Methotrexate Response In Treatment of UC

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DESCRIPTION (provided by applicant): Patients with active ulcerative colitis (UC) despite of a therapy with 5-aminosalicylates and steroids represent a clinical challenge, since the alternatives in medical therapy are considerably fewer compared to those for patients with active Crohn's disease (CD). Methotrexate (MTX) is an established therapeutic agent in patients with CD. Small clinical trials employing MTX in UC patients failed so far to demonstrate a significant clinical benefit. In these comparative studies, however, lower MTX doses were applied in the UC trials compared to CD trials (12.5 vs 25 mg, respectively) and different routes of administration (oral in UC, intramuscularly in CD) were used. In contrast, retrospectively collected data employing the same route of application and dose of MTX in UC patients as in patients with CD suggest a significant therapeutic efficacy. We hypothesize that 25 mg subcutaneously applied MTX has significant clinical efficacy in UC patients, who suffer from steroid-dependent disease course or who have failed or did not tolerate a therapy with anti-TNF agents, azathioprine or 6-MP. Using the framework of the Crohn's and Colitis Clinical Research Alliance we plan to perform a multicenter, placebo-controlled clinical study investigating the short and long-term efficacy of MTX in patients with active UC. The study is planned for 160 patients in 25-30 centers. The specific scope of this U34 application is to finalize the study protocol and all related study manuals and forms (manual of operations, data and safety monitoring plan, investigator brochure, consent forms). We will also develop and establish a specific web-based data monitoring and management plan for this study. Furthermore, the IRB approval process will be initiated and subcontracts will be developed with all involved sites and contracts and standard operating procedures will be established with a central pharmacy and a central laboratory.