Ocrevus appears to be better than rituximab at preventing MS relapses

Ocrevus (ocrelizumab) appears to be more effective than rituximab at reducing relapse activity in people with relapsing-remitting multiple sclerosis (RRMS), but disability progression outcomes are comparable between the therapies, an observational study of patients reported.

“Study findings suggest that the effectiveness of rituximab on MS relapses was inferior to that of [Ocrevus],” the researchers wrote. “The study did not find evidence for a difference in the probability of disability accumulation or improvement.”

The study, “Rituximab vs Ocrelizumab in Relapsing-Remitting Multiple Sclerosis,” was published in JAMA Neurology.

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June 9, 2023 News by Lindsey Shapiro, PhD

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Research lacking into comparable effectiveness of Ocrevus and rituximab

Anti-CD20 monoclonal antibodies are a class of MS disease-modifying therapies that work to reduce disease activity by depleting B-cells, a type of inflammatory immune cell.

Three anti-CD20 monoclonal antibodies have been approved in the U.S. to treat relapsing forms of MS: Ocrevus followed by Kesimpta (ofatumumab), and, more recently, Briumvi (ublituximab-xiiy).

Rituximab is an anti-CD20 antibody that was developed before any of the currently approved MS therapies. While rituximab has never been formally approved to treat MS — it was originally developed to treat B-cell cancers — it long has been used as an off-label alternative. As an older medication no longer covered by patent protections, it is notably cheaper than the approved MS therapies.

Molecular differences between rituximab and the newer anti-CD20 therapies, like Ocrevus, might make the newer therapies more effective. However, there hasn’t been much research directly comparing the efficacy of these different treatments.

An international group of researchers used data from two large databases — the international MSBase and the Danish Multiple Sclerosis Registry — to compare outcomes among RRMS patients treated with either Ocrevus or rituximab.

“Although both therapies have similar mechanisms of action, the significantly lower cost of rituximab may motivate its preferential use despite off-label status. Whether these 2 therapies are interchangeable, however, remains an ongoing topic of debate,” the researchers wrote.

They identified more than 1,500 people who received one of the two therapies for at least six months between 2015 and 2021. However, there were notable differences between the two groups prior to treatment — patients given rituximab generally had more pronounced disability and more disease activity before starting treatment.

To account for these differences, the researchers conducted matching analyses to identify people on these therapies who were similar in their pretreatment characteristics.

“To our knowledge, the present study is the first noninferiority direct comparison of [Ocrevus] and rituximab, using rigorous methodology to mitigate group differences that allows direct comparison between therapies,” the researchers wrote.

80% lower risk of relapse among Ocrevus- vs. rituximab-treated patients

The final analysis included data on 710 people given Ocrevus and 186 treated with rituximab, who were followed on average for more 1.4 years. Most patients had been living with MS for more than a decade, and they had tried two or three other therapies before anti-CD20 treatment. Thus, the researchers noted that findings from this analysis may not apply to other populations, such as newly diagnosed patients starting on a first treatment.

Results showed that the average relapse rate was significantly lower for patients given Ocrevus compared with those given rituximab: 0.09 vs. 0.2 relapses per year, which works out to an 80% lower risk of relapse with Ocrevus.

The difference remained statistically significant in further sensitivity analyses and after allowing for potential unmeasured confounding variables.

Rates of disability worsening or improvement, as measured by Expanded Disability Status Scale (EDSS) scores, were not significantly different between patients given Ocrevus or rituximab. Still, the researchers noted that the relatively short follow-up time may not have been sufficient to fully measure differences in long-term disability.

Treatment discontinuation was three times more common among patients using rituximab than those on Ocrevus. But most patients who stopped rituximab switched to Ocrevus, and the researchers said this likely reflects a patient choosing to move to the newer therapy after it became available.

The researchers highlighted that this study is limited by its observational nature, and unlike clinical trials where conditions are rigorously controlled, real-world data is messier and can have undetected biases.

Clinical trials directly comparing rituximab and Ocrevus are ongoing, such as the Phase 3 study DanNORMS (NCT04688788) taking place in Denmark.

Editorial notes cost difference, ‘very low relapse rates’ with both treatments

In an accompanying editorial, a pair of scientists noted that the study’s authors matched patients based on clinical features like age and relapse activity, but they did not have data on race or socioeconomic status, which could have skewed the results.

“There may be a real-world tendency to use rituximab in underinsured patients or cost-pressured systems, representing some potential overlap with demographic and environmental risk factors that may predispose patients both to more inflammatory disease as well as greater risk for neurodegeneration,” they wrote.

Their editorial also noted that, while the difference in relapse rate between the two therapies was statistically significant (meaning not due to random chance), both therapies resulted in very low relapse rates overall, so it’s debatable whether this difference is clinically meaningful for patients.

Regardless, they noted that rituximab is less expensive and more widely available, so “in cost-pressured populations in which obtainment of more expensive high-efficacy therapies may be precluded, rituximab would still retain value as a high-efficacy treatment.”

This study was funded by Australia’s National Health and Medical Research Council and MS Australia. The MSBase database also receives financial support from pharmaceutical companies that include Biogen, Novartis, Merck, Roche, Teva, and Sanofi Genzyme. Ocrevus is marketed by Roche, which was not directly involved in this study.