Treatment effects of immunomodulatory therapies at different stages of multiple sclerosis in short-term trials

Abstract

Intervention with interferon-β (IFNβ) therapy counters early inflammatory damage to myelin and protects axons; such therapy might demonstrate greater efficacy earlier in the disease course compared with later when permanent damage has already occurred. Clinical trials conducted in patients with clinically isolated syndrome (CIS) show clinical benefits of early treatment of multiple sclerosis (MS), as evidenced by delayed conversion to clinically definite multiple sclerosis and reduced disability 3 years later; however, statistical significance is lost at 5 years. Moreover, in the CIS trials, patients who began treatment later in the course of MS did not benefit as much as those who began treatment earlier. In the treatment of relapsing-remitting multiple sclerosis (RRMS), immunomodulatory drug (IMD) therapy markedly reduced relapse rates and the burden of disease, as assessed by MRI. IFNβ therapy has demonstrated greater benefits in RRMS than in secondary progressive multiple sclerosis (SPMS). The SPMS trials consistently show reduction in relapse rates and accumulation of new MRI lesions, but have conflicting results for time to disability progression, which is the primary outcome measure in SPMS trials. Current evidence suggests that IFNβ therapy may be more effective in the early stages of SPMS, characterized by relapsing episodes and MRI evidence of greater brain lesion disease activity. Thus, intervention with IFNβ therapy is appropriate for all stages of MS except PPMS or non-relapsing SPMS. Intervention with glatiramer acetate is appropriate for RRMS. The balance of evidence indicates that early therapy is essential to delay the accumulation of irreversible neurologic damage and consequent disability.