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Ocrelizumab vs Ofatumumab: Relapse and Disability Outcomes (public)

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September 4, 2025

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

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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

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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 (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; 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

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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

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

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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, G. Borriello, S. Bonavita, R. Fantozzi, E. Signoriello, and 12 more\ (2024).Ocrelizumab and ofatumumab comparison: an Italian real-world propensity score matched study. Journal of Neurology

Sahla El Mahdaoui, J. Christensen, M. Magyari, M. Wandall-Holm, F. Sellebjerg\ (2022).Intravenous ofatumumab treatment of multiple sclerosis and related disorders: An observational study. Multiple Sclerosis and Related Disorders

X. Montalban, P. Matthews, A. Simpson, John L. Petrie, C. Sammon, and 3 more\ (2023).Real‐world evaluation of ocrelizumab in multiple sclerosis: A systematic review. Annals of Clinical and Translational Neurology

Chao Zhu, Zhen Zhou, I. Roos, Daniele Merlo, T. Kalincik, and 24 more\ (2022).Comparing switch to ocrelizumab, cladribine or natalizumab after fingolimod treatment cessation in multiple sclerosis. Journal of Neurology Neurosurgery & Psychiatry

I. Roos, S. Hughes, G. McDonnell, C. Malpas, S. Sharmin, and 31 more\ (2023).Rituximab vs Ocrelizumab in Relapsing-Remitting Multiple Sclerosis. JAMA Neurology

I. Roos, S. Sharmin, J. Lechner-Scott, K. Buzzard, O. Skibina, and 8 more\ (2022).2242 Comparison of the effectiveness of ocrelizumab vs interferon β, fingolimod and natalizumab on relapses in relapsing-remitting multiple sclerosis. Abstracts

C. Boz, S. Ozakbas, M. Terzi, R. Karabudak, S. Sevim, and 15 more\ (2023).The comparative effectiveness of fingolimod, natalizumab, and ocrelizumab in relapsing-remitting multiple sclerosis. Neurological Sciences

Samantha Epstein, K. Fong, P. D. De Jager, Libby Levine, C. Riley, and 3 more\ (2021).Evaluation of ocrelizumab in older progressive multiple sclerosis patients. Multiple Sclerosis and Related Disorders

E. Ellwardt, L. Rolfes, J. Klein, K. Pape, T. Ruck, and 6 more\ (2020).Ocrelizumab initiation in patients with MS. Neurology: Neuroimmunology & Neuroinflammation

M. Cellerino, G. Boffa, C. Lapucci, F. Tazza, E. Sbragia, and 11 more\ (2021).Predictors of Ocrelizumab Effectiveness in Patients with Multiple Sclerosis. Neurotherapeutics

K. Bigaut, L. Kremer, Thibaut Fabacher, G. Ahle, Mathilde Goudot, and 5 more\ (2022).Ocrelizumab versus fingolimod after natalizumab cessation in multiple sclerosis: an observational study. Journal of Neurology

Y. Foong, Daniel Merlo, M. Gresle, K. Buzzard, Michael Zhong, and 18 more\ (2024).Comparing ocrelizumab to interferon/glatiramer acetate in people with multiple sclerosis over age 60. Journal of Neurology Neurosurgery & Psychiatry

E. Muros-Le Rouzic, Y. Heer, Sean Yiu, Viola Tozzi, S. Braune, and 5 more\ (2024).Five-year efficacy outcomes of ocrelizumab in relapsing multiple sclerosis: A propensity-matched comparison of the OPERA studies with other disease-modifying therapies in real-world lines of treatments. Journal of Central Nervous System Disease

Chao Zhu, T. Kalincik, D. Horáková, Zhen Zhou, K. Buzzard, and 37 more\ (2023).Comparison Between Dimethyl Fumarate, Fingolimod, and Ocrelizumab After Natalizumab Cessation. JAMA Neurology

Amanda Claudia Schuldesz, R. Tudor, A. Cornea, Dorina Nicola Geni, Irina Lata, and 1 more\ (2025).Effectiveness of Ocrelizumab on Disease Progression and Disability Status in Multiple Sclerosis Patients: A Two-Year Prospective Cohort Study. Journal of Clinical Medicine

L. A. R. de Antonio, Ines Cuberta-Gonzalez, I. García-Castañón, C. Oreja-Guevara\ (2022).Relapsing-remitting and primary progressive multiple sclerosis treated with ocrelizumab: A comparative study. Multiple Sclerosis and Related Disorders

G. Giovannoni, L. Kappos, J. Seze, S. Hauser, J. Overell, and 5 more\ (2022).020  Long-term efficacy of ocrelizumab in relapsing multiple sclerosis: 6 study years. Journal of Neurology Neurosurgery & Psychiatry

C. Alcalá, C. Quintanilla-Bordás, F. Gascón, Á. Sempere, L. Navarro, and 13 more\ (2022).Effectiveness of rituximab vs. ocrelizumab for the treatment of primary progressive multiple sclerosis: a real-world observational study. Journal of Neurology

B. Yamout, R. Alroughani, Samar Frouk Ahmed Mohamed, A. Al-Mahdawi, S. Khoury, and 19 more\ (2025).Comparative effectiveness of natalizumab and anti-CD20 monoclonal antibodies in relapsing-remitting multiple sclerosis: a real-world propensity-score matched study. Journal of Neurology Neurosurgery & Psychiatry

H. Butzkueven, T. Spelman, T. Kalincik, K. Buzzard, A. Walt, and 6 more\ (2021).010 Real-world experience with ocrelizumab in the MSBase registry – Australian RRMS cohort. Oral abstracts

I. Roos, S. Sharmin, C. Malpas, S. Ozakbas, J. Lechner-Scott, and 41 more\ (2024).Effectiveness of cladribine compared to fingolimod, natalizumab, ocrelizumab and alemtuzumab in relapsing-remitting multiple sclerosis. Multiple Sclerosis

Michael Zhong, A. van der Walt, J. Stankovich, T. Kalincik, K. Buzzard, and 27 more\ (2021).Prediction of multiple sclerosis outcomes when switching to ocrelizumab. Multiple Sclerosis

K. Pape, L. Rolfes, Falk Steffen, M. Muthuraman, Melanie Korsen, and 3 more\ (2022).Comparative effectiveness of natalizumab versus ocrelizumab in multiple sclerosis: a real-world propensity score–matched study. Therapeutic Advances in Neurological Disorders

Elena Barbuti, Alessia Castiello, Valeria Pozzilli, A. Carotenuto, Ilaria Tomasso, and 7 more\ (2025).Comparative effectiveness, safety and persistence of ocrelizumab versus natalizumab in multiple sclerosis: A real-world, multi-center, propensity score-matched study. Neurotherapeutics

R. Alroughani, J. Al-Hashel, S. Ahmed\ (2024).Substantial and comparable suppression of disease activity following early initiation of cladribine tablets, ocrelizumab or alemtuzumab as first pharmacologic treatment for relapsing multiple sclerosis: A real world study. Clinical neurology and neurosurgery (Dutch-Flemish ed. Print)

Tiziana Zaccone, L. Moiola, S. Guerrieri, A. Nozzolillo, C. Zanetta, and 7 more\ (2025).Long-term effectiveness and safety of ocrelizumab: a single-centre real-world study. Journal of Neurology

Martin S. Weber, M. Buttmann, S. Meuth, P. Dirks, E. Muros-Le Rouzic, and 4 more\ (2022).Safety, Adherence and Persistence in a Real-World Cohort of German MS Patients Newly Treated With Ocrelizumab: First Insights From the CONFIDENCE Study. Frontiers in Neurology

T. Guerra, F. Caputo, Antonella Bianco, D. Paolicelli, P. Iaffaldano\ (2025).Long-Term Evaluation of Effectiveness and Immunological Implications of Ocrelizumab in a Real-World Cohort. Drugs - real world outcomes

Paolo A Muraro, Antonio Zito, Alessio Signori, M. Sormani, Eleonora Rigoni, and 12 more\ (2025).Effectiveness of Autologous Hematopoietic Stem Cell Transplantation versus Alemtuzumab and Ocrelizumab in Relapsing Multiple Sclerosis: A Single Center Cohort Study. Annals of Neurology

L. Lorefice, P. Mellino, J. Frau, G. Coghe, G. Fenu, and 1 more\ (2024).Ocrelizumab use in multiple sclerosis: a real-world experience in a changing therapeutic scenario. Neurological Sciences

Mathias Buttmann, Martin S. Weber, Sven G. Meuth, Sandra Blümich, S. Hieke-Schulz, and 3 more\ (2025).CONFIDENCE treatment success: long-term real-world effectiveness and safety of ocrelizumab in Germany. Frontiers in Neurology

S. Pfeuffer, L. Rolfes, J. Ingwersen, R. Pul, Konstanze Kleinschnitz, and 10 more\ (2023).Effect of Previous Disease-Modifying Therapy on Treatment Effectiveness for Patients Treated With Ocrelizumab. Neurology: Neuroimmunology & Neuroinflammation

S. Braune, P. Dirks, Seya Colloud, Qing Wang, Evan Davies, and 4 more\ (2025).Persistence to Ocrelizumab Compared with Other Disease-Modifying Therapies for Multiple Sclerosis: Results from the German NeuroTransData Registry. Neurological Therapeutics

Moein Amin, Tucker Harvey, Dan Michael Pineda, Ming-Hui Tai, Qiujun Shao, and 5 more\ (2025).Real world effectiveness, persistence, tolerability, and safety of ofatumumab in clinical practice. Neurodegenerative Disease Management

Pilar Santiago-Setien, Cristina Barquín-Rego, P. Hernández-Martínez, María Ezquerra-Marigómez, Marta Torres-Barquin, and 8 more\ (2023).Switch to ocrelizumab in MS patients treated with natalizumab in extended interval dosing at high risk of PML: A 96-week follow-up pilot study. Frontiers in Immunology

Mahsa Ghajarzadeh, Mohsen Rastkar, E. Mowry, B. Nourbakhsh\ (2025).Clinical and radiological activity after extended interval and standard interval dosing of ocrelizumab in multiple sclerosis: A systematic review and meta-analysis. Neurological Sciences

No authors found (2022).ePosters. European Journal of Neurology

Franziska Axhausen, Anne Mrochen, Pia Winter, Romy Baumgart, Pauline Mühlenbrock, and 5 more\ (2025).Disease outcomes following lateral switch among different CD20-antibodies in active multiple sclerosis. Multiple Sclerosis

Carolina Cunha, Sara Matos, Catarina Bernardes, Inês Carvalho, João Cardoso, and 6 more\ (2025).Effectiveness of anti-CD20 therapies following natalizumab discontinuation: insights from a cohort study. Multiple Sclerosis and Related Disorders

Martina Nasello, Valeria Zancan, Virginia Rinaldi, Antonio Marrone, R. Reniè, and 6 more\ (2024).Clinical and Immunological Impact of Ocrelizumab Extended Interval Dosing in Multiple Sclerosis: A Single-Center, Real-World Experience. International Journal of Molecular Sciences

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280 data points extracted

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Safety, Adherence and Persistence in a Real-World Cohort of German MS Patients Newly Treated With Ocrelizumab: First Insights From the CONFIDENCE Study

Martin S. Weber, M. Buttmann, S. Meuth, P. Dirks, E. Muros-Le Rouzic, Julius C. Eggebrecht, S. Hieke-Schulz, J. Leemhuis, T. Ziemssen

Frontiers in Neurology·

2022·

15 citations

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Study Design

Prospective, observational, multicenter, cohort study

Patient Population Characteristics

- Total number of patients: 1,702 (RMS), 398 (PPMS) - Mean age: RMS - 41.59 years (SD: 11.24), PPMS - 50.95 years (SD: 9.88) - Gender distribution: RMS - 66.9% female, PPMS - 52.3% female - Multiple sclerosis type: RMS, PPMS - Mean disease duration: not reported - Baseline EDSS score: RMS - 3.18 (SD: 1.87), PPMS - 4.41 (SD: 1.59) - Treatment-naive status vs. previous treatment history: RMS - 82.7% had prior therapy, PPMS - 32.6% had prior therapy

Interventions Compared

- Drug names: Ocrelizumab - Dosage: Not specified - Treatment duration: Up to 10 years - Number of patients in each treatment group: 1,702 with RMS, 398 with PPMS

Annualized Relapse Rate (ARR)

Not mentioned (the paper does not provide specific numerical values for ARR, confidence intervals, or statistical significance)

Disability Progression

Not mentioned (the paper does not provide specific data on disability progression from the CONFIDENCE study)

Follow-up Duration

- Total follow-up period: Up to 10 years - Median follow-up time: Not explicitly mentioned - Range of follow-up times: 0.0 to 2.5 years

Safety Outcomes

- Treatment-related side effects: Infections and infestations were the most common adverse events. - Infection rates: 21.0% of RMS patients experienced infections; serious infection rates were 2.5% for RMS and 1.5 events/100 PY for PPMS. - Infusion-related reactions: Only serious or life-threatening reactions were recorded; no specific data provided. - Serious adverse events: Deaths (0.2% RMS, 0.5% PPMS), malignancies (0.4% RMS, 0.8% PPMS), and a single case of suspected carry-over PML.

Background Real-world relapsing multiple sclerosis (RMS) and primary progressive MS (PPMS) populations may be more diverse than in clinical trials. Here, we present a first analysis of safety, adherence and persistence data from a real-world cohort of patients newly treated with ocrelizumab. Methods CONFIDENCE (ML39632, EUPAS22951) is an ongoing multicenter, non-interventional post authorization safety study assessing patients with RMS or PPMS newly treated with ocrelizumab or other disease-modifying therapies for up to 10 years. For this analysis, patients newly treated with ocrelizumab were analyzed in subgroups by MS phenotype and age over a mean ~1 year of exposure totaling 2,329 patient years [PY]). Results At data cutoff (14 October 2020), 1,702 patients with RMS and 398 patients with PPMS were treated with ≥1 dose of ocrelizumab. At baseline, the mean ages (SD) of patients with RMS and PPMS were 41.59 (11.24) and 50.95 (9.88) years and the mean EDSS (Expanded Disability Status Scale) was 3.18 (1.87) and 4.41 (1.59), respectively. The most common adverse events (AEs) and serious AEs across both phenotypes were infections and infestations, with infection SAE rates of 2.8 events/100 PY and 1.5 events/100 PY in patients with RMS and PPMS, respectively. Across all phenotypes, ocrelizumab persistence was 92% at 24 months; median time between doses was ~6 months. Conclusions The ocrelizumab safety profile observed in the CONFIDENCE real-world MS population was consistent to the one observed in pivotal clinical trials. High treatment persistence and adherence were observed. Trial Registration ML39632, EUPAS22951

INTRODUCTION

Multiple sclerosis (MS) is a chronic disease of the central nervous system (CNS) with a complex immunopathogenesis of inflammation and neurodegeneration with two major disease phenotypes: relapsing MS (RMS) and primary progressive MS (PPMS). MS often warrants long-term drug therapy. Thus, the benefits of a disease-modifying therapy (DMT) must outweigh its long-term risks (1).

Ocrelizumab (Ocrevus R ) is a monoclonal antibody that specifically binds to CD20, modulating the immunopathogenesis of MS by depleting CD20 + B-cells. As the first anti-CD20 monoclonal antibody approved for the treatment of RMS and PPMS, ocrelizumab remains the only approved treatment for PPMS to date (2,3). Pivotal trial data shows that treatment with ocrelizumab has significant effects on slowing disease progression, annualized relapse rate and magnetic resonance imagery outcomes, with no signal of a higher rate of serious infections, compared with interferon in patients with RMS and placebo in patients with PPMS (4,5). Ocrelizumab efficacy was sustained in the open-label extension phases of the pivotal trials, where adverse events (AEs) were generally consistent with those from the controlled periods and no new safety signals emerged with prolonged treatment (6,7).

Integrated safety analysis of the data from 11 clinical trials and open-label extension periods (up to 7 years of continuous ocrelizumab treatment) demonstrated a favorable and manageable safety profile (8). There was no indication of higher rates of malignancy compared with matched reference MS and general populations over 8 years (8).

Real-world populations may be more diverse than those included in randomized clinical trials (RCTs), comprising patients with more prior MS-specific treatments, a longer duration of disease, more physical disability, older age (9) or more comorbidities that may affect safety of treatment (10). CONFIDENCE (ML39632, EUPAS22951) is a large, ongoing, non-interventional post-authorization safety study (PASS) that assesses the long-term safety and effectiveness of ocrelizumab and other DMTs in a real-world MS population in Germany (11). As the central study of the ocrelizumab post-marketing safety program, safety data from CONFIDENCE is integrated into the two multi-source, real-world studies VERISMO (EUPAS30752) and MANUSCRIPT (EUPAS28619). Here, we present an analysis of baseline characteristics, safety, adherence and persistence from patients newly treated with ocrelizumab in CONFIDENCE over a mean of ∼1 year of exposure (max 2.5 years).

Study Design

CONFIDENCE assesses the long-term safety and effectiveness of patients newly treated with ocrelizumab or other selected DMTs (i.e., alemtuzumab, cladribine, dimethyl fumarate, fingolimod, natalizumab, or teriflunomide). Recruitment was initiated in April 2018 with a target enrollment of 3,000 patients with RMS (relapsing remitting MS or relapsing secondary progressive MS) or PPMS newly treated with ocrelizumab and 767 patients with RMS newly treated with other selected DMTs at ∼185 centers in Germany. Full details on the CONFIDENCE study design and inclusion/exclusion have been previously published (11).

The decision to prescribe the treatment must be made prior to and independent of participation in this study; patients are to be treated according to local label. Key inclusion criteria are ≥18 years of age at enrollment and treatment with ocrelizumab or the respective DMT for the first time during the course of MS therapy. Patients participating in an interventional study examining a MS DMT and patients previously treated with rituximab or any other anti-CD20 antibody for MS are excluded.

Overall, patients will be observed with regular ∼6-month follow-up visits for up to 10 years regardless of treatment change. CONFIDENCE completion is expected in 2029. Data are collected by site staff and entered into an electronic case report form (eCRF) based on the MS management system 3D (MSDS3D; MedicalSyn, Stuttgart, Germany) (12,13). Patient demographics and informed consent are collected at screening. Other baseline characteristics such as MS disease and treatment history, general medical history and comorbidities (previous and current diseases and disorders in the patient's medical history), pregnancy status and history, malignancy risk factors, cancer screening and MS disease activity are documented at the baseline visit (first ocrelizumab administration).

Here, we present a first analysis of safety, adherence and persistence of patients treated with ocrelizumab (data cutoff 14 October 2020). Other DMT cohorts were not included in this analysis due to insufficient patient numbers.

Safety Endpoints

AEs and serious AEs (SAEs) were recorded according to system organ class (SOC) and preferred term (PT) of the Medical Dictionary for Regulatory Activities (MedDRA; version 23.1). As of a protocol amendment in July 2019, infusionrelated reactions (IRRs) were only to be recorded if judged as serious or life-threatening. Malignancies were identified using the SOC "Neoplasms benign, malignant and unspecified (incl. cysts and polyps)" and further defined using the standardized MedDRA queries (SMQ) "Malignant tumor (narrow)". Reasons for discontinuations were reported by the investigator from multiple choices. No specific details were collected for reasons such as "patient wish" or "insufficient efficacy". Adjunct data from the Roche safety database was used to consummate patient narratives.

Statistical Analysis

This analysis was based on data prior to the cutoff. Patients who received at least one dose of ocrelizumab were included for analysis of all safety endpoints (safety analysis set). Persistence and adherence endpoints were analyzed in patients in the safety analysis set with at least one documentation after start of the therapy (full analysis set). Persistence was estimated by Kaplan-Meier time-to-treatment discontinuation, in which patients without discontinuation were censored with their last assessment visit date recorded. Adherence was evaluated by median time interval (interquartile range) between dosing. All outcomes were assessed using descriptive statistics. Analysis of patients with PPMS >55 years old at baseline was prespecified in the statistical analysis plan; patients with RMS >55 years old were assessed in a post-hoc analysis.

Patient Population and Treatment Exposure

As of the data cutoff, 1,702 patients with RMS and 398 patients with PPMS have been treated with ≥1 dose of ocrelizumab and were included in the safety analysis. The mean exposure time (standard deviation, SD) to ocrelizumab was 1.03 (0.70) years for patients with RMS (range 0.0-2.5 years; totaling 1,877 patientyears [PY]) and 1.06 (0.68) years for patients with PPMS (range 0.0-2.5 years; totaling 452 PY).

Mean age (SD) of patients with RMS was 41.59 (11.24) years, 66.9% were females and 82.7% had ≥1 MS-specific prior therapy. The mean (SD) baseline EDSS (Expanded Disability Status Scale) of patients with RMS was 3.18 (1.87) in the total cohort, and 4.54 (1.64) in patients >55 years old. At baseline, 66.0% of ocrelizumab-treated patients with RMS had comorbidities. The most common comorbidities (PT) of patients with RMS were vitamin D deficiency, hypertension and depression (Table 1 ). In patients with RMS >55 years old, 80.5% had comorbidities, with the most common (PT) being hypertension (Table 1 ). Patients with PPMS were mean (SD) 50.95 (9.88) years old, 52.3% female, and 32.6% had ≥1 MS-specific prior therapy (Table 1 ). Patients with PPMS had a mean (SD) baseline EDSS of 4.41 (1.59) and 4.73 (1.48) in patients >55 years old. At baseline, 74.4% of patients with PPMS had comorbidities, most commonly (PT) hypertension and vitamin D deficiency. In patients with PPMS > 55 years, 86.0% had comorbidities with the most common (PT) being hypertension (Table 1 ).

Infections and Infestations

Overall, 21.0% of patients with RMS experienced infections [32.2 events/100 PY]. The most common infections were nasopharyngitis [8.3 events/100 PY], urinary tract infections [6.2 events/100 PY] and respiratory tract infections (for a list of all infections, please see Supplementary Table 2 ). Serious infections were experienced by 2.5% of patients with RMS [2.8 events/100 PY] (Table 2 ), including 13 events of serious urinary tract infections [0.7 events/100 PY; 12 recovered/recovering and one unknown outcome] and six events of serious pneumonia [0.3 events/100 PY; all recovered/recovering] (Table 2 ).

A single case of suspected carry-over progressive multifocal leukoencephalopathy (PML), associated with prior natalizumab therapy, was reported in 2018. The case was assessed by an independent panel of PML experts and was classed as suspected rather than confirmed carry-over PML. The patient had magnetic resonance imaging findings suggestive of PML, but the cerebrospinal fluid was negative for JC virus DNA and no clinical symptoms consistent with PML were reported, therefore, the case did not meet the American Association of Neurology criteria for confirmed PML (14) Five patients with RMS who experienced seven serious infections were >55 years old [2.9 events/100 PY]; these included urinary tract infection (3, all recovered/recovering); urosepsis (2, recovered and unknown outcome); sinusitis (1, recovered) ; and viral pharyngitis (1, recovered) .

Overall, 15.8% of patients with PPMS experienced infections [19.7 events/100 PY], including nasopharyngitis [5.8 events/100 PY] and urinary tract infections [4.9 events/100 PY]. Seven patients with PPMS [1.5 events/100 PY] had serious infections and infestations, (2 pneumonia, recovered and recovered with sequelae; 2 urinary tract infections, recovered and unknown outcome; 1 diverticulitis, recovered; 1 encephalitis, recovered; and 1 urosepsis, recovered). Among patients with PPMS and >55 years old, one case of diverticulitis and one case of encephalitis occurred [1.2 events/100 PY] (for further details see Supplementary Table 4 ).

Fatal Events

Three patients with RMS [0.2%; 0.2 events/100 PY; ≤55 years old] and 2 patients with PPMS [0.5%; 0.4 events/100 PY; >55 years old] died. Among the patients with RMS, one event was reported as "death" with no specific cause given; one patientwho had a history of tobacco use-died of bronchial carcinoma, and one patient died of myocarditis. In patients with PPMS, one event was reported as "death" (not further specified), and one patient with PPMS completed suicide (for further details see the Supplementary Material).

Malignancies

Seven patients with RMS experienced malignancies, defined as standardized MedDRA queries (SMQ) "Malignant tumor (narrow)" [0.4%; 0.5 events/100 PY; all ≤55 years old]. These included female breast cancer (two cases, 54 and 53 years old at baseline), malignant melanoma (two cases; one including metastases to the mediastinum; 38 and 45 years) and one case each of bronchial carcinoma (54 years), thyroid cancer (52 years) and basal cell carcinoma (42 years). Six of seven patients with a malignancy were female. Three patients with PPMS experienced a malignancy [0.8%; 0.7 events/100 PY], including malignant melanoma (55 years old at baseline), squamous cell carcinoma of the skin (60 years) and basal cell carcinoma (44 years). Two patients were female, and one was male. Further information on patient history and risk factors can be found in the Supplementary Material.

Discontinuation, Persistence, and Adherence

Of patients with RMS, 80 (4.7%) discontinued ocrelizumab; the most common reasons were "patient wish" (37), AE (13) and "insufficient efficacy" (12). Fourteen patients >55 years old (7.0%) discontinued, most commonly due to "patient wish" (7), AE (3) and "insufficient efficacy" (3) (Table 3 ).

Of patients with PPMS, 19 (4.8%) discontinued ocrelizumab; the most common reasons were "patient wish" (9), AE (4) and "insufficient efficacy" (3). Ten patients >55 years old (7.0%) discontinued, most commonly due to "patient wish" (4), AE (3) and "insufficient efficacy" (2) (Table 3 ). Known AEs that led to discontinuation are listed in Supplementary Table 5 .

Persistence and adherence were examined in the full analysis set (all patients in the safety set with at least one documentation after start of the therapy; RMS n = 1,510; PPMS n = 363). Kaplan-Meier analysis showed that patients treated with ocrelizumab achieved 96% and 92% persistence at 12 and 24 months, regardless of MS phenotype (Figures 1A, B ). Patients >55 years old (n = 184) achieved a 95% and 87% persistence at 12 and 24 months. Patients >55 years with PPMS (n = 143) achieved a 95% and 86% persistence at 12 and 24 months.

The median time between infusions was ∼6 months, regardless of age group or MS phenotype; and infusion intervals remained stable throughout the treatment duration (Table 4 ). Mo, months. Data were analyzed in the full analysis set (all enrolled patients who received at least one dose of ocrelizumab with at least one documentation after start of the therapy). Q, quartile.

DISCUSSION

Real-world studies provide data to further evaluate the risk/benefit profiles described for new therapies in RCTs. To mitigate potential confounding factors, RCTs include selected patient populations. Real-world studies include diverse patient populations, reflecting features of daily clinical practice. This analysis of the CONFIDENCE study represents a real-world cohort of patients with comorbidities and no limits regarding maximum age or EDSS. According to the later onset of disease, patients with PPMS were on average slightly older and had a higher EDSS than patients with RMS. As ocrelizumab is the only treatment currently available for PPMS, a higher proportion of patients with PPMS were treatment-naïve. Irrespective of MS phenotype, patients >55 years had a higher average baseline EDSS (RMS 4.54; PPMS 4.73) and more comorbidities (RMS 80.5%; PPMS 86.0%) than their respective total phenotypic cohorts.

Although there were no restrictions on the disability status of enrolled patients, average baseline EDSS scores were similar to pivotal trials (4,5). However, patients in CONFIDENCE were on average older than in pivotal trials, with ∼12% of patients with RMS and ∼36% of patients with PPMS >55 years (a population excluded from pivotal trials). In addition, patients had longer times since diagnosis, and a greater proportion of patients with RMS had prior MS therapy (∼83 vs ∼27% in pivotal trials) (4). Moreover, this study includes patients with comorbid conditions who were excluded from RCTs, such as patients with a history of malignancy or congestive heart failure (4,5). Comorbid conditions often observed in real-world MS populations such as cardiovascular disorders and mood disorders (15) were also seen in CONFIDENCE.

To date, real-world data from large ocrelizumab cohorts that may reflect treatment patterns are rare. CONFIDENCE is a German study and baseline characteristics are largely comparable to another German real-world cohort of ocrelizumab treated patients (16). Compared to a recent smaller US cohort (17), patients with RMS in CONFIDENCE had similar mean EDSS and fewer patients in CONFIDENCE were treated with firstline ocrelizumab. With respect to ocrelizumab treated patients documented in the global MSBase registry (2), CONFIDENCE populations had similar age profiles. Patients with RMS tended to have a higher EDSS and proportions of patients without prior therapy were similar. However, patients with PPMS had a lower EDSS and were more often treatment-naïve.

In alignment with populations reported in large realworld studies examining other highly effective DMTs, the CONFIDENCE population was largely similar regarding age, types of comorbidities, baseline EDSS scores, and the majority of patients had been treated with ≥1 prior MS therapy (3,18).

No new safety signals were identified in this analysis, where many patients had comorbidities and many RMS patients had multiple previous therapies (∼35% had ≥3). Patients with PPMS in CONFIDENCE experienced numerically lower rates of both AEs and SAEs than patients with RMS. Patients with PPMS >55 years experienced SAEs at approximately half the rate (SAE/100 PY) of patients with RMS >55 years. Nevertheless, patients with PPMS comprised a smaller population, and patients with PPMS >55 years were less likely to have previous/multiple previous therapies and had shorter disease durations since diagnosis. As expected, patients >55 years (irrespective of MS phenotype) had higher SAE rates than their respective total cohorts. Compared with the general population, patients with MS experience infections and hospitalizations due to infections at higher rates (19). Accordingly infections were among the most common AEs reported in CONFIDENCE. However, rates of serious infections remained low. Patients with PPMS had a numerically lower rate of infections and serious infections than patients with RMS. Patients >55 years, however, experienced similar rates of serious infections to that of their overall respective populations. Overall, infections most often reported in CONFIDENCE (respiratory infections and urinary tract infections) were consistent with the described ocrelizumab safety profile (8) and the general MS population (19). The single case of suspected PML in a patient with RMS was considered a carry-over from previous natalizumab treatment.

During this analysis (data cutoff 14/Oct/2020), six patients were reported to have COVID-19 or COVID-19 pneumonia (all with RMS). Two cases were considered serious with only one requiring hospitalization. All patients with known COVID-19 outcomes recovered.

Presented data on COVID-19 are from an early time (pre vaccination era) in the COVID-19 pandemic. A recent analysis (May 2021) using the ocrelizumab post-marketing safety database and clinical trial data show that COVID-19 infections in patients treated with ocrelizumab were mostly mild to moderate, and risk factors known to be associated with severe disease course in the general population were associated with severity in ocrelizumab-treated (20). However, a number of real-world studies (21)(22)(23)(24) suggest an increased risk of severe COVID-19 in patients with MS treated with anti-CD20 treatments although subject to potential limitations, including biases, confounding, sample size and data completeness (25). Further analyses are required to understand the risk and severity of COVID-19 in ocrelizumab treated patients.

Another important question will be to determine the clinical protection conferred by SARS-CoV-2 vaccines against severe forms of COVID-19. Attenuated humoral immune response has been associated with ocrelizumab treatment to non-live vaccines (26). However, the development of a protective immune response after vaccination involves a variety of mechanisms, of which T and B cells are variably involved (27). In the context of COVID-19, whether antibody production is the appropriate or sole immune correlate of protection is currently unknown and the role of T or B cell-mediated immunity for effective clinical protection requires additional investigations. Available data report impaired humoral response to SARS-CoV-2 infection or vaccines in ocrelizumab treated patients, but induced robust cellular response (28)(29)(30)(31)(32)(33)(34)(35), significantly boosted after a third vaccine dose (36), or preserved against SARS-CoV-2 Delta or Omicron variants (37). Despite the impaired humoral immune response to SARS-CoV2 infection or vaccine, no known correlation with clinical severity has been established, as compensatory cellular-mediated immune response could provide protection against serious complications from COVID-19 infection.

Immunoglobulins and B-cell levels are not routinely checked for in clinical practice and neither the assessment nor the collection of corresponding data are mandatory in this real-world study. Available data collected on immunoglobulins and B-cell levels as part of the CONFIDENCE study are limited in time and potentially biased by lack of systematic data collection across participating centers, therefore they do not allow to assess the association between serious infections, duration of treatment and respective laboratory values.

There was no indication of increased malignancy rates in analyses of the overall ocrelizumab clinical program and postmarketing data compared with matched reference MS and general populations (8,38). In this analysis of CONFIDENCE, rates of malignancy resembled previously published data from RCTs including open-label extension phases, which were within the expected epidemiological ranges (8,39).

Persistence and adherence to an effective DMT are associated with lower relapse rates, better clinical outcomes, and reductions in the cost of patient care (40,41) and can be related to treatment satisfaction and safety (42). Data in CONFIDENCE were consistent with US claims data (43), which show that ocrelizumab has a high persistence. Persistence remained high in patients >55 years across all MS phenotypes. Because there were few discontinuations, no major reasons could be identified. Furthermore, discontinuations due to AEs were rare. Adherence was consistent across MS phenotypes and age groups, with median intervals of ∼6 months in between ocrelizumab infusions, in accordance with the regulatory label.

CONFIDENCE is a real-world study and is thus susceptible to the limitations of non-interventional studies (e.g., potential enrollment and channeling biases between cohorts). Efforts to mitigate limitations and biases associated with long-term real-world cohort studies (such as healthy user bias and depletion of susceptibles) included only enrolling patients newly treated with ocrelizumab or selected DMTs. All study sites underwent standardized training and used standardized documentation for the completion of eCRFs at enrollment and for each follow-up assessment, specifically for collecting exposure and outcome variable information. Due to the observational nature of the CONFIDENCE study and spontaneous reporting of AEs, a bias in the reporting of AEs cannot be excluded (e.g., underreporting of non-serious AEs and overrepresentation of SAEs) and information on fatal cases and laboratory values (e.g., Immunoglobulins, B-cell levels) is limited.

Overall, CONFIDENCE represents the use of ocrelizumab in clinical practice and includes patients with physical disability, with comorbid conditions, and patients >55 years. No new safety signals were detected in this analysis, confirming the tolerability and safety of ocrelizumab treatment in a real-world population over a mean of ∼1 year of exposure (max 2.5 years). High adherence and persistence to ocrelizumab were observed in patients with RMS or PPMS, and discontinuations were rare due to AE. Further analyses of this large, real-world study will be conducted on a regular basis to provide continuing safety and effectiveness data for the treatment of patients with ocrelizumab for up to 10 years.

DATA AVAILABILITY STATEMENT

The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author.

ETHICS STATEMENT

The studies involving human participants were reviewed and approved by Ethikkommission an der Technischen Universität Dresden, Germany (12 February 2018 and 10 April 2019; reference EK 62022018). The patients/participants provided their written informed consent to participate in this study.

AUTHOR CONTRIBUTIONS

All authors analyzed and interpreted the data in study, participated in the writing, and approved the final version of this manuscript.

SUPPLEMENTARY MATERIAL

The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fneur. 2022.863105/full#supplementary-material Conflict of Interest: MW receives research support from the Deutsche Forschungsgemeinschaft (DFG; WE 3547/5-1), from Novartis, TEVA, Biogen-Idec, Roche, Merck and the ProFutura Programm of the Universitätsmedizin Göttingen. MW is serving as an editor for PLoS ONE, received travel funding and/or speaker honoraria from Biogen-Idec, Merck Serono, Novartis, Roche, TEVA, Bayer and Genzyme. MB received honoraria for lecturing, consulting and/or travel expenses for attending meetings from Bayer, Biogen, Boehringer, Bristol Myers Squibb, Coloplast, Daiichi-Sankyo, Das Fortbildungskolleg, Medscape, Merck, Novartis, Roche, Sandoz, Sanofi, and Teva. SM received honoraria for lecturing and travel expenses for attending meetings from Almirall, Amicus Therapeutics Germany, Bayer Health Care, Biogen, Celgene, Diamed, Genzyme, MedDay Pharmaceuticals, Merck Serono, Novartis, Novo Nordisk, ONO Pharma, Roche, Sanofi-Aventis, Chugai Pharma, QuintilesIMS, and Teva, research is funded by the German Ministry for Education and Research (BMBF), Bundesinstitut für Risikobewertung (BfR), Deutsche Forschungsgemeinschaft (DFG), Else Kröner Fresenius Foundation, Gemeinsamer Bundesausschuss (G-BA), German Academic Exchange Service, Hertie Foundation, Interdisciplinary Center for Clinical Studies (IZKF) Muenster, German Foundation Neurology and Alexion, Almirall, Amicus Therapeutics Germany, Biogen, Diamed, Fresenius Medical Care, Genzyme, HERZ Burgdorf, Merck Serono, Novartis, ONO Pharma, Roche and Teva. PD is an employee of F. Hoffmann-La Roche AG and shareholder of F. Hoffmann-La Roche AG. JE is an employee of Roche Pharma AG and shareholder of F. Hoffmann-La Roche AG. SH-S is an employee of Roche Pharma AG. JL is an employee of Roche Pharma AG and shareholder of F. Hoffmann-La Roche AG. EM-LR is an employee of F. Hoffmann-La Roche AG and shareholder of F. Hoffmann-La Roche AG. TZ reports grants and personal fees from Biogen, Roche, TEVA and grants, personal fees from Almirall, Biogen, Celgene, Biogen, Novartis, Merck, TEVA, Janssen, Roche.

The authors declare that this study received funding from Roche. The funder had the following involvement in the study: study design, analysis, interpretation of data, the writing of this article and the decision to submit it for publication.

Acknowledgements

ACKNOWLEDGMENTSThe authors thank Kelly Zalocusky (Genentech, South San Francisco, CA, USA) for her assistance with statistical analysis for this manuscript.We thank Malgorzata Sierzega, Dusanka Zecevic, Louise Whitley and Kocho Fitovski (F.Hoffmann-La Roche Ltd, Basel, Switzerland) for critically reading and reviewing this manuscript.

Funding

FUNDINGThe CONFIDENCE study was funded by Roche Pharma AG (Grenzach-Wyhlen, Germany).Financial support for Medical writing services from Ashfield MedComms GmbH (Mannheim, Germany) was provided by Roche Pharma AG (Grenzach-Wyhlen, Germany).

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