Objective:

To evaluate the noninferiority of rituximab compared to ocrelizumab in preventing new or enlarging T2-weighted MRI lesions in patients with newly diagnosed relapsing multiple sclerosis.

Approach:

• Trial Design: Randomized, double-blind, multicenter, noninferiority trial conducted at 12 neurology departments in Norway and Sweden.
• Participants: 218 participants aged 18 to 60 years with newly diagnosed relapsing MS were randomized in a 3:2 ratio to receive either rituximab or ocrelizumab.
• Treatment Regimen: Rituximab 1000 mg at baseline followed by 500 mg every 6 months; ocrelizumab 600 mg at baseline and every 6 months.
• Endpoints: Primary endpoint was absence of new or enlarging lesions on T2-weighted MRI from month 6 to month 24.

Key Findings:

• Rituximab was noninferior to ocrelizumab regarding the primary endpoint, with 89% of rituximab and 93% of ocrelizumab participants showing no new or enlarging lesions.
• Serious adverse events occurred at similar rates (8% for rituximab, 7% for ocrelizumab), but infections were more common with rituximab (82% vs 69%).
• Estimated annualized relapse rates were 0.09 for rituximab and 0.04 for ocrelizumab, with 92% of participants receiving rituximab and 94% receiving ocrelizumab remaining relapse-free through 24 months.

Interpretation:

The trial did not establish superiority or equivalence between rituximab and ocrelizumab in preventing MRI lesions.

Limitations:

• The trial was not powered to detect differences in secondary endpoints or rare safety outcomes.
• Follow-up was limited to 30 months, and the study population may not be generalizable to patients with longer disease duration or previous treatment exposure.
• Randomization implementation errors occurred at some sites.

Conclusion:

The trial results indicate the need for further studies to assess the comparative effectiveness of rituximab and ocrelizumab.

Sources:

• The New England Journal of Medicine