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28-06-2023 | Multiple Sclerosis | Editor's Choice | News

Rituximab may not be a suitable alternative to ocrelizumab in treating RRMS

Author: Matthew Williams


medwireNews: Rituximab is inferior to ocrelizumab for the treatment of relapsing–remitting multiple sclerosis (RRMS) in terms of relapse rate, finds a real-world study published in JAMA Neurology.

While both these anti-CD20 monoclonal antibodies have similar mechanisms of action, rituximab costs significantly less and this “may motivate its preferential use despite off-label status,” say the researchers, adding: “Whether these 2 therapies are interchangeable, however, remains an ongoing debate.”

Thomas Kalincik (Royal Melbourne Hospital, Victoria, Australia) and team conducted an observational cohort study between 2015 and 2021 of 1613 patients with RRMS recruited from the MSBase Registry and Danish MS Registry.

Included patients had a moderate degree of disability, a mean MS duration of 11 years, and they had previously received two to three MS therapies. Of these, 710 were treated with two 300-mg doses of ocrelizumab given 14 days apart followed by 600 mg given every 6 months, while 186 received two 1000-mg doses of rituximab given 14 days apart followed by 500–1000 mg every 6 months for at least 6 months.

The primary outcome of the trial was noninferiority of annualized relapse rate (ARR) with rituximab versus ocrelizumab according to a prespecified noninferiority margin of 1.63. This was based on the known efficacy of ocrelizumab and the smallest clinically relevant difference in effectiveness between the two treatments of one relapse every 10 patient–years.

Relapse was defined as new symptoms or exacerbation of symptoms for at least 24 hours without concurrent illness or fever occurring at least 30 days after the previous relapse. This did not require confirmation with a change in disability score, however.

The results showed that patients in the rituximab group had a significantly higher ARR ratio, of 0.20 compared with 0.09 among those in the ocrelizumab group. The researchers say this translates to “a difference of 1 relapse every 9 patient–years.”

The ARR ratio was 1.8, which was above the predefined margin, as was the upper limit of the 95% confidence interval (1.4–2.4) and therefore “lack of a clinically relevant difference in the effectiveness between these 2 therapies should not be assumed,” say Kalincik and team.

They report that the cumulative risk for relapses was also twofold higher among the rituximab than the ocrelizumab group, although there was no difference between the two in the risk for disability accumulation or improvement on the Expanded Disability Status Scale.

Treatment discontinuation was a significant three times more common among patients given rituximab than ocrelizumab, but only a respective nine and 16 patients discontinued due to intolerance. Also, the researchers note that most patients discontinuing rituximab switched to ocrelizumab after it became available. 

In an accompanying editorial, Lauren Oommen (University of California, San Francisco, USA) and Stephen Krieger (Icahn School of Medicine at Mount Sinai, New York, USA) comment that “this study represents an important entry toward determination of comparative efficacy between 2 of the most widely used anti-CD20 [monoclonal antibodies] for MS worldwide.”

They point out, however, that prior to study treatment there was a trend toward higher disability and relapse in the rituximab group than the ocrelizumab group and greater exposure to more disease modifying therapies, which may not have been fully corrected in propensity matching. There was also no analysis of racial or socioeconomic data.

“There may be a real-world tendency to use rituximab in uninsured 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 explain.

Oommen and Krieger also question whether the outcome difference between the two study groups is “clinically meaningful and cost warranting,” especially in “cost-pressured populations in which obtainment of more expensive high-efficacy therapies may be precluded,” and where “rituximab would still retain value as a high-efficacy treatment.”

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2023 Springer Healthcare Ltd, part of the Springer Nature Group

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