Natalizumab reduces relapse clinical severity and improves relapse recovery in MS

Objectives: Compare relapse clinical severity, post-relapse residual disability, and the probability of confirmed complete recovery from relapse between patients who relapsed during natalizumab (n=183/627 [29%]) and placebo (n=176/315 [56%]) treatments in the AFFIRM trial. Methods: In this post-hoc analysis, relapse clinical severity and residual disability were defined by change in Expanded Disability Status Scale (EDSS) score occurring between pre- relapse and at-relapse assessment and between pre-relapse and post-relapse assessment, respectively. Patients were considered completely recovered from relapse when their post- relapse EDSS score was less than or equal to their pre-relapse EDSS score, and this was maintained for 12 or 24 weeks. Results: At relapse, an increase in EDSS score of >0.5 points occurred in 71% of natalizumab and 84% of placebo patients (P=0.0088); an increase of >1.0 point occurred in 49% of natalizumab and 61% of placebo patients (P=0.0349) (mean increase in EDSS at relapse: natalizumab = 0.77; placebo=1.09; P=0.0044). After relapse, residual disability of >0.5 EDSS points remained in 31% of natalizumab and 45% of placebo patients (P=0.0136) (mean post- relapse residual EDSS increase: natalizumab = 0.06; placebo=0.28; P=0.0170). In patients with an increase in EDSS of > 0.5 or >1.0 during relapse, natalizumab increased the probability of 12-week confirmed complete recovery from relapse by 55% (hazard ratio [HR] = 1.554; P=0.0161) and 67% <HR=1.673; P=0.0319) compared to placebo, respectively. Conclusions: In AFFIRM, natalizumab treatment decreased the clinical severity of relapses and improved recovery from disability induced by relapses. These beneficial effects would limit the step-wise accumulation of disability.