Efficacy of Disease-Modifying Therapies in Relapsing Remitting Multiple Sclerosis: A Systematic Comparison

Abstract

The treatment of relapsing-remitting multiple sclerosis (RRMS) has become more effective over the last decade with the advent of the currently available disease-modifying therapies (DMTs). Pivotal clinical studies differ in many characteristics, such that cross-comparisons of relative risk reductions are of limited value and can be misleading. Our objective was to compare the clinical efficacy of currently approved first-line DMTs in patients with RRMS, applying an evidence-based medicine approach. We reviewed all phase III pivotal trials of DMTs. Six clinical trials of Avonex®, Betaseron®, Copaxone®, Rebif® and Tysabri® in patients with RRMS were identified for analysis. Only randomized, placebo-controlled, double-blind studies were included. The clinical efficacy endpoints compared were: proportion of relapse-free patients at 1 and 2 years; annualized relapse rate at 2 years; proportion of progression-free patients at 2 years, and proportion of patients free of gadolinium-enhancing lesions at 1 year or 9 months. Based on these analyses, Betaseron, Rebif, and Tysabri show comparable effects, whereas for several endpoints Avonex or Copaxone did not significantly differ from placebo. In the absence of head-to-head studies for all products used to treat RRMS, it still may be possible to compare treatment effects by applying evidence-based medicine principles.

Interferon therapy in relapsing-remitting multiple sclerosis: A systematic review and meta-analysis of the comparative trials

“…An early systematic review comparing placebo controlled, double blind clinical trials concluded that all three INF-ß agents demonstrate equivalent efficacy between low and high dose interferon treatments [1]. However, in the recent systematic reviews of placebo controlled trials conducted by Freedman et al [2] and Goodin [3] both concluded that high dose interferon treatment had superior effectiveness on MRI and relapse outcomes.…”

The potential teratogenic effects of interferon beta-1a and interferon beta-1b on in vitro embryonic development

“…Various disease-modifying drugs, including IFNb-1a and IFNb-1b, glatiramer acetate, natalizumab, mitoxantrone, and fingolimod that are licensed worldwide to reduce the frequency of clinical attacks with the expectation of slowing disability progression [14]. Great majority of studies related to IFNs have been directed towards to determination of their effects on diseases and biological structures [9,39].…”

Autologous Hematopoietic Stem Cell Transplantation as a Treatment Option for Aggressive Multiple Sclerosis

“…The most effective currently available treatment is natalizumab, a humanized monoclonal antibody against CD49d/very late antigen-4 (VLA-4), which is generally also well tolerated, but has led to progressive multifocal leukoencephalopathy (PML), an opportunistic and often fatal infection of the brain by the polyoma virus JC, in over 300 patients so far. A chemotherapeutic agent, mitoxantrone, is used as second-line therapy for more severe RRMS and also for SPMS [5]. Mitoxantrone can only be given for a very limited period of time due to its cardiac toxicity, and secondary leukemias have occurred in up to 2.…”