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 relapses compared with three other established therapies. The findings, based on real-world data from over 16,000 patients, highlight the CD20-targeting monoclonal antibody's effectiveness while revealing potential limitations in current MS treatment approaches.
Multi-Registry Analysis Reveals Significant Differences
The comprehensive analysis evaluated ocrelizumab using real-world data from three large MS registries: MSBase, OFSEP, and the Danish MS Registry. Researchers 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.
The most striking differences emerged in the fingolimod comparison, where MS relapse rates were significantly lower with ocrelizumab (0.06 vs 0.14; p<0.001). Fingolimod patients demonstrated more than twice the risk of relapse (HR 2.26, 95% CI 1.98–2.58), along with a higher risk of relapse-associated worsening and a lower likelihood of disability improvement.
Modest but Consistent Benefits Against High-Efficacy Therapies
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.
Dr. Izanne Roos, lead author of the study from the University of Melbourne, noted the clinical context of these findings: "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."
Treatment Tolerability and Persistence
The study examined treatment persistence as a proxy for tolerability, given that adverse event data were not consistently available across registries. The analysis revealed favorable tolerability profiles, with only 8% of natalizumab patients and 6% of ocrelizumab patients discontinuing treatment due to poor tolerability, suggesting both therapies are generally well-tolerated.
Implications for Progressive Disease Management
Despite ocrelizumab's consistent reduction in relapses and relapse-associated worsening, the study found no evidence of differences in progression independent of relapse activity or disability improvement compared with the other high-efficacy therapies. This finding has significant implications for the future direction of MS treatment development.
"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.
The research underscores both the therapeutic value of ocrelizumab in relapse prevention and the ongoing challenge of addressing progressive aspects of multiple sclerosis that occur independently of inflammatory relapses.
