Beyond these insights there are further applications and future challenges.

نویسنده

  • O Jolobe
چکیده

Beyond these insights there are further applications and future challenges Sir, Insights into the genetic susceptibility to Crohn's disease (CD) 1 would be incomplete without recognition that the unrivalled success of azathioprine in inducing and maintaining remission in corticoster-oid-dependent CD 2 ought to go hand in hand with a wider application of pharmacogenetic testing 3 so as to optimize efficacy and safety of this agent. The rationale for pharmacogenetic testing is that poly-morphism at the gene locus for thiopurine trans-methylase (TPMT) is the operative mechanism for determining tissue levels of this enzyme and, hence, the degree to which any individual patient might be at risk of myelosuppression attributable to suboptimal inactivation of azathioprine by TPMT. 2 However, notwithstanding the human and financial cost of inadvertent myelosuppression, in a national survey of consultant gastroenterologists, dermatologists and rheumatologists, where the response rate was 70%, only 60% of gastroenterologists reportedly tested their patients for TPMT activity before prescribing azathioprine. 3 Suboptimal TPMT testing might be have been attributable to insufficient recognition that pharmacogenetic tests not only offer patient benefits but also 'have an impact on finite healthcare resources'. 4 The latter is a principle also translatable to cancer management, where pharmacogenetic testing has the potential, not only to 'identify individuals predisposed to a high risk of toxicity and low response from standard doses of anticancer drugs', 5 but, arguably, also to predict which patients will achieve a good therapeutic response without experiencing severe side effects. For example, had pharmacogenetic profiling been part of the strategy for evaluating the cost-effectiveness of temsirolimus, the chemotherapeutic agent for advanced renal cell carcinoma, instead of the evidence presented to National Institute for Health and Clinical Excellence being 'convincing [only] for the overall data but not for the subgroup data', 6 subgroups might have emerged with benefit vs. risk profiles so favourable as to relegate drug costs to lower priority, thereby justifying inclusion of this drug in the National Health Service therapeutic armamentarium. Thiopurine treatment in inflammatory bowel disease. Clinical pharmacology and implication of pharmacogeneti-cally guided dosing. Shaffer JL, et al. Current use of pharmacogenetic testing: a national survey of thiopurine methyltranferase testing prior to azathioprine prescription. polymorphisms of drug-metabolising enzymes and drug transporters in the chemotherapeutic treatment of cancer.

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عنوان ژورنال:
  • QJM : monthly journal of the Association of Physicians

دوره 103 4  شماره 

صفحات  -

تاریخ انتشار 2010