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

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.

Keywords: Disease-modifying therapy; Drug safety; Drug toxicity; Genetics; Multiple sclerosis; Pharmacogenomics.