Intervention: Methotrexate
Trial phase: Phase 2
ATC code: L01BA01 | L04AX03
SMILES: CN(Cc1cnc2nc(N)nc(N)c2n1)c1ccc(C(=O)N[C@@H](CCC(=O)O)C(=O)O)cc1
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 44
Group description: 25 mg MTX sq once weekly + 1 mg folic acid daily + 2.4 g mesalamine
Eligibility criteria:
Inclusion Criteria:

Signed informed consent.
Man or woman between 18 and 70 years of age.
UC 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)

and at least ONE of the following criteria:

Steroid dependent UC *
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

Steroid dependence is defined as a clinical response to treatment with prednisone 40 to 60 mg/day and relapse within 30 days after prednisone treatment was completed or as a requirement for a daily dosage of not less than 10 mg of prednisone and impossibility of weaning the patient off steroid without clinical relapses (two attempts to discontinue the medication within the preceding six months of the start of the study).

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
Patients with serum albumin < 2.5 g/dl at baseline
Low serum folate defined as decrease of >10% below normal range
Patients with WBC< 3.0 x109th/L at baseline
Patients with platelet count < 100 x109th/L
Patients with an underlying infection with C. difficile at Screening visit
Patients with pre-existing hepatic disease
Patients with known non-alcoholic fatty liver disease (NAFLD)
Patients with known Hepatitis B or Hepatitis C
Patients with pre-existing renal dysfunction (creatinine >1.5 mg/dl).
Patients with a pre-existing chronic lung disease other than well controlled asthma
Patients with interstitial lung disease of unknown cause
Patients with a 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* (men and women) within the next 12 months. (*Methotrexate should not be used for at least 3 months before planned pregnancy for men and 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.