The Efficacy of Interferon Beta in Delaying Conversion to Clinically Definite Multiple Sclerosis

Abstract

More than half of patients with a clinically isolated syndrome (CIS) develop clinically definite multiple sclerosis (CDMS). Patients at high risk for CDMS often present with asymptomatic lesions characteristic of CDMS on magnetic resonance imaging scans, although an absence of asymptomatic lesions is not atypical. Phase 3 studies of interferon beta in patients with a CIS suggest that this treatment can delay conversion to CDMS and reduce the risk of new asymptomatic white matter lesions. We reviewed phase 3 studies (CHAMPS, BENEFIT, and ETOMS) and post hoc analyses assessing the efficacy of interferon beta in delaying CDMS in patients with a CIS. The evidence supports early initiation of treatment. Int J MS Care. 2010;12:42-50. Multiple sclerosis (MS) is a chronic, demyelinating disorder of the central nervous system (CNS), with evidence of both inflammatory and neurodegenerative pathogenic features. A clinically isolated syndrome (CIS) such as acute monocular optic neuritis, partial transverse myelitis, or acute brainstem syndrome can be the first indication of MS, 1 and approximately 50% of patients who develop a CIS are eventually diagnosed with clinically definite MS (CDMS). 2Studies demonstrate that 80% of MS cases begin with a relapsing-remitting (RR) course 3 characterized by subacute development of neurologic symptoms and findings (relapses), followed by a recovery period of weeks to months. Despite significant recovery in the majority of cases, relapses appear to be the major cause of increases in sustained disability, with approximately 28% of patients with RRMS experiencing a 1-point or greater increase on the Expanded Disability Status Scale 4 (EDSS) following each relapse recovery. 5,6 The median time to reach a fixed EDSS score of 6.0-a disability milestone almost always associated with a secondary progressive (SP) phase of the disease-is 15 to 28 years. 3,7,8 In the course of MS, progression of disability is accompanied by accumulation of CNS abnormalities (including contrast-enhancing lesions, T2 lesions, T1 "black holes," and brain atrophy) and eventual loss of tissue caused by inflammation and axonal injury.9 It has been reported that inflammatory lesion activity in early relapsing MS, as detected by serial monthly magnetic resonance imaging (MRI) studies, may be ten times more frequent than clinical relapses and signals an ongoing pathologic process.9 Widespread inflammationindependent axonal damage has also been demonstrated in patients with a CIS.10 Although inflammatory demyelination is reversible, chronic demyelination and axonal degeneration are irreversible and result in progressive neurologic disability. 11This article reviews the rationale for early treatment of MS, assesses the available clinical evidence for the efficacy of interferon beta (IFNβ) therapy in slowing the development of MS in patients with a CIS, 12-15 and identifies the types of patients who may benefit the most from early treatment. Early Prognostic Factors of Disease Activity and DisabilityThe clinical course of MS v...