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Safety and Effectiveness of Long-term AllopurinolThiopurine Maintenance Treatment in Inflammatory Bowel Disease

Hoentjen, Frank MD, PhD*,†; Seinen, Margien L. MD; Hanauer, Stephen B. MD, PhD*; de Boer, Nanne K.H. MD, PhD; Rubin, David T. MD*; Bouma, Gerd MD, PhD; Harrell, Laura E. MD*; van Bodegraven, Adriaan A. MD, PhD

Inflammatory Bowel Diseases:
doi: 10.1002/ibd.23021
Original Clinical Articles
Abstract

Background: Thiopurines are the mainstay of conventional maintenance therapy in inflammatory bowel disease (IBD). Unfortunately, up to 50% of patients discontinue immunosuppressive therapy within 2 years due to intolerance or lack of efficacy. Allopurinol with low-dose thiopurine can optimize thiopurine metabolism for IBD patients with preferential shunting toward 6-methyl mercaptopurine (6-MMP) formation. The aim of this study was to assess long-term maintenance effectiveness and tolerability of allopurinol-thiopurine therapy in a larger multicenter cohort of IBD patients.

Methods: Enrolled patients who failed monotherapy with thiopurines due to a skewed metabolism were subsequently treated with a combination therapy of allopurinol and low-dose thiopurine. Adverse events were monitored and therapeutic adherence was assessed. Seventy-seven IBD patients were enrolled with a mean follow-up of 19 months.

Results: The median 6-thioguanine nucleotide concentration increased from 145 during monotherapy to 271 pmol/8 × 108 red blood cell (RBC) after at least 8 weeks of combination therapy while reducing the thiopurine dosage (P < 0.001). In contrast, median 6-MMP concentrations decreased from 10,110 to 265 pmol/8 × 108 RBC (P < 0.001). Leukopenia occurred in 12 patients (16%), requiring dose adaptation. Liver test abnormalities normalized in 81% of patients after the addition of allopurinol. Sixteen (21%) patients had to discontinue combination therapy. The percentage of patients still using combination therapy at 6, 12, 24, and 60 months was 87%, 85%, 76%, and 65%, respectively.

Conclusions: Long-term combination therapy with allopurinol and low-dose thiopurines is an effective and well-tolerated treatment in IBD patients with a skewed thiopurine metabolism.

In Brief

Article first published online 17 May 2012

Author Information

*Inflammatory Bowel Disease Center, University of Chicago, Chicago, Illinois

Inflammatory Bowel Disease Center, Radboud University Medical Center, Nijmegen, The Netherlands

Department of Gastroenterology, VU University Medical Center, Amsterdam, The Netherlands.

Reprints: Frank Hoentjen, MD, PhD, Department of Gastroenterology, Radboud University Medical Center, PO Box 9101, 6500 HB Nijmegen, The Netherlands (e-mail: frankhoentjen@gmail.com).

The first two authors contributed equally to this study.

Received March 19, 2012

Accepted April 25, 2012

© Crohn's & Colitis Foundation of America, Inc.

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