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Rituximab is noninferior to ocrelizumab in suppressing T2-weighted MRI lesions from month 6 to 24Trial shows rituximab works as well as ocrelizumab for MS

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Key Takeaway
Note that rituximab is noninferior to ocrelizumab for suppressing T2-weighted MRI lesions from month 6 to 24.

This Phase 3 multicenter randomized controlled trial evaluated 216 patients with newly diagnosed relapsing multiple sclerosis and recent disease activity. Participants were randomized to receive either rituximab or ocrelizumab every 6 months for a total duration of 24 months.

The primary outcome was the absence of new or enlarging lesions on T2-weighted magnetic resonance imaging (MRI) from month 6 to month 24. Results showed 92.2% with rituximab versus 94.8% with ocrelizumab, a difference of -2.6 percentage points (95% CI: -9.4 to 4.3). Noninferiority was met for the primary endpoint.

Secondary outcomes including relapse rates, disability outcomes, and cognitive-performance profiles appeared similar in both treatment groups. Regarding safety, infections were more common in the rituximab group (82%) compared to the ocrelizumab group (69%). Serious adverse events occurred in 8% of the rituximab group and 7% of the ocrelizumab group.

Limitations were not reported. Clinical practice relevance suggests that rituximab is noninferior to ocrelizumab in suppressing disease activity as detected by MRI from 6 to 24 months with a similar incidence of serious adverse events.

How this fits prior evidence

How this fits prior evidence: This finding addresses the management of relapsing multiple sclerosis, a condition also discussed in previous coverage regarding natalizumab's impact on disability progression and cladribine's reduction of annualized relapse rates by 58%. While those studies focused on different treatment modalities, this trial provides specific data comparing rituximab to ocrelizumab for MRI lesion suppression. It contributes to the evidence base for selecting appropriate disease-modifying therapies in newly diagnosed patients.

Living with multiple sclerosis means facing a condition that can cause unpredictable changes in the body. For people newly diagnosed, finding a reliable treatment to slow down disease activity is a top priority. A recent trial compared two specific medications, rituximab and ocrelizumab, to see how they performed over a 24-month period.

The study focused on adults with new relapsing multiple sclerosis. The results showed that both drugs were highly effective at preventing new or growing lesions on MRI scans. Specifically, 92.2% of patients on rituximab and 94.8% of those on ocrelizumab showed no new lesions between months 6 and 24. Other factors, like relapse rates and cognitive performance, remained similar for both groups.

Safety is a major consideration when choosing a treatment path. While both drugs had similar rates of serious side effects (8% for rituximab and 7% for ocrelizumab), infections were more common in the group receiving rituximab. Because these results are based on MRI findings rather than clinical outcomes as the primary measure, talk to your doctor to see which option fits your specific needs.

What this means for you:
Rituximab showed similar success to ocrelizumab in stopping brain lesions for people with new multiple sclerosis.

Common questions

How effective was rituximab compared to ocrelizumab?

The study found that both drugs were very similar in their effectiveness. Between months 6 and 24, 92.2% of patients taking rituximab had no new or enlarging lesions on MRI scans, while 94.8% of those taking ocrelizumab saw the same result.

Are there different side effects for these two treatments?

Both medications had similar rates of serious adverse events (8% for rituximab and 7% for ocrelizumab). However, infections were more common in the group receiving rituximab, occurring in 82% of those patients compared to 69% in the ocrelizumab group.

Who is this finding relevant for?

This study specifically involved adults who were newly diagnosed with relapsing multiple sclerosis and showed recent disease activity. If you have been recently diagnosed, speak with your doctor about these options.

Study Details

Study typeRct
Sample sizen = 218
EvidenceLevel 2
Follow-up6.0 mo
PublishedJul 2026
View Original Abstract ↓
BACKGROUND: Anti-CD20 monoclonal antibodies are effective for relapsing multiple sclerosis. However, data from head-to-head trials are lacking. METHODS: In this phase 3, multicenter, double-blind, noninferiority trial, we randomly assigned adults with newly diagnosed relapsing multiple sclerosis and recent disease activity in a 3:2 ratio to receive rituximab or ocrelizumab every 6 months for 24 months. The primary end point was the absence of new or enlarging lesions on T2-weighted magnetic resonance imaging (MRI) from month 6 to month 24. Noninferiority was defined as a lower limit of the 95% confidence interval for the risk difference (rituximab minus ocrelizumab) of greater than or equal to -10 percentage points. Secondary end points included efficacy and safety. RESULTS: A total of 218 participants underwent randomization; 216 received treatment (132 assigned to the rituximab group and 84 assigned to the ocrelizumab group). Between months 6 and 24, the estimated probability of having no new or enlarging lesions detected on T2-weighted MRI was 92.2% with rituximab and 94.8% with ocrelizumab, corresponding to a risk difference of -2.6 percentage points (95% confidence interval, -9.4 to 4.3), which met the prespecified noninferiority criterion. Relapse rates, disability outcomes, and cognitive-performance profiles appeared to be similar in the two groups. Infections were more common in the rituximab group than in the ocrelizumab group (in 82% vs. 69% of participants), although the percentage of participants with serious adverse events was similar in the two groups (8% and 7%, respectively). CONCLUSIONS: In participants with newly diagnosed relapsing multiple sclerosis and recent disease activity, rituximab was noninferior to ocrelizumab in suppressing disease activity as detected by MRI from 6 to 24 months, with a similar incidence of serious adverse events. (Funded by the Research Council of Norway and others; OVERLORD-MS ClinicalTrials.gov number, NCT04578639; EudraCT number, 2020-001205-23; EU Clinical Trials Register number, 2024-510716-71-00.).
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