Comparison of Methotrexate vs Placebo in Corticosteroid-dependent Ulcerative Colitis
Condition: Ulcerative Colitis
MeSH terms: Colitis; Colitis, Ulcerative; Ulcer
Study type: Interventional
Phase: Phase 2

Summary: 
      -  PHASE: II

        -  TYPE OF STUDY : With direct benefit

        -  DESCRIPTIVE: Multicenter, randomized, double-blind study

        -  INCLUSION CRITERIA: Steroid-dependent ulcerative colitis

        -  OBJECTIVES: To show superiority of methotrexate vs placebo in inducing steroid-free
           remission in steroid-dependent ulcerative colitis

        -  STUDY TREATMENTS: Methotrexate 1 intramuscular injection (25 mg) per week Placebo 1
           intramuscular injection per week

        -  NUMBERS OF PATIENTS: 55 patients in each group, i.e. a total of 110 patients

        -  INCLUSION PERIOD: 24 months

        -  STUDY DURATION: 36 months

        -  EVALUATION CRITERIA: Remission without steroids, immunosuppressives and without
           colectomy at 16 weeks of treatment.
    

Detailed description: 
      Ulcerative colitis (UC) is a chronic inflammatory bowel disease that slightly reduces life
      expectancy, strongly reduces its quality and can lead to serious complications such as acute
      colitis, dysplasia and colon cancer. About 40'000 patients are affected in France Among them,
      15% suffer from a chronic active form that often leads to an extended steroid therapy, and
      its known side effects. Azathioprine has already proven its efficacy in this indication but
      brings a lasting remission without steroid in only 41% of the patients (1-4). What are the
      medications available for the patients who failed in maintaining a remission with
      azathioprine ? Cyclosporin is designed for severe or steroid-resistant forms. (5). The
      results of two recent studies have showed that infliximab is more efficacious than placebo in
      active UC (6, 7). Infliximab is expensive, its efficacy in steroid-dependent UC has not been
      specifically tested yet, and its tolerance on the long term remains uncertain. Methotrexate
      proved its efficacy in Crohn's disease with an intramuscular dose of 25mg/week (8). In UC a
      controlled trial has been negative with an oral dose of 12.5mg/week (9). Another study
      compared mercaptopurine, methotrexate (15mg/week) and 5-aminosalicylate in 72
      steroid-dependent patients with CD or UC (10). The remission rates obtained were 58% after 30
      weeks with methotrexate (not significantly different from 5-ASA) and 14% after 106 weeks (not
      significantly different from 5-ASA). Few data are available on the efficacy of methotrexate
      in UC, at a dose which is active in Crohn's disease (25mg intramuscular/week). Several
      uncontrolled series have been published, including 91 patients whose remission failed under
      azathioprine.

      Methotrexate is cheap and its patent has fallen in the public domain. Only institutional
      research will be able to finance a study in this new indication.

      This is a prospective, controlled, randomized, double-blind study of methotrexate with an
      intramuscular dose of 25mg/week vs placebo in patients with steroid-dependent UC.

      This multicenter study will take place under the aegis of the Therapeutic Study Group for
      Inflammatory Digestive Diseases (G.E.T.A.I.D.) and with the help of the gastroenterologists
      network of the CIC. The issue of this study is important. If the hypothesis is borne out, a
      cheap, efficacious medication will be available for chronic active UC.
    

Intervention name(s): methotrexate; placebo
Intervention type(s): Drug; Drug
Intervention description(s): 25 mg per week IM or SC during 24 weeks; one intramuscular injection per week
Intervention MeSH terms: Methotrexate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment