Increased dosing requirements for 6-mercaptopurine and azathioprine in inflammatory bowel disease patients six years and younger
Article first published online: 11 FEB 2008
Copyright © 2008 Crohn's & Colitis Foundation of America, Inc.
Inflammatory Bowel Diseases
Volume 14, Issue 6, pages 750–755, June 2008
How to Cite
Grossman, A. B., Noble, A. J., Mamula, P. and Baldassano, R. N. (2008), Increased dosing requirements for 6-mercaptopurine and azathioprine in inflammatory bowel disease patients six years and younger. Inflamm Bowel Dis, 14: 750–755. doi: 10.1002/ibd.20387
- Issue published online: 5 MAY 2008
- Article first published online: 11 FEB 2008
- Manuscript Accepted: 12 DEC 2007
- Manuscript Received: 10 OCT 2007
- dose escalation;
Background: 6-Mercaptopurine (6-MP) and its prodrug azathioprine (AZA) are effective for the induction and maintenance of remission and reduction of corticosteroid exposure for pediatric inflammatory bowel disease (IBD). The standard dose of 6-MP is 1.0–1.5 mg/kg/day and for AZA is 2.0–2.5 mg/kg/day. The aim of this study was to determine whether IBD patients 6 years of age and younger require higher than standard doses of 6-MP/AZA to achieve clinical remission.
Methods: Clinical data was collected retrospectively for all IBD patients 6 years of age or younger treated with 6-MP/AZA at The Children's Hospital of Philadelphia.
Results: Thirty patients met the inclusion criteria. IBD was diagnosed at a median age of 3.3 years (25–75th %ile 2.3–4.6 years) and 6-MP/AZA was initiated at a median age of 3.9 years (range 0.8–6.8 years). After dose escalation, the median AZA-equivalent dose was 3.1 mg/kg/day (25–75th %ile 2.5–3.5, max. dose 5.1 mg/kg/day). At the final recorded dose, 8/13 (62%) patients receiving AZA >3.0 mg/kg/day achieved clinical remission, compared to 2/12 (17%) receiving 2–3 mg/kg/day (P = 0.02). The risk of having active disease was on average 85% lower if the AZA-equivalent dose was >3.0 mg/kg/day (95% confidence interval [CI] 72%–93%). Adverse events were experienced by 4/30 patients (hepatitis, n = 2; leukopenia, n = 2). No patients had to discontinue 6-MP/AZA, and all laboratory abnormalities improved spontaneously or with dose reduction.
Conclusions: The standard dose of 6-MP/AZA may not be adequate for IBD patients 6 years of age and younger. Closely monitored dose escalation beyond the standard dosing range is effective and well-tolerated.
(Inflamm Bowel Dis 2008)