SPI2 is a phase III trial investigating the safety and efficacy of MD1003 (high-dose biotin) in patients with PPMS and SPMS. Here, we assess at baseline the impact of sex, age, disability status, and type of progressive MS on the ratio of total N-acetyl groups (NA) to creatine (Cr), a marker of neuroaxonal integrity, measured by MRS.

We used proton magnetic resonance spectroscopy (MRS) to measure potential differences in axonal integrity between primary and secondary progressive multiple sclerosis (PPMS, SPMS) in a cohort of patients from the SPI2 study.

SPI2 inclusion required documented, relapse-free, disability progression in expanded disability status scale (EDSS) over 2 years. MRS data from a central brain single voxel positioned on the body of the corpus callosum were obtained at participating centers having the necessary capabilities. Spectra were analyzed and NA/Cr computed centrally.

As of July 2018, 642 pts with PPMS or SPMS were randomised 1:1 to MD1003 300 mg/day or placebo. The MRS analysis included 422 patients: 60% had SPMS, 52.6% were females, and 65.9% had EDSS>5. The mean NA/Cr ratio was significantly higher (P<0.05) in females versus males within patients with PPMS. We observed a trend toward a higher mean NA/Cr ratio in female patients with PPMS versus female patients with SPMS, and a trend toward a lower mean NA/Cr ratio in male patients with PPMS versus male patients with SPMS. There were no differences in NA/Cr between SPMS and PPMS linked to patient age. Baseline NA/Cr was not correlated with EDSS.

MRS measures of brain neuronal integrity were higher in female patients with PPMS than in male patients with PPMS. Whether neuronal degeneration differs in PPMS between men and women, and between PPMS and SPMS patients warrants further study.