To externally validate the previously developed sustained progression score which established 6-month confirmed disability progression events as indicators of long-term disability worsening in randomized double-blind CLARITY (Cladribine Tablets Treating MS Orally) trials.

Prevention of disability over the long-term is the main treatment goal in multiple sclerosis (MS), however, randomized clinical trials provide only short-term (3-6-month) treatment effect on disability.

Data from the CLARITY and CLARITY 2-year Extension study were used. The 3-and 6-month confirmed disability progression events and the time over which progression remained sustained were identified. Clinico-demographic characteristics of patients at the time of progression previously associated with the likelihood of improvement after confirmed progression event were used to calculate the sustained progression score for each progression event. A Cox proportional hazards model was used to validate the association of the score calculated for each 6-month confirmed disability progression event with time to improvement. To demonstrate application of the score in trial setting, effect of cladribine on 3-month confirmed progression events with any score and score?1.5 was evaluated.

A total of 667 6-month confirmed disability progression events were identified in the combined dataset, of which only 12 were followed by a 6-month confirmed disability improvement. The external validation of the score illustrated a trend towards a decrease in the likelihood of disability improvement in progression events with higher score (Hazard Ratio HR=0.72, 95% CI: 0.21-2.42). Results confirmed that oral cladribine reduced the risk of disability progression that was likely to be sustained over the long-term (only events with score?1.5; HR: 0.64; 95% CI: 0.47-0.87).

The sustained progression score, estimated using the characteristics of confirmed progression events, provides important complementary information that will allow future trials to establish the effect of therapy not only on short-term but also on long-term disability accrual.