Spinal cord atrophy as a primary outcome measure in phase II trials of progressive multiple sclerosis.

ABSTRACT

OBJECTIVES: To measure the development of spinal cord (SC) atrophy over 1 year in patients with progressive multiple sclerosis (PMS) and determine the sample sizes required to demonstrate a reduction in spinal cord cross-sectional area (SC-CSA) as an outcome measure in clinical trials. METHODS: In total, 44 PMS patients (26 primary progressive multiple sclerosis (PPMS), 18 secondary progressive multiple sclerosis (SPMS)) and 29 healthy controls (HCs) were studied at baseline and 12 months. SC-CSA was measured using the three-dimensional (3D) fast field echo sequences acquired at 3T and the active surface model. Multiple linear regressions were used to investigate changes in imaging measurements. RESULTS: PPMS patients had shorter disease duration, lower Expanded Disability Status Scale (EDSS) and larger SC-CSA than SPMS patients. All patients together showed a significantly greater decrease in percentage SC-CSA change than HCs, which was driven by the PPMS. All patients deteriorated over 1 year, but no association was found between percentage SC-CSA change and clinical changes. The sample size per arm required to detect a 50% treatment effect over 1 year, at 80% power, was 57 for PPMS and 546 for SPMS. CONCLUSION: SC-CSA may become an outcome measure in trials of PPMS patients, when they are at an early stage of the disease, have moderate disability and modest SC atrophy.