#ECTRIMS2022 – Ocrevus Seems to Beat Rituximab in Reducing Relapses

Ocrevus (ocrelizumab), an anti-CD20 therapy developed by Genentech, seems to be superior to rituximab at lowering relapse rates among patients with relapsing-remitting multiple sclerosis (RRMS), according to data from two large MS registries.

Overall, the findings suggest that rituximab cannot be considered just as good as — or non-inferior to — Ocrevus, despite their similar mechanism of action. Rituximab is a cancer treatment that can be used off-label for multiple sclerosis (MS).

“Rituximab patients had a higher rate and risk of relapse than [Ocrevus]-treated patients,” said Izanne Roos, MD, PhD, a postdoctoral researcher in the Clinical Outcomes Research Unit at the University of Melbourne, and neurologist at the Royal Melbourne Hospital, in Australia.

However, it’s important that the findings are “explored further in a randomized non-inferiority clinical trial,” which is already ongoing in Denmark, according to Roos.

Roos discussed the findings in an oral presentation, titled “A non-inferiority study of rituximab versus ocrelizumab in relapsing-remitting multiple sclerosis,” at the 38th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), held Oct. 26–28 virtually and in Amsterdam.

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Cancer treatment rituximab used off-label for MS

Generally, CD20-targeted therapies are designed to kill off B-cells, the immune cells responsible for producing antibodies, including the self-reactive antibodies that drive MS and other autoimmune diseases.

One such therapy, rituximab, has been used for many years to treat various types of cancer and immune diseases. A few Phase 2 clinical trials have also demonstrated benefits of rituximab in RRMS patients, and the treatment is generally considered highly effective in MS. However, rituximab is not approved for the neurodegenerative disease and is thus used off-label for MS.

Ocrevus, which works similarly to rituximab, was approved in the U.S. for treating relapsing and progressive forms of MS, and is now approved in more than 95 countries. But no clinical trial has yet directly compared the effectiveness of Ocrevus and rituximab.

Rituximab patients had a higher rate and risk of relapse than [Ocrevus]-treated patients

In their study, the researchers examined data from two large MS registries — the international MSBase registry and the Danish MS Registry — to compare the two treatments.

The analysis included RRMS patients who had been treated with Ocrevus or rituximab after 2015 and for at least six months. Patients in the two groups were closely matched based a number of clinical and demographic factors, including age, sex, disease duration, disability level, relapse rates and MRI disease activity, and country.

After matching, a total of 710 patients who received Ocrevus and 186 treated with rituximab were included in the analysis. On average, the age in both groups was around 41 years, and they had been living with MS for about 11 years and had moderate disability. Patients also had experienced a median of 0.7 relapses in the year before treatment.

Study to determine if rituximab was as good as or non-inferior to Ocrevus

The main goal of this study was to determine if rituximab was as good, or non-inferior, to Ocrevus at lowering annual relapse rates. Other outcome measures compared between the groups included the risk of relapses as well as confirmed disability progression and improvement.

When comparing the annual relapse rate ratio between treatments, a ratio over 1 means that one treatment is superior to the other and a ratio below 1 favours the other treatment. In this particular analysis, a ratio over 1 would generally favor Ocrevus, and a ratio below 1 would favor rituximab.

However, for non-inferiority purposes, the team determined that at a ratio around 1.2, the two treatments could be considered reasonably similar, and thus, rituximab would be deemed non-inferior to Ocrevus.

This ratio of 1.2 would amount to a difference of about one relapse every five years between the two treatments. If the ratio was above that threshold, however, rituximab would be considered inferior to Ocrevus.

Results showed that, over a mean follow-up of 1.4 years, annual relapse rates were significantly higher for rituximab than Ocrevus: 0.2 vs. 0.09 relapses per year. The relapse rate ratio was 1.8, which was significantly higher than the non-inferiority margin of 1.2.

“Based on these results, we therefore cannot conclude non-inferiority of rituximab compared to [Ocrevus],” Roos said.

Over about three years of follow-up, the risk of relapse also was twofold higher among patients who received rituximab compared with those given Ocrevus.

No differences were observed between the two groups in terms of disability accumulation or improvements (less disability). However, Roos noted that an average follow-up time of 1.4 years “is probably a little bit short to make conclusions about these two treatments on disability.”

The findings overall do not support rituximab’s non-inferiority to Ocrevus.

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Ongoing Phase 3 trial comparing rituximab against Ocrevus

Because there are several biosimilars of rituximab, and the therapy is used off-label, treatment schedules and individual dosing may have varied across patients. Nonetheless, in an analysis of the subgroup of rituximab patients who received a known dose of 1,000 mg, the findings were largely similar.

Still, randomized, controlled clinical trials are needed to confirm the findings, according to Roos.

An ongoing Phase 3 trial called DanNORMS (NCT04688788) is currently comparing rituximab against Ocrevus in up to 594 adults, ages 18–65, with active MS, including RRMS, secondary-progressive MS, and primary-progressive MS.

Participants will be randomly assigned to receive one of the two therapies for two years, after which they will have the option to join an open-label extension phase and continue treatment for three more years.

The trial’s primary goal is to assess the percentage of patients without new or enlarging brain lesions on MRI scans. Secondary goals include measures of disability progression, relapse rates, motor and cognitive function, and quality of life. The trial may still be recruiting at sites in Denmark.

Note: The Multiple Sclerosis News Today team is providing in-depth coverage of the ECTRIMS Forum 2022 Oct. 26-28. Go here to see the latest stories from the conference.