A pilot trial of ocrelizumab for modulation of meningeal enhancement in multiple sclerosis

Background: Autopsy data suggests that meningeal inflammation in multiple sclerosis (MS) is driven by CD20+ Bcells. Ocrelizumab is an anti-CD20 monoclonal antibody, and thus could potentially ameliorate meningeal inflammation in MS. Leptomeningeal enhancement (LME) on MRI is suggested as a surrogate biomarker of meningeal inflammation in MS, and thus may be a way of monitoring for this treatment effect. Objectives: To determine if ocrelizumab impacts meningeal enhancement (ME) on 7T MRI in MS. Methods: Twenty-two patients with MS started on ocrelizumab by their treating physician were enrolled into this single-center, open-label, prospective trial. Participants underwent 7T MRI of the brain prior to first infusion, with screening for the presence of LME. Fourteen patients (48 +/- 11 years; 11 women) had LME on the baseline scan and were invited to return for an additional 7T MRI after 1 year of treatment. Fourteen MS patients (49 +/- 10 years; 11 women) on non-CD20 treatment from a separate observational cohort of annual 7T MRIs were used for comparison - matched for LME at baseline, age, and sex. Post-contrast FLAIR and subtraction images were reviewed for LME and paravascular and dural enhancement (PDE). Results: All subjects in the ocrelizumab and comparison groups had LME and PDE on their baseline scan. At the beginning of the study the mean number of foci of LME and PDE in the study group were 2.3 +/- 1.7 and 6.6 +/- 3.9 respectively. Mean LME and PDE count for the comparison group were 1.7 +/- 1.5 and 7.8 +/- 5.5. Mean volume of LME in the study group was 50.5 mm3 +/- 65.0 mm3 and that of the PDE was 866 mm3 +/- 937.9. Mean volume of LME and PDE for comparison group were 28.4 mm3 +/- 36.0 and 885 mm3 +/- 947.7 respectively. At follow-up, the number of patients with LME decreased to 8 (57 %) in both groups, whereas the proportion of patients with PDE was unchanged. Minimal mean change in the number of LME after 1 year were seen in both the study group (0.07 +/- 2.9, p = 0.97) and comparison group (-0.71 +/- 1.5, p = 0.08). Minimal mean change was seen in the volume of LME in both the study group (-21.91 mm3 +/- 77.66, p = 0.27) and comparison group (3.4 mm3 +/- 32.11, p = 0.77). There was minimal change in the mean number of foci of PDE after 1 year in both the study group (-0.71 +/- 2.36, p = 0.32) and in the comparison group (-0.17 +/- 3.89, p = 0.15). Mean change in volume of PDE was measurable, but not significant in both the study group (-397.1 mm3 +/- 959.6, p = 0.80) and in the comparison group (-417.0 mm3 +/- 922.7) (p = 0.80). Comparisons between the changes in foci count and volume for both LME and PDE in the study versus comparison groups showed no significant differences. Conclusion: In this small pilot trial, ocrelizumab did not significantly reduce the number or volume of foci of LME or PDE in MS patients.