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.

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.

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.

• 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

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.

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 (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
... (additional studies not displayed to reduce length)

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 ...

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

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.
X. Montalban et al. (2023). Real‐world evaluation of ocrelizumab in multiple sclerosis: A systematic review. Annals of Clinical and Translational Neurology.
... (additional references not displayed for brevity)