NEW HORIZON FOR TREATMENT IN…
IL-23 inhibitors in pediatric IBD: what have we learnt so far?
Luca Scarallo, Martina Di Benedetto
Gastroenterology and Nutrition Unit, Meyer Children’s Hospital IRCCS, Italy
Inflammatory bowel diseases (IBD) are chronic immune-mediated disorders with significant morbidity. Despite the introduction of anti-TNF biologics, up to one-third of patients experience primary non-response, and many lose efficacy over time. Additionally, anti-TNF therapies are associated with infections, malignancy risk, and paradoxical adverse events, highlighting the need for novel, more targeted therapeutic strategies. Selective IL-23p19 inhibitors, including guselkumab, risankizumab, and mirikizumab, represent a new class of biologics designed to modulate a central driver of intestinal inflammation. By specifically targeting IL-23, these agents inhibit Th17-mediated pro-inflammatory pathways while sparing other immune functions, potentially improving safety and tolerability. Phase III trials in adults with IBD have demonstrated significant efficacy in inducing and maintaining clinical and endoscopic remission, including patients with prior biologic failure. Comparative analyses suggest subtle differences among agents, which may reflect molecular characteristics, study populations, and trial design. In pediatric populations, data are currently limited to mirikizumab phase II studies in ulcerative colitis, showing promising efficacy and pharmacokinetic profiles. Ongoing phase III and real-world studies are expected to clarify the role of IL-23p19 inhibitors in children. Overall, selective IL-23p19 blockade represents a major advancement in precision therapy for IBD. By providing targeted modulation of central inflammatory pathways, these agents offer the potential to improve long-term outcomes, particularly in patients refractory to conventional biologics. Further head-to-head trials and real-world evidence will be critical to define optimal positioning and maximize their prognostic impact across different patient populations.