Methotrexate ulcerative colitis

Therapeutic pyramid approach to inflammatory bowel diseases. Treatment choice is predicated on both the severity of the illness and the responsiveness to therapy. Agents at the bottom of the pyramid are less efficacious but carry a lower risk of serious adverse effects. Drugs may be used alone or in various combinations. Patients with mild disease may be treated with 5-aminosalicylates (with ulcerative colitis or Crohn s colitis), topical corticosteroids (ulcerative colitis), antibiotics (Crohn s colitis or Crohn s perianal disease), or budesonide (Crohn s ileitis). Patients with moderate disease or patients who fail initial therapy for mild disease may be treated with oral corticosteroids to promote disease remission immunomodulators (azathioprine, mercaptopurine, methotrexate) to promote or maintain disease remission or anti-TNF antibodies. Patients with moderate disease who fail other therapies or patients with severe disease may require intravenous corticosteroids, anti-TNF antibodies, or surgery. Natalizumab is reserved for patients with severe Crohn s disease who have failed immunomodulators and TNF antagonists. Cyclosporine is used primarily for patients with severe ulcerative colitis who have failed a course of intravenous corticosteroids. TNF, tumor necrosis factor. 

Methotrexate is used to induce and maintain remission in patients with Crohn s disease. Its efficacy in ulcerative colitis is uncertain. To induce remission, patients are treated with 15-25 mg of methotrexate once weekly by subcutaneous injection. If a satisfactory response is achieved within 8-12 weeks, the dose is reduced to 15 mg/wk. 

Purine analogs and antimetabolites, eg, 6-mercaptopurine, methotrexate Mechanism uncertain may promote apoptosis of immune cells Generalized suppression of immune processes Moderately severe to severe Crohn s disease and ulcerative colitis GI upset, mucositis myelosuppression purine analogs may cause hepatotoxicity, but rare with methotrexate at the low doses used... 

Methotrexate can be helpful in controlling relapses of Crohn s disease unresponsive to corticosteroid or azathioprine. It has also been used with benefit in ulcerative colitis. Its short- and long-term use are limited by a wide profile of adverse effects including bone marrow suppression and pulmonary and hepatic fibrosis (see p. 291). 

Methotrexate generally is reserved for patients whose IBD is either steroid-resistant or steroid-dependent. In Crohn s disease, it both induces and maintains remission, generally with a more rapid response than that seen with mercaptopurine or azathioprine. Only limited studies have examined the role of methotrexate in ulcerative colitis. 

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