Treatment Options for Multiple Sclerosis: Current and Emerging Therapies

Kristen M. Gawronski, Pharm.D.; Michelle M. Rainka, Pharm.D.; Malti J. Patel, M.D.; Francis M. Gengo, Pharm.D., FCP

Disclosures

Pharmacotherapy. 2010;30(9):916-927. 

In This Article

Abstract and Introduction

Abstract

Multiple sclerosis is a chronic autoimmune disease affecting the central nervous system, more specifically, the myelin sheath covering of nerve fibers in the brain and spinal cord. This disease requires lifelong disease-modifying therapy, and all of the currently available first-line disease-modifying agents are parenteral formulations only. To date, eight drugs have entered or completed phases II and III clinical trials, four of which are oral drugs. These include five immunomodulators—cladribine, fingolimod, laquinimod, teriflunomide, and dimethyl fumarate—and three monoclonal antibodies— alemtuzumab, daclizumab, and rituximab. Although comparing these new drugs with available therapies is difficult, they do show promise as potential first-line agents for the treatment of multiple sclerosis. This marks a new frontier in the treatment of this disease, as the advent of new oral drugs will lead to increased patient compliance and contribute to longer sustained symptom-free periods and less marked disability.

Introduction

Multiple sclerosis is a chronic autoimmune disease included within a spectrum of idiopathic inflammatory demyelinating diseases, characterized by inflammation, demyelination, and axonal injury. Multiple sclerosis affects approximately 2.5 million people worldwide, and the disease is diagnosed in an estimated 200 Americans every week.[1] Symptom onset and diagnosis occur typically between ages 20 and 50 years, and women are 2–3 times more likely to be affected than men.[1,2]

Multiple sclerosis is more common in colder climates, above 40° latitude, and in people of Northern European descent; however, it can affect any ethnic group.[1] Multiple sclerosis generally is diagnosed after excluding other disease states that may explain the patient's symptoms. Based on the 2005 revised McDonald criteria, the diagnosis of multiple sclerosis is made by clinical presentation as well as by imaging and laboratory data.[3] Diagnosis requires at least two documented clinical exacerbations separated by at least 30 days.[3] Magnetic resonance (MR) imaging is sometimes used for diagnosing multiple sclerosis in the absence of clinical symptoms. The diagnosis requires two distinct gadolinium-enhancing lesions on MR images with at least 3 months between images, or two distinct T2 lesions on MR images separated by 30 days.[3] These MR images, however, are not considered to correlate to disease severity or progression. Improved MR imaging outcomes may not signify disease improvement, and other information such as number of relapses per year or Expanded Disability Status Scale (EDSS) score must be taken into consideration when evaluating the efficacy of disease-modifying agents.[4] One documented clinical exacerbation with evidence of lesions on MR images and positive cerebrospinal fluid findings is also diagnostic of multiple sclerosis.[3]

Patients can be classified as having one of four types of multiple sclerosis; the boundaries between categories, however, are often blurred. The most common type, affecting 85% of patients, is known as relapsing-remitting multiple sclerosis (RRMS). In RRMS, when patients experience worsening of preexisting symptoms or onset of new symptoms for periods longer than 48 hours without concomitant fever, these are known as relapses of multiple sclerosis. These are contrasted by symptom-free periods, known as remissions, where the patient's symptoms partially or completely disappear. Before the development of disease-modifying drugs, 50% of patients with RRMS commonly developed secondary-progressive multiple sclerosis (SPMS) after 10–15 years. This disease course is steadily progressive and can manifest with or without clear-cut relapses. Primary-progressive multiple sclerosis (PPMS), another form of the disease, is relatively rare, affecting approximately 10% of patients. This disease course is characterized by steady decline, without clear-cut relapses. The last type of multiple sclerosis, known as progressive-relapsing multiple sclerosis (PRMS), is characterized by a steady disease progression, in addition to clear-cut periods of exacerbations of multiple sclerosis. This is the rarest form of the disease, affecting approximately 5% of patients.[1]

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