Cognitive test performance and disease progression in primary and secondary progressive MS: An analysis of the SPRINT-MS study.

Abstract

Background: Clinical trials of disease-modifying therapies (DMTs) for multiple sclerosis (MS) increasingly incorporate cognitive outcomes, although effects of DMTs on cognition remain unknown.

Methods: In this secondary analysis of data from SPRINT-MS, a phase 2 randomized, placebo-controlled trial of ibudilast for progressive MS, we evaluated performance on Symbol Digit Modalities Test (SDMT) and Selective Reminding Test (SRT) in relation to physical disability, brain volume assessed with magnetic resonance imaging, and retinal nerve fiber layer (RNFL) thickness over 96-week follow-up. We hypothesize that trial participants would show a decline in cognitive test scores over 96 weeks of follow-up, with a possible between-group difference in favor of ibudilast.

Results: Data from 255 participants were analyzed. On average, physical outcome measures, brain parenchymal fraction, and RNFL thickness worsened; average SDMT and SRT scores remained largely unchanged. There were no differences between treatment groups in cognitive outcomes at 96-week follow-up. Practice effects likely contributed to results.

Conclusions: Observed stability of cognitive scores in individuals with progressive MS over 96-week follow-up may reflect true cognitive stability. However, the possibility that current cognitive measurement instruments are psychometrically flawed remains, warranting further research.