Methotrexate for inflammatory bowel disease: pharmacology and preliminary results.
OBJECTIVE
To review the limited published experience with methotrexate treatment for inflammatory bowel disease, to examine the proposed anti-inflammatory and immune-modifying mechanism of action and pharmacologic properties of methotrexate, and to detail its limiting toxicities.


METHODS
A comprehensive synopsis of methotrexate is presented to aid physicians who treat patients with inflammatory bowel disease.


RESULTS
Methotrexate and its polyglutamate metabolites are folic acid analogues with inhibitory activity against many enzymes in the metabolic pathway of folic acid. Long-term low-dose methotrexate therapy (25 mg or less once a week) inhibits production of thymidylate, purines, and methionine and leads to accumulation of adenosine, a potent anti-inflammatory substance. These actions inhibit cellular proliferation, decrease formation of antibodies, and decrease production of mediators of inflammation such as interleukins and eicosanoids. Three uncontrolled trials and two controlled trials have demonstrated efficacy of low-dose methotrexate therapy for induction of remission in Crohn's disease and have also suggested possible benefit for ulcerative colitis and for remission maintenance indications in both diseases. Although methotrexate is generally well tolerated for long-term use at a low dose, several serious toxicities potentially limit its use.


CONCLUSIONS
Methotrexate is a promising new agent for the treatment of inflammatory bowel disease.
Inflammatory Bowel Disease Clinic, Mayo Clinic Rochester, MN 55905, USA.
L J
LJ
Egan
W J
WJ
Sandborn
D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000494:pharmacology*; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D008727:Methotrexate / Q000009:adverse effects / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D007166:Immunosuppressive Agents; D008727:Methotrexate