Characterization of Biologic Discontinuation Among Pediatric Patients with Crohn’s Disease

Background and Aims Biologic therapies may effectively treat Crohn’s disease (CD), and pediatric patients who discontinue multiple biologics risk exhausting treatment options. The frequency and context of biologic discontinuation has not been well characterized. We aimed to determine patterns of biologic use, discontinuation, and evaluation in pediatric patients with CD. Methods Pediatric patients with CD at seven US centers (2010-2020) were identified. Prospective ImproveCareNow registry data were supplemented with medical record abstraction. Biologics included monoclonal antibody and small molecule medications. Therapeutic drug monitoring (TDM) was considered induction if <14 weeks after biologic start, proactive if later during quiescent disease, and reactive during active disease. Results Of 823 patients included (median age 13.0 years, 40% female), 86% started biologics (78% infliximab, 21% adalimumab, <1% others). 26% used concomitant immunomodulators for ≥12 months. Most (85%) measured TDM including 47% induction, 69% proactive, and 24% reactive. 29% discontinued their first biologic after median 793 days due to inefficacy (34%), anti-drug antibodies (8%), adverse events (8%), or non-adherence (12%). If inefficacy, 86% underwent pre-discontinuation evaluation. If infliximab or adalimumab inefficacy and TDM was done, 62% had levels <10 μg/ml. Proactive TDM and concomitant immunomodulators were associated with 60% and 32% reduced biologic discontinuation. Conclusion Most children with CD are treated with biologics, 25-37% discontinue biologics resulting in 1 in 12 using >2 biologics during pediatric care. Half of patients discontinued biologics without trial of high-dose therapy, and 14% without any evaluation. Concomitant immunomodulator use and proactive TDM decreased risk of biologic discontinuation. Strategies are needed to preserve biologic efficacy and prevent biologic discontinuation.