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

Ocrelizumab vs Ofatumumab: Relapse and Disability Outcomes

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?

Data Extraction

We asked a large language model to extract each data column below from each paper:

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)
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
Interventions Compared: List the specific treatments being compared:
- Drug names
- Dosage (if specified)
- Treatment duration
- Number of patients in each treatment group
Annualized Relapse Rate (ARR): Extract ARR data:
- Baseline ARR
- On-treatment ARR
- Confidence intervals
- Statistical significance of differences between groups
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
Follow-up Duration: Record:
- Total follow-up period
- Median follow-up time
- Range of follow-up times
Safety Outcomes: Extract information on:
- Treatment-related side effects
- Infection rates
- Infusion-related reactions
- Any serious adverse events

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
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); natalizumab: 0.11 (0.09–0.14); cladribine: 0.25 (0.12–0.57)	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 (0.06–0.11); natalizumab: 0.09 (0.07–0.12); fingolimod: 0.17 (0.15–0.19)	Relapsing-remitting multiple sclerosis	ocrelizumab/natalizumab similar, both superior to fingolimod
Zhu et al., 2023	ocrelizumab: 0.06 (0.04–0.08); fingolimod: 0.26 (0.12–0.48); dimethyl fumarate: 0.27 (0.12–0.56)	Relapsing-remitting multiple sclerosis post-natalizumab	ocrelizumab superior to both
Roos et al., 2024	ocrelizumab: 0.05; cladribine: 0.09; natalizumab: 0.06	Relapsing-remitting multiple sclerosis	ocrelizumab superior to cladribine/fingolimod, similar to natalizumab/alemtuzumab

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: 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

Comparative Effectiveness

Direct registry-based comparisons of ocrelizumab and ofatumumab highlight no significant difference in annualized relapse rate or confirmed disability progression in studies.

Registry Data Considerations

The evidence base for ofatumumab is limited, with only a few small, short-term studies.
Observational design and differences in patient populations may affect comparability across studies.