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

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.

Automated summary

This study aimed to investigate the impact of early immunomodulator (IMM) therapy on the treatment outcomes of pediatric inflammatory bowel disease (pIBD) patients. The results showed that early combo-therapy with IMM significantly prolonged the effectiveness of infliximab treatment. This is of great importance for optimizing second-line treatments for children with IBD.