A multicenter trial of 6-mercaptopurine and prednisone in children with newly diagnosed Crohn's disease.
OBJECTIVE
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 x kg(-1) x 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.
Markowitz
J
J
Department of Pediatrics, North Shore-Long Island Jewish Health System, New York University School of Medicine, Manhasset, New York, USA. jamesm@nshs.edu
Grancher
K
K
Kohn
N
N
Lesser
M
M
Daum
F
F
D000293:Adolescent; D002648:Child; D003424:Crohn Disease / Q000188:drug therapy*; D018572:Disease-Free Survival; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005938:Glucocorticoids / Q000009:adverse effects / Q000627:therapeutic use; D006128:Growth; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D015122:Mercaptopurine / Q000009:adverse effects / Q000627:therapeutic use*; D011241:Prednisone / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies
D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D015122:Mercaptopurine; D011241:Prednisone