Rituximab Vs Ocrelizumab in Newly Diagnosed Relapsing MS

Key Takeaways

• Rituximab was reported to meet the trial's prespecified noninferiority threshold versus ocrelizumab for the MRI lesion outcome from months 6 to 24.
• Relapse, disability, and cognitive-performance findings were reported as similar between groups, although those measures were summarized qualitatively.
• Infections were reported more often with rituximab, while serious adverse event rates were similar between groups.

In a head-to-head rituximab versus ocrelizumab trial, 92.2% of adults with newly diagnosed relapsing multiple sclerosis and recent disease activity remained free of new or enlarging T2 lesions with rituximab. The corresponding estimate with ocrelizumab was 94.8%, leaving the groups close on the prespecified MRI comparison. Investigators evaluated whether rituximab would stay within a planned noninferiority boundary rather than exceed the comparator. The comparison tracked MRI-detected disease activity across the 24-month treatment period.

The phase 3 trial used a multicenter, double-blind, noninferiority design in adults with newly diagnosed relapsing multiple sclerosis and recent disease activity. It provided a direct randomized comparison of two anti-CD20 regimens in this setting. Investigators randomly assigned 218 participants in a 3:2 ratio to rituximab or ocrelizumab. Of those randomized, 216 received treatment, including 132 assigned to rituximab and 84 assigned to ocrelizumab. Both study drugs were administered every 6 months throughout the 24-month treatment course, aligning dosing with the prespecified MRI window.

The primary MRI endpoint was the absence of new or enlarging lesions on T2-weighted MRI from month 6 to month 24. Noninferiority required the lower limit of the 95% confidence interval for the rituximab-minus-ocrelizumab risk difference to be at least -10 percentage points. The reported risk difference was -2.6 percentage points, with a 95% confidence interval of -9.4 to 4.3. Because the interval's lower bound stayed above the prespecified threshold, the planned MRI comparison supported a noninferiority conclusion. Taken together, these data showed that the prespecified MRI noninferiority end point was met.

Safety findings differed mainly on infections, which were more common with rituximab than with ocrelizumab, at 82% versus 69%. Serious adverse events were reported at similar rates, occurring in 8% and 7% of participants, respectively. Overall, rituximab was noninferior to ocrelizumab in suppressing MRI-detected disease activity from 6 to 24 months.