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. More on methods

Papers identified with Elicit search

n = 999

Papers screened using: Multiple Sclerosis Population, Target Medications, Real-World Data Source, Relevant Outcomes, Appropriate Study Design, MS-Focused Study, Adequate Study Type, Adult or Mixed Population

n = 999

Papers screened out

n = 959

Papers included for extraction

n = 40

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

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

Summary of study characteristics:

Study design:
- 28 studies were retrospective.
- 7 studies were prospective.
- 2 studies were systematic reviews or meta-analyses.
- 19 studies were multicenter; 11 were single-center or monocentric.
- 14 studies were described as observational; 9 as cohort studies.
- 34 studies used registry-based data.
- 9 studies used propensity score matching or similar methods; 3 used inverse probability of treatment weighting.
- Other designs included randomized controlled trial/open-label extension (1), chart review (2), cross-sectional (1), post-authorization (1), and Bayesian propensity score matching (1).
Registry source:
- 24 studies used a named registry, most commonly MSBase (8 studies), NTD (2), CONFIDENCE (2), OPERA (2), MENACTRIMS (1), DMSR (1), Kuwait (1), Danish (1), and Bari (1).
- 4 studies used multiple or unspecified registries.
- No registry source was found for 12 studies.
- Countries/regions represented include Germany (at least 5 studies), Italy (at least 3), United Kingdom (at least 2), France, Denmark, Turkey, Australia, and Kuwait.
Population size:
- 8 studies included fewer than 100 participants.
- 14 studies included 100–499 participants.
- 6 studies included 500–999 participants.
- 10 studies included 1000 or more participants.
- No mention of population size was found for 5 studies.
Follow-up duration:
- 6 studies had follow-up durations of less than 1 year.
- 8 studies had follow-up durations of 1–2 years.
- 15 studies had follow-up durations of 2–5 years.
- 4 studies had follow-up durations longer than 5 years.
- No mention of follow-up duration was found for 7 studies.

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	(p=0.185)	Relapsing multiple sclerosis	No significant difference
Zhu et al., 2022	ocrelizumab: 0.07	(0.04–0.13); 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	(0.06–0.11); natalizumab: 0.09	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	Relapsing-remitting multiple sclerosis post-natalizumab	ocrelizumab superior to both
Roos et al., 2024	ocrelizumab: 0.05	cladribine: 0.09; natalizumab: 0.06; fingolimod: 0.12; alemtuzumab: 0.04	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	(SD 0.31)	Relapsing multiple sclerosis	Annualized relapse rate declines over 5 years
Guerra et al., 2025	ocrelizumab: 0.02	(0.004–0.062) (year 2)	Relapsing-remitting/primary progressive/secondary progressive multiple sclerosis	Annualized relapse rate drops from 0.61 pre-treatment

Summary of annualized relapse rate findings:

Range of annualized relapse rate for ocrelizumab:0.014 to 0.11 across 12 studies reporting this outcome.
Direct head-to-head comparisons:9 studies included direct comparisons between ocrelizumab, ofatumumab, or rituximab and other disease-modifying therapies.
Within-group changes:5 studies reported a drop in annualized relapse rate after switching to ocrelizumab, with pre-treatment rates as high as 0.8 and post-treatment rates as low as 0.014.
Comparative effectiveness:
- Ocrelizumab was reported as superior to at least one comparator in 5 studies (most often fingolimod or cladribine).
- Ocrelizumab was reported as similar in effectiveness to comparators (most often natalizumab or alemtuzumab) in 7 studies.
- Ocrelizumab was reported as inferior to a comparator in 1 study (lower than natalizumab in Zhu et al., 2022).
Ofatumumab data:Only 1 study (Zanghì et al., 2024) reported annualized relapse rate for ofatumumab, finding no significant difference compared to ocrelizumab.
Rituximab data:1 study (Cunha et al., 2025) reported annualized relapse rate for rituximab post-switch.
Comparators:Natalizumab and fingolimod were the most common comparators, each included in 5–6 studies.
Reporting gaps:5 studies did not mention annualized relapse rate or comparative effectiveness for ocrelizumab, ofatumumab, or rituximab.

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
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

Summary of confirmed disability progression findings:

Studies with ocrelizumab as a treatment group:7 studies.
Studies with ofatumumab alone:1 study.
Studies with ocrelizumab/ofatumumab combined:3 studies.
Other treatments compared:rituximab (1 study), natalizumab (2 studies, plus 1 ocrelizumab/natalizumab), fingolimod (2 studies), cladribine (1 study).
Numerical confirmed disability progression rates or event counts:Found in 6 studies, with reported values including 0% (2 studies), 48 events (ocrelizumab), 184 events (fingolimod), 26.4% (year 2) → 7.85% (year 4), standard interval dosing 8.3%, extended interval dosing 10.9%, and for subtypes: relapsing-remitting multiple sclerosis >97% confirmed disability progression-free, secondary progressive multiple sclerosis 48.9%, primary progressive multiple sclerosis 57.2%.
Time to progression or follow-up duration:Reported in 9 studies, ranging from 6 months to 5 years. The most common time points were 12 months (2 studies) and 5 years (2 studies).
Statistical significance of confirmed disability progression or progression comparisons:
- 8 studies reported no significant difference or comparable effectiveness between groups.
- 3 studies reported a significant difference, with ocrelizumab associated with lower risk than fingolimod (1 study), lower risk than cladribine (1 study), and a significant effect only in secondary progressive multiple sclerosis (1 study).
- No mention of statistical significance was found in 4 studies.

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.

Comparative findings for ocrelizumab:

In these studies, ocrelizumab was reported to be superior to fingolimod and cladribine for annualized relapse rate, and similar to natalizumab and alemtuzumab.
Confirmed disability progression rates were low and similar between ocrelizumab and natalizumab, and lower than fingolimod.
Safety profiles were not systematically reported; we did not find mention of new safety signals in the available studies.

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