Meta-analysis of randomised controlled MS trials

Epub ahead of printZintzaras et al.  Network Analysis of Randomized Controlled Trials in Multiple Sclerosis. Clin Ther. 2012 Mar 21. 

BACKGROUND: The optimal treatment of MS is not yet well-defined.

OBJECTIVE: To estimate the relative effectiveness of treatments in MS, we performed a network of multiple-treatments meta-analysis of randomized controlled trials (RCTs) for relapsing MS using three main efficacy outcomes: relapse-free patients, patients without disease progression, and patients without magnetic resonance imaging progression.

METHODS: We systematically searched PubMed and the Cochrane Central Register of Controlled Trials to identify English-language articles with RCTs that compared pharmaceutical treatments using the terms multiple sclerosis and randomized controlled trial. All RCTs that involved patients with definite relapsing MS and provided data for calculating the odds ratios for the main outcomes were considered. First, comparative effectiveness relative to placebo was assessed using direct analysis. Then, each therapy was compared with interferon beta-1b (250μg) in direct and indirect analyses. Effect sizes were estimated by applying a random-effects model.

RESULTS: We identified 4165 titles; after screening, 109 articles were eligible for inclusion. In total, 26,828 patients were included. The network consisted of 145 treatments involving 59 direct comparisons with placebo and 8 direct comparisons with interferon beta-1b (250μg). Two treatments showed better response compared with placebo (direct analysis) for all three efficacy outcomes: natalizumab (300mg) and fingolimod (0.5mg). In comparing treatments with interferon beta-1b (250μg), the network analysis revealed that no therapy shows better response for all 3 efficacy outcomes and alemtuzumab, 12 and 24 mg, have better response for 2 of the outcomes (relapse-free patients and patients without disease progression).

CONCLUSIONS: Although some treatments seem to have better efficacy, the results should be interpreted with caution because the network was dominated by indirect comparisons. Data from the selected studies included in the network cannot be extrapolated beyond them. Large RCTs that make head-to-head comparisons between treatments are needed to draw safe conclusions for the optimal treatment of MS.

"Did we need a meta-analysis to tell us that Natalizumab, Fingolimod and Alemtuzumab are more efficacious than interferon beta-1b and that glatiramer acetate and interferon beta-1a are similar in efficacy to interferon beta-1b? Almost certainly not!"

"The good news is that we are entering an era were will have access to therapies which are on average more effective than interferon beta and glatiramer acetate. I am sure that these treatments will make it easier for us to assess the impact on suppressing relapses on disease course. I have little doubt that MSers on these therapies will do better in the long-term."

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