Initial clinical experience with allopurinol-thiopurine combination therapy in pediatric inflammatory bowel disease
Article first published online: 2 JUN 2008
Copyright © 2008 Crohn's & Colitis Foundation of America, Inc.
Inflammatory Bowel Diseases
Volume 14, Issue 12, pages 1678–1682, December 2008
How to Cite
Rahhal, R. M. and Bishop, W. P. (2008), Initial clinical experience with allopurinol-thiopurine combination therapy in pediatric inflammatory bowel disease. Inflamm Bowel Dis, 14: 1678–1682. doi: 10.1002/ibd.20522
- Issue published online: 13 NOV 2008
- Article first published online: 2 JUN 2008
- Manuscript Accepted: 2 MAY 2008
- Manuscript Received: 8 APR 2008
- thiopurine metabolism;
- inflammatory bowel disease
Background: Thiopurines are a mainstay of immunomodulator therapy in inflammatory bowel disease (IBD). Despite their efficacy, some patients may have a poor response due to inability to achieve adequate levels of the active metabolite, 6-thioguanine (6-TGN). Others experience hepatotoxicity, which correlates with excessive 6-methylmercaptopurine (6-MMP) levels. Two adult studies have demonstrated successful manipulation of thiopurine metabolism with allopurinol, a xanthine oxidase inhibitor, to achieve more optimal thiopurine levels. The aim was to retrospectively characterize the utility of allopurinol to optimize thiopurine metabolite levels in pediatric IBD patients.
Methods: Thirteen patients received allopurinol daily (100 mg in patients ≥30 kg and 50 mg <30 kg), and their thiopurine dose was simultaneously reduced to 25%–50% of the previous maintenance dose. Metabolite levels and other screening labs were checked 2–4 weeks later.
Results: The mean azathioprine dose was decreased from 148.1 to 59.6 mg daily (60% of the mean original dose). The mean 6-TGN level increased from 173 to 303 pmol/8 × 108 red blood cell count (RBC) (P = 0.03), and the mean 6-MMP level decreased from 7888 to 2315 pmol/8 × 108 RBC (P < 0.001). Elevated transaminase levels improved or resolved in all patients. Two patients experienced reversible neutropenia. At the conclusion of the study 9 patients (69%) remained on combination therapy with a mean duration of follow-up of 162.8 ± 119.2 days.
Conclusions: Combination therapy successfully shunted thiopurine metabolites to a more favorable pattern. Reversible neutropenia was the most common side effect (2 patients). Long-term prospective studies are needed in this patient population.
(Inflamm Bowel Dis 2008)