An Open-Label Pilot Study Using Thioguanine as a Therapeutic Alternative in Crohn's Disease Patients Resistant to 6-Mercaptopurine Therapy (original) (raw)

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*Division of Gastroenterology, Department of Medicine, Cedars-Sinai Medical Center, UCLA, Los Angeles, California;

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†Division of Gastroenterology, Department of Medicine, Ottawa General Hospital, University of Ottawa, Ottawa, Ontario; and

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‡Division of Gastroenterology & Nutrition, Department of Pediatrics, Sainte-Justine Hospital, University of Montréal, Montréal, Québec, Canada

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*Division of Gastroenterology, Department of Medicine, Cedars-Sinai Medical Center, UCLA, Los Angeles, California;

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*Division of Gastroenterology, Department of Medicine, Cedars-Sinai Medical Center, UCLA, Los Angeles, California;

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*Division of Gastroenterology, Department of Medicine, Cedars-Sinai Medical Center, UCLA, Los Angeles, California;

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*Division of Gastroenterology, Department of Medicine, Cedars-Sinai Medical Center, UCLA, Los Angeles, California;

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Received:

22 January 2001

Published:

01 August 2001

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Marla C. Dubinsky, Philip V. Hassard, Ernest G. Seidman, Lori Y. Kam, Maria T. Abreu, Stephan R. Targan, Eric A. Vasiliauskas, An Open-Label Pilot Study Using Thioguanine as a Therapeutic Alternative in Crohn's Disease Patients Resistant to 6-Mercaptopurine Therapy, Inflammatory Bowel Diseases, Volume 7, Issue 3, 1 August 2001, Pages 181–189, https://doi.org/10.1097/00054725-200108000-00001
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Summary

Background and Aims

A substantial number of patients with inflammatory bowel disease (IBD) fail to achieve a complete clinical response with 6-mercaptopurine (6-MP) and azathioprine (AZA). Inability to achieve therapeutic 6-thioguanine nucleotide (6-TGN) levels due to the preferential overproduction of 6-methylmercaptopurine ribonucleotides (6-MMPR) upon dose escalation characterizes a newly described subgroup of IBD patients resistant to 6-MP/AZA therapy. Treatment with 6-thioguanine (6-TG), a related thiopurine, which forms 6-TGNs more directly may be beneficial in such patients. This pilot study evaluated the safety, tolerance, and efficacy of 6-TG in the subgroup of Crohn's disease (CD) patients failing to attain adequate disease control with traditional 6-MP/AZA therapy.

Methods

Ten CD patients with preferential 6-MMPR production upon 6-MP/AZA dose escalation were enrolled in an open-label pilot study. Seven of 10 patients had experienced dose-related 6-MP toxicities.

Results

Seventy percent of the patients (7 of 10) responded or were in remission at week 16. Clinical response was evident by week 4 in most. 6-TGN levels were nine-fold higher with 6-TG treatment than with 6-MP, whereas 6-MMPR levels were undetectable. No patient developed a recurrence of hepatic or hematological toxicity.

Conclusions

6-TG was a safer and more efficacious thiopurine in this subgroup of IBD patients resistant to 6-MP therapy. Larger controlled trials are warranted to further evaluate both the short-and long-term safety and efficacy in this subgroup of patients as well as a broader spectrum of IBD patients.

© 2001 Crohn's & Colitis Foundation of America, Inc.

Topic:

• crohn's disease
• inflammatory bowel disease
• 6-mercaptopurine
• methylthioinosine
• thioguanine
• toxic effect
• thiopurine
• disease remission

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