Advanced Myelin-related MRI Measures in Relapsing Multiple Sclerosis Patients treated with Ocrelizumab or Interferon Beta-1a Over 96 Weeks (P6.371)

Objective: To evaluate the effect of ocrelizumab (OCR) and interferon beta-1a (IFNb-1a) on myelin-related MRI outcomes over 2 years in relapsing multiple sclerosis (MS). Background: Conventional MRI is routinely used to assess treatment effects in MS on the prevention of new lesion development, but does not evaluate disease-related changes in normal-appearing white matter (NAWM). mcDESPOT is an advanced MRI technique that estimates a volume fraction of myelin (VFM) by isolating signal from water trapped between myelin bilayers. Magnetization transfer ratio (MTR) is related to the macromolecule content found in myelin. Design/Methods: 56 relapsing MS patients from a single centre participating in a multi-centre randomized clinical trial of OCR versus IFNb-1a (OPERA II; NCT01412333) underwent MRI examinations at weeks 0, 24, 48 and 96. A subset of patients underwent VFM (N=53) and MTR imaging (N=37). 24 matched healthy controls were also examined. Average VFM and MTR were calculated at each time-point across all NAWM, and 4 WM tracts: corpus callosum, corticospinal tract, inferior and superior longitudinal fasciculi. Results: All regions showed interactions between visit and treatment group for VFM, indicating a favourable treatment effect for OCR versus IFNb-1a (p-values across WM regions ranged from 0.01 to 0.04). Compared to healthy controls over 96 weeks, VFM for OCR increased or remained stable in all regions (e.g. +0.8% (standard error 0.7%) across all NAWM), while it decreased for IFNb-1a (−1.1% (0.8%) in NAWM). MTR results demonstrated a similar pattern (NAWM in OCR +0.2% (0.3%); IFNb-1a −0.7% (0.3%)). Conclusions: Consistent longitudinal changes across WM regions examined in this study provide support for the hypothesis that OCR prevents diffuse myelin loss in NAWM over 2 years. This may relate to its prevention of new lesion development and subsequent Wallerian degeneration and/or suppression of diffuse inflammation and microglial activation. Study Supported by: Sponsored by Genentech, Inc. Disclosure: Dr. Kolind has received personal compensation for activities Genzyme, Vertex Pharmaceuticals and Rocheas a speaker and/or consultant. Dr. Vasavour has nothing to disclose. Dr. Tang has received research support from Roche. Dr. Tam has received personal compensation for activities with Novartis as a speaker. Dr. Tam has received research support from Roche. Dr. Rauscher has nothing to disclose. Dr. Clayton has received personal compensation for activities with Genentech, Inc. as an employee. Dr. Levesque has received personal compensation for activities with Genentech, Inc. as an employee. Dr. Carruthers has received personal compensation for activities with Roche, Novartis, Biogen, Genzyme and Teva as a consultant/speaker. Dr. Carruthers has received research support from Teva. Dr. White has nothing to disclose. Dr. Li has received personal compensation for activities with Roche, Nuron and Opexa as a consultant. Dr. Traboulsee has received personal compensation for activities with Genzyme and Roche as a consultant. Dr. Traboulsee has received research support from Genzyme, Roche, and Chugai.