The Effect of Disease Modifying Therapies on Disability Progression in Multiple Sclerosis: A Systematic Overview of Meta-Analyses

Abstract

Background: Disease modifying therapy (DMT) efficacy trials make an essential contribution to the development of evidence-based clinical treatments and practices for people with multiple sclerosis (MS). Meta-analysis is a critical part of this process and provides a powerful tool to assess the effects of DMT on MS progression. However, although there have been several meta-analyses on the effect of DMT on MS disease progression, they often do not reach the same conclusions.Objective: Our aim was to better understand and contextualize the results of meta-analyses evaluating DMT, identify differences in methodology that might explain their differing conclusions, and highlight areas for future research that will improve our ability to develop clinical recommendations.Methods: We conducted an overview of systematic reviews with meta-analyses assessing the efficacy of DMT on disability progression in people with MS in PubMed (Medline) and the Cochrane Database of Systematic Reviews.Results: We included 22 meta-analyses in this overview: eight general (on >3 DMT), 11 specific (on ≤3 DMT), 2 that evaluated subsets, and 1 that evaluated long-term effects. We found that there is good evidence that DMT improve short-term (≤2–3 years) disability progression outcomes relative to placebo in people with relapsing-remitting MS. However, results varied substantially between meta-analyses, and there is little evidence of their efficacy in other populations or over longer periods. The relative effects of individual DMT also remain unclear. The variance in results between meta-analyses may be related to the substantial differences in inclusion criteria, which was reflected in the limited overlap in included studies, as well as the year of meta-analysis publication. Of the 123 total unique studies included in the general meta-analyses, 77 (62.6%) were included in only one meta-analysis. This incongruence was also evident in the included DMT. Six of the 16 (37.5%) DMT evaluated in the general meta-analyses were only included in one meta-analysis.Conclusions: Translating DMT efficacy studies into evidence-based clinical practice requires greater methodological consistency in meta-analyses, more data on the relative effects of DMT through head-to-head clinical trials, and better reporting of adverse events.

Multiple Sclerosis in the Campania Region (South Italy): Algorithm Validation and 2015–2017 Prevalence

“…This cohort is part of the Italian MS Registry [7] and has already been used for a number of cohort studies [22,23]. Of note, a recent meta-analysis defined this cohort at moderate risk of bias, compared with the serious risk of other similar cohorts [24,25]. The Venn diagram shows the number and the proportions of patients identified from different data sources from the overall population (n = 5362).…”

Overview of Differences and Similarities of Published Mixed Treatment Comparisons on Pharmaceutical Interventions for Multiple Sclerosis

“…In the last 8 years, the number of approved disease-modifying therapies (DMTs) for multiple sclerosis (MS), a chronic autoimmune-mediated inflammatory disease of the central nervous system, has more than doubled. In contrast with the requirements of regulatory bodies for randomised controlled trials (RCTs) directly comparing new treatments with placebo and/or one active comparator [1], a broader evidence base is needed to inform how new medicines should fit into existing treatment algorithms [2]. Mixed treatment comparisons (MTCs) utilise a totality of data by combining both direct and indirect evidence [3].…”

Impact of Repetitive Transcranial Magnetic Stimulation on Neurocognition and Oxidative Stress in Relapsing-Remitting Multiple Sclerosis: A Case Report

“…Depending on its severity, MS can limit the daily activities of patients and end up producing a relevant degree of disability. Hence, it is the main reason for non-traumatic, invalidating neurological disease in young adults, and is the principal cause of disability acquired between 20 and 40 years of age ( 1 , 2 ).…”

“…Given the heterogeneity of the forms and manifestations of MS, its treatment has to be individualized and there are diverse drugs available within the therapeutic arsenal. In spite of this, on many occasions the disease advances inexorably ( 2 , 3 ).…”