Overall Disability Response Score: An integrated endpoint to assess disability improvement and worsening over time in patients with multiple sclerosis.

BACKGROUND: Overall Disability Response Score (ODRS) is a composite endpoint including Expanded Disability Status Scale, Timed 25-foot Walk, and 9-Hole Peg Test, designed to quantify both disability improvement and worsening in multiple sclerosis (MS). OBJECTIVE: To assess the sensitivity and clinical meaningfulness of ODRS using natalizumab Phase 3 data sets (AFFIRM in relapsing-remitting MS and ASCEND in secondary progressive MS). METHODS: Differences in ODRS over 96 weeks, ODRS at Week 96, and slope of ODRS change per year between natalizumab and placebo groups were analyzed. Correlation between ODRS and changes in patient-reported outcomes was also analyzed. RESULTS: The difference (95% confidence interval (CI)) in the ODRS over 96 weeks between natalizumab and placebo groups was 0.34 (0.21-0.46) in AFFIRM (p < 0.001), and 0.18 (0.03-0.34) in ASCEND (p = 0.021). Significant differences between treatment arms were also observed in ODRS at Week 96 and in the slope of change per year in both studies. There was a significant linear correlation between ODRS at Week 96 and the change from baseline in both the physical and mental components of the 36-item Short Form Survey (SF-36) in both studies. CONCLUSION: This analysis supports ODRS as a sensitive and potentially clinically meaningful disability outcome measure in MS.