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Content Update

July 3, 2019

New Disease Modifying Therapies (DMTs) for Relapsing Forms and Active Secondary Progressive Multiple Sclerosis: In March 2019, two disease modifying therapies (DMTs) were approved by the U.S Food and Drug Administration (FDA) for treatment of certain types of multiple sclerosis (MS). Siponimod (Mayzent®) is a sphingosine 1-phosphate (S1P) receptor modulator that showed a reduction in annualized relapse rates and disability progression with a side effect profile similar to the other available S1P receptor modulator, fingolimod. Cladribine (Mavenclad®) depletes lymphocytes and also showed efficacy by reducing annualized relapse rates and lesions on MRI; however, the side effects of cladribine can be serious and limit its use to patients with more active disease.

LEARNING OBJECTIVES

LEARNING OBJECTIVES

Upon completion of the chapter, the reader will be able to:

  1. Identify risk factors for multiple sclerosis (MS).

  2. Distinguish between forms of MS based on patient presentation and disease course.

  3. Compare and contrast MS disease-modifying treatment choices for a given patient.

  4. Determine appropriate symptomatic treatment choices for a given patient.

  5. Develop a monitoring plan for a patient placed on specific medications.

INTRODUCTION

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS). Multiple describes the number of CNS lesions, and sclerosis refers to the demyelinated lesions, today called plaques.

EPIDEMIOLOGY AND ETIOLOGY

Epidemiology

Approximately 2.3 million people worldwide have MS.1 Diagnosis usually occurs between 20 and 50 years, affecting at least twice as many women as men.1 Whites and people of northern European heritage are more likely to develop MS.1 Risk factors include family history of MS, autoimmune diseases, or migraine; personal history of autoimmune diseases or migraine; and cigarette smoke exposure.

Etiology

The cause of MS is unknown, but may be genetic, environmental, or both. Genetic risks may explain up to 35% of cases.2 Environmental theories involve infectious agents or decreased patient or maternal vitamin D serum concentrations or other infectious exposures.2,3

PATHOPHYSIOLOGY

While the causative agent of MS is unclear, the result is the development of an autoimmune disorder with areas of CNS inflammation and degeneration.

Inflammation

An unknown antigen presented by the major histocompatibility complex (MHC) class II molecules causes T-cells to become autoreactive (Figure 30–1). Autoreactive T-cells enter lymphatic tissues to expand. Upon a signal involving sphingosine-1-phosphate, T-cells reenter the circulation.4 Once activated, T-cells cause blood–brain barrier breakdown and enter the CNS. These T-cells come into contact with antigen-presenting cells (APCs) and proliferate and differentiate. Th1 cells secrete cytokines that enhance macrophage and microglial cells that attack ...

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