Efficacy and Safety of the Newer Multiple Sclerosis Drugs Approved Since 2010

Abstract

Multiple sclerosis treatment faces tremendous changes as a result of the approval of new medications. The new medications have differing safety considerations and risks after long-term treatment, which are important for treating physicians to optimize and individualize multiple sclerosis care. Since the approval of the first multiple sclerosis capsule, fingolimod, the armamentarium of multiple sclerosis therapy has grown with the orally available medications dimethyl fumarate and teriflunomide. Fingolimod is mainly associated with cardiac side effects, dimethyl fumarate with bowel symptoms. Several reports about progressive multifocal leukoencephalopathy as a result of dimethyl fumarate or fingolimod therapy raised the awareness of fatal opportunistic infections. Alemtuzumab, a CD52-depleting antibody, is highly effective in reducing relapses but leads to secondary immunity with mainly thyroid disorders in about 30% of patients. Development of secondary B-cell-mediated disease might also be a risk of this antibody. The follow-up drug of the B-cell-depleting antibody rituximab, ocrelizumab, is mainly associated with infusion-related reactions; long-term data are scarce. The medication daclizumab high yield process, acting via the activation of CD56^bright natural killer cells, can induce the elevation of liver function enzymes, but also fulminant liver failure has been reported. Therefore, daclizumab has been retracted from the market. Long-term data on the purine nucleoside cladribine in MS therapy, recently authorized in the European Union, have been acquired during the long-term follow-up of the cladribine studies. The small molecule laquinimod is currently under development. We review data of clinical trials and their extensions regarding long-term efficacy and side effects, which might be associated with long-term treatment.