Ensayos clínicos

Inclusion Criteria

• Signed informed consent
• Male or female
• Age between 18 and 70 years
• Ulcerative colitis diagnosed by routine clinical, radiographic, endoscopic, and pathological criteria
• Active UC with a Mayo score of 6 to 12 points and moderate-to severe active disease on sigmoidoscopy (Mayo endoscopic subscore of at least 2)
• At least one of the following
  • Steroid dependent UC (defined as)
    • Clinical response to prednisone 40 to 60 mg/day and relapse within 30 days after treatment completed 
    • Requirement for a daily dosage of at least 10 mg of prednisone and impossibility of weaning  off without relapses (two attempts within the preceding six months of the start of the study)
  • Primary failure or loss of response to an anti-TNF (infliximab, adalimumab, golimumab) in the past
  • Primary failure or loss of response to vedolizumab in the past
  • Intolerance/failure of azathioprine/6-MP therapy in the past
  • Failure of 5-ASA therapy

Exclusion Criteria

• Failure to respond to 40 mg of prednisone or higher/day in the last 2 weeks before inclusion
• Concomitant use of azathioprine (AZA) or 6-mercaptopurine (6-MP)
  • Must be discontinued at least 2 weeks before inclusion into the study (week 0 visit)
• Anti-TNF therapy in the 2 weeks before the week 0 visit
• Failure of cyclosporine therapy in the previous 6 months prior to screening visit
• Serum albumin < 2.5 g/dl at baseline
• Low serum folate defined as decrease of >10% below normal range
• WBC < 3.0 x109th/L at baseline
• Platelet count < 100 x109th/L
• Underlying infection with C. difficile at screening visit
• Pre-existing hepatic disease
• Known non-alcoholic fatty liver disease (NAFLD)
• Known Hepatitis B or Hepatitis C
• Pre-existing renal dysfunction (creatinine >1.5 mg/dl)
• Pre-existing chronic lung disease other than well controlled asthma
• Interstitial lung disease of unknown cause
• BMI >35
• Known previous or concurrent malignancy (other than that considered surgically cured, with no evidence for recurrence for 5 years
  • Basal cell does not exclude
• Existing pregnancy, lactation, or planned pregnancy (male or female) within the next 12 months
  • Methotrexate should not be used for at least 3 months before planned pregnancy for men or women and should not be used during pregnancy or breast feeding
• High alcohol consumption (more than seven drinks per week)
• Non-steroidal inflammatory medications (NSAIDs) as long-term treatment, defined as use for at least 4 days a week each month
• Continuous treatment with one of the following drugs
  • Probenecid
  • Trimethoprim/sulfamethoxazole
  • Sulfasalazine
  • Acitretin
  • Streptozocin
• Non-use of appropriate contraceptives in females of childbearing potential (e.g. condoms, intrauterine device {IUD}, hormonal contraception, or other means considered adequate by the responsible investigator) or in males with a child-fathering potential (condoms, or other means considered adequate by the responsible investigator during treatment
• Participation in another clinical trial within the last 30 days, simultaneous participation in another clinical trial, or previous participation in this trial
• Well-founded doubt about the patient's cooperation