Longitudinal magnetic resonance spectroscopy study of metabolite changes over 2 years in relapsing and primary progressive multiple sclerosis treated with ocrelizumab

BACKGROUND: Magnetic resonance spectroscopy (MRS) offers non‐invasive assessments of neuron‐oligodendrocyte coupling and neuroinflammation to monitor treatment response in multiple sclerosis (MS). OBJECTIVE: To track changes in N‐acetylaspartate and myo‐inositol in relapsing MS (RMS) and primary progressive MS (PPMS) patients treated with ocrelizumab over 2 years. METHODS: Single‐voxel MRS at 3T was acquired at baseline in 10 healthy controls (HCs), and weeks 0, 12, 24, 52, and 96 in MS participants at a single center. RESULTS: Baseline myo‐inositol was higher in PPMS than RMS (p = 0.047) and HC (p = 0.001), and correlated with disability across both MS groups (r = 0.57, p = 0.0006). Following treatment with ocrelizumab, both RMS and PPMS demonstrated declines in myo‐inositol over time, returning toward HC levels (RMS p = 0.016; PPMS p = 0.004). Conversely, N‐acetylaspartate was not different between groups and remained stable over time. CONCLUSION: Ocrelizumab treatment is associated with declining myo‐inositol levels measured by MRS in both RMS and PPMS. Myo‐inositol offers a unique biomarker to track resolution of gliosis and reactive microglia with treatment. Furthermore, the relationship between a higher concentration of myo‐inositol and greater disability across both MS subtypes at baseline supports the presence of "smouldering inflammation" as a disease process across the spectrum of MS. CLINICAL TRIAL: Sub‐study of the Ocrelizumab Biomarker Outcome Evaluation (OBOE; ML29966) trial: https://clinicaltrials.gov/study/NCT02688985.