title: A randomized dose-response and pharmacokinetic study of methotrexate for refractory inflammatory Crohn's disease and ulcerative colitis.
abstract: OBJECTIVE
  The optimum initial dose of methotrexate for steroid-requiring inflammatory bowel disease is not known.
  
  
  OBJECTIVE
  To compare directly the efficacy and toxicity of methotrexate 15 and 25 mg/week, and to explore the value of methotrexate blood levels as predictors of outcome.
  
  
  METHODS
  A 16-week randomized single-blind comparison of subcutaneous methotrexate 15 or 25 mg/week was performed in 32 patients with steroid-requiring Crohn's disease or ulcerative colitis. Patients who did not respond to methotrexate 15 mg/week were further studied for an additional 16 weeks on methotrexate 25 mg/week. Blood was drawn every 2 weeks for methotrexate levels.
  
  
  RESULTS
  After 16 weeks, 17% of patients in each group achieved remission; 39% of patients randomized to 15 mg/week and 33% of patients randomized to 25 mg/week improved (P=N.S. ). Clinical status improved in four out of 11 patients after methotrexate dose escalation from 15 to 25 mg/week. Toxicity was not different between the treatment groups. Methotrexate blood levels did not predict efficacy or toxicity.
  
  
  CONCLUSIONS
  For induction of remission in steroid-requiring inflammatory bowel disease, subcutaneous methotrexate at initial doses of 15 and 25 mg/week are equally efficacious. At these doses, response is not associated with blood methotrexate concentrations.
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: L J
authors.initials: LJ
authors.lastname: Egan
authors.forename: W J
authors.initials: WJ
authors.lastname: Sandborn
authors.forename: W J
authors.initials: WJ
authors.lastname: Tremaine
authors.forename: J A
authors.initials: JA
authors.lastname: Leighton
authors.forename: D C
authors.initials: DC
authors.lastname: Mays
authors.forename: M G
authors.initials: MG
authors.lastname: Pike
authors.forename: A R
authors.initials: AR
authors.lastname: Zinsmeister
authors.forename: J J
authors.initials: JJ
authors.lastname: Lipsky
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D003424:Crohn Disease / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D008297:Male; D008727:Methotrexate / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use*; D008875:Middle Aged; D016037:Single-Blind Method; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D008727:Methotrexate