Short-Term Relapse Quantitation as a Fully Surrogate Endpoint for Long-Term Sustained Progression of Disability in RRMS Patients Treated with Natalizumab

Table 1

Summary of time to sustained progression of disability at two years as measured by increase in EDSS—ITT population.

	Placebo	Natalizumab	𝑃 value^a
Number of subjects randomized	315 (100)	627 (100)
Number of subjects progressed	84 (27)	104 (17)
Time (yr) to progression^b
Mean and 95% CI	1.78 (1.72, 1.84)	1.90 (1.87, 1.94)
Estimated proportion of progression at 2 years^b	0.29	0.17
Hazard ratio (natalizumab/placebo) and 95% CI	0.58 (0.43, 0.77)		<0.001

Note: sustained progression of disability is defined as at least a 1.0-point increase on the EDSS from a baseline EDSS ≥ 1.0 sustained for 12 weeks or at least a 1.5-point increase on the EDSS from a baseline EDSS of 0 sustained for 12 weeks.
^a: 𝑃 value assessing the difference between the treatment groups, from Cox proportional hazards model, adjusted for baseline EDSS values and age (<40 versus ≥40).
^b: Estimated time to progression and proportion of subjects with progression based on the Kaplan-Meier product limit method.