TOPLINE

Rituximab was noninferior to ocrelizumab in preventing new disease activity and had a similar safety profile in patients with newly diagnosed relapsing multiple sclerosis (MS), a trial showed.

METHODOLOGY

• Researchers conducted this phase 3, randomized, double-blind noninferiority trial involving 216 patients with newly diagnosed relapsing MS diagnosed in the previous 12 months at 12 neurology departments in Norway and Sweden from 2020 to 2022.
• Patients were randomly assigned in a 3:2 ratio to receive either intravenous rituximab 1000 mg at baseline and then 500 mg every 6 months (n = 132; mean age, 37.4 years; 72% women) or intravenous ocrelizumab 600 mg at baseline and every 6 months (n = 84; mean age, 36.6 years; 68% women), with treatment continuing for 24 months and follow-up extending to 30 months.
• Noninferiority was defined as a lower limit of the two-sided 95% CI for the risk difference (rituximab minus ocrelizumab) of at least -10 percentage points. MRI scans were obtained at baseline and at 6, 12, and 24 months.
• The primary endpoint was the absence of new or enlarging lesions on T2-weighted MRI from month 6 to month 24 in both groups. Secondary endpoints included the annualized relapse rate, freedom from relapse, confirmed disability progression and improvement, and safety profiles.

TAKEAWAY

• 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 (risk difference, -2.6 percentage points), meeting the prespecified noninferiority criterion (two-sided P = .03).
• The annualized relapse rates were not significantly different between the groups: 0.09 with rituximab and 0.04 with ocrelizumab. At month 24, no significant difference was observed among the proportion of patients who remained relapse-free (92% with rituximab; 94% with ocrelizumab).
• Confirmed disability progression and confirmed lessening of disability were not significantly different between groups.
• Serious adverse events occurred in 8% vs 7% of patients in the rituximab group vs the ocrelizumab group. Infections were more common in the rituximab group than in the ocrelizumab group (82% vs 69%), but the percentage of serious infections was similar (8% vs 7%, respectively).

IN PRACTICE

“In this trial, rituximab was noninferior to ocrelizumab, on the basis of a 10-percentage-point noninferiority margin, in preventing new disease activity on MRI from 6 to 24 months after the start of treatment in newly diagnosed relapsing multiple sclerosis,” the investigators of the study wrote.

SOURCE

The study was led by Øivind Torkildsen, MD, PhD, Neuro-SysMed, Haukeland University Hospital, Bergen, Norway. It was published online on July 1 in The New England Journal of Medicine.

LIMITATIONS

The small number of MRI and clinical events limited the precision of secondary analyses and prevented meaningful subgroup analyses. The trial was not powered to detect differences in safety outcomes or rare adverse events, and the follow-up period was too short to exclude potential longer-term differences in outcomes. About half of participants came from a single, high-volume center; the trial population was predominantly of Northern European ancestry and was enrolled largely from a publicly funded healthcare system; and the study included only treatment-naive patients, all of which may limit generalizability.

DISCLOSURES

The study was funded by the Research Council of Norway and KLINBEFORSK, with additional funding from the Swedish Research Council, Region Stockholm, the Swedish Brain Fund, the Erling Persson Foundation, and the Horizon Europe Framework Programme. Disclosure information for the study investigators is available in the original study publication.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.