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The potential role of pharmacogenomics in the prevention of serious adverse drug reactions in multiple sclerosis

  • Kaarina Kowalec
    Affiliations
    Neuroscience Program, University of British Columbia (UBC), Vancouver, Canada

    Child & Family Research Institute, Vancouver, Canada

    Pharmaceutical Outcomes Programme, BC Children’s Hospital, Vancouver, Canada
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  • Bruce Carleton
    Affiliations
    Child & Family Research Institute, Vancouver, Canada

    Pharmaceutical Outcomes Programme, BC Children’s Hospital, Vancouver, Canada

    Department of Pediatrics, Faculty of Medicine, UBC, Vancouver, Canada
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  • Helen Tremlett
    Correspondence
    Corresponding author at: Room S178, 2211 Wesbrook Mall, University of British Columbia, Vancouver, British Columbia, Canada V6T 2B5. Tel.: +1 604 822 0957.
    Affiliations
    Neuroscience Program, University of British Columbia (UBC), Vancouver, Canada

    Division of Neurology, Faculty of Medicine, UBC, Vancouver, Canada
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Published:January 11, 2013DOI:https://doi.org/10.1016/j.msard.2012.11.003

      Abstract

      The immunomodulatory drugs for multiple sclerosis (MS) are associated with a variety of adverse drug reactions, including liver and cardiac injury, acute leukemia and progressive multifocal leukoencephalopathy. Minimizing or preventing the toxicity of MS drugs represents a major clinical objective. The science of pharmacogenomics is used to identify genetic variants associated with a high or low risk of experiencing a specific adverse drug reaction or therapeutic response. Combined with clinical and demographic factors, pharmacogenomics holds promise to better optimize a drugs’ risk/benefit profile. The application of pharmacogenomics for MS therapies is currently focused on finding markers of drug response.
      This review highlights the potential for pharmacogenomics to assist in predicting and/or preventing some of the more severe adverse reactions associated with MS therapies. We reviewed the literature surrounding seven serious adverse drug reactions associated with MS therapies, to serve as a springboard for future research: interferon-beta associated liver injury; lipoatrophy related to glatiramer acetate; progressive multifocal leukoencephalopathy associated with natalizumab, mitoxantrone associated cardiotoxicity and leukemia; and viral infections and cardiac effects associated with fingolimod. Predictive genetic testing for adverse drug reactions in the MS clinic could lead to a better risk profiling of patients before an MS therapy is initiated.

      Highlights

      • MS immunomodulatory drugs are associated with a variety of adverse reactions.
      • Pharmacogenomics and clinical factors can optimize a drugs’ benefit/risk profile.
      • The application of pharmacogenomics to MS is currently focused on drug response.
      • We review target adverse drug reactions in MS for future research purposes.

      Keywords

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