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Optimization and individualization of thiopurine therapy in inflammatory bowel disease: the great variability among drug responses

The Pharmacogenomics Journal volume 3, pages 66–68 (2003)Cite this article

‘If it were not for the great variability among individuals, medicine might as well be a science and not an art.’ Sir William Osler.1892

Science reclaims the art of individual medicine through pharmacogenomics, which serves as the gateway to understanding heterogeneity among invididuals. Pharmacogenomics teaches that different patients respond differently to medications. In the arenas of therapeutic optimization and individualization strategies, pharmacogenetic testing is used with increasing frequency and is defining a new frontier in diagnostic and therapeutic patient approaches. The study of molecular diagnostic testing of our pharmacogenetic traits and criminal justice system are evolving in parallel: both have shifted away from isolated reliance on biological phenotypes, such as clinical variability or fingerprints, toward more reliable and quantifiable molecular markers, such as polymorphisms in DNA sequence.1

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References

  1. Cummings CA, Relman DA . Genomics and microbiology. Microbial forensics—'cross-examining pathogens'. Science 2002; 296: 1976–1979.

    Article  CAS  Google Scholar 

  2. Evans W, Relling M . Pharmacogenomics: translating functional genomics into rational therapeutics. Science 1999; 286: 487–491.

    Article  CAS  Google Scholar 

  3. Schwab M, Schaffler E, Marx C, Fischer C, Lang T, Behrens C et al. Azathioprine therapy and adverse drug reactions in patients with inflammatory bowel disease: impact of thiopurine S-methyltransferase polymorphism. Pharmacogenetics 2002; 12: 429–436.

    Article  CAS  Google Scholar 

  4. Willoughby JM, Beckett J, Kumar PJ, Dawson AM . Controlled trial of azathioprine in Crohn's disease. Lancet 1971; 2: 944–947.

    Article  CAS  Google Scholar 

  5. Present DH, Korelitz BI, Wisch N, Glass JL, Sachar DB, Pasternack BS . Treatment of Crohn's disease with 6-mercaptopurine. A long-term, randomized, double-blind study. N Engl J Med 1980; 302: 981–987.

    Article  CAS  Google Scholar 

  6. Sandborn W, Sutherland L, Pearson D, May G, Modigliani R, Prantera C . Azathioprine or 6-Mercaptopurine for Inducing Remission of Crohn's Disease. Cochrane Database Systems Review, issue 3. Update Software: Oxford, 2001.

    Google Scholar 

  7. Steinhart AH, Hawley CJ, Modigliani R . 6-Mercaptopurine and Azathioprine for Maintaining Remission in Ulcerative Colitis. Cochrane Database Systems Review, issue 3. Update Software: Oxford, 2001.

    Google Scholar 

  8. Dubinsky MC, Lamothe S, Yang HY, Targan SR, Sinnett D, Theoret Y, Seidman EG . Pharmacogenomics and metabolite measurement for 6-mercaptopurine therapy in inflammatory bowel disease. Gastroenterology 2000; 118: 705–713.

    Article  CAS  Google Scholar 

  9. Dubinsky M, Hanard P, Yang HY, Kam L, Abreu M, Seidman E et al. 6-MP metabolite levels correlate with clinical response to drug toxicity in adults. IBD (abstr). Am J Gastroenterol 1999; 94: A258.

    Google Scholar 

  10. Cuffari C, Theoret Y, Latour S, Seidman G . 6-Mercaptopurine metabolism in Crohn's disease: correlation with efficacy and toxicity. Gut 1996; 39: 401–406.

    Article  CAS  Google Scholar 

  11. Lennard L . The clinical pharmacology of 6-mercaptopurine. Eur J Clin Pharmacol 1992; 43: 329–339.

    Article  CAS  Google Scholar 

  12. Weinshilboum RM, Sladek SL . Mercaptopurine pharmacogenetics: monogenic inheritance of erythrocyte thiopurine methyltransferase activity. Am J Hum Genet 1980; 32: 651–662.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Yates CR, Krynetski EY, Loennechen T, Fessing MY, Tai HL, Pui CH et al. Molecular diagnosis of thiopurine S-methyltransferase deficiency: genetic basis for azathioprine and mercaptopurine intolerance. Ann Intern Med 1997; 126: 608–614.

    Article  CAS  Google Scholar 

  14. Dubinsky M, Yang H, Hassard PV, Seidman EG, Kam LY, Abreu MT et al. 6-MP metabolite profiles provide a biochemical explanation for 6-MP resistance in patients with inflammatory bowel disease. Gastroenterology 2002; 122: 904–915.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors would like to acknowledge the support of the New York Crohn's Foundation.

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Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, The Weill Medical College of Cornell University, The New York Presbyterian Hospital, New York, USA

    E Scherl & K Subbaramiah

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  1. E Scherl
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  2. K Subbaramiah
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Correspondence to E Scherl.

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DUALITY OF INTEREST

Ellen Scherl would like to disclose her affiliations with the following companies and organizations:

AstraZeneca; Centocor, Inc.; Crohn's and Colitis Foundation of America; Proctor and Gamble; Prometheus Laboratories; Salix Pharmaceuticals, Inc.; Shire, Inc.; TAP Pharmaceuticals, Inc.

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Scherl, E., Subbaramiah, K. Optimization and individualization of thiopurine therapy in inflammatory bowel disease: the great variability among drug responses. Pharmacogenomics J 3, 66–68 (2003). https://doi.org/10.1038/sj.tpj.6500162

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