domingo, 20 de noviembre de 2011

Pharmacogenomics and Your Practice: Abacavir

 

Pharmacogenomics and Your Practice: Abacavir

Michael Scott Bowen, MPH
Posted: 11/07/2011




Hi, I am Scott Bowen from the Office of Public Health Genomics at the Centers for Disease Control and Prevention (CDC). I am speaking to you as part of the CDC Expert Commentary Series on Medscape. Our topic today is pharmacogenomics and what providers need to know about this emerging field of clinical practice.
Adverse drug events are a serious public health problem. Consider the following facts:
  • An estimated 82% of American adults take at least 1 medication and 29% take 5 or more;
  • 700,000 emergency department visits and 120,000 hospitalizations are due to adverse drug events annually;
  • $3.5 billion is spent on extra medical costs of adverse drug events annually; and
  • At least 40% of costs associated with adverse drug events occurring outside hospitals can be prevented.
How can the emerging science of genomics help? Pharmacogenomics is the study of genetic variation as a factor in drug response, affecting both safety and effectiveness. The intended applications of pharmacogenomics research include indentifying responders and nonresponders to medications, avoiding adverse events, optimizing drug doses, and avoiding unnecessary healthcare costs. The US Food and Drug Administration has added pharmacogenomic information to the labeling for more than 70 drugs. Labels may include information on genetic determinants of clinical response or risk for adverse events.
In spite of current enthusiasm about pharmacogenomics in the research community, very few pharmacogenomic tests have been validated for use in clinical practice at this time by professional societies and independent evidence review groups. Although considerable information is accumulating on the relationship between genetic variation, drug metabolism, and adverse effects, precious little evidence exists for their added value in clinical practice.

One pharmacogenomic test that is recommended for use is a test for HLA-B*5701 to identify people at risk for an adverse effect of HIV treatment with abacavir. An open-access journal, PLoS Currents Evidence on Genomic Tests , recently summarized evidence supporting the use of this test as follows: "There are approximately 33 million people worldwide who are living with HIV/AIDS. Among them are approximately 1.2 million Americans, with an estimated 48,100 newly diagnosed infections each year. Combination antiretroviral therapy is the most effective pharmacotherapy for HIV treatment." One of these drugs is abacavir. "Abacavir hypersensitivity reaction affects 5%-8% of patients and can be observed during the first 6 weeks of antiretroviral therapy. Symptoms of an abacavir hypersensitivity reaction include skin rash, fever, malaise, gastrointestinal symptoms, and respiratory symptoms." Rarely more severe forms of disease can occur. "If a patient experiences a hypersensitivity reaction, abacavir is discontinued and symptoms generally resolve within 72 hours. Restarting abacavir is contraindicated as it can result in a potentially life-threatening reaction and even death. The HLA-B*5701 pharmacogenomic test minimizes potential toxicities to the drug abacavir by identifying patients who may be at risk of developing a hypersensitivity reaction." Testing for HLA-B*5701 prior to initiation of abacavir has been recommended by the US Department of Health and Human Services Panel on Antiretroviral Guidelines for Adults and Adolescents.[1]

Many other pharmacogenomic tests that are subjects of active research and debate -- such as pharmacogenomic testing to guide warfarin dosing -- have the potential for public health impact. For most of these tests, however, there simply is not enough evidence to warrant their use in practice at this time.
The promise of pharmacogenomic tests for improving public health is great in the long run. But we should not take shortcuts in using them prematurely without the necessary scientific evidence that shows their added value in terms of improved health outcomes and reduced healthcare costs. Doctors, nurses, and other healthcare providers have an important role in monitoring emerging pharmacogenomic tests and ensuring that new tests have demonstrated validity and utility prior to implementing them in practice. Thank you.

Web Resources
CDC Medication Safety Program. Medication Safety Basics
CDC Public Health Genomics
CDC Public Health Genomics: Genomics and Health Frequently Asked Questions
US Food and Drug Administration: Table of Pharmacogenomic Biomarkers in Drug Labels
Wang L, McLeod HL, Weinshilboum RM. Genomics and drug response. N Engl J Med. 2011;364:1144-1153. http://www.nejm.org/doi/full/10.1056/NEJMra1010600

Ma JD, Lee KC, Kuo GM. HLA-B*5701 testing to predict abacavir hypersensitivity [Internet]. Version 14. PLoS Currents Evidence on Genomic Tests. 2010 Dec 3 [revised 2010 Dec 7]:PMC3000684. http://knol.google.com/k/joseph-d-ma/hla-b-5701-testing-to-predict-abacavir/2twojvq0wfutb/1?collectionId=28qm4w0q65e4w.50#

Prejean J, Song R, Hernandez A, et al. Estimated HIV incidence in the United States, 2006-2009. PLoS ONE 6: e17502. http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0017502

Michael Scott Bowen is the Deputy Director of CDC's Office of Public Health Genomics (OPHG). The Office was formed in 1997 to assess the impact of advances in human genetics and the Human Genome Project on public health and disease prevention. OPHG serves as the focus for integrating genomics into public health research and programs for disease prevention and health promotion. Mr. Bowen oversees the development of national projects to establish public health research and program capacity in genomics, industry and academic partnerships, and health agency program development. Much of Mr. Bowen's career has been focused on innovation to improve public health science and practice. Mr. Bowen joined CDC in 1992 and has also worked for the Agency for Toxic Substances and Disease Registry (ATSDR) where he served as a lead epidemiologist working on Superfund sites and as Deputy Chief of ATSDR's Health Investigations Branch. His past CDC roles include service as the Management Officer for the CDC Office of the Director and as the Deputy Director for CDC’s Division of Public Health Surveillance and Informatics.

Mr. Bowen earned a Bachelor's degree in Economics from Georgia State University and a Master of Public Health degree in Epidemiology from Tulane University's School of Public Health and Tropical Medicine.
Pharmacogenomics and Your Practice: Abacavir

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