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 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

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)

• 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

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

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.

Confirmed Disability Progression

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

• 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
• Chao Zhu et al., 2022. Comparing switch to ocrelizumab, cladribine or natalizumab after fingolimod treatment cessation in multiple sclerosis. Journal of Neurology Neurosurgery & Psychiatry
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