Letters to the Editors
Letter: thiopurine blood monitoring for patients with inflammatory bowel disease – authors' reply
Article first published online: 20 FEB 2012
© 2012 Blackwell Publishing Ltd
Alimentary Pharmacology & Therapeutics
Volume 35, Issue 6, pages 743–744, March 2012
How to Cite
Chouchana, L., Narjoz, C., Beaune, P., Loriot, M.-A. and Roblin, X. (2012), Letter: thiopurine blood monitoring for patients with inflammatory bowel disease – authors' reply. Alimentary Pharmacology & Therapeutics, 35: 743–744. doi: 10.1111/j.1365-2036.2012.05003.x
- Issue published online: 20 FEB 2012
- Article first published online: 20 FEB 2012
We read carefully the letter from Dr El-Matary regarding our review on the benefits of pharmacogenetics for improving thiopurine therapy in inflammatory bowel disease.[1, 2] We agree that performing blood testing remain a matter of debate for the prevention of thiopurine toxicity.
First, neutropenia, strongly linked to high 6-thioguanine nucleotide blood level, is a frequent and serious adverse event of thiopurine therapy, potentially lethal. It frequently occurs in the first months of therapy, starting from 2 weeks, mostly in thiopurine S-methyltransferase deficient patients. However, neutropenia can happen anytime during therapy, until 27 years in long-term follow-up. Moreover, as Connell et al. showed, blood count is often normal, 1 month before the occurrence of a moderate or severe leucopenia. Nevertheless, this suggests that performing blood counts in a 3 months basis may have limited efficacy to predict early bone marrow suppression. Actually, early neutropenia probably differs from delayed toxicity, in which a dosage alteration, a therapy change or a deficiency in vitamin B12 or folates can be involved.
Second, hepatotoxicity, probably related to elevated and lasting 6-methylmercaptopurine blood level, is commonly represented as mild, transient or reversible, elevation in serum transaminase. Thiopurine-induced liver injury occurs more frequently within the first months of treatment between, 1.5 and 5 months, although it can also occur after long-term treatment.[6, 7] Thus, despite no consensus, liver tests can be easily added to routine blood count determinations.
A recent meta-analysis did not conclude for clear benefits to maintain thiopurine therapy after 18 months. However, relapse occurs between 14% and 41% for the first subsequent year after therapy cessation.[9, 10] In this meta-analysis, as the authors acknowledged, only two studies with high heterogeneity and poor statistical power were included for the assessment of relapse until 5 years. Finally, stopping an effective and well-tolerated thiopurine therapy is still questionable.
Declaration of personal and funding interests: None.
- 1Letter: thiopurine blood monitoring for patients with inflammatory bowel disease. Aliment Pharmacol Ther 2012; 35: 742..
- 3Thiopurine-induced myelotoxicity in patients with inflammatory bowel disease: a review. Am J Gastroenterol 2008; 103: 1783–800., .Direct Link:
- 6Thiopurine-induced liver injury in patients with inflammatory bowel disease: a systematic review. Am J Gastroenterol 2007; 102: 1518–27., , .Direct Link: