ATI patients and 50% of high‐ATI patients could continue with IFX without steroids. Thirteen of 30 high‐ATI patients (43%) switched to another anti‐TNF agent, of whom 54% and 46% had clinical response at 6 and 24 months, respectively.ConclusionsDose optimization and/or adding an immunomodulator seem effective in suppressing low ATI titers. This strategy could also be considered in high ATI titers before switching.

Publisher

Wiley

Subject

Gastroenterology,Pediatrics, Perinatology and Child Health

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