MS Speaks

[S34.007] Measuring Enduring Worsening Of Multiple Sclerosis In The CombiRx Study

Fred Lublin,1Stacey Cofield,2Flavia Nelson,3Ponnada Narayana,3,3Tarah Gustafson,1Jerry Wolinsky,3Gary Cutter,2for the CombiRx Investigators

1New York, NY, USA, 2Birmingham, AL, USA, 3Houston, TX, USA

OBJECTIVE:

We sought to explore which metric of EDSS change represented a better and more durable worsening of MS.

BACKGROUND:

Measurement of disability progression is an important metric in MS clinical trials. The current standard of confirmed worsening of the EDSS has known reliability issues.

DESIGN/METHODS:

This analysis was carried out using the clinical data from 1008 RRMS subjects enrolled in the CombiRx trial, a multi-center, phase-III investigation of combination therapy of interferon and glatiramer acetate.

We evaluated several potential indicators of worsening disease and their association with relapses. These included 6 month confirmed 1 point worsening of EDSS, ever reaching an EDSS of 4 or 6, an EDSS increase of 2 points and successive confirmed EDSS worsening of 1 point + 1 point (1+1). Durability was determined by ending study at the same or higher EDSS than that which defined the metric.

RESULTS:

6 month confirmed EDSS had the greatest number of occurrences and the third best percentage for not reverting to a lower EDSS by study end. 1+1 had the smallest number of occurrences, but the best reversion rate and the greatest percentage ending study with an EDSS higher than baseline. Ever achieving EDSS 6 had a small N but fewer reverters to a lower EDSS, similar to 1+1. Ever reaching EDSS 4 or a 2 point increase in EDSS had the largest percent reverting back. Relationship to relapses will be presented.

CONCLUSIONS:

This study demonstrates that of the various measures of worsening, 6 month confirmed increase of EDSS occurred more frequently than the other metrics, but was less durable than some. The 1+1 assessment produced the greatest percentage worsening from baseline and was the most durable metric. Ever reaching EDSS 6 had similarly good durability and second best percentage ending study above baseline.

Once correlated with relapse activity, these assessments may serve as a basis for defining secondary progressive MS.

________

Study Supported by:

NIH/NINDS NS045719
Category - MS and CNS Inflammatory Disease: Clinical Science


S34: Platform Blitz: MS and CNS Inflammatory Disease: Risk Factors for Multiple Sclerosis Disease and Course