title: Methotrexate induces clinical and histologic remission in patients with refractory inflammatory bowel disease.
abstract: OBJECTIVE
  To determine whether methotrexate has anti-inflammatory activity in refractory inflammatory bowel disease.
  
  
  METHODS
  Nonrandomized, open-label, preliminary trial of methotrexate along with standard medications for 12 weeks.
  
  
  METHODS
  Referral-based gastroenterology practice.
  
  
  METHODS
  Twenty-one patients with refractory inflammatory bowel disease (14, Crohn disease; 7, chronic ulcerative colitis); 17 taking variable doses of corticosteroids and 14 on sulfasalazine or metronidazole. Of the 21 patients, 10 had previously failed azathioprine or 6-mercaptopurine trials.
  
  
  METHODS
  Sulfasalazine and metronidazole were continued and prednisone dose was tapered according to clinical response. Methotrexate was given as a 25-mg intramuscular injection weekly for 12 weeks, then switched to a tapering oral dose if a clinical and objective improvement was noted.
  
  
  RESULTS
  Sixteen of twenty-one patients (11 of 14 patients with Crohn disease, 5 of 7 patients with chronic ulcerative colitis) had an objective response as measured by disease activity indices (modified Crohn's Disease Activity Index, 13.3 to 5.4 [P = 0.0001], Ulcerative Colitis Activity Index, 13.3 to 6.3 [P = 0.007]). Prednisone dosage decreased from 21.4 mg +/- 5.6 (SEM) to 5.5 mg +/- 2.0; P = 0.006 and 38.6 mg +/- 6.35 to 12.9 mg +/- 3.4; P = 0.01, respectively. Five patients with Crohn colitis had colonoscopic healing and 4 had normal histology at 12 weeks. In contrast, none of the 7 patients with ulcerative colitis had normal flexible sigmoidoscopies, despite histologic improvement in 5. Side effects included mild rises in transaminase levels in 2 patients, transient leukopenia in 1, self-limited diarrhea and nausea in 2 patients, and 1 case each of brittle nails and atypical pneumonitis.
  
  
  CONCLUSIONS
  Although this pilot study is encouraging, further work is needed before methotrexate can be recommended for inflammatory bowel disease.
authors.affiliation: Virginia Mason Clinic, Seattle, Washington.
authors.forename: R A
authors.initials: RA
authors.lastname: Kozarek
authors.forename: D J
authors.initials: DJ
authors.lastname: Patterson
authors.forename: M D
authors.initials: MD
authors.lastname: Gelfand
authors.forename: V A
authors.initials: VA
authors.lastname: Botoman
authors.forename: T J
authors.initials: TJ
authors.lastname: Ball
authors.forename: K R
authors.initials: KR
authors.lastname: Wilske
mesh_terms: D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000473:pathology; D003113:Colonoscopy; D003424:Crohn Disease / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use*; D010289:Parenteral Nutrition, Total; D011241:Prednisone / Q000008:administration & dosage; D012812:Sigmoidoscopy
chemical_list: D011241:Prednisone; D008727:Methotrexate