Gastroenterology

Gastroenterology

Volume 119, Issue 4, October 2000, Pages 895-902
Gastroenterology

Alimentary Tract
A multicenter trial of 6-mercaptopurine and prednisone in children with newly diagnosed Crohn's disease,☆☆

https://doi.org/10.1053/gast.2000.18144Get rights and content

Abstract

Background & Aims: Clinical experience suggests that 6-mercaptopurine (6-MP) is effective therapy for children with active steroid-dependent Crohn's disease (CD). We report the results of a prospective, placebo-controlled, multicenter trial evaluating the combination of 6-MP and prednisone as therapy for children with newly diagnosed moderate-to-severe CD. Methods: Fifty-five children (age, 13 ± 2 years) were randomized to treatment with 6-MP (1.5 mg · kg−1 · day−1) or placebo within 8 weeks of initial diagnosis. Both groups also received prednisone (40 mg/day). Prednisone dosage adjustments were based on a defined schedule determined by the change in a subject's disease activity score, and steroid administration was discontinued as remission was achieved. Study treatment with 6-MP or placebo continued for 18 months. Results: Groups were comparable for age, sex, and site and activity of disease. In the 6-MP group, the duration of steroid use was shorter (P < 0.001) and the cumulative steroid dose lower at 6, 12, and 18 months (P < 0.01). Although remission was induced in 89% of both groups, only 9% of the remitters in the 6-MP group relapsed compared with 47% of controls (P = 0.007). Growth was comparable in both groups. No clinically significant adverse events occurred, although mild leukopenia and increases in aminotransferase activity were noted in the 6-MP group. Conclusions: Addition of 6-MP to a regimen of corticosteroids significantly lessens the need for prednisone and improves maintenance of remission. 6-MP should be part of the initial treatment regimen for children with newly diagnosed moderate-to-severe CD.

GASTROENTEROLOGY 2000;119:895-902

Section snippets

Study design

This prospective, double-blind, placebo-controlled 18-month clinical trial involved 18 U.S. pediatric centers (Appendix 1). The protocol was approved by the institutional review board of each collaborating investigator. Written informed consent was obtained from parents. Children older than 12 years signed a statement of assent. All subjects were <18 years of age, had CD diagnosed within 8 weeks of randomization, and had disease activity scores in the moderate-to-severe range. Children with

Study population

Sixty-five children were randomized at 18 collaborating sites (range, 1–12 subjects per site), but 10 were excluded from analysis, including 7 whose parents changed their minds about participating in the study before initiating treatment and 2 (1 from each treatment group) whose poor compliance with follow-up appointments resulted in significantly incomplete and noninterpretable data records. One additional randomized subject took <85% of the prescribed dose of medication within the first 2

Discussion

This is the first prospective, placebo-controlled trial to evaluate the effects of 6-MP in a pediatric population with CD. It is also the first to assess the efficacy of 6-MP as part of an initial treatment regimen for patients of any age with newly diagnosed CD. The results clearly support the use of 6-MP in the initial treatment of children and adolescents with moderate-to-severe CD. Compared with subjects treated with prednisone alone, those receiving 6-MP in addition to prednisone

References (35)

Cited by (0)

Supported by grants from the Crohn's and Colitis Foundation of America and from Reach Out for Youth with Ileitis and Colitis.

☆☆

Address requests for reprints to: James Markowitz, M.D., Division of Pediatric Gastroenterology and Nutrition, North Shore–Long Island Jewish Health System, 300 Community Drive, Manhasset, New York 11030. e-mail: [email protected]; fax: (516) 562-2527.

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