Ocrelizumab provides superior control of multiple sclerosis relapses compared to other therapies

New research presented at the 41st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS 2025) demonstrates that ocrelizumab provides superior control of multiple sclerosis (MS) relapses compared with fingolimod, natalizumab, and alemtuzumab.

Ocrelizumab, a monoclonal antibody targeting CD20+ B cells, was evaluated using real-world data from three large MS registries: MSBase, OFSEP, and the Danish MS Registry. The analysis compared ocrelizumab-treated patients with cohorts receiving fingolimod (2,600 vs. 4,103 patients), natalizumab (3,197 vs. 2,437 patients), and alemtuzumab (2,960 vs. 644 patients), all with at least six months of treatment and follow-up.

In the fingolimod comparison, MS relapse rates were significantly lower with ocrelizumab (0.06 vs 0.14; p<0.001). Fingolimod patients had a more than twice the risk of relapse (HR 2.26, 95% CI 1.98–2.58), a higher risk of relapse-associated worsening, and a lower likelihood of disability improvement.

Compared with natalizumab and alemtuzumab, ocrelizumab also showed lower relapse rates (0.07 vs 0.10 and 0.12 vs 0.18, respectively; both p<0.001). Additionally, ocrelizumab reduced the risk of relapse-associated worsening compared with natalizumab, while no such difference was observed compared with alemtuzumab.

While the differences between ocrelizumab and natalizumab or alemtuzumab were statistically significant, they were modest. For example, there was approximately one fewer relapse per 33 patient-years when comparing natalizumab to ocrelizumab. These differences were most pronounced in patients with recent disease activity, prior treatment failure, or those not treatment naïve."

Dr. Izanne Roos, lead author of the study

Adverse event data were not consistently available across registries. As a proxy for tolerability, the study examined treatment persistence. Only 8% of natalizumab patients and 6% of ocrelizumab patients discontinued treatment due to poor tolerability, suggesting both therapies are generally well-tolerated.

While ocrelizumab consistently reduced relapses and relapse-associated worsening, there was no evidence of differences in progression independent of relapse activity or disability improvement compared with the other high-efficacy therapies.

"These findings suggest we may have reached the ceiling of disability benefit achievable via relapse suppression alone, highlighting the urgent need for treatments that target relapse-independent progression," Dr. Roos concluded.