Is the effect of drugs in progressive MS only due to an effect on inflammation? A subgroup meta-analysis of randomised trials

Background: It is unclear whether drugs approved for the treatment of progressive multiple sclerosis (PMS) are effective in disability progression only because of their effect on the inflammatory component of the disease. Objective: This meta-analysis aimed to evaluate whether the benefits of PMS treatments are mediated by its effect on the active component of the disease. Methods: We conducted a systematic search to identify randomised, double-blind, placebo-controlled trials evaluating the efficacy of disease-modifying therapies on disability progression for primary or secondary PMS. The primary endpoint of the analysis was disability progression based on the expanded disability status scale. A subgroup meta-analysis evaluated the effects of treatment according to disease activity at baseline. Results: Twelve trials (a total of 8659 PMS cases) were selected. Analysis of the included trials demonstrated that treatment benefit appears to be mainly confined to the group with active disease (hazard ratio (HR) = 0.67; 95% confidence interval (CI): 0.58-0.79) as compared to the group with inactive disease (HR = 0.90; 95% CI: 0.79-1.02, interaction test: p = 0.005). Conclusions: This study showed that the benefit of treating patients with PMS was mostly confined to those with the more active disease. Drugs targeting specific pathological processes leading to disability progression remain necessary