Perianal fistulizing Crohn's disease increases infliximab clearance and causes low infliximab exposure (ATLANTIC).
4 affiliations
- 1Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands.
- 2Biologics Laboratory, Sanquin Diagnostic Services, Amsterdam, The Netherlands.
- 3Tytgat Institute for Liver and Intestinal Research, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands.
- 4Department of Hospital Pharmacy and Clinical Pharmacology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Abstract
Background and aims
In perianal fistulizing Crohn's disease (PFCD), higher infliximab (IFX) serum concentrations are associated with improved outcomes. PFCD patients frequently require dose intensification to reach recommended therapeutic targets. IFX pharmacokinetics (PK) in PFCD have not been previously characterized. We hypothesized that drug clearance (CL) is increased in PFCD compared to luminal Crohn's disease (LCD).Methods
Patients with PFCD and LCD starting standard-dose intravenous IFX (5 mg/kg at weeks 0, 2, and 6, thereafter every 8 weeks) were enrolled. At every visit, serum samples were collected until week 52 to measure IFX trough levels (TL) and anti-drug antibodies. A population PK model was constructed using nonlinear mixed-effects modeling and adjusted for clinically relevant covariates.Results
A total of 148 patients were included (62 PFCD, 86 LCD) with 756 serum samples analyzed. IFX PK was described by a two-compartment model with linear elimination. After adjusting for dose, weight, serum albumin, and anti-drug antibodies, population PK modeling revealed a 23% increase in IFX CL among patients with progressive perianal fistulas during the first 14 weeks (P = .007). During induction, recommended target IFX TL was achieved in fewer PFCD than LCD patients (43% vs 57%, P = .04). At week 14, PFCD patients had lower median IFX TL than LCD (2.9 vs 4.8 μg/mL, P = .02), with fewer PFCD patients reaching phenotype-specific target TL (9% vs 46%, P < .001) compared to LCD.Conclusion
The presence of perianal fistulas increases IFX CL in patients with Crohn's disease, resulting in significantly lower and frequently subtherapeutic serum concentrations after standard induction dosing.
Related
- Prenatal alcohol and cannabinoid co-exposure increases ethanol-seeking in adult offspring and produces sex-dependent medial prefrontal cannabinoid receptor 1 expression.
- Developmental cold exposure increases the ability to maintain body temperature during future cold challenges in a free-living altricial bird
- Inflammatory Bowel Disease Patients’ Acceptance for Switching from Intravenous Infliximab or Vedolizumab to Subcutaneous Formulation: The Nancy Experience
- Overcoming primary non-response to infliximab in ulcerative colitis: monocyte-derived PTGS2 as a therapeutic target
- Efficacy analysis of the Turnbull–Cutait procedure in refractory perianal Crohn’s disease: a two-centre retrospective study
BibTeX
@article{mulders2026perianal,
title = {{Perianal fistulizing Crohn's disease increases infliximab clearance and causes low infliximab exposure (ATLANTIC).}},
author = {Lieven G M Mulders and Suzanne I Anjie and Manon Chevallot-Beroux and Floris Loeff and Manon E Wildenberg and Ron A A Mathôt and Geert R A M D'Haens and Krisztina B Gecse},
journal = {Journal of Crohn's \& colitis},
year = {2026},
month = oct,
doi = {10.1093/ecco-jcc/jjag151},
url = {https://europepmc.org/article/MED/42909465},
note = {CC BY},
}
RIS
TY - JOUR
TI - Perianal fistulizing Crohn's disease increases infliximab clearance and causes low infliximab exposure (ATLANTIC).
AU - Lieven G M Mulders
AU - Suzanne I Anjie
AU - Manon Chevallot-Beroux
AU - Floris Loeff
AU - Manon E Wildenberg
AU - Ron A A Mathôt
AU - Geert R A M D'Haens
AU - Krisztina B Gecse
PY - 2026
DA - 2026/10/01
JO - Journal of Crohn's & colitis
DO - 10.1093/ecco-jcc/jjag151
UR - https://europepmc.org/article/MED/42909465
AB - Background and aims In perianal fistulizing Crohn's disease (PFCD), higher infliximab (IFX) serum concentrations are associated with improved outcomes. PFCD patients frequently require dose intensification to reach recommended therapeutic targets. IFX pharmacokinetics (PK) in PFCD have not been previously characterized. We hypothesized that drug clearance (CL) is increased in PFCD compared to luminal Crohn's disease (LCD).Methods Patients with PFCD and LCD starting standard-dose intravenous IFX (5 mg/kg at weeks 0, 2, and 6, thereafter every 8 weeks) were enrolled. At every visit, serum samples were collected until week 52 to measure IFX trough levels (TL) and anti-drug antibodies. A population PK model was constructed using nonlinear mixed-effects modeling and adjusted for clinically relevant covariates.Results A total of 148 patients were included (62 PFCD, 86 LCD) with 756 serum samples analyzed. IFX PK was described by a two-compartment model with linear elimination. After adjusting for dose, weight, serum albumin, and anti-drug antibodies, population PK modeling revealed a 23% increase in IFX CL among patients with progressive perianal fistulas during the first 14 weeks (P = .007). During induction, recommended target IFX TL was achieved in fewer PFCD than LCD patients (43% vs 57%, P = .04). At week 14, PFCD patients had lower median IFX TL than LCD (2.9 vs 4.8 μg/mL, P = .02), with fewer PFCD patients reaching phenotype-specific target TL (9% vs 46%, P < .001) compared to LCD.Conclusion The presence of perianal fistulas increases IFX CL in patients with Crohn's disease, resulting in significantly lower and frequently subtherapeutic serum concentrations after standard induction dosing.
SN - 1873-9946
SN - 1876-4479
ER -