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. More on methods
Papers identified with Elicit search
n = 999
Papers screened out
n = 959
Papers included for extraction
n = 40
Data extraction
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
- 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.
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 | ocrelizumab: median 1.8 years; cladribine: 1.1 years; natalizumab: 3.6 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 (range 30–1674) | No |
| Cellerino et al., 2021 | Prospective, single-center, observational | No mention found | 153 | Median 1.9 years (1.3–2.7) | 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 |
Effects
Annualized Relapse Rate
| Study | Treatment | Annualized Relapse Rate (95% CI) | Study Population | Effect Size |
|---|---|---|---|---|
| Zanghì et al., 2024 | ocrelizumab: 0.059; ofatumumab: 0.038 | Relapsing multiple sclerosis | No significant difference | |
| Zhu et al., 2022 | ocrelizumab: 0.07; natalizumab: 0.11 | 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 | |
| Boz et al., 2023 | ocrelizumab: 0.08; natalizumab: 0.09 | Relapsing-remitting multiple sclerosis | ocrelizumab/natalizumab similar, both superior to fingolimod | |
| Zhu et al., 2023 | ocrelizumab: 0.06; fingolimod: 0.26 | Relapsing-remitting multiple sclerosis post-natalizumab | ocrelizumab superior to both | |
| Roos et al., 2024 | ocrelizumab: 0.05; cladribine: 0.09 | Relapsing-remitting multiple sclerosis | ocrelizumab superior to cladribine/fingolimod, similar to natalizumab/alemtuzumab | |
| Roos et al., 2022 | ocrelizumab: 0.08 vs interferon: 0.27; ocrelizumab: 0.03 vs fingolimod: 0.14; ocrelizumab: 0.06 vs natalizumab: 0.08 | Relapsing-remitting multiple sclerosis | ocrelizumab superior to interferon/fingolimod, similar to natalizumab | |
| Axhausen et al., 2025 | ocrelizumab/ofatumumab: no mention found | Active multiple sclerosis | Effectiveness comparable | |
| Buttmann et al., 2025 | ocrelizumab: 0.11 | Relapsing multiple sclerosis | Annualized relapse rate declines over 5 years | |
| Guerra et al., 2025 | ocrelizumab: 0.02 (year 2) | Relapsing-remitting/primary progressive/secondary progressive multiple sclerosis | Annualized relapse rate drops from 0.61 pre-treatment |
Confirmed Disability Progression
| Study | Treatment | Confirmed Disability Progression Rate | Time to Progression | Statistical Significance |
|---|---|---|---|---|
| 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: Expanded Disability Status Scale increased (p=0.022) | No mention found | No significant difference for ocrelizumab/ofatumumab | |
| Boz et al., 2023 | ocrelizumab/natalizumab/fingolimod: no mention found | 1–2 years | No significant difference | |
| Zhu et al., 2023 | ocrelizumab: 48 events; fingolimod: 184 events | No mention found | Fingolimod higher risk than ocrelizumab (hazard ratio 1.49, p=0.02) | |
| Roos et al., 2024 | ocrelizumab: hazard ratio 0.45 (0.26–0.78) vs cladribine | No mention found | ocrelizumab lower risk than cladribine | |
| Axhausen et al., 2025 | ocrelizumab/ofatumumab: no mention found | No mention found | Comparable effectiveness | |
| Buttmann et al., 2025 | ocrelizumab: no mention found | 5 years | No mention found | |
| Guerra et al., 2025 | ocrelizumab: 26.4% (year 2) → 7.85% (year 4) | 4 years | Significant only in secondary progressive multiple sclerosis | |
| Santiago-Setien et al., 2023 | ocrelizumab: 0% | 96 weeks | No difference |
Comparative Effectiveness
Direct registry-based comparisons of ocrelizumab and ofatumumab:
- Zanghì et al., 2024 (large, multicenter, propensity-matched study): No significant difference in annualized relapse rate or confirmed disability progression between ocrelizumab and ofatumumab over 12 months.
- Axhausen et al., 2025: Lateral switching between ocrelizumab and ofatumumab did not reduce effectiveness.
- Cunha et al., 2025 (small cohort post-natalizumab): No significant difference in annualized relapse rate or Expanded Disability Status Scale change for ocrelizumab and ofatumumab.
The evidence base for ofatumumab is much smaller and less mature than for ocrelizumab, with limited sample sizes and shorter follow-up.