Richard A. Kozarek, MD; David J. Patterson, MD; Martin D. Gelfand, MD; V. Alin Botoman, MD; Terrence J. Ball, MD; Kenneth R. Wilske, MD
Study Objective: To determine whether methotrexate has anti-inflammatory activity in refractory inflammatory bowel disease.
Design: Nonrandomized, open-label, preliminary trial of methotrexate along with standard medications for 12 weeks.
Setting: Referral-based gastroenterology practice.
Patients: 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.
Interventions: 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.
Measurements and Main 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 12.9mg ±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.
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Kozarek RA, Patterson DJ, Gelfand MD, Botoman VA, Ball TJ, Wilske KR. Methotrexate Induces Clinical and Histologic Remission in Patients with Refractory Inflammatory Bowel Disease. Ann Intern Med. 1989;110:353-356. doi: 10.7326/0003-4819-110-5-353
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Published: Ann Intern Med. 1989;110(5):353-356.
Gastroenterology/Hepatology, Inflammatory Bowel Disease.
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Print ISSN: 0003-4819 | Online ISSN: 1539-3704
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