Ocrelizumab vs Ofatumumab: Relapse and Disability Outcomes

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

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.

Paper search

Using your research question “What is the annualized relapse rate and confirmed disability progression with ocrelizumab vs ofatumumab in registry data?”, we searched across over 126 million academic papers from the Semantic Scholar corpus. We retrieved the 999 papers most relevant to the query.

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?

We considered all screening questions together and made a holistic judgement about whether to screen in each paper.

Data extraction

We asked a large language model to extract each data column below from each paper. We gave the model the extraction instructions shown below for each column.

• Study Design:

Identify and extract the specific type of study design. Look in the methods section for details such as:

• Retrospective or prospective
• Observational (registry, cohort) or interventional
• Multicenter or single-center
• Matching method used (e.g., propensity score matching)

If multiple design characteristics are present, list all. If unclear, note “design not clearly specified”. Prioritize the most specific description of the study design.

• Patient Population Characteristics:

Extract key patient demographic and clinical characteristics:

• Total number of patients
• Mean/median age
• Gender distribution
• Multiple sclerosis type (RRMS, PPMS, aSPMS)
• Mean disease duration
• Baseline Expanded Disability Status Scale (EDSS) score
• Treatment-naive status vs. previous treatment history

If ranges or confidence intervals are provided, include those. If data is missing for any characteristic, note “not reported”.

• Interventions Compared:

List the specific treatments being compared:

• Drug names
• Dosage (if specified)
• Treatment duration
• Number of patients in each treatment group

If multiple comparisons were made, list all. Ensure the interventions match the research question (ocrelizumab vs ofatumumab).

• Annualized Relapse Rate (ARR):

Extract ARR data:

• Baseline ARR
• On-treatment ARR
• Confidence intervals
• Statistical significance of differences between groups

Record the exact numerical values and confidence intervals. If ARR is reported differently (e.g., percentage of relapse-free patients), note this explicitly.

• Disability Progression:

Extract confirmed disability progression data:

• Method of measuring disability progression (e.g., 12-week confirmed disability progression)
• Percentage of patients with disability progression
• Changes in EDSS score
• Statistical significance of differences between groups

If multiple time points are reported, prioritize the primary follow-up period specified in the study.

• Follow-up Duration:

Record:

• Total follow-up period
• Median follow-up time
• Range of follow-up times

If multiple follow-up periods are reported, note the primary analysis period. If not clearly specified, note “follow-up duration not clearly reported”.

• Safety Outcomes:

Extract information on:

• Treatment-related side effects
• Infection rates
• Infusion-related reactions
• Any serious adverse events

If no safety issues are reported, explicitly note “no significant safety concerns reported”. Quantify side effects if possible (percentage of patients affected).

Results

Characteristics of Included Studies

Effects

Annualized Relapse Rate

Confirmed Disability Progression

Registry Data Considerations

• Several studies of ocrelizumab included large sample sizes and long follow-up (for example, CONFIDENCE and MSBase registries).
• The evidence base for ofatumumab is limited, with only a few small, short-term studies.
• Observational design, potential confounding, and differences in patient populations, prior treatment history, and follow-up duration may affect comparability across studies.
• The diversity of registry cohorts supports generalizability of findings for ocrelizumab, but the limited data for ofatumumab restricts conclusions about its comparative effectiveness in broader populations.

References

1. A. Zanghì, G. Borriello, S. Bonavita, R. Fantozzi, E. Signoriello, and others (2024). Ocrelizumab and ofatumumab comparison: an Italian real-world propensity score matched study. Journal of Neurology
2. Sahla El Mahdaoui, J. Christensen, M. Magyari, M. Wandall-Holm, F. Sellebjerg (2022). Intravenous ofatumumab treatment of multiple sclerosis and related disorders: An observational study. Multiple Sclerosis and Related Disorders
3. X. Montalban et al. (2023). Real‐world evaluation of ocrelizumab in multiple sclerosis: A systematic review. Annals of Clinical and Translational Neurology
4. Chao Zhu et al. (2022). Comparing switch to ocrelizumab, cladribine or natalizumab after fingolimod treatment cessation in multiple sclerosis. Journal of Neurology Neurosurgery & Psychiatry
5. I. Roos et al. (2023). Rituximab vs Ocrelizumab in Relapsing-Remitting Multiple Sclerosis. JAMA Neurology
6. I. Roos et al. (2022). 2242 Comparison of the effectiveness of ocrelizumab vs interferon β, fingolimod and natalizumab on relapses in relapsing-remitting multiple sclerosis. Abstracts
7. C. Boz et al. (2023). The comparative effectiveness of fingolimod, natalizumab, and ocrelizumab in relapsing-remitting multiple sclerosis. Neurological Sciences
8. Samantha Epstein et al. (2021). Evaluation of ocrelizumab in older progressive multiple sclerosis patients. Multiple Sclerosis and Related Disorders
9. E. Ellwardt et al. (2020). Ocrelizumab initiation in patients with MS. Neurology: Neuroimmunology & Neuroinflammation
10. M. Cellerino et al. (2021). Predictors of Ocrelizumab Effectiveness in Patients with Multiple Sclerosis. Neurotherapeutics
11. K. Bigaut et al. (2022). Ocrelizumab versus fingolimod after natalizumab cessation in multiple sclerosis: an observational study. Journal of Neurology
12. Y. Foong et al. (2024). Comparing ocrelizumab to interferon/glatiramer acetate in people with multiple sclerosis over age 60. Journal of Neurology Neurosurgery & Psychiatry
13. E. Muros-Le Rouzic et al. (2024). Five-year efficacy outcomes of ocrelizumab in relapsing multiple sclerosis: A propensity-matched comparison of the OPERA studies with other disease-modifying therapies in real-world lines of treatments. Journal of Central Nervous System Disease
14. Chao Zhu et al. (2023). Comparison Between Dimethyl Fumarate, Fingolimod, and Ocrelizumab After Natalizumab Cessation. JAMA Neurology
15. Amanda Claudia Schuldesz et al. (2025). Effectiveness of Ocrelizumab on Disease Progression and Disability Status in Multiple Sclerosis Patients: A Two-Year Prospective Cohort Study. Journal of Clinical Medicine
16. L. A. R. de Antonio et al. (2022). Relapsing-remitting and primary progressive multiple sclerosis treated with ocrelizumab: A comparative study. Multiple Sclerosis and Related Disorders
17. G. Giovannoni et al. (2022). Long-term efficacy of ocrelizumab in relapsing multiple sclerosis: 6 study years. Journal of Neurology Neurosurgery & Psychiatry
18. C. Alcalá et al. (2022). Effectiveness of rituximab vs. ocrelizumab for the treatment of primary progressive multiple sclerosis: a real-world observational study. Journal of Neurology
19. B. Yamout et al. (2025). Comparative effectiveness of natalizumab and anti-CD20 monoclonal antibodies in relapsing-remitting multiple sclerosis: a real-world propensity-score matched study. Journal of Neurology Neurosurgery & Psychiatry
20. H. Butzkueven et al. (2021). Real-world experience with ocrelizumab in the MSBase registry – Australian RRMS cohort. Oral abstracts