Long-term safety and durability of multiple anti-TNFα switches in pediatric inflammatory bowel disease: A Italian society of pediatric gastroenterology, hepatology and nutrition multicenter study.

OBJECTIVES

To evaluate the long-term safety, immunogenicity, and treatment durability of multiple sequential intramolecular switches of anti-tumor necrosis factor (TNF)-α agents (infliximab and adalimumab) in pediatric inflammatory bowel disease (IBD).

METHODS

A multicenter, retrospective cohort study was conducted across seven Italian pediatric IBD centers (2011-2024) under the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition IBD Working Group. Patients diagnosed with IBD before 18 years and undergoing ≥1 anti-TNF-α switch with ≥18 months follow-up were included. Switches were classified as originator-to-biosimilar, biosimilar-to-originator, or biosimilar-to-biosimilar, and as medically or nonmedical (supply-driven). Therapeutic switches between different anti-TNF-α molecules (e.g., infliximab to adalimumab or vice versa) were not included. The primary outcome was treatment persistence; secondary outcomes included relapse, adverse events (AEs), and anti-drug antibody detection.

RESULTS

A total of 185 patients (57% male; median age 11.9 years) were included; 73.5% had Crohn's disease. Over a median 5.5-year follow-up, 28% underwent a second and 9% a third switch, predominantly nonmedical and biosimilar-to-biosimilar. After the first switch, relapse occurred in 8.1%, infusion reactions in 4.3%, and other AEs in 3.8%, with no differences across switch types. Treatment discontinuation occurred in 21.1%, mainly due to loss of response (48.7%) or AEs (28.2%). Medically driven switching independently predicted discontinuation (hazard ratio; 3.1, 95% confidence interval [CI] 1.5-6.4, p = 0.002). Treatment durability did not differ by number of switches (log-rank p = 0.635). At final follow-up, 92.5% were in remission.

CONCLUSIONS

Multiple, predominantly nonmedical anti-TNF-α switches were not associated with increased relapse, AEs, or reduced durability in pediatric IBD. These findings support the safety of sequential switching under physician supervision, though prospective pediatric data remain warranted.