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

Objectives Antibodies 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. Methods This multicenter retrospective study included children with IBD (4–18 years) on infliximab. Therapeutic drug monitoring (TDM) 30 AU/mL). Results Anti‐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. Conclusions Dose 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. The development of antibodies to infliximab (ATIs) commonly causes a loss of response in children with inflammatory bowel disease. This retrospective cohort study showed that treatment escalation with infliximab (dose optimization and/or adding an immunomodulator) seems to be an effective strategy to suppress ATIs in patients with low ATI titers (≤30 AU/mL). For high ATI titers, this strategy could also be considered before switching. What is Known • Pharmacokinetic loss of response to infliximab in pediatric inflammatory bowel disease (IBD) is commonly caused by anti‐infliximab antibodies (ATIs). What is New • Treatment escalation (dose optimization and/or adding an immunomodulator) resulted in 92% and 71% ATI suppression, at any time point,