This document is a living guideline from the American Gastroenterological Association (AGA) on the pharmacological management of moderate-to-severe ulcerative colitis. It presents recommendations based on a synthesis of studies, including network meta-analyses, concerning the efficacy and safety of various treatments. Recommendations cover initial and subsequent drug selection, including advanced biologic therapies and immunomodulators, as well as therapeutic strategies (top-down vs. bottom-up therapy). The emphasis is on shared decision-making between patient and practitioner, taking into account individual factors and treatment risks. Clinical decision aids are provided.

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