Newer agents in the treatment of multiple sclerosis.

Abstract

Multiple sclerosis (MS) is the most common cause of nontraumatic neurological disability in young adults. There is great need for developing effective treatments to arrest the disease. As of today, there is no cure for MS but several agents mitigating its effects are available. The era of disease-modifying therapy began with the use of interferon beta and glatiramer acetate in the 1990s. Given the injectable nature and the limited efficacy of these agents, efforts are ongoing to develop new treatments. We provide an overview of the ongoing developments in MS therapy. After considering the clinical features and measures of drug efficacy in MS clinical trials, we report the phase-III clinical trials results of: (1) 3 oral agents approved within the last 5 years, fingolimod (Gilenya), dimethylfumarate (Tecfidera), and teriflunomide (Aubagio); (2) the oral agent laquinimod; and (3) the monoclonal antibodies daclizumab, ocrelizumab, and alemtuzumab. We will then briefly mention remyelinating and neuroprotective agents that are in very early studies. We will end with a possible approach to different clinical scenarios to guide the choice of disease-modifying therapy in patients. The newer agents offer the convenience of oral administration (for the oral agents) and potentially higher efficacy, but their long-term safety profile remains unknown. All available agents attack only 1 aspect of MS, that is, inflammatory demyelination. Arresting or reversing the progression of disability will be feasible only with agents affecting remyelination and neuroprotection, still in relatively early research.