A National Danish Effectiveness Study of Ocrelizumab Versus Natalizumab in Multiple Sclerosis

BACKGROUND: Ocrelizumab and natalizumab are highly effective disease-modifying treatments for relapsing-remitting multiple sclerosis (RRMS). Direct comparison of effectiveness is crucial for optimizing treatment decisions and improving patient outcomes. The aim was to compare any difference in effectiveness of ocrelizumab and natalizumab on disease activity and progression in RRMS. METHODS: This was a national multicenter comparative effectiveness research study using data from the nationwide population-based registry of MS cases in Denmark. Patients were included from January 2018 to April 2023 with a history of RRMS treated with ocrelizumab or natalizumab. Inverse probability of treatment weighting based on propensity scores was applied. Main outcomes were the comparison of annualized relapse rate (ARR), time to first progression independent of relapse activity (PIRA), and time to first occurrence of new/enlarging T2 or contrast-enhancing lesions on cerebral MRI scans. RESULTS: We found no statistically significant differences in the ARR between ocrelizumab-treated (n = 542) and natalizumab-treated (n = 384) patients (mean [95% CI] ARR of 0.071 [0.057-0.088] and 0.071 [0.054-0.092], respectively) and in the ARR ratio (0.996, 95% CI [0.687-1.444], p = 0.983). Similarly, we did not find differences between the two groups in terms of time to first PIRA (HR, 1.34; 95% CI, 0.88-2.02; p = 0.17) and time to first inflammatory activity in MRI scans (HR, 1.04; 95% CI, 0.74-1.25; p = 0.78). CONCLUSIONS: The study could not demonstrate a difference in effectiveness of ocrelizumab and natalizumab treatment in this nationwide population-based registry study in risk of relapses, disability progression, and MRI activity.