Moving Towards a Cure for MS: Increased Immunosuppression and Striving for No Evidence of Disease Activity (NEDA)

Multiple sclerosis (MS) is a chronic central nervous system demyelinating disease. The cause is unknown, but likely results from a combination of genetic predisposition and environmental exposures leading to autoimmune destruction of the brain and spinal cord. The most common phenotype of MS is relapsing-remitting (RRMS), characterized by episodes of neurological symptoms, typically lasting days to weeks, followed by symptom remission. After years of disease, the majority of RRMS cases transform into secondary progressive MS (SPMS), characterized by slowly worsening symptoms and progressive neurological disability, which may or may not be also accompanied by superimposed relapses. A third distinct phenotype, primary progressive MS (PPMS) is characterized by slowly worsening neurological symptoms and disability from disease onset, without clinical relapses.1 The first disease-modifying agent was approved by the FDA in 1993. There are now 14 FDA-approved disease-modifying therapies (DMTs) with almost all agents indicated for relapsing forms of MS. The medical management of multiple sclerosis has changed dramatically over the past decade as the number of available DMTs has increased (See Table 1). Most of the newer agents have been shown to decrease clinical relapse rates to a greater degree than the older agents. These DMTs frequently also decrease the rate of disability progression in MS. With the increased immunosuppression of the newer therapies comes the potential for more serious side effects. Balancing efficacy with potential adverse events is a primary consideration of patients and clinicians treating MS today. The potential for near complete control of the disease is becoming a reality in select cases, and a new goal of "no evidence of disease activity" (NEDA) may be supplanting the previous aim of relapse rate reduction.