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.
Highlights
Disease modifying therapies (DMT) that modulate, modify, or suppress the immune system are a medication class used to treat people living with multiple sclerosis (MS)
One evaluated short-term suboptimal response criteria to first-line DMT (17), and the second evaluated the effect of DMT on brain atrophy, a potential but unvalidated marker of MS disease progression (18)
There is evidence that DMT improve disability progression outcomes in people living with relapsing MS relative to placebo, but further work is needed to develop robust, comprehensive clinical recommendations
Summary
Disease modifying therapies (DMT) that modulate, modify, or suppress the immune system are a medication class used to treat people living with multiple sclerosis (MS) (see Supplementary Table 1 for a list of FDA-approved DMT). As with other pharmacological treatments, systematic reviews and meta-analyses of DMT efficacy are essential for the development of effective, evidence-based clinical guidelines (1). There are two main disease phenotypes: relapsing-remitting (intermittent periods of markedly increased disability, followed by significant or complete remission), and primary progressive (continuous increase in disability with no remission). These phenotypes are not evenly distributed through the population: about 80–85% of people with MS initially experience relapsingremitting MS (RRMS) and the remaining 15–20% experience primary progressive MS (PPMS) (2). 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). There have been several meta-analyses on the effect of DMT on MS disease progression, they often do not reach the same conclusions
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