Anti-CD20 therapies for multiple sclerosis have come to dominate the therapeutic (and publishing) landscape. Thus far in 2026, six studies have compared the relative efficacy and safety of ocrelizumab and rituximab.
In the phase III OVERLORD-MS study, 216 newly-diagnosed MS patients were randomized to ocrelizumab or rituximab every six months for 24 months (Torkildsen et al. N Engl J Med 2026;395:44-53). From month 6 to 24, the estimated probability of having no new/enlarging T2 lesions was slightly higher with ocrelizumab compared to rituximab (94.8% vs. 92.2%), which met non-inferiority criteria. Relapse rates, disability and cognitive performance were similar with the two treatments. Infections were more common in rituximab-treated patients (82% vs. 69%). OVERLORD-MS is the first of four trials (DanNORMS, Noisy Rebels and TRIO) in the ROC-MS initiative that will compare rituximab to ocrelizumab (Schoof et al. Mult Scler Relat Disord 2026:105:106858).
A propensity score-matched study in British Columbia also compared rituximab with ocrelizumab (Chu et al. Mult Scler 2026; epublished July 3, 2026). The annualized relapse rate (ARR) after a median of two years was somewhat lower with ocrelizumab (0.03 vs. 0.05). The adjusted ARR ratio for rituximab vs. ocrelizumab was 1.76; the adjusted cumulative risk of relapses was two-fold higher with rituximab (HR 2.17). The authors noted that comparisons were underpowered since relapses in both groups were rare.
A retrospective registry-based study examined 112 patients treated with rituximab or ocrelizumab in Finland in the period 2018-2024 (Savolainen et al. Eur J Neurol 2026;33:e70625). Mean ARR was 0.03 for both groups, there was no difference in relapse-free survival, and no significant differences in T2 lesion changes. The mean change from baseline in IgG was -13% with both therapies. Similarly, a Swedish cohort study reported that the rates of relapse reduction and infection with ocrelizumab and rituximab were comparable (Frisell et al. Ann Neurol 2026; epublished June 17, 2026).
A German cohort study conducted a three-way comparison of rituximab, ocrelizumab and ofatumumab in 262 patients treated for a median of 36 months (Stogbauer et al. Front Immunol 2026:17:1738865). For ocrelizumab vs. ofatumumab, there were no significant differences in ARR (0.11 vs. 0.08) or relapse-free survival. Median EDSS increased from baseline to month 24 from 3.5 to 4.5 with ocrelizumab, and from 2.25 to 3.0 with ofatumumab. Infection rates were lowest with ofatumumab. The proportion of patients who developed hypogammaglobulinemia was 15.1% with ocrelizumab, 22.7% with ofatumumab and 42.3% with rituximab. Hypogammaglobulinemia developed more quickly during treatment with rituximab.
A prior systematic review also reported a higher rate of hypogammaglobulinemia, infections and genitourinary infections with rituximab compared to ocrelizumab (Scavone et al. Expert Opin Drug Saf 2025; epublished October 24, 2025). There was a higher prevalence of serious infections (6%) with ocrelizumab. A separate analysis by the University of California reported a more favourable safety profile with ocrelizumab, with rituximab associated with higher rates of all-cause hospitalizations (rate ratio 4.54) and hypogammaglobulinemia (HR 4.59) (Cerono et al. Ann Neurol 2026;99:248-260).