Comparative efficacy of switching to natalizumab in active multiple sclerosis

Objective: To compare treatment efficacy and persistence in patients whoswitched to natalizumab versus those who switched between glatiramer acetate(GA) and interferon-beta (IFNb) after an on-treatment relapse on IFNb or GAusing propensity score matched real-world datasets. Methods: Patients includedwere registered in MSBase or the TYSABRI Observational Program (TOP), hadrelapsed on IFNb or GA within 12 months prior to switching to another ther-apy, and had initiated natalizumab or IFNb/GA treatment ≤6 months afterdiscontinuing prior therapy. Covariates were balanced across post switch treat-ment groups by propensity score matching at treatment initiation. Relapse, per-sistence, and disability measures were compared between matched treatmentarms in the total population (n = 869/group) and in subgroups defined by priortreatment history (IFNb only [n = 578/group], GA only [n = 165/group], orboth IFNb and GA [n = 176/group]). Results: Compared to switching betweenIFNb and GA, switching to natalizumab reduced annualized relapse rate inyear one by 65–75%, the risk of first relapse by 53–82% (mean follow-up1.7–2.2 years) and treatment discontinuation events by 48–65% (all P ≤ 0.001).In the total population, switching to natalizumab reduced the risk of confirmeddisability progression by 26% (P = 0.036) and decreased the total disability bur-den by 1.54 EDSS-years (P < 0.0001) over the first 24 months post switch. Interpretation: Using large, real-world, propensity-matched datasets we demon-strate that after a relapse on IFN b or GA, switching to natalizumab (rather thanbetween IFNb and GA) led to superior outcomes for patients in all measuresassessed. Results were consistent regardless of the prior treatment identity.