Vedolizumab Monotherapy Vs Combination Therapy With Tacrolimus in UC

Inclusion Criteria: 1. Patients aged 18 to 65 years with a confirmed diagnosis of UC. 2. Diagnosis of UC established at least 6 months before enrollment or evidence of chronicity in colonic biopsies. 3. Patients with UC disease extent beyond 15 cm (must involve at least the sigmoid colon) 4. In female patients: * Post-menopausal for ≥1 year before screening, or * Surgically sterile, or * Agree to be on a contraceptive method from the screening visit through 4 weeks after discontinuing tacrolimus (or placebo), or * Completely abstain from heterosexual intercourse. 5. In male patients: o Agreement not to father a child through 4 weeks after discontinuing tacrolimus (through contraception or abstinence). 6. Moderate to severe UC * Mayo Clinic partial UC score of 6 to 12, with a baseline sigmoidoscopy sub-score of at least 2, and disease that extended 15 cm or more from the anal verge. * Steroid dependent patients (Appendix 1) * Steroid naïve or steroid responsive 7. Patients are planned to start vedolizumab as part of their clinical care. 8. 5-aminosalicilates (oral or topical) are permitted as long as the dose is stable for at least 2 weeks before screening. 9. Patients with or without previous exposure to anti-TNF agents can be included. Patients with previous exposure to anti-TNF must be off infliximab for 8 weeks and off adalimumab for 4 weeks. 10. Anti-diarrheals (eg, loperamide, diphenoxylate with atropine) for control of chronic diarrhea are not permitted.The patient must be off anti-diarrheal at the time of screening. 11. Immunosupressants (thiopurines or methotrexate) must be stopped 4 weeks prior to starting the study medications. 12. Patients with previous Clostridium Difficile infection can be included as long as they received a full course of therapy and have a negative Clostridium Difficile PCR test and are infection free for 60 days prior to screening. Exclusion Criteria: 1. Positive stool test for parasites or stool culture for pathologic bacteria within 30 days prior to enrollment. 2. Evidence or history of Clostridium Difficile infection within 60 days prior to enrollment. 3. Active Cytomegalovirus (CMV) infection evidenced by a positive CMV PCR in serum and/or positive immunohistochemistry stain in colonic tissue. 4. Uncontrolled hypertension. 5. Chronic kidney disease (defined as a glomerular filtration rate \< 60 mL/min, calculated using the Modification of Diet in Renal Disease (MDRD) formula) 6. Chronic liver disease. 7. A refractory electrolyte disorder (e.g. hypomagnesemia). 8. Persistent hypomagnesemia that does not respond to oral magnesium supplementation defined as a value \<1.3 mEq/L in two separate readings, despite the administration of oral magnesium \[10 meq of slow-release magnesium chloride three times per day for 48 hours\]. 9. Persistent hypophosphatemia defined as levels \<2.2 mg/dL in two separate readings, 48 hours apart despite phosphate supplementation (sodium phosphate/potassium phosphate 500 mg up to three times daily for 48 hours). 10. Creatinine values of 1.5 mg/dL in 2 separate readings. 11. Established diagnosis of diabetes mellitus. 12. Clinical or radiological evidence of megacolon. 13. Intestinal perforation, or abdominal abscess within 3 months prior to enrollment. 14. Active clinically significant bacterial infection (within 30 days of enrollment). 15. Personal history of total or sub-total colectomy. 16. Current Pregnancy or lactation. 17. Unstable or uncontrolled medical disorder. 18. Personal history of malignant neoplasm. 19. Inability to give informed consent. 20. History of alcohol or illicit drug abuse in the previous 6 months to enrollment. 21. Patient that have received any experimental drug within 6 months prior to enrollment. 22. Patients with previous exposure to vedolizumab, cyclosporine or tacrolimus. 23. Personal history of congenital or acquired immunodeficiency (eg, common variable immunodeficiency, human immunodeficiency virus \[HIV\] infection, organ transplantation) excluding pharmacologic immunosuppressant. 24. Any of the following laboratory abnormalities during the screening period: 1. Hemoglobin level \<9 g/dL 2. WBC count \<3 × 109/L 3. Lymphocyte count \<0.5 × 109/L 4. Platelet count \<100 × 109/L or \>1200 × 109/L 5. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>2 × the upper limit of normal (ULN) 25. To avoid interactions, patients on medications that induce or inhibit the Cytochrome p450 family 3, subfamily A (CYP3A) will be excluded. CYP3A inducers and inhibitors are shown in Appendix 3