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Early Infliximab Clearance Predicts Remission in Children with Crohn’s Disease

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Abstract

Background and Aims

Children with Crohn’s disease have lower response rates to infliximab, lower infliximab levels, and higher infliximab clearance on weight-based dosing than adults. We hypothesize infliximab clearance is a predictive of later outcomes on infliximab in children with Crohn’s disease.

Methods

In this single-center retrospective study, data were collected from charts on diagnosis, anthropometry, routine labs, infliximab therapeutic drug monitoring, infliximab dosing, disease activity, and other treatments. With these data we generated a population pharmacokinetic model using non-linear mixed effects modeling and calculated infliximab clearance for each patient over time. Patients were classified as in remission, responder-only or non-responder at 5, 10 and 16 months. Regression and ROC analyses were used to assess for early predictors of remission and response to infliximab.

Results

Eighty-five subjects were included, with a median follow-up of 22.3 months (IQR 10.1–36.8). Our pharmacokinetic model showed infliximab clearance was positively associated with CRP and weight, while negatively associated with albumin. In regression analyses, early infliximab clearance was the only significant, consistent predictor of remission. A 0.1 L/day increase in infliximab clearance predicted remission with an OR between 0.179 and 0.426. Differences in dosing did not account for differences in outcome. Infliximab clearance alone had moderate predictive accuracy of remission, with an AUC between 0.682 and 0.738.

Conclusions

Early infliximab clearance is strongly associated with remission in children with Crohn’s disease. It may be useful as a marker of response in proactive therapeutic drug monitoring to guide early dose optimization and/or changes in treatment for betterment of long-term outcomes.

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Acknowledgments

We thank the nursing staff Cheryl Kluthe, Leanne Shirton and Jason Wang who were involved in the care of the patients in the study and assisted in some of the data collection. We are grateful for Women and Children's Health Research Institute (WCHRI) in providing resources such as Redcap support in this study. Lastly, we are grateful for the North American Society For Pediatric Gastroenterology, Hepatology & Nutrition (NASPGHAN) Foundation’s supporting of the mentor-mentee relationship between Dr. Hien Huynh and Aaron Chung.

Funding

This research is funded by the generous support of the Stollery Children's hospital foundation through the Women and Children's Health Research Institute (WCHRI). Aaron Chung's summer studentship was supported by the 2021 North American Society For Pediatric Gastroenterology, Hepatology & Nutrition (NASPGHAN) Foundation’s Medical Student Mentored Summer Research Program.

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Authors and Affiliations

  1. Division of Pediatric Gastroenterology, Faculty of Medicine, University of Alberta, Edmonton, Canada

    Aaron Chung, Matthew Carroll, Patricia Almeida, Alexandra Petrova, Daniela Isaac, Eytan Wine & Hien Huynh

  2. Projections Research Inc, Phoenixville, USA

    Diane Mould

  3. Division of Pediatric GI Nutrition, Department of Pediatrics, University of Alberta Faculty of Medicine & Dentistry, ECHA 4-579 11405 87 Ave NW, Edmonton, AB, T6G1C9, Canada

    Hien Huynh

Authors
  1. Aaron Chung
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  2. Matthew Carroll
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  3. Patricia Almeida
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  4. Alexandra Petrova
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  8. Hien Huynh
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Contributions

The following authors were involved in the conception and design of the study, and revising the article critically for important intellectual content: HQH, EW, MWC, DI. The following author was involved in the conception and design of the study, drafting the article, acquisition of data, and analysis and interpretation of data: AC. The following authors were involved in acquisition of data, analysis and interpretation of data, and revising the article critically for important intellectual content: DM, PA, AP. All authors were involved in final approval of the version to be submitted.

Corresponding author

Correspondence to Hien Huynh.

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Conflict of interest

Hien Q Huynh has received educational grants from AbbVie and Janssen and served as an advisory board member for BioJamp. He has also received speaker fees from AbbVie, Janssen and Fresenius. Eytan Wine has received speaker fees from AbbVie, Janssen, Nestle Health Sciences, BioJamp, Pfizer, and Mead Johnson Nutrition. Matthew W Carroll has received speaker fees from AbbVie. Diane R Mould is the president of Projections Research Inc, a consulting company for the pharmaceutical industry.

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Conference Presentation

Name: 16th Congress of ECCO, ECCO-IBD 2021. Location: Virtual. Year: 2021. Work presented: A Chung, M Carroll, P Almeida, A Petrova, D Mould, E Wine, H Huynh, Edmonton Pediatric IBD Clinic (EPIC), P337 Early infliximab clearance predicts remission in children with Crohn’s Disease, Journal of Crohn's and Colitis, Volume 15, Issue Supplement_1, May 2021, Pages S362–S363, https://doi.org/10.1093/ecco-jcc/jjab076.461.

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Chung, A., Carroll, M., Almeida, P. et al. Early Infliximab Clearance Predicts Remission in Children with Crohn’s Disease. Dig Dis Sci 68, 1995–2005 (2023). https://doi.org/10.1007/s10620-022-07783-3

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  • DOI: https://doi.org/10.1007/s10620-022-07783-3

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