Ocrevus Outperforms Rebif in Preventing Myelin Loss in Trial

Ocrevus appears to protect against demyelination in brain white matter, lesions

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Two years of treatment with Ocrevus (ocrelizumab) outperformed Rebif (interferon beta-1a) at preventing myelin loss in people with relapsing multiple sclerosis (MS), according to a new analysis of data from the OPERA II clinical trial.

Ocrevus’ protection against demyelination was observed both in MS lesions, where brain structures are damaged due to a misguided inflammatory attack, and in regions of normal brain matter.

The study, “Myelin water imaging in relapsing multiple sclerosis treated with ocrelizumab and interferon beta-1a,” was published in NeuroImage: Clinical. The work was funded by Roche, which sells Ocrevus, with additional support from Michael Smith Health Research BC.

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MS is caused by inflammation in the central nervous system that damages the myelin sheath, a fatty covering around nerve fibers that is essential for the rapid transmission of electric signals.

Ocrevus, administered directly into the bloodstream, is a B-cell-depleting therapy that is widely approved to treat relapsing forms of MS and primary progressive disease.

Approvals of the medication were supported in part by the OPERA I (NCT01247324) and OPERA II (NCT01412333) Phase 3 clinical trials, which compared Ocrevus against Rebif in more than 1,500 relapsing MS patients. Results from the trials demonstrated that Ocrevus outperformed Rebif at reducing relapse rates and brain lesions, as well as slowing the progression of disability.

What is myelin water fraction?

Now, a team led by scientists at the University of British Columbia in Canada conducted an analysis of myelin water fraction (MWF) data for a subset of patients in the OPERA II trial.

MWF is a MRI-based technique that, as its name suggests, measures myelin content in the nervous system by assessing water content around nerve fibers. This technique “is generally considered to provide the most specific measure of myelin using MRI,” the researchers wrote.

The analysis included data for 55 relapsing MS patients who participated in the two-year OPERA II trial, as well as 23 age- and sex-matched healthy controls who were followed for two years.

Participants included 27 patients who were treated with Ocrevus and 28 given Rebif in OPERA II. After two years in the trial, all entered the OPERA II open-label extension (OLE) and were treated with Ocrevus for another two years.

At the start of the OPERA II trial, there was no difference in MWF measures between patients assigned to Ocrevus or Rebif. However, over two years in the trial, average MWF values declined for all brain regions in participants given Rebif, indicating a gradual loss of myelin among these patients.

By contrast, for patients on Ocrevus, MWF values were generally stable or improved after two years in the trial. In the healthy individuals, MWF values were stable over time.

In the OLE part, MWF values remained generally stable after in patients initially given Ocrevus and were generally stable or improved among those who switched from Rebif to Ocrevus upon entering the OLE.

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Yet, analyses considering all four years of available data from the trial showed that MWF values were higher among patients who started on Ocrevus, compared with those who initially were given Rebif and then switched to Ocrevus in the OLE. This indicated that starting Ocrevus earlier is better at preventing myelin loss than delayed treatment initiation.

These trends from overall brain matter also were seen in analyses that specifically looked at MS lesions in the patients.

“Data from our present advanced MRI substudy suggest that ocrelizumab [Ocrevus] prevents demyelination in [normal-appearing brain matter] and in chronic lesions compared to” Rebif, the researchers concluded.

The fact that an increase in MWF was observed for some patients on Ocrevus suggests “that [Ocrevus] may create a more permissive environment for remyelination to occur in both focal and diffusely damaged tissue,” they added.

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