Pediatric IBD Patients Treated With Infliximab and Proactive Drug Monitoring Benefit From Early Concomitant Immunomodulatory Therapy: A Retrospective Analysis of a 10-Year Real-Life Cohort

• Published in: Inflammatory bowel diseases 2024-11, Vol.30 (11), p.2004-2018
• Main Authors: Hoelz, Hannes, Bragagna, Lena, Litwin, Anna, Koletzko, Sibylle, Le Thi, Thu Giang, Schwerd, Tobias
• Format: Article
• Language: English
• Subjects: Adolescent; Child; Child, Preschool; Colitis, Ulcerative - drug therapy; Drug Monitoring - methods; Drug Therapy, Combination; Female; Follow-Up Studies; Gastrointestinal Agents - administration & dosage; Gastrointestinal Agents - therapeutic use; Humans; Immunomodulating Agents - therapeutic use; Inflammatory Bowel Diseases - drug therapy; Infliximab - administration & dosage; Infliximab - therapeutic use; Kaplan-Meier Estimate; Male; Retrospective Studies; Treatment Outcome
• ISSN: 1078-0998; 1536-4844; 1536-4844
• DOI: 10.1093/ibd/izad277

Abstract Background Limited approval of second-line treatments in pediatric inflammatory bowel disease (pIBD) necessitates optimized use of infliximab (IFX) with proactive therapeutic drug monitoring (TDM). We investigated whether early combo-therapy with an immunomodulator (IMM) provides additional benefit. Methods In the retrospectively reviewed medical records of all children treated with IFX and proactive TDM between 2013 and 2022, IMMearly (IMM ≤3 months since IFX start) was evaluated against IMMother/no (late/short or no IMM) over follow-up of 3 to 60 months. Kaplan-Meier analysis was used to analyze time to loss of response (LOR) with IFX discontinuation or time to antibodies-to-IFX (ATI) development. Results Three hundred fifteen patients with pIBD were reviewed; of those, 127 with 2855 visits were included (77 CD, 50 UC/IBD-unclassified). Sixty patients received IMMearly, 20 patients IMMother, and 47 had IFX monotherapy. Median follow-up time was 30 and 26 months for IMMearly and IMMother/no, respectively, with comparable proactive TDM. Infliximab treatment persistence was 68% after 60 months. Loss of response was observed in 7 IMMearly and 15 IMMother/no patients (P = .16). Early combo-therapy significantly delayed LOR with IFX discontinuation (median LOR free interval IMMearly 30 months vs IMMother/no 9 months, P = .01). Patients with IMMother/no were 10-, 3- and 2-times more likely to experience LOR with IFX discontinuation after 1, 3, and 5 years, respectively. There were no significant group differences regarding the presence of any positive (>10 arbitrary units per milliliter [AU/mL]) or high (>100 AU/mL) ATI, median ATI concentrations, and ATI-free interval. Conclusions Early IMM combo-therapy in proactively monitored patients with pIBD significantly prolonged the median LOR free interval compared with late/short or no IMM treatment. Graphical Abstract Graphical Abstract