Clinical Outcome Measures Poster Presentation

P0131 - Predicting long-term sustained disability progression in multiple sclerosis: application in the CLARITY trial (ID 1071)

Speakers
  • S. Sharmin
Authors
  • S. Sharmin
  • F. Bovis
  • M. Sormani
  • H. Butzkueven
  • T. Kalincik
Presentation Number
P0131
Presentation Topic
Clinical Outcome Measures

Abstract

Background

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.

Objectives

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. A higher score indicates a greater probability of a progression event to be sustained over the long-term.

Methods

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. Patient characteristics at the time of progression previously associated with the likelihood of improvement after confirmed progression event (age, primary progressive MS, a relapse in previous month, expanded disability status scale score≥6 and its change from baseline, number of affected functional system domains, and worsening in pyramidal, brainstem and sensory domains) 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, the analysis of the CLARITY study were repeated estimating the effect of therapy on long-term disability outcomes. Effect of cladribine on 3-month confirmed progression events with any score and score˃1.5 was evaluated.

Results

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 of the original trial were confirmed in addition to 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).

Conclusions

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.

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