Current Disease-Modifying Therapies in Multiple Sclerosis

Bernd C. Kieseier, M.D., Hans-Peter Hartung, M.D.

Disclosures

Semin Neurol. 2003;23(2) 

In This Article

Abstract and Introduction

In recent years, the usefulness of interferon beta and glatiramer acetate in the treatment of relapsing-remitting multiple sclerosis (RRMS) has been established. Interferon beta has also been shown to be efficacious in secondary-progressive multiple sclerosis (SPMS) as well as in patients with isolated syndromes at risk to develop clinically definite multiple sclerosis (MS). Mitoxantrone is another disease-modifying drug that is available for SPMS and severe cases of RRMS. The clinical utility of disease-modifying agents in MS will be reviewed with respect to the anti-inflammatory, immunomodulatory, and immunosuppressive treatments that are currently available. Symptomatic therapies will not be considered.
Objectives: Upon completion of this article, the reader will understand current treatment strategies for the various clinical subtypes of multiple sclerosis.
Accreditation: The Indiana University School of Medicine is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.
Credit: The Indiana University School of Medicine designates this educational activity for a maximum of 1 category 1 credit toward the AMA Physicians Recognition Award. Each physician should claim only those hours of credit that he/she actually spent in the educational activity.
Disclosure: Statements have been obtained regarding the authors' relationships with financial supporters of this activity. There is no apparent conflict of interest related to the context of participation of the authors of this article.

Multiple sclerosis (MS) is an inflammatory autoimmune disorder of the central nervous system (CNS) and the most common disabling neurologic disease of young adults with a lifetime risk of 1 in 400.[1,2] The clinical diagnosis of the disease is based on demonstrating the dissemination of lesions of the CNS in time and space (i.e., the occurrence of a second clinical episode at a different site in the CNS). The risk of developing MS after an isolated clinical deficit, such as optic neuritis, is greater the longer the follow-up period. In one series of patients with optic neuritis, the 10-year risk of clinically definite MS (CDMS) was 39%, the 20-year risk was 49%, the 30-year risk was 54%, and the 40-year risk was 60%.[3] The strongest predictor for the development of MS is the presence of asymptomatic white-matter lesions on magnetic resonance imaging (MRI) of the brain.[4] Consequently, an international panel has published diagnostic criteria for MS (McDonald criteria), suggesting that MRI evidence of dissemination of CNS lesions in time and space is sufficient for the diagnosis of MS even before clinical dissemination has occurred.[5]

The multiplicity of neurological deficits, the relative admixture of relapses/remissions, with or without overall progression, and the severity of disease leads to marked clinical heterogeneity in patients with MS. To standardize the terminology for MS subtypes the following classification has been established (Figure 1)[6]:

  • Relapsing-remitting MS (RRMS). The majority of MS patients (approximately 85%) initially present with this form of the disease, characterized by clearly defined disease relapses with full recovery or with sequelae and residual deficit upon recovery. RRMS is not classified as a progressive form of multiple sclerosis, but residual deficits can be established with each exacerbation.

  • Secondary progressive MS (SPMS). At least 50% of patients with RRMS will transition into this subform, characterized by disease progression with or without occasional relapses, minor remissions, and plateaus.

  • Primary progressive MS (PPMS). Approximately 10% of the MS population presents a disease progression from the onset with occasional plateaus and temporary improvements.

  • Progressive-relapsing MS (PRMS). The least common form is a progressive disease from onset with acute relapses, with or without full recovery, with periods between relapses characterized by continuous progression.

The natural history of the disease is that the majority of MS patients will exhibit a progressive neurologic deterioration. Approximately 50% of patients diagnosed with MS will require the use of a cane to ambulate safely within 10 years; approximately 90% of MS patients have transitioned to a progressive form of the disease 25 years from the time of diagnosis and can be characterized as having substantial clinical disability.[7,8] The timing of accrued disability is apparently strongly influenced by the number of exacerbations during the early phases of the disease. Although clinically isolated syndromes (CIS) and RRMS are not classified as progressive forms of the disease, irreversible deficits can be established with each exacerbation and as such contribute to persistent clinical impairment. Consequently, MS treatment should be initiated at the earliest possible time to prevent disability.

The therapeutic approaches to the various forms of MS have changed dramatically over the past decade, and various disease-modifying therapies have successfully been introduced and established.[9,10,11] This review will address current treatment strategies in various clinical subtypes of MS.

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