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.
Kozarek RA, Patterson DJ, Gelfand MD, et al. Methotrexate Induces Clinical and Histologic Remission in Patients with Refractory Inflammatory Bowel Disease. Ann Intern Med. 1989;110:353–356. doi: https://doi.org/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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