Natalizumab, ocrelizumab equally effective in multiple sclerosis

In patients with relapsing or progressing multiple sclerosis (MS), clinical outcomes are similar following treatment with natalizumab vs ocrelizumab, according to a retrospective study.

Analysis of data from a propensity-score matched cohort of natalizumab- and ocrelizumab-treated patients demonstrated no significant difference in the proportion of those showing no evidence of disease activity based on the following parameters (NEDA-3): absence of clinical relapses, disease activity on MRI, and sustained disability worsening. The NEDA-3 rates over a 5-year follow-up were 50.5 percent and 65 percent, respectively (hazard ratio [HR], 0.64, 95 percent confidence interval [CI], 0.34–1.24; p=0.187). [Neurotherapeutics 2025;22:e00537]

Neither natalizumab nor ocrelizumab was better than the other at preventing relapses (HR, 0.41, 95 percent CI, 0.11–1.57; p=0.193), new T2 hyperintense lesions on MRI (HR, 0.37, 95 percent CI, 0.10–1.44; p=0.152), and disability progression (assessed using the Expanded Disability Status Scale [EDSS]; HR, 1.43, 95 percent CI, 0.60–3.40; p=0.417).

With regard to safety, ocrelizumab-treated patients had greater odds of experiencing adverse events (AEs) compared with those who received natalizumab (odds ratio [OR], 4.50, 95 percent CI, 1.53–16.50; p=0.011). The most common AEs were abnormalities in blood test (anaemia, lymphocytopenia, hypogammaglobulinemia), SARS-CoV-2 infections, and infusion-related reactions. None of these AEs were considered life-threatening.

Treatment was discontinued in 21 patients in the natalizumab group, due mostly to John Cunningham (JC) virus positivity JCV positivity (n=15). In the ocrelizumab group, 14 patients discontinued treatment for reasons including transfer to another MS centre, pregnancy, and patient decision. The difference in the incidence of treatment discontinuation between the two groups was not significant (OR, 0.58, 95 percent CI, 0.26–1.26; p=0.174).

“In our study, we evaluated a mixed cohort of relapsing-remitting, secondary progressive, and primary progressive MS patients. In clinical practice monoclonal antibodies like natalizumab and ocrelizumab are often prescribed as highly effective treatments not only to reduce early inflammatory activity but also to prevent progression independent of relapse activity, both in treatment-naïve patients and those switching from other disease-modifying treatments,” said lead researcher Dr Elena Barbuti from Sapienza University, Rome, Italy, who presented the study at EAN 2025.

Barbuti noted that the findings are consistent with earlier research, which showed no significant difference in effectiveness between ocrelizumab and natalizumab, particularly in treatment-naïve relapsing-remitting MS patients. [Mult Scler Relat Disord 2024;87:105594; Ann Clin Transl Neurol 2024;11:2008-2015]

“Our study extends those findings to patients transitioning from other disease-modifying treatments and provides insights into progressive MS patients, who constitute 20 percent of the total population analysed, thereby reflecting a more typical clinical population,” she said.

For the study, Barbuti and colleagues looked at the medical records of MS patients treated at two Italian tertiary centres. They used propensity scores to match 70 natalizumab-treated patients to 70 ocrelizumab-treated patients. The mean age was 45 years, and 65.7 percent of the patients were female. The mean disease duration was 14 years, and the mean follow-up duration was 60 months. Treatment duration was longer in the natalizumab group than in the ocrelizumab group (mean, 77.8 vs 71.2 months; p=0.045).