A Trial for Acute Severe Ulcerative Colitis

Inclusion Criteria for Clinical trial patients: Diagnosis of ulcerative colitis (verified by a typical clinical history as well as characteristic appearance on endoscopy and histology) Current hospital admission for ulcerative colitis treatment (expecting Intravenous (IV) corticosteroid initiation) Meeting definition of acute severe ulcerative colitis according to Truelove and Witt's Criteria (≥6 bowel movements per day with visible blood) and at least one of the following: (Temperature > 37.5 celsius, Pulse > 90 beats per minutes, hemoglobin < 10.5 grams per deciliter (g/dL), erythrocyte sedimentation rate > 30millimeters per hour (mm/h), c-reactive protein ≥ 4.5 milligrams per decilitre mg/dL) Prior history of receiving at least one dose of adalimumab, certolizumab, infliximab, or golimumab originator or biosimilars Participants who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, daily bowel movement symptoms surveys, and other study procedures Stated willingness to comply with all study procedures and availability for the duration of the study Ability to take oral medication and be willing to adhere to the study intervention regimen For females of reproductive potential (i.e., females <55 years of age with intact ovaries and fallopian tubes) a negative pregnancy test on admission and intent to use highly effective contraception during 3-month follow-up period (per protocol). Exclusion Criteria for Clinical trial patients: Presence of indeterminate colitis, microscopic colitis, ischemic colitis, infectious colitis, or clinical findings suggestive of Crohn's disease On IV corticosteroids for ≥ 72 hours prior to enrollment continuously (at any institution) Currently pregnant or breastfeeding Patients who meet diagnostic criteria for toxic megacolon during this current admission. This will be determined by the study team and inpatient treatment team according to the protocol. Known hypersensitivity to any of the following drugs or constituents: methylprednisone, cyclosporine, tofacitinib, or Upadacitinib Patients who had previous exposure to Upadacitinib. Previous exposure to other Janus kinase (JAK) inhibitors (eg, tofacitinib, baricitinib, or filgotinib) are permissible. Positive stool examinations for enteric pathogens, pathogenic ova or parasites, or Clostridium difficile toxin at screening Patients with ongoing infection, including untreated or inadequately treated latent or active tuberculosis (TB) Active Cytomegalovirus (CMV) colitis with >5 CMV inclusion bodies per high powered field in any one ulcer at baseline. If CMV colitis is confirmed on subsequent endoscopy the patient can remain in the trial if permissible by the infectious disease team and if concomitant anti-viral therapy is initiated. Patients who had received any investigational agent or procedure within 30 days or five half-lives prior to baseline, whichever is longer, or were enrolled in an interventional study Current malignancy or a history of malignancy, with the exception of adequately treated or excised non-metastatic basal cell or squamous cell carcinoma of the skin. Patients who had a history of colectomy (total or subtotal), ileoanal pouch, Kock pouch, or ileostomy or were planning bowel surgery Moderate or severe renal, hematological, gastrointestinal, metabolic, endocrine, pulmonary, cardiac, neurological, or psychiatric condition per protocol. Mild to severe hepatic impairment: Child-Pugh score ≥5 History of uncontrolled hypertension (systolic blood pressure >160 millimetres of mercury (mmHg) or diastolic blood pressure > 100 millimetres of mercury (mmHg) despite anti-hypertensives) Certain cardiovascular or thrombotic conditions per protocol Patients with total cholesterol <80 mg/dL at baseline Patients who had a history of an allergic reaction or significant sensitivity to constituents of the treatment (and its excipients) and/or other products in the same class of medication (ex., tofacitinib) Patients who had hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infection defined per protocol. Solid organ or bone marrow transplant within 1 year or expected transplant within 6 months History of more than one episode of herpes zoster, a history of disseminated herpes zoster or disseminated herpes simplex Current use of medications which significantly increase the risk of venous thromboembolic event as determined by the investigator Vaccination with live or attenuated live vaccines within 6 weeks of baseline or scheduled to receive these vaccines during study period or within 140 days (20 weeks) after last dose of study medication. History of any lymphoproliferative disorder (such as Epstein-Barr virus (EBV)-related lymphoproliferative disorder), history of lymphoma, leukemia, myeloproliferative disorders, multiple myeloma, or signs and symptoms suggestive of current hematologic disease. Patients who had a history of spontaneous gastrointestinal (GI) perforation (other than appendicitis or mechanical injury), diverticulitis, or significantly increased risk of GI perforation per investigator's judgement Actively receiving strong CYP3A4 inducers or inhibitors prior to the first dose of study drug or are expected to receive any of these medications during the study period. The presence of any condition possibly affecting oral drug absorption (e.g., gastrectomy, clinically significant diabetic gastroenteropathy, or certain types of bariatric surgery such as gastric bypass). Procedures such as gastric banding that simply divide the stomach into separate chambers are not exclusionary. Patients who had a history of a clinically significant medical condition or any other reason which, in the opinion of the investigator, would have interfered with the patient's participation in this study, would have made the patient an unsuitable candidate to receive treatment, or would have put the patient at risk by participating in the protocol Inclusion criteria for Physicians: - Clinicians (Internal medicine residents, gastroenterology fellows, and attending gastroenterologists) caring for the patients enrolled in the clinical trial Exclusion criteria for Physicians: - Non-clinicians not caring for the enrolled patient