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October 2013

Therapeutic Decisions in Multiple SclerosisMoving Beyond Efficacy

Author Affiliations
  • 1Department of Neuropathology, University Medical Centre, Göttingen, Germany
  • 2Department of Neurology, University Medical Centre, Göttingen, Germany
  • 3Research Department of Neuroscience, Neurologische Universitätsklinik, St Josef Hospital, Faculty of Medicine, Bochum, Germany
  • 4Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles
  • 5Department of Neurology, Multiple Sclerosis Unit, Hospital Universitario San Carlos, Madrid, Spain
  • 6Center of Excellence in Neuromics, Centre hospitalier de l’Université de Montréal, Montreal, Quebec, Canada
  • 7Department of Neurology, Stanford University School of Medicine, Stanford, California
  • 8Centre d’Esclerosi Múltiple de Catalunya, Unitat de Neuroimmunologia Clínica, Servei de Neurologia, Hospital Vall d’Hebron, Barcelona, Spain
  • 9Department of Neurology, School of Medicine, University of Colorado Denver, Aurora
  • 10MS Center Dresden, Neuroimmunological Laboratory, Center of Clinical Neuroscience, Department of Neurology, University Clinic Carl Gustavus Carus, Dresden University of Technology, Dresden, Germany
  • 11Department of Neurology, University of California, San Francisco
  • 12Program in Immunology, University of California, San Francisco
JAMA Neurol. 2013;70(10):1315-1324. doi:10.1001/jamaneurol.2013.3510

Several innovative disease-modifying treatments (DMTs) for relapsing-remitting multiple sclerosis have been licensed recently or are in late-stage development. The molecular targets of several of these DMTs are well defined. All affect at least 1 of 4 properties, namely (1) trafficking, (2) survival, (3) function, or (4) proliferation. In contrast to β-interferons and glatiramer acetate, the first-generation DMTs, several newer therapies are imbued with safety issues, which may be attributed to their structure or metabolism. In addition to efficacy, understanding the relationship between the mechanism of action of the DMTs and their safety profile is pertinent for decision making and patient care. In this article, we focus primarily on the safety of DMTs in the context of understanding their pharmacological characteristics, including molecular targets, mechanism of action, chemical structure, and metabolism. While understanding mechanisms underlying DMT toxicities is incomplete, it is important to further develop this knowledge to minimize risk to patients and to ensure future therapies have the most advantageous benefit-risk profiles. Recognizing the individual classes of DMTs described here may be valuable when considering use of such agents sequentially or possibly in combination.