Switching Between Anti-TNFs and Other Biologic Drugs in Paediatric Inflammatory Bowel Disease: A Narrative Review and...

Anti-tumour necrosis factor (anti-TNF) agents, particularly infliximab and adalimumab, represent first-line biologic therapy for moderate-to-severe paediatric inflammatory bowel disease (IBD). However, approximately one-third of patients experience treatment failure over time, predominantly due to secondary loss of response (LOR), while primary non-response (PNR) occurs in approximately 8% of cases. Strategies for switching and structured treatment optimization are required to address these issues.

To provide an organized, evidence-based clinical guide on biologic switching strategies in paediatric IBD, including intra-class and inter-class approaches, and to propose an author-derived, evidence-informed clinical framework for practical decision-making.

A narrative review was conducted using PubMed/MEDLINE, Embase, and the Cochrane Library to identify relevant studies on biologic switching strategies in paediatric IBD. Data from randomised controlled trials, cohort studies, registry analyses, systematic reviews, and international guidelines published between 2007 and 2026 were included. A total of 119 references, comprising approximately 60% paediatric studies and 40% supportive adult studies, were synthesised qualitatively, focusing on efficacy, safety, therapeutic drug monitoring (TDM), and treatment sequencing.

Intra-class switching between anti-TNF agents achieves remission in approximately 43% of patients overall, with higher success rates in intolerance (61%) and secondary LOR (45%) than in PNR (30%). TDM is central to guiding switching decisions: pharmacokinetic failure-characterised by low drug levels with or without anti-drug antibodies-may benefit from dose optimization or within-class switching, whereas pharmacodynamic failure generally requires transition to a different therapeutic class. Among second-line therapies, vedolizumab and ustekinumab show disease-specific differences; available evidence suggests that vedolizumab may be more effective in ulcerative colitis (UC), while current data indicate that ustekinumab may be more effective in Crohn's disease (CD), particularly after anti-TNF exposure. JAK inhibitors, notably upadacitinib, and S1P receptor modulators show promising results, although paediatric data remain limited. An author-derived, evidence-informed stepwise clinical framework integrating objective disease assessment, TDM-guided failure classification, and phenotype-driven therapy selection is proposed.

Biologic switching in paediatric IBD requires a mechanism-based, individualised approach integrating TDM, disease phenotype, and prior treatment exposure. Early optimisation and appropriate sequencing are critical to improve long-term outcomes. The proposed clinical framework is intended to support, rather than replace, individualized clinical judgment.