Comparing Ocrelizumab and Ofatumumab for Relapsing Multiple Sclerosis: A Comprehensive Patient Guide

Table of Contents

• Introduction: Why This Research Matters
• Study Methods: How the Research Was Conducted
• Key Findings: Detailed Results with All Numbers
• Clinical Implications: What This Means for Patients
• Limitations: What the Study Couldn't Prove
• Recommendations: Actionable Advice for Patients
• Source Information

Introduction: Why This Research Matters

Multiple sclerosis is a complex neurological condition where the immune system mistakenly attacks the protective covering of nerve fibers. For patients with relapsing forms of MS (RMS), B-cell-depleting therapies have revolutionized treatment by targeting specific immune cells that drive disease activity.

Two leading treatments in this category are ocrelizumab (OCR) and ofatumumab (OFA), both approved by regulatory agencies for RMS. While both medications work by targeting CD20 proteins on B-cells, they differ in important ways. OCR is typically administered intravenously (through a vein) every six months, while OFA is given subcutaneously (under the skin) once monthly.

Despite both medications showing effectiveness in clinical trials, no real-world studies had directly compared their effectiveness until now. This research gap left patients and doctors without clear guidance on whether one treatment might be more effective than the other in everyday clinical practice.

This German multicenter study followed 1,138 patients across three medical centers to provide the first comprehensive comparison of these two important MS treatments in real-world conditions, offering valuable insights for patients considering treatment options.

Study Methods: How the Research Was Conducted

Researchers designed a prospective cohort study, meaning they followed patients forward in time from September 2021 through June 2024. The study was conducted at three major tertiary medical centers in Germany: Duesseldorf, Essen, and Giessen.

The study included adult patients with relapsing multiple sclerosis who met the 2017 revised McDonald diagnostic criteria. All participants were eligible for treatment with either OCR or OFA according to standard medical guidelines. Importantly, the choice between treatments was made through shared decision-making between patients and their doctors before study enrollment.

Several exclusion criteria were applied to ensure a clean comparison:

• Previous treatment with any B-cell-depleting therapy
• Previous treatment with alemtuzumab or cladribine
• Patients who met criteria for progressive MS at baseline

Researchers used sophisticated statistical methods called propensity-score matching to create balanced comparison groups. This technique helped ensure that patients receiving OCR and OFA were similar in terms of age, disease duration, previous relapse rate, disability level, and other important factors that could influence outcomes.

The final analysis included 544 patients receiving OCR and 417 patients receiving OFA after matching, totaling 961 patients. These patients were followed for a cumulative total of 18,873 patient-months (approximately 1,573 patient-years), providing substantial data for analysis.

Outcomes measured included:

1. Clinical relapses (defined as worsening of neurological symptoms lasting at least 24 hours)
2. New or enlarging MRI lesions (T2-hyperintense lesions)
3. 6-month confirmed disability worsening (CDW)
4. Progression independent of relapse activity (PIRA)
5. Relapse-associated worsening (RAW)

MRI scans were performed according to standardized international protocols and evaluated by experienced neuroradiologists who were unaware of which treatment patients received.

Key Findings: Detailed Results with All Numbers

The matched patient groups were well-balanced with an average age of 35.4 years and relatively short disease duration of 44.9 months since MS onset. The cohort was predominantly female (67.1% in OCR group, 69.5% in OFA group), reflecting the typical gender distribution in MS.

Patients had active disease before starting treatment, with an average of 0.76 relapses per year in the OCR group and 0.92 relapses per year in the OFA group in the year before treatment. Baseline MRI showed an average of 19.2 T2 lesions in OCR patients and 19.1 lesions in OFA patients.

Regarding previous treatments:

• 30.9% of OCR patients and 35.3% of OFA patients were treatment-naïve
• 24.4% of OCR patients and 15.1% of OFA patients had previously taken natalizumab
• 16.9% of OCR patients and 17.5% of OFA patients had taken S1P receptor modulators
• The remainder had taken various platform therapies

Relapse Outcomes: During the study period, 168 patients experienced clinical relapses - 101 patients (18.6%) in the OCR group and 67 patients (16.1%) in the OFA group. The annualized relapse rate dropped dramatically from 0.76 to 0.11 in the overall cohort, showing both treatments were highly effective at reducing relapse activity.

MRI Outcomes: Researchers detected 278 new or enlarging T2 lesions in 213 patients. Specifically, 126 OCR patients (23.2%) developed 174 lesions, while 87 OFA patients (20.9%) developed 104 lesions. MRI data was highly complete, with 97.2% of scheduled scans available for analysis in both groups.

Disability Outcomes: A total of 147 patients (15.6%) experienced confirmed disability worsening. This included 93 OCR patients (17.1%) and 54 OFA patients (12.9%). The disability worsening was categorized as:

• Relapse-associated worsening (RAW): 80 patients total (8.4% OCR, 8.2% OFA)
• Progression independent of relapse activity (PIRA): 67 patients total (8.6% OCR, 4.8% OFA)

Non-inferiority Analysis: The primary analysis established that OFA was non-inferior to OCR across all measured outcomes. Using statistical methods that accounted for a 15% non-inferiority margin (meaning OFA could be up to 15% less effective and still be considered non-inferior), researchers found no significant differences between the two treatments.

Subgroup Analyses: When examining patients based on their previous treatments, researchers found consistent results for treatment-naïve patients and those switching from platform therapies. However, potential differences emerged in patients switching from S1P receptor modulators (like fingolimod) or natalizumab, though these findings require further validation in larger studies.

Among patients previously treated with S1PRM, 26.1% of those switching to OCR and 17.8% switching to OFA did so due to disease activity. The remaining switched due to adverse events including lymphopenia (49%), infections (35%), skin reactions (8%), syncope (5%), and increased eye pressure (3%).

Clinical Implications: What This Means for Patients

This study provides reassuring evidence that both OCR and OFA are highly effective treatments for relapsing multiple sclerosis. The finding that OFA is non-inferior to OCR means patients and doctors can choose between these treatments based on individual preferences and practical considerations rather than effectiveness concerns.

For patients who prefer less frequent treatments and don't mind intravenous infusions, OCR administered every six months might be preferable. For those who prefer self-administration at home and more frequent dosing, monthly subcutaneous OFA might be the better choice. Both options provide comparable protection against relapses, disability progression, and new MRI lesions.

The dramatic reduction in annualized relapse rates from approximately 0.84 before treatment to 0.11 after treatment highlights the powerful effect of B-cell-depleting therapies. This translates to most patients experiencing no relapses while on treatment, which significantly improves quality of life and reduces disease burden.

The similar outcomes in treatment-naïve patients and those switching from platform therapies suggest that both OCR and OFA are appropriate choices regardless of previous treatment history. This is particularly important for patients considering escalation therapy after less effective treatments.

The potential differences observed in patients switching from S1P receptor modulators or natalizumab suggest that doctors might need to consider individual patient history when choosing between these treatments. However, these findings are preliminary and require confirmation in future studies.

Overall, this research empowers patients with more choice and confidence in their treatment decisions, knowing that both options provide excellent disease control in real-world settings.

Limitations: What the Study Couldn't Prove

While this study provides valuable real-world evidence, several limitations should be considered when interpreting the results. The observational nature of the study means that treatment assignment wasn't random, though researchers used advanced statistical methods to minimize this limitation.

The follow-up period, while substantial at up to 2.5 years, may not be long enough to detect differences in long-term outcomes or rare side effects. Multiple sclerosis is a lifelong condition, and longer observation is needed to understand how these treatments perform over decades.

The study was conducted at tertiary centers in Germany, which might limit generalizability to other healthcare systems or patient populations. Treatment patterns, monitoring protocols, and patient characteristics might differ in other countries or practice settings.

While researchers included various patient subgroups based on previous treatments, the sample sizes for some subgroups (particularly those switching from newer S1P modulators like ozanimod and ponesimod) were relatively small. This limits the confidence in subgroup findings and highlights the need for larger studies.

The study didn't comprehensively evaluate safety and side effects, which are crucial considerations for treatment decisions. While both treatments are generally well-tolerated, individual patients might experience different side effect profiles that could influence treatment choice.

Finally, the non-inferiority design can establish that OFA isn't worse than OCR by a certain margin, but it cannot prove that the treatments are exactly equivalent. There might be small differences that this study wasn't designed to detect.

Recommendations: Actionable Advice for Patients

Based on this research, patients with relapsing multiple sclerosis can consider the following recommendations when discussing treatment options with their healthcare providers:

1. Discuss both options with your neurologist. Both OCR and OFA are highly effective treatments, and the choice should consider your lifestyle, preferences, and individual circumstances.
2. Consider administration preferences. If you prefer less frequent treatments and don't mind clinic visits for infusions, OCR might be suitable. If you prefer self-administration at home and more frequent dosing, OFA might be preferable.
3. Review your treatment history. While both treatments work well for most patients, those switching from S1P receptor modulators or natalizumab should have detailed discussions with their doctors about potential differences observed in this study.
4. Monitor your response. Regardless of which treatment you choose, regular monitoring through clinical assessments and MRI scans remains important to ensure the treatment is working effectively.
5. Report any side effects. Both treatments can cause side effects, though they're generally well-tolerated. Report any concerns to your healthcare team promptly.
6. Stay informed about new research. As more studies emerge, particularly longer-term data and additional subgroup analyses, treatment recommendations might evolve. Maintain open communication with your treatment team about new evidence.

Remember that treatment decisions should be made through shared decision-making between you and your healthcare provider, considering all available evidence, your individual circumstances, and your personal preferences.

Source Information

Original Article Title: Different Treatment Outcomes of Multiple Sclerosis Patients Receiving Ocrelizumab or Ofatumumab

Authors: Sven G. Meuth, Stephanie Wolff, Anna Mück, Alice Willison, Konstanze Kleinschnitz, Saskia Räuber, Marc Pawlitzki, Franz Felix Konen, Thomas Skripuletz, Matthias Grothe, Tobias Ruck, Hagen B. Huttner, Christoph Kleinschnitz, Tobias Bopp, Refik Pul, Bruce A. C. Cree, Hans-Peter Hartung, Kathrin Möllenhoff, Steffen Pfeuffer

Publication: Annals of Neurology, 2025;97:583–595

DOI: 10.1002/ana.27143

This patient-friendly article is based on peer-reviewed research published in a leading medical journal. It aims to make complex scientific information accessible to patients while preserving all important findings and data from the original study.