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Role of Thiopurine Metabolite Testing and Thiopurine Methyltransferase Determination in Pediatric IBD

Benkov, Keith*; Lu, Ying; Patel, Ashish; Rahhal, Riad§; Russell, Gary||; Teitelbaum, Jonathan; for the NASPGHAN Committee on Inflammatory Bowel Disease


“Role of Thiopurine Metabolite Testing and Thiopurine Methyltransferase Determination in Pediatric IBD,” which appeared in the March 2013 issue, has Continuing Medical Education (CME) activity content and should have been linked to the NASPGHAN CME site for instructions, documentation, and the complete necessary steps to receive CME credit for reading the article. The link is

Journal of Pediatric Gastroenterology and Nutrition. 56(5):582, May 2013.

Journal of Pediatric Gastroenterology & Nutrition: March 2013 - Volume 56 - Issue 3 - p 333–340
doi: 10.1097/MPG.0b013e3182844705
Clinical Report

ABSTRACT: Thiopurines have been used in inflammatory bowel disease (IBD) for >30 years, and measurements of both thiopurine methyltransferase (TPMT) and thiopurine (TP) metabolites, 6-thioguanine nucleotides (6-TGN) and 6-methylmercaptopurine (6-MMP), have been readily available. The North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) Committee on Inflammatory Bowel Disease thought it appropriate to review the present indications for use of TPMT and TP metabolite testing. Substantial evidence demonstrates that TP therapy is useful for both Crohn disease and ulcerative colitis. Review of the existing data yielded the following recommendations. TPMT testing is recommended before initiation of TPs to identify individuals who are homozygote recessive or have extremely low TPMT activity, with the latter having more reliability than the former. Individuals who are homozygous recessive or have extremely low TPMT activity should avoid the use of TPs because of concerns for significant leukopenia. TMPT testing does not predict all cases of leukopenia and has no value to predict hypersensitivity adverse effects such as pancreatitis. Any potential value to reduce the risk of malignancy has not been studied. All individuals taking TPs should have routine monitoring with complete blood cell count and white blood cell count differential to evaluate for leukopenia regardless of TPMT testing results. Metabolite testing can be used to determine adherence with TP therapy. Metabolite testing can be used to guide dose increases or modifications in patients with active disease. Consideration would include either increasing the dose, changing therapy or for those with elevated transaminases or an elevated 6-MMP, using adjunctive allopurinol to help raise 6-thioguanine metabolites and suppress formation of 6-MMP. Routine and repetitive metabolite testing has little or no role in patients who are doing well and taking an acceptable dose of a TP.

*Mount Sinai School of Medicine, New York, NY

Cohen Children's Medical Center of New York, Lake Success

Children's Medical Center of Dallas, Dallas, TX

§University of Iowa, Iowa City

||MassGeneral Hospital for Children, Harvard Medical School, Boston

Drexel University School of Medicine, Philadelphia, PA.

Address correspondence and reprint requests to Keith Benkov, MD, Mount Sinai School of Medicine, New York, NY 10029 (e-mail:

Received 10 December, 2012

Accepted 17 December, 2012

The authors report no conflicts of interest.

Copyright 2013 by ESPGHAN and NASPGHAN