Brief Reports
Copyright ©2005 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 21, 2005; 11(35): 5540-5544
Published online Sep 21, 2005. doi: 10.3748/wjg.v11.i35.5540
On tolerability and safety of a maintenance treatment with 6-thioguanine in azathioprine or 6-mercaptopurine intolerant IBD patients
Nanne KH de Boer, Luc JJ Derijks, Lennard PL Gilissen, Daniel W Hommes, Leopold GJB Engels, Sybrand Y de Boer, Gijsbertus den Hartog, Piet M Hooymans, Anja BU Mäkelburg, Barend D Westerveld, Anton HJ Naber, Chris JJ Mulder, Dirk J de Jong
Nanne KH de Boer, Chris JJ Mulder, Department of Gastroenterology and Hepatology, VU University Medical Centre, Amsterdam, The Netherlands
Luc JJ Derijks, Department of Clinical Pharmacy, Maxima Medical Centre, Veldhoven, The Netherlands
Lennard PL Gilissen, Department of Gastroenterology and Hepatology, Academic Hospital, Maastricht, The Netherlands
Daniel W Hommes, Department of Gastroenterology and Hepatology, Academic Medical Centre, Amsterdam, The Netherlands
Leopold GJB Engels, Department of Gastroenterology and Hepatology, Maasland Hospital, Sittard, The Netherlands
Sybrand Y de Boer, Gijsbertus den Hartog, Department of Gastroenterology and Hepatology, Rijnstate Hospital, Arnhem, The Netherlands
Piet M Hooymans, Department of Clinical Pharmacy, Maasland Hospital, Sittard, The Netherlands
Anja BU Mäkelburg, Barend D Westerveld, Department of Gastroenterology and Hepatology, Isala Clinics Location Sophia, Zwolle, The Netherlands
Anton HJ Naber, Dirk J de Jong, Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Centre, The Netherlands
Author contributions: All authors contributed equally to the work.
Correspondence to: Professor Chris JJ Mulder, Department of Gastroenterology and Hepatology, VU University Medical Centre, PO Box 7057, 1007 MB Amsterdam, The Netherlands. cjmulder@vumc.nl
Telephone: +31-20-4440613 Fax: +31-20-4440554
Received: January 4, 2005
Revised: February 15, 2005
Accepted: February 18, 2005
Published online: September 21, 2005
Abstract

AIM: To determine the tolerability and safety profile of a low-dose maintenance therapy with 6-TG in azathioprine (AZA) or 6-mercaptopurine (6-MP) intolerant inflammatory bowel disease (IBD) patients over a treatment period of at least 1 year.

METHODS: Database analysis.

RESULTS: Twenty out of ninety-five (21%) patients discontinued 6-TG (mean dose 24.6 mg; mean 6-TGN level 540 pmol/8×108 RBC) within 1 year. Reasons for discontinuation were GI complaints (31%), malaise (15%) and hepatotoxicity (15%). Hematological events occurred in three patients, one discontinued treatment. In the 6-TG-tolerant group, 9% (7/75) could be classified as hepatotoxicity. An abdominal ultrasound was performed in 54% of patients, one patient had splenomegaly.

CONCLUSION: The majority of AZA or 6-MP-intolerant IBD patients (79%) is able to tolerate maintenance treatment with 6-TG (dosages between 0.3 and 0.4 mg/kg per d). 6-TG may still be considered as an escape maintenance immunosuppressant in this difficult to treat group of patients, taking into account potential toxicity and efficacy of other alternatives. The recently reported hepatotoxicity is worrisome and 6-TG should therefore be administered only in prospective trials.

Keywords: 6-Thioguanine; Azathioprine; 6-Mercaptopurine; Crohn’s disease; Ulcerative colitis; Side effects; Tolerance; Safety