Table 1.

Focused clinical questions on the pharmacological management of moderate to severe ulcerative colitis, and corresponding questions in PICO format addressed in this technical review

S#	Focused Question	PICO Question
		Patients	Intervention	Comparator	Critical Outcomes
OUTPATIENTS with MODERATE TO SEVERE UC
1.	In adult outpatients with moderate to severe UC, what is the overall efficacy of TNF-α antagonists (infliximab, adalimumab, golimumab), vedolizumab, tofacitinib and ustekinumab for induction and maintenance of remission?	Adult outpatients with moderate to severe UC	TNF-α antagonists (infliximab, adalimumab, golimumab) Vedolizumab Tofacitinib Ustekinumab	Placebo	Induction of remission Maintenance of remission
2.	In adult outpatients with moderate to severe UC, what is the comparative efficacy of different biologic agents (infliximab, adalimumab, golimumab, vedolizumab, ustekinumab) and tofacitinib, in biologic-naïve and in patients with prior TNF-α antagonist exposure, for induction and maintenance of remission?	Adult outpatients with moderate to severe UC, (A) biologic-naïve and (B) prior exposure to TNF-α antagonist	Infliximab Adalimumab Golimumab Vedolizumab Tofacitinib Ustekinumab	Placebo or another active comparator	Induction of remission Maintenance of remission
3.	In adult outpatients with moderate to severe UC, what is the efficacy of immunomodulator monotherapy (thiopurines, methotrexate) for induction and maintenance of remission?	Adult outpatients with moderate to severe UC	Thiopurines (azathioprine, mercaptopurine) Methotrexate (oral or subcutaneous)	Placebo (or 5-aminosalicylates)	Achieving remission Prevention of relapse (≈maintenance of remission)
4.	In adult outpatients with moderate to severe UC, is biologic monotherapy (infliximab, adalimumab, golimumab, vedolizumab, ustekinumab) or tofacitinib superior to immunomodulator monotherapy (thiopurines, methotrexate) for induction and maintenance of remission?	Adult outpatients with moderate to severe UC	Monotherapy with TNF-α antagonists (infliximab, adalimumab, golimumab) Vedolizumab Ustekinumab Tofacitinib	Immunomodulators (thiopurines or methotrexate)	Induction of remission Maintenance of remission
5.	In adult outpatients with moderate to severe UC, is combination therapy of a biologic agent (infliximab, adalimumab, golimumab, vedolizumab, ustekinumab) with an immunomodulator (thiopurines or methotrexate) superior to biologic monotherapy or immunomodulator monotherapy for induction and maintenance of remission?	Adult outpatients with moderate to severe UC	Combination therapy with of a biologic agent (infliximab, adalimumab, golimumab, vedolizumab, ustekinumab) + immunomodulator (thiopurines or methotrexate)	Biologic monotherapy (infliximab, adalimumab, golimumab, vedolizumab, ustekiumab) Immunomodulator monotherapy (thiopurines or methotrexate)	Induction of remission Maintenance of remission
6.	In adult outpatients with moderate to severe ulcerative colitis, is top-down therapy superior to step therapy for induction and maintenance of remission?	Adult outpatients with moderate to severe UC	Top-down therapy Upfront use of biologics and/or immunomodulator therapy Upfront use of biologic-based combination therapy	Step therapy Acceleration to biologic and/or immunomodulator therapy only after failure of 5-aminosalicylates Initial use of immunomodulator or biologic monotherapy	Induction of remission Maintenance of remission
7.	In adult outpatients with moderate to severe UC with prior failure of 5-aminosalicylates, currently being treated with immunomodulators, biologic therapy or tofacitinib, is continuing 5-aminosalicylates superior to stopping 5-aminosalicylates for inducing and maintaining remission?	Adult outpatients with moderate to severe UC with prior failure of 5-ASA, currently being treated with immunomodulators or biologic therapy	Continuation of 5-ASA	Stopping 5-ASA	Induction of remission Maintenance of remission
HOSPITALIZED patients with ACUTE SEVERE ULCERATIVE COLITIS
8.	In hospitalized patients with acute severe ulcerative colitis, what is the optimal dose of intravenous methylprednisolone for decreasing risk of colectomy?	Adults hospitalized with acute severe ulcerative colitis	Intravenous methylprednisolone equivalent of 40–60mg/d	Intravenous methylprednisolone equivalent of >60mg/d	Short-term colectomy (within 3 months of hospitalization)
9.	In hospitalized patients with acute severe ulcerative colitis, without gastrointestinal infection, is adjunctive antibiotic therapy more effective than no antibiotic therapy for decreasing risk of colectomy?	Adults hospitalized with acute severe ulcerative colitis being treated with intravenous corticosteroids	Antibiotics	Placebo or no antibiotics	Short-term colectomy
10.	In hospitalized patients with acute severe ulcerative colitis, refractory to intravenous corticosteroids, what is the overall efficacy of TNF-α antagonists (infliximab, adalimumab, golimumab), vedolizumab, tofacitinib, immunomodulators, cyclosporine and tacrolimus for decreasing risk of colectomy?	Adults hospitalized with acute severe ulcerative colitis, refractory to intravenous corticosteroids	TNF-α antagonists (infliximab, adalimumab, golimumab) Vedolizumab Tofacitinib Immunomodulators (thiopurines, methotrexate) Calcineurin inhibitors (cyclosporine, tacrolimus)	Placebo	Short-term colectomy
11.	In hospitalized patients with acute severe ulcerative colitis, refractory to intravenous corticosteroids, is infliximab superior to cyclosporine for decreasing risk of colectomy?	Adults hospitalized with acute severe ulcerative colitis, refractory to intravenous corticosteroids	Infliximab	Intravenous cyclosporine	Short-term colectomy
12.	In hospitalized patients with acute severe ulcerative colitis being treated with infliximab, is routine administration of intensive dosing regimens superior to standard dosing regimens in decreasing risk of colectomy?	Adults hospitalized with acute severe ulcerative colitis, refractory to intravenous corticosteroids, being treated with infliximab	Intensive infliximab dosing regimen (shortened interval between infliximab doses or dose stacking and/or induction with higher dose infliximab)	Standard infliximab induction regimen	Short-term colectomy