Increased dosing requirements for 6-mercaptopurine and azathioprine in inflammatory bowel disease patients six years and younger

✍ Scribed by Andrew B. Grossman; Angela J. Noble; Petar Mamula; Robert N. Baldassano

• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 83 KB
• Volume: 14
• Category: Article
• ISSN: 1078-0998
• DOI: 10.1002/ibd.20387

✦ Synopsis

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.