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