AGA Technical Review on the Management of Moderate to Severe Ulcerative Colitis

Abstract A subset of patients with ulcerative colitis (UC) present with, or progress to, moderate to severe disease activity. These patients are at high-risk for colectomy, hospitalization, corticosteroid-dependence, and serious infections. The risk of life-threatening complications and emergency colectomy is particularly high among those patients hospitalized with acute severe ulcerative colitis (ASUC). Optimal management of outpatients or inpatients with moderate-severe UC often requires the use of immunomodulator and/or biologic therapies including thiopurines, methotrexate, cyclosporine, tacrolimus, tumor necrosis factor (TNF)-α antagonists, vedolizumab, tofacitnib or ustekinumab, either as monotherapy, or in combination (with immunomodulators), to mitigate these risks. Decisions about optimal drug therapy in moderate-severe UC are complex, with limited guidance on comparative efficacy and safety of different treatments, leading to considerable practice variability. Therefore, the American Gastroenterological Association prioritized development of clinical guidelines on this topic. To inform the clinical guidelines, this technical review was completed in accordance with the GRADE framework. Focused questions in adult outpatients with moderate-severe UC included: (1) overall and comparative efficacy of different medications for induction and maintenance of remission in patients with or without prior exposure to TNF-α antagonists, (2) comparative efficacy and safety of biologic monotherapy vs. combination therapy with immunomodulators, (3) comparative efficacy of top-down (upfront use of biologics and/or immunomodulator therapy) vs. step-up therapy (acceleration to biologic and/or immunomodulator therapy only after failure of 5-aminosalicylates), and (4) role of continuing vs. stopping 5-aminosalicylates in patients being treated with immunomodulator and/or biologic therapy for moderate-severe UC. Focused questions in adults hospitalized with ASUC included: (5) overall and comparative efficacy of pharmacological interventions for inpatients refractory to corticosteroids, in reducing risk of colectomy, (6) optimal dosing regimens for intravenous corticosteroids and infliximab in these patients and (7) role of adjunctive antibiotics in the absence of confirmed infections.