Keywords:Ulcerative Colitis , Methotrexate
Sub Specialty:Inflammatory Bowel Disease/Crohn's/Ulcerative Colitis
Study Purpose and Objectives:
The therapeutic armamentarium for patients with active UC despite 5-aminosalycilates and steroids is considerably smaller than for patients with CD (therapeutic choices for steroid dependent UC patients: azathioprine, infliximab - therapeutic choices for steroid dependent CD patients: azathioprine, methotrexate, infliximab, adalimumab, certolizumab, natalizumab), there is clearly a need for further exploration of new therapies with a calculable risk profile for this patient group. Currently several new therapeutic approaches investigating the role of different “biologics” e.g. in the inhibition of the co-stimulation of T cells (Abatacept) or selective blockade of interactions between leukocytes and vascular endothelium (MLN 0002 antibody) are being tested in clinical trials. However, given the high costs of biologics, there is an additional need for affordable, easy to administer therapies such as MTX. Additionally, use of small molecules is favorable over biologics as the risk of anti-medication antibody formation is less likely. Since MTX is an old and non-patented drug, it is highly unlikely that this drug will be ever prospectively investigated in patients with UC.
Given the lack of large placebo controlled prospective studies investigating doses of MTX, which were clinically effective in inducing steroid free remission in CD patients, so far neither a negative nor a positive conclusion can be drawn from the published data about the clinical efficacy of MTX in UC. Due to an obvious dose –response relationship observed for MTX in the treatment of rheumatoid arthritis, there seems to be an unmet need for investigating prospectively MTX in higher doses in patients with UC using a subcutaneous or intramuscular application.
MTX applied subcutaneously (sq) once weekly is effective to induce and maintain steroid free remission or response in patients with active ulcerative colitis , who have either failed 5-aminosalicylic acid (5-ASA) therapy, or are steroid dependent or have failed or are intolerant to azathioprine or 6-mercaptopurine therapy or failed to respond or lost response to anti-TNF therapy, compared to placebo.
Principle Investigator: John Valentine
Principle Department: Gastroenterology
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 as defined by the Clinical Trials Task Force of the International Organization of Inflammatory Bowel Disease (IOIBD) 2
Primary failure or loss of response to infliximab in the past
Intolerance/failure of azathioprine/6-MP therapy in the past
Failure of 5-ASA therapy