Comparative efficacy of switching to natalizumab in active multiple sclerosis

Objective: To compare treatment efficacy and persistence in patients who switched to natalizumab versus those who switched between glatiramer acetate (GA) and interferon-beta (IFN beta) after an on-treatment relapse on IFN beta or GA using propensity score matched real-world datasets. Methods: Patients included were registered in MSBase or the TYSABRI Observational Program (TOP), had relapsed on IFN beta or GA within 12 months prior to switching to another therapy, and had initiated natalizumab or IFN beta/GA treatment <= 6 months after discontinuing prior therapy. Covariates were balanced across post switch treatment groups by propensity score matching at treatment initiation. Relapse, persistence, and disability measures were compared between matched treatment arms in the total population (n = 869/group) and in subgroups defined by prior treatment history (IFN beta only [n = 578/group], GA only [n = 165/group], or both IFN beta and GA [n = 176/group]). Results: Compared to switching between IFN beta and GA, switching to natalizumab reduced annualized relapse rate in year one by 65-75%, the risk of first relapse by 53-82% (mean follow-up 1.7-2.2 years) and treatment discontinuation events by 48-65% (all P <= 0.001). In the total population, switching to natalizumab reduced the risk of confirmed disability progression by 26% (P = 0.036) and decreased the total disability burden by 1.54 EDSS-years (P < 0.0001) over the first 24 months post switch. Interpretation: Using large, real-world, propensity-matched datasets we demonstrate that after a relapse on IFN beta or GA, switching to natalizumab ( rather than between IFN beta and GA) led to superior outcomes for patients in all measures assessed. Results were consistent regardless of the prior treatment identity.