麻豆传媒

Rituximab (Rituxan) did not show noninferiority compared with ocrelizumab (Ocrevus) in relapsing-remitting multiple sclerosis (MS), according to registry data.

The annualized relapse rate (ARR) was higher in MS patients treated with rituximab compared with ocrelizumab (ARR 0.20 vs 0.09, P<0.01; relapse rate ratio 1.8, 95% CI 1.4-2.4) over a mean follow-up of 1.5 years, reported Izanne Roos, PhD, of the University of Melbourne in Australia.

The cumulative relapse hazard was also higher among patients treated with rituximab versus ocrelizumab (HR 2.1, 95% CI 1.5-3.0), Roos said in a late-breaking presentation at the 2022 meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

No difference emerged between groups in disability accumulation over a mean follow-up of 1.44 years.

In pivotal trial data, ocrelizumab, a humanized monoclonal antibody targeting CD20+ B cells, by 46% and disability worsening by 40% compared with interferon beta-1a in relapsing-remitting MS. Rituximab, a chimeric monoclonal anti-CD20 drug, is prescribed as an off-label alternative to ocrelizumab.

"Rituximab has been around for 20 years and is used most commonly in the treatment of oncological malignancies, as well as rheumatological conditions," Roos said. "Despite a successful randomized phase II controlled trial of rituximab in remitting-relapsing multiple sclerosis, this drug was ... not pursued in favor of ocrelizumab."

"Ocrelizumab subsequently became our first licensed B-cell therapy for remitting-relapsing multiple sclerosis," she noted. "Despite this, rituximab is still used as an off-label alternative to ocrelizumab. This might be due to clinician choice, availability, or costs, and we know from randomized trials subsequently, as well as observational data, that rituximab is a highly effective therapy."

"However, we have never had a comparative effectiveness study looking at ocrelizumab and rituximab head-to-head," Roos said. "We therefore aimed to perform a noninferiority study looking precisely at this."

The researchers used data from two large MS observational registries -- and the Danish Multiple Sclerosis Registry () -- to identify relapsing-remitting MS patients treated after 2015 for 6 months or longer with either drug. All participants had at least 6 months of follow-up.

Patients with comparable baseline characteristics were matched by propensity score on age, sex, MS duration, disability as measured by Expanded Disability Status Scale () scores, prior relapse rate, prior therapy, disease activity, MRI lesion burden, and country.

A total of 710 ocrelizumab-treated patients (415 from MSBase and 285 from DMSR) were matched with 186 rituximab-treated patients (110 from MSBase and 76 from DMSR). Mean age in each group was about 41.5, mean disease duration was about 11.5 years, and mean EDSS scores were about 3.5. Women made up 68% of both groups.

The primary endpoint was ARR, with a prespecified noninferiority margin of 1.2 rate ratio. Secondary endpoints were relapse and 6-month confirmed disability accumulation outcomes in pairwise-censored groups.

The study had several limitations, Roos acknowledged. Ocrelizumab is a single product, while rituximab treatment may have included generic and biosimilar drugs. Rituximab treatment schedules -- as well as individual dosing, which could have ranged between 500 to 1,000 mg at each administration -- may have varied.

"It is therefore possible there might be differential responses within that single group," Roos said. "However, when looking at it more carefully, and only including patients who we know received 1,000-mg doses, our results were consistent."

In addition, only clinical outcomes were evaluated in the study. The 1.44-year average follow-up for disability outcomes was insufficient to draw conclusions, Roos noted.

"We did not show noninferiority of treatment with rituximab compared to ocrelizumab. However, I do think it's important for this to be explored further in a randomized , which is already in process," she added.

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