Alimentary TractPharmacogenomics and metabolite measurement for 6-mercaptopurine therapy in inflammatory bowel disease☆,☆☆,★,★★
Section snippets
Patient population
Patients less than 19 years of age followed up by the clinical investigators (M.C.D. and E.G.S.) at Ste-Justine Hospital IBD Center were eligible for inclusion if they had undergone 6-MP or AZA treatment for at least 4 months. Diagnoses of CD, ulcerative colitis (UC), or indeterminate colitis were established by standard clinical, radiological, histological, and endoscopic criteria.28 Patients with leukopenia or increased serum hepatic or pancreatic enzyme activities before initiation of
Metabolite levels and therapeutic response
The study population was divided into patients with a satisfactory clinical response and those who failed therapy. In the single-sampled patient group, 27 of 46 (59%) responded and 19 of 46 (41%) failed. In the multisampled patients, 20 of 46 (43%) had a response sustained at each clinical evaluation point, 11 (24%) never achieved a clinical response, and 15 (33%) responded inconsistently over time. Among all 173 metabolite measurements, 103 (60%) corresponded to patients with a clinical
Discussion
This study demonstrates that erythrocyte 6-TG concentration, not drug dose, is significantly and independently associated with therapeutic response to 6-MP in children with IBD. Our data corroborate our previous pilot study in IBD,26 as well as reports in acute lymphoblastic leukemia, suggesting that 6-TG levels above particular cutoff points are related to disease-free survival, independent of other factors known to affect prognosis, including standardized dosing regimens.22, 24, 25 Our
Acknowledgements
The authors thank Hughes Sinnett and Sylvain Latour for technical support.
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Address requests for reprints to: Ernest G. Seidman, M.D., Division of Gastroenterology and Nutrition, Sainte-Justine Hospital, 5734, 3175 Cote-St-Catherine Road, Montreal, Quebec, Canada H3T 1C5. e-mail: [email protected]; fax: (514) 345-4999.
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Drs. Sinnett, Théorêt, and Seidman share equal senior authorship.
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Supported by the Charles Bruneau Foundation (to D.S. and Y.T.), Fonds de la Recherche en Santé du Québec (Scholarships to D.S. and E.G.S.), and Fonds pour la Formation de Chercheurs et l'Aide à la Recherche (Studentship to S.L.).
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Dr. Targan is a Founder of Prometheus Labs; Ste-Justine Hospital and Drs. Sinnett, Théorêt, and Seidman have a royalty agreement for the use of the described tests for the management of IBD with Prometheus Labs.