who have previously been exposed to infliximab, particularly those with primary nonresponse, the AGA suggests using ustekinumab or tofacitinib rather than vedolizumab or adalimumab for induction of remission. Conditional Low 3a. In adult outpatients with active moderate to severe UC, the AGA suggests against using thiopurine monotherapy for induction of remission. Conditional Very low 3b. In adult outpatients with moderate to severe UC in remission, the AGA suggests using thiopurine monotherapy rather than no treatment for maintenance of remission. Conditional Low 3c. In adult outpatients with moderate to severe UC, the AGA suggests against using methotrexate monotherapy for induction or maintenance of remission. Conditional Low 4a. In adult outpatients with active moderate to severe UC, the AGA suggests using biologic monotherapy (TNF-a antagonists, vedolizumab, or ustekinumab) or tofacitinib rather than thiopurine monotherapy for induction of remission. Conditional Low 4b. In adult outpatients with moderate to severe UC in remission, the AGA makes no recommendation in favor of or against using biologic monotherapy or tofacitinib rather than thiopurine monotherapy for maintenance of remission. No recommendation Knowledge gap 5a. In adult outpatients with moderate to severe UC, the AGA suggests combining TNF-a antagonists, vedolizumab or ustekinumab with thiopurines or methotrexate rather than biologic monotherapy. Comment: Patients, particularly those with less severe disease, who place higher value on the safety of biologic monotherapy and lower value on the efficacy of combination therapy may reasonably chose biologic monotherapy. Conditional Low 5b. In adult outpatients with moderate to severe UC, the AGA suggests combining TNF-a antagonists, vedolizumab, or ustekinumab with thiopurines or methotrexate rather than thiopurine monotherapy. Conditional Low 6. In adult outpatients with moderate to severe UC, the AGA suggests early use of biologic agents with or without immunomodulator therapy rather than gradual step up after failure of 5-ASA. Comment: Patients, particularly those with less severe disease, who place higher value on the safety of 5-ASA therapy and lower value on the efficacy of biologic agents or tofacitinib may reasonably chose gradual step therapy with 5-ASA therapy. Conditional Very low 7. In adult outpatients with moderate to severe UC who have achieved remission with biologic agents and/or immunomodulators or tofacitinib, the AGA suggests against continuing 5-ASA for induction and maintenance of remission. Conditional Very low 8. In hospitalized adult patients with ASUC, the AGA suggests using intravenous methylprednisolone dose equivalent of 40–60 mg/d rather than higher doses of intravenous corticosteroids. Conditional Very low 9. In hospitalized adult patients with acute severe UC without infection, the AGA suggests against adjunctive antibiotics. Conditional Very low 10. In hospitalized adult patients with ASUC refractory to intravenous corticosteroids, the AGA suggests using infliximab or cyclosporine. Conditional Low 11. In hospitalized adult patients with acute severe UC being treated with infliximab, the AGA makes no recommendation on routine use of intensive vs standard infliximab dosing. No recommendation Knowledge gap April 2020 AGA Guidelines on Management of Moderate to Severe UC 1453 CLINICAL PRACTICE GUIDELINES the medication. At higher doses, an unexpected increase in risk of pulmonary embolism and all-cause mortality has been observed. The overall quality of evidence for this recommendation was moderate for both induction and maintenance of remission. Although the majority of the studies were registration trials sponsored by industry, there was no important bias, inconsistency, or indirectness. The evidence was rated down for imprecision due to the lower number of events (< 0.01). In included trials, different intravenous corticosteroid regimens (different formulations given once daily vs multiple times daily vs as continuous infusion) were used, and none was superior to others. Based on models estimating risk and risk factors for colectomy in patients