Comparison of Ustekinumab, Infliximab and Combination Therapy in Moderately to Severely Active Ulcerative Colitis

Exclusion Criteria

• •1. Previous use of the study drug IFX or UST.
• •2. Hypersensitivity to the active substance or excipients.
• •3. Moderate or severe myocardial insufficiency (NYHA III or IV).
• •4. Unstable coronary artery disease.
• •5. History of serious cerebrovascular disease (stroke, intracranial hemorrhage, transient cerebral ischemia) within the last 24 weeks prior to screening.
• •6. Chronic respiratory failure.
• •7. Severe chronic renal failure.
• •8. Severe chronic liver failure.
• •9. Demyelinating syndrome or symptoms resembling the syndrome.
• •10. Alcoholic disease, post-alcoholic liver damage.
• •11. Diagnosis of malignant neoplasms, including within 5 years preceding the time of eligibility for the program (except for carcinoma in situ of the cervix, and non-melanoma skin cancers).
• •12 Complications requiring other management (e.g., surgery). 13. Current or recent (defined as an incident within 12 weeks prior to randomization) documented episode of fulminant colitis, or intra-abdominal abscess, or acute colonic distension, or bowel perforation.
• •14\. Status after extensive colorectal resection, subtotal or total colectomy with or without colostomy, or J-pouch reservoir.
• •15\. Indication of surgical intervention due to underlying disease or when there is a suspicion of need for such intervention during the course of the study.
• •16\. History of current or previously documented unclassified colitis or ischemic colitis.
• •17\. History of colonic diverticulitis within the last 60 days prior to the randomization visit.
• •18\. Current adenomatous polyps of the colon, small- or large-grade dysplasia in colon specimens, or previously diagnosed foci of large-grade dysplasia that have not been treated.
• •19\. Enteral nutrition or total parenteral nutrition. 20. Pregnancy or breastfeeding. 21. Taking medications on the prohibited drugs list (Section 7.4.6). 22. daily dose of prednisone\> 40 mg (or equivalent other corticosteroid) or budesonide MMX \> 9 mg.
• •23\. Status after bone marrow transplantation. 24. Condition after apheresis 12 months prior to the randomization visit. 25. Period after administration of allowed biologic drugs shorter than the drug's washout period from the body (Section 7.2).
• •26\. Period after intestinal microbiota transplantation less than 8 weeks before signing informed consent to participate in the study.
• •27\. Active or latent form of tuberculosis. 28. HIV infection. 29. Treatment period for active lesions of chronic infections (including pneumocystodosis, CMV, HPV, HSV infection, atypical mycobacteriosis, invasive bacterial or fungal infections).
• •30 History of HSV, HPV, influenza virus, SARS-CoV2 infection within 12 weeks prior to randomization or history of disseminated or complicated HSV infection.
• •31\. History of congenital or acquired immunodeficiency. 32. receipt of live vaccine within 30 days prior to randomization. 33. infection with HBV or HCV. 34. Clinically significant changes on chest X-ray or ECG. 35 Clinically significant changes observed in laboratory test results:
• •1. ALT activity \>3x the upper limit of normal (GGN)
• •2. AST activity \>3x GGN
• •3. Total bilirubin level \>2x GGN (exception is Gilbert syndrome when other causes of isolated hyperbilirubinemia are excluded).
• •4. ALP or GGTP activity \>3x GGN
• •5. Creatinine level \>2x GGN or impaired renal function (eGFR) \<45mL/min calculated by MDRD formula.
• •6. Hemoglobin level \<9g/dL
• •7. Absolute leukocyte count \<3000/mm3
• •8. Absolute lymphocyte count \<750/mm3
• •9. Neutrophil level \<1000/mm3
• •10. Platelet level \<100000/mm3. 36. Positive stool culture for bacteria/fungus (if clinically relevant in the opinion of the investigator).
• •37.Positive stool culture for Clostridioides difficile. 38. Use of treatment not permitted under this protocol.