Current evidence for first-line advanced therapies in pediatric ulcerative colitis: a critical review.
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BACKGROUND: The therapeutic landscape of pediatric ulcerative colitis (UC) has evolved substantially with the introduction of multiple advanced therapies, creating new challenges in selecting the most appropriate initial treatment. While infliximab has long served as the reference biologic, biologics with different mechanisms of action and small-molecule therapies have expanded therapeutic options. However, the pediatric evidence supporting first-line advanced therapy remains heterogeneous across currently available agents. METHODS: This review critically summarizes the current pediatric evidence supporting first-line advanced therapies for UC, focusing on anti-tumor necrosis factor therapy, vedolizumab, ustekinumab, selective interleukin-23 inhibitors, and other emerging advanced therapies. We evaluate the maturity, characteristics, and direct applicability of the available evidence to biologic-naïve pediatric patients and discuss the major limitations of the current literature. RESULTS: Among currently available therapies, anti-tumor necrosis factor therapy, particularly infliximab, is supported by the most comprehensive prospective pediatric evidence. In contrast, evidence for vedolizumab, ustekinumab, and selective IL-23 inhibitors has accumulated more recently and remains comparatively limited. Across all therapeutic classes, direct comparative studies in biologic-naïve pediatric patients are lacking, and evidence supporting individualized treatment selection remains insufficient. CONCLUSIONS: Current pediatric evidence supports the efficacy of multiple advanced therapies and has characterized important safety outcomes; however, evidence establishing therapeutic efficacy should be distinguished from evidence directly informing first-line treatment selection. Future pediatric research should increasingly generate comparative and predictive evidence that informs which effective advanced therapy should be selected first and for whom.