In pilot trial, Ocrevus failed to reduce MS inflammation in meninges

Failure may be tied to lack of penetration in blood-brain barrier, or inadequate measures

Andrea Lobo, PhD avatar

by Andrea Lobo, PhD |

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Ocrevus (ocrelizumab) did not significantly reduce the number or volume of inflammatory lesions in the meninges in people with multiple sclerosis (MS), according to a recent pilot study.

While inflammation in the meninges, the protective membranes that surround the brain and spinal cord, is thought to be driven by B-cells — the immune cells Ocrevus targets — the findings support previous data that show the antibody-based medication was no better than other therapies at reducing it.

“In combination with other similar prospective trials, the evidence for the ability of anti-CD20 therapy to suppress meningeal [inflammation] in MS is weakened by our data,” the researchers wrote in “A pilot trial of ocrelizumab for modulation of meningeal enhancement in multiple sclerosis,” which was published in Multiple Sclerosis and Related Disorders.

MS inflammation mostly impacts the white matter, regions in the brain and spinal cord composed mainly of nerve fibers and myelin, which is the substance targeted by the immune system. The overactive immune response may also damage gray matter, which is made of nerve cell bodies, and the meninges. While most inflammation in the meninges is widespread, there are regions that contain immune cell structures with adjacent neuronal degeneration and loss of myelin, or demyelination.

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Effect of Ocrevus on meningeal inflammation in MS

As a large number of cells in these structures are B-cells, researchers have wondered if therapies such as Ocrevus could reduce meningeal inflammation and the related damage to adjacent gray matter regions, leading scientists at the University of Maryland School of Medicine to assess in a small open-label clinical study (NCT03396822) the therapy’s impact on meningeal inflammation in patients who’d recently been prescribed it.

Meningeal inflammation was identified and tracked with high-resolution MRI scans, taken before Ocrevus was started and then after a year of follow-up. Specifically, the researchers used two measures called leptomeningeal enhancement (LME) and paravascular and dural enhancement (PDE) as biomarkers of meningeal inflammation.

The trial enrolled 14 patients with relapsing or progressing forms of MS who had signs of meningeal inflammation when they started Ocrevus. They were mostly women (77%), with a mean age of 47.8 and a mean disease duration of 10.8 years.

The participants were compared with a control group who received other MS disease-modifying therapies, none of which targeted B-cells directly. These patients had relapsing-remitting MS (RRMS) and were a mean age of 47.9 with a mean disease duration of 14 years.

At the start of treatment, there were no significant differences in the number of LME or PDE lesions in both groups. There were also no differences regarding the volume of lesions.

After a year, both groups saw minimal changes in LME and PDE lesion number and volume, but the differences were not statistically significant between them.

The findings suggest Ocrevus has no impact on meningeal inflammation, which may be associated with the lack of penetration in the blood-brain barrier, the semi-permeable barrier that protects the brain from harmful substances in the blood. It’s also possible the measures used are not adequate to evaluate meningeal inflammation in MS.

“This finding suggests that either [Ocrevus] may not have a treatment effect upon meningeal inflammation or rather that LME and/or PDE may not be … appropriate [markers] of meningeal inflammation in MS,” the researchers said, adding more research on a larger scale may help to know more about the “physiologic meaning of meningeal enhancement.”