Causes of Treatment Failure In Children With Inflammatory Bowel Disease Treated With Infliximab: A Pharmacokinetic Study

Objectives: Anti-tumor necrosis factor antibodies have led to a revolution in the treatment of inflammatory bowel diseases (IBD), however a sizable proportion of patients do not respond to therapy. There is increasing evidence suggesting that treatment failure may be classified as mechanistic, pharmacokinetic, or immune-mediated. Data regarding the contribution of these factors in children with IBD treated with infliximab (IFX) are still incomplete. The aim was to assess the causes of treatment failure in a prospective cohort of pediatric patients treated with IFX. Methods: This observational study considered 49 pediatric (median age 14.4) IBD patients (34 Crohn's disease, 15 ulcerative colitis) treated with IFX. Serum samples were collected at 6, 14, 22 and 54 weeks, before IFX infusions. IFX and anti-infliximab antibodies (AIA) were measured using ELISA assays. Disease activity was determined by PCDAI or PUCAI. Results: Clinical remission, defined as a clinical score 3.11 μg/ml emerged as the strongest predictor of sustained clinical remission. AIA concentrations were correlated inversely with IFX concentrations and directly with adverse reactions. Conclusions: Most cases of therapeutic failure were associated with low serum drug levels. IFX trough levels at the end of induction are associated with sustained long-term response. Address correspondence and reprint requests to Gabriele Stocco, Department of Life Sciences, University of Trieste, via Fleming 22, I-34127 Trieste, Italy (e-mail: stoccog@units.it). Received 26 February, 2018 Accepted 16 July, 2018 Samuele Naviglio and Doriana Lacorte: these authors contributed equally to the article. Stefano Martelossi: at present: Dipartimento Materno Infantile, Ospedale Ca' Foncello, Treviso, Italy Declaration of funding: None Conflict of interest: None Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal's Web site (www.jpgn.org). © 2018 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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