Elicit: Ocrelizumab vs Ofatumumab: Relapse and Disability Outcomes (public)

Ocrelizumab vs Ofatumumab: Relapse and Disability Outcomes (public)

What is the annualized relapse rate and confirmed disability progression with ocrelizumab vs ofatumumab in registry data?

In registry studies, ocrelizumab and ofatumumab show comparable annualized relapse rates (0.059 vs 0.038, p = 0.185) and both achieve 0% confirmed disability progression at 12 months.

Abstract

Registry studies in multiple sclerosis report that ocrelizumab and ofatumumab yield comparable outcomes. In one large, multicenter, propensity‐matched study (Zanghì et al., 2024), the annualized relapse rate was 0.059 with ocrelizumab versus 0.038 with ofatumumab (p = 0.185), and both treatments showed 0% confirmed disability progression over 12 months. A small post–natalizumab cohort (Cunha et al., 2025) likewise observed no significant change in relapse rate or in Expanded Disability Status Scale scores between ocrelizumab and ofatumumab. Other registry reports of ocrelizumab document relapse rates ranging from 0.014 to 0.11, with very low rates of confirmed disability progression over follow-up intervals from 6 months to several years.

These findings indicate that, based on available registry data, ocrelizumab and ofatumumab produce similar outcomes in annualized relapse rate and short-term disability progression among patients with multiple sclerosis.

Methods

We analyzed 40 sources from an initial pool of 999, using 8 screening criteria. Each paper was reviewed for 7 key aspects that mattered most to the research question.

Screening

We screened in sources based on their abstracts that met these criteria:

Multiple Sclerosis Population: Does this study include patients with multiple sclerosis (any subtype)?
Target Medications: Does this study report outcomes for patients treated with ocrelizumab and/or ofatumumab, allowing for direct or indirect comparison between these treatments?
Real-World Data Source: Does this study utilize registry data, real-world databases, or observational cohorts (rather than randomized controlled trials)?
Relevant Outcomes: Does this study report annualized relapse rate and/or confirmed disability progression?
Appropriate Study Design: Is this study an observational study (cohort study, case-control study), systematic review, or meta-analysis?
MS-Focused Study: Is this study NOT focusing exclusively on conditions other than multiple sclerosis?
Adequate Study Type: Is this study NOT a case report, case series, editorial, letter, or conference abstract?
Adult or Mixed Population: Is this study NOT focusing exclusively on pediatric populations?

Results

Characteristics of Included Studies

Study	Study Design	Registry Source	Population Size	Follow-up Duration	Full text retrieved
Zanghì et al., 2024	Retrospective cohort, multicenter, propensity-matched	Italian multiple sclerosis centers	396 (ocrelizumab: 216, ofatumumab: 180)	Mean 13.2 months	Yes
Zhu et al., 2022	Retrospective, multicenter, inverse probability of treatment weighting, registry	MSBase	1045	Median 1.8 years	Yes
Ghajarzadeh et al., 2025	Systematic review/meta-analysis	Multiple	No mention found	No mention found	No
Cunha et al., 2025	Retrospective cohort	No mention found	59	No mention found	No
Epstein et al., 2021	Retrospective chart review	No mention found	56	2 years	No
Ellwardt et al., 2020	Retrospective, multicenter, observational	3 neurology centers	210	Median 200 days	No
Cellerino et al., 2021	Prospective, single-center, observational	No mention found	153	Median 1.9 years	Yes
Muros-Le Rouzic et al., 2024	Retrospective, registry, multicenter, propensity score matching	OPERA, NTD	611 (OPERA), 7141 (NTD)	5.5 years	No
Zhu et al., 2023	Retrospective, multicenter, inverse probability of treatment weighting, registry	MSBase	1386	Median 2.7 years	Yes
Schuldesz et al., 2025	Prospective, single-center, cohort	No mention found	98	2 years	No

Annualized Relapse Rate

Study	Treatment	Annualized Relapse Rate (95% CI)	Study Population
Zanghì et al., 2024	ocrelizumab: 0.059; ofatumumab: 0.038 (p=0.185)	Relapsing multiple sclerosis	No significant difference
Zhu et al., 2022	ocrelizumab: 0.07 (0.04–0.13)	Relapsing-remitting multiple sclerosis post-fingolimod	ocrelizumab superior to cladribine, lower than natalizumab
Cunha et al., 2025	rituximab: 0.08 (post-switch); ocrelizumab/ofatumumab: no significant change	Post-natalizumab	No significant change for ocrelizumab/ofatumumab

Confirmed Disability Progression

Study	Treatment	Confirmed Disability Progression Rate	Time to Progression
Zanghì et al., 2024	ocrelizumab/ofatumumab: 0%	12 months	No difference
Zhu et al., 2022	ocrelizumab/natalizumab: no mention found	No mention found	No significant difference
Cunha et al., 2025	ocrelizumab/ofatumumab: no significant change; rituximab: EDSS increased (p=0.022)	No mention found	No significant difference for ocrelizumab/ofatumumab

Comparative Effectiveness

Direct registry-based comparisons of ocrelizumab and ofatumumab:

Zanghì et al., 2024: No significant difference in annualized relapse rate or confirmed disability progression between ocrelizumab and ofatumumab over 12 months.
The evidence base for ofatumumab is much smaller and less mature than for ocrelizumab, with limited sample sizes and shorter follow-up.

References

[A. Zanghì et al., (2024). Ocrelizumab and ofatumumab comparison: an Italian real-world propensity score matched study. Journal of Neurology]

[Sahla El Mahdaoui et al., (2022). Intravenous ofatumumab treatment of multiple sclerosis and related disorders: An observational study. Multiple Sclerosis and Related Disorders]

[Chao Zhu et al., (2022). Comparing switch to ocrelizumab, cladribine or natalizumab after fingolimod treatment cessation in multiple sclerosis. Journal of Neurology Neurosurgery & Psychiatry]

[I. Roos et al., (2023). Rituximab vs Ocrelizumab in Relapsing-Remitting Multiple Sclerosis. JAMA Neurology]

[I. Roos et al., (2022). Comparison of the effectiveness of ocrelizumab vs interferon β, fingolimod and natalizumab on relapses in relapsing-remitting multiple sclerosis.]