Literature DB >> 16222751

On tolerability and safety of a maintenance treatment with 6-thioguanine in azathioprine or 6-mercaptopurine intolerant IBD patients.

Nanne-K-H de Boer1, Luc-J-J Derijks, Lennard-P-L Gilissen, Daniel-W Hommes, Leopold-G-J-B Engels, Sybrand-Y de-Boer, Gijsbertus den Hartog, Piet-M Hooymans, Anja-B-U Mäkelburg, Barend-D Westerveld, Anton-H-J Naber, Chris-J-J Mulder, Dirk-J de Jong.   

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 x 10(8) 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.

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Year:  2005        PMID: 16222751      PMCID: PMC4320368          DOI: 10.3748/wjg.v11.i35.5540

Source DB:  PubMed          Journal:  World J Gastroenterol        ISSN: 1007-9327            Impact factor:   5.742


  16 in total

1.  Why measure thiopurine methyltransferase activity? Direct administration of 6-thioguanine might be the alternative for 6-mercaptopurine or azathioprine.

Authors:  D de Jong; C J Mulder; A A van Sorge
Journal:  Gut       Date:  2001-12       Impact factor: 23.059

Review 2.  The state of the art in the management of inflammatory bowel disease.

Authors:  Stephen B Hanauer; Daniel H Present
Journal:  Rev Gastroenterol Disord       Date:  2003

3.  Utilisation of erythrocyte 6-thioguanine metabolite levels to optimise azathioprine therapy in patients with inflammatory bowel disease.

Authors:  C Cuffari; S Hunt; T Bayless
Journal:  Gut       Date:  2001-05       Impact factor: 23.059

4.  Pharmacogenomics and metabolite measurement for 6-mercaptopurine therapy in inflammatory bowel disease.

Authors:  M C Dubinsky; S Lamothe; H Y Yang; S R Targan; D Sinnett; Y Théorêt; E G Seidman
Journal:  Gastroenterology       Date:  2000-04       Impact factor: 22.682

5.  Thiopurine pharmacogenetics: clinical and molecular studies of thiopurine methyltransferase.

Authors:  R Weinshilboum
Journal:  Drug Metab Dispos       Date:  2001-04       Impact factor: 3.922

6.  6-Mercaptopurine in the management of inflammatory bowel disease: short- and long-term toxicity.

Authors:  D H Present; S J Meltzer; M P Krumholz; A Wolke; B I Korelitz
Journal:  Ann Intern Med       Date:  1989-10-15       Impact factor: 25.391

7.  Thiopurine methyltransferase activity and the use of azathioprine in inflammatory bowel disease.

Authors:  A Ansari; C Hassan; J Duley; A Marinaki; E-M Shobowale-Bakre; P Seed; J Meenan; A Yim; J Sanderson
Journal:  Aliment Pharmacol Ther       Date:  2002-10       Impact factor: 8.171

8.  6-thioguanine can cause serious liver injury in inflammatory bowel disease patients.

Authors:  Marla C Dubinsky; Eric A Vasiliauskas; Hardeep Singh; Maria T Abreu; Kostas A Papadakis; Tram Tran; Paul Martin; John M Vierling; Stephen A Geller; Stephan R Targan; Fred F Poordad
Journal:  Gastroenterology       Date:  2003-08       Impact factor: 22.682

9.  6-Thioguanine seems promising in azathioprine- or 6-mercaptopurine-intolerant inflammatory bowel disease patients: a short-term safety assessment.

Authors:  Luc J J Derijks; Dirk J de Jong; Lennard P L Gilissen; Leopold G J B Engels; Piet M Hooymans; Jan B M J Jansen; Chris J J Mulder
Journal:  Eur J Gastroenterol Hepatol       Date:  2003-01       Impact factor: 2.566

10.  Thioguanine: a potential alternate thiopurine for IBD patients allergic to 6-mercaptopurine or azathioprine.

Authors:  Marla C Dubinsky; Edward J Feldman; Maria T Abreu; Stephan R Targan; Eric A Vasiliauskas
Journal:  Am J Gastroenterol       Date:  2003-05       Impact factor: 10.864

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  9 in total

Review 1.  Optimizing 6-mercaptopurine and azathioprine therapy in the management of inflammatory bowel disease.

Authors:  Kara Bradford; David Q Shih
Journal:  World J Gastroenterol       Date:  2011-10-07       Impact factor: 5.742

Review 2.  Start low, go slow, but don't go this way yet.

Authors:  Brian Bressler; Robert Enns
Journal:  Can J Gastroenterol       Date:  2008-02       Impact factor: 3.522

Review 3.  Clinical Pharmacokinetic and Pharmacodynamic Considerations in the Treatment of Inflammatory Bowel Disease.

Authors:  Luc J J Derijks; Dennis R Wong; Daniel W Hommes; Adriaan A van Bodegraven
Journal:  Clin Pharmacokinet       Date:  2018-09       Impact factor: 6.447

Review 4.  Contemporary review of drug-induced pancreatitis: A different perspective.

Authors:  Whitney Y Hung; Odaliz Abreu Lanfranco
Journal:  World J Gastrointest Pathophysiol       Date:  2014-11-15

5.  A systematic survey evaluating 6-thioguanine-related hepatotoxicity in patients with inflammatory bowel disease.

Authors:  Alexander Teml; Matthias Schwab; Daan W Hommes; Sven Almer; Milan Lukas; Thomas Feichtenschlager; Timothy Florin; Julia Seiderer; Wolfgang Petritsch; Bernd Bokemeyer; Wolfgang Kreisel; Klaus R Herrlinger; Peter Knoflach; Bruno Bonaz; Thomas Klugmann; Hans Herfarth; Nikolaus Pedarnig; Walter Reinisch
Journal:  Wien Klin Wochenschr       Date:  2007       Impact factor: 1.704

6.  Safety and efficacy of the immunosuppressive agent 6-tioguanine in murine model of acute and chronic colitis.

Authors:  Miloslav Kverka; Pavel Rossmann; Helena Tlaskalova-Hogenova; Klara Klimesova; Bindia Jharap; Nanne K de Boer; Rene M Vos; Adriaan A van Bodegraven; Milan Lukas; Chris J Mulder
Journal:  BMC Gastroenterol       Date:  2011-05-05       Impact factor: 3.067

Review 7.  Efficacy of thioguanine treatment in inflammatory bowel disease: A systematic review.

Authors:  Berrie Meijer; Chris Jj Mulder; Godefridus J Peters; Adriaan A van Bodegraven; Nanne Kh de Boer
Journal:  World J Gastroenterol       Date:  2016-10-28       Impact factor: 5.742

Review 8.  Analytical Pitfalls of Therapeutic Drug Monitoring of Thiopurines in Patients With Inflammatory Bowel Disease.

Authors:  Melek Simsek; Berrie Meijer; Chris J J Mulder; Adriaan A van Bodegraven; Nanne K H de Boer
Journal:  Ther Drug Monit       Date:  2017-12       Impact factor: 3.681

9.  Sustained effectiveness, safety and therapeutic drug monitoring of tioguanine in a cohort of 274 IBD patients intolerant for conventional therapies.

Authors:  Melek Simsek; Debbie S Deben; Carmen S Horjus; Melanie V Bénard; Birgit I Lissenberg-Witte; Hans J C Buiter; Matthijs van Luin; Margien L Seinen; Chris J J Mulder; Dennis R Wong; Nanne K H de Boer; Adriaan A van Bodegraven
Journal:  Aliment Pharmacol Ther       Date:  2019-05-16       Impact factor: 8.171

  9 in total

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