Inflamm Bowel Dis. 2024 Nov 4;30(11):2004-2018. doi: 10.1093/ibd/izad277.

Hannes Hoelz ¹, Lena Bragagna ¹, Anna Litwin ¹, Sibylle Koletzko ^1 2, Thu Giang Le Thi ¹, Tobias Schwerd ¹

Author information

¹Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, LMU Munich, Germany.

²Department of Pediatrics, Gastroenterology and Nutrition, School of Medicine Collegium Medicum University of Warmia and Mazury, Olsztyn, Poland.

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.