The association of infliximab trough levels with disease activity in pediatric inflammatory bowel disease

Abstract

Objective. Low serum trough levels (TLs) of infliximab (IFX) and antibodies to IFX (ATIs) are associated with the loss of therapeutic response in adults with inflammatory bowel disease (IBD) receiving IFX. Until now, pediatric data are scarce. Therefore, we aimed to cross-sectionally investigate the association between ATIs and IFX TLs, and clinical and biochemical disease activity in children receiving IFX for IBD. Material and methods. Children aged <18 years receiving IFX maintenance treatment for Crohn’s disease (CD) or ulcerative colitis (UC) at three Dutch hospitals were included. Prior to two consecutive IFX infusions, IFX TLs and ATI levels were measured. Clinical disease activity was determined by Pediatric Crohn’s Disease Activity Index (PCDAI) and Pediatric Ulcerative Colitis Activity Index (PUCAI), for CD and UC, respectively. Biochemical disease activity was assessed by serum C-reactive protein (CRP) and fecal calprotectin (FC). Clinical remission was defined as a PUCAI or PCDAI score of <10. Therapeutic range of IFX was considered 3–7 µg/ml. Results. Thirty-nine patients were included (31 CD; 16 females). Median age was 15 years. Median IFX TL was 3.5 µg/ml [IQR 2–7]. Subtherapeutic and supratherapeutic TLs were found in 38% and 23% of children, respectively. ATIs were detected in four patients. A correlation was found between IFX TL and CRP [r_s = −0.51; p < 0.01] and FC [r_s = −0.49; p < 0.01]. However, when only clinical disease activity was considered, no difference in median TL was found between remission and active disease (resp. 3.5 µg/ml [IQR 2–5] and 2.3 µg/ml [IQR 0.3–4.6]; p = 0.2). Conclusions. IFX TLs are related to biochemical markers of disease activity. This could provide a rationale for monitoring TLs in children receiving IFX for IBD.

Key Words:

• Children
• Crohn’s disease
• inflammatory bowel disease
• infliximab trough levels
• ulcerative colitis

Acknowledgements

Statement of authorship: D. R. Hoekman, J. F. Brandse, M. Löwenberg, A. Kindermann, and M. A. Benninga contributed to the conception and design of the study. D. R. Hoekman, T. G. de Meij, T. Z. Hummel, and A. Kindermann contributed to the acquisition of data. D. R. Hoekman, J. F. Brandse, and A. Kindermann contributed to the analysis and interpretation of data. D. R. Hoekman drafted the article. J. F. Brandse, T. G. de Meij, T. Z. Hummel, M. Löwenberg, M. A. Benninga, G. R. D’Haens, and A. Kindermann critically revised the article. All authors read and approved the final manuscript.

Declaration of interest: D. R. Hoekman has nothing to disclose; J. F. Brandse has served as a speaker for AbbVie, MSD and Takeda, outside the submitted work; T. G. de Meij has nothing to disclose; T. Z. Hummel has nothing to disclose; M. Löwenberg has served as speaker and/or principal investigator for AbbVie, Covidien, Dr. Falk, Ferring, MSD, Receptos, Takeda and Tramedico and has received research funding from AbbVie, MSD and Achmea Healthcare outside the submitted work; M. A. Benninga has received research funding from Janssen Biologics, outside the submitted work; G. R. D’Haens has served as a speaker for Abbott, Ferring, MSD, Norgine, Shire, Tillotts, Tramedico, UCB, as a consultant for Abbott, Actogenix, Centocor, Cosmo, Engene, Ferring, GlaxoSmithKline, Janssen Biologics, Millenium Pharmaceuticals, MSD, Novonordisk, PDL Biopharma, Pfizer, SetPoint, Shire, Takeda, Teva, UCB, and has received research funding from Abbott, Janssen Biologics, Given Imaging, MSD, Dr. Falk, Photopill, outside the submitted work; A. Kindermann has received research funding from Janssen Biologics, outside the submitted work. The authors alone are responsible for the content and writing of the paper.