Post hoc analysis of the OPERA I (NCT01247324) and II (NCT01412333) clinical trials demonstrated that treatment with Ocrevus (ocrelizumab; Genentech, South San Francisco, CA) was associated with a greater improvement in processing speed and a lower risk of confirmed cognitive decline compared with interferon beta (IFNβ)-1a treatment in individuals with relapsing multiple sclerosis (RMS). These results were published in Multiple Sclerosis and Related Disorders. Study authors note that additional studies are needed to assess the effect of Ocrevus on cognition due to methodological limitations of the analysis.

This pooled analysis included 1656 participants with RMS who were randomized to receive either intravenous Ocrevus (600 mg every 24 weeks; n=827) or subcutaneous IFNβ-1a (44 μg 3 times weekly; n=829). Cognitive function was assessed using the written or oral Symbol Digit Modalities Test (SDMT) at baseline and every 12 weeks for 96 weeks. Longitudinal linear models were used to assess change from baseline, and Cox regression models estimated risk of confirmed SDMT decline of ≥4 points sustained over 12 or 24 weeks.

Key results include:

  • Ocrevus treatment was associated with a greater mean SDMT improvement over 96 weeks (5.4 points; 95 % CI, 4.4 to 6.5) compared with IFNβ-1a treatment (4.0 points; 95% CI, 3.0 to 5.1).
  • Ocrevus treatment was associated with a lower risk of clinically meaningful SDMT decline (≥4 points) compared with IFNβ-1a treatment at ≥12 weeks confirmed decline (12.7 % vs 18.4%; hazard ratio [HR] 0.63; 95% CI, 0.47 to 0.85; P=.003) and ≥24 weeks confirmed decline (7.9% vs 12.9 %; HR 0.57; 95% CI, 0.39 to 0.82; P=.003).

Source: Benedict RH, Kappos L, Miller A, et al. Cognitive effects of ocrelizumab vs interferon β-1a in relapsing multiple sclerosis: a post hoc analysis of the OPERA I/II trials. Mult Scler Relat Disord. 2025;95:106310. doi:10.1016/j.msard.2025.106310