ClinGastroenterolHepatol. 2024Oct;22(10):20752083.e1.doi:10.1016/j.cgh.2024.03.043. Epub 2024 May 8.

Sabina Ali ¹, Brad Pasternak ², Jonathan Moses ³, David L Suskind ⁴, Charles Samson ⁵, Jess Kaplan ⁶, Jana Creps ⁷, Lauren Manning ⁸, Michaella Baker ⁸, Dianne Singer ⁸, Perseus Patel ¹, Becca Trombler ⁹, Archana Anandakrishnan ², Camila Khorrami ⁴, Maya Feldman ⁶, Molly McGoldrick ⁶, Jeremy Adler ¹⁰

Author information

¹Division of Pediatric Gastroenterology, Hepatology, and Nutrition, UCSF Benioff Children's Hospital, Oakland, California.

²Pediatric Gastroenterology, Phoenix Children's Hospital, Phoenix, Arizona.

³Division of Gastroenterology, Hepatology, and Nutrition, UH Rainbow Babies & Children's, Cleveland, Ohio.

⁴Division of Gastroenterology and Hepatology, Seattle Children's Hospital, Seattle, Washington.

⁵Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Washington University School of Medicine in St Louis, St Louis, Missouri.

⁶Division of Pediatric Gastroenterology, Mass General for Children and Harvard Medical School, Boston, Massachusetts.

⁷Department of Surgery, Section of Pediatric Surgery, University of Michigan Medical School, Ann Arbor, Michigan.

⁸Susan B. Meister Child Health Evaluation and Research Center, University of Michigan, Ann Arbor, Michigan.

⁹Division of Pediatric Gastroenterology, Hepatology, and Nutrition, UCSF Benioff Children's Hospital, San Francisco, California.

¹⁰Susan B. Meister Child Health Evaluation and Research Center, University of Michigan, Ann Arbor, Michigan; Division of Pediatric Gastroenterology, Michigan Medicine, Ann Arbor, Michigan. Electronic address: jeradler@umich.edu.

Abstract

Background & 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 have 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 7 U.S. 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). Twenty-six percent used concomitant immunomodulators for ≥12 months. Most (85%) measured TDM including 47% induction, 69% proactive, and 24% reactive. Twenty-nine percent discontinued their first biologic after median 793 days because of 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.

Conclusions: 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.