Comparing Rituximab and Ocrelizumab for Relapsing-Remitting Multiple Sclerosis: What Patients Need to Know

Table of Contents

• Introduction: Understanding B-Cell Therapies for MS
• Study Design and Methods
• Patient Characteristics
• Key Findings: Relapse Rates and Disability Outcomes
• Treatment Persistence and Discontinuation
• Clinical Implications for Patients
• Study Limitations
• Recommendations for Patients
• Source Information

Introduction: Understanding B-Cell Therapies for MS

Multiple sclerosis (MS) is an autoimmune condition where the body's immune system attacks the protective covering of nerve fibers. B-cell depletion therapies represent a significant advancement in MS treatment, targeting specific immune cells that contribute to the disease process. Ocrelizumab (Ocrevus) was the first B-cell therapy specifically approved for relapsing-remitting MS (RRMS) after demonstrating a 46% reduction in relapses and 40% reduction in disability progression compared to interferon therapy in clinical trials.

Rituximab (Rituxan), while approved for other conditions like certain cancers and rheumatoid arthritis, is often used "off-label" for MS treatment. Despite sharing a similar mechanism of action (both target CD20 proteins on B-cells), these medications have important differences. Ocrelizumab is a "humanized" antibody designed to potentially cause fewer immune reactions, while rituximab is a "chimeric" antibody containing mouse components.

This study addressed a crucial question for patients and clinicians: Is rituximab equally effective as ocrelizumab for controlling MS activity? The answer has significant implications for treatment decisions, insurance coverage, and patient outcomes.

Study Design and Methods

Researchers conducted a large observational study using data from two major MS registries: the international MSBase registry and the Danish Multiple Sclerosis Registry (DMSR). The study period spanned from January 2015 to March 2021, including patients who received either ocrelizumab or rituximab treatment during this time.

To ensure fair comparisons, researchers used sophisticated statistical methods to match patients with similar characteristics:

• Minimum 6 months of treatment and follow-up
• Detailed baseline assessments including disability scores (Expanded Disability Status Scale or EDSS)
• Previous relapse history and treatment experience
• MRI (magnetic resonance imaging) findings including lesion burden
• Age, sex, and disease duration

The primary goal was to determine whether rituximab was "noninferior" to ocrelizumab—meaning not unacceptably worse. Researchers set a predefined margin: if rituximab showed no more than 1.63 times the relapse rate of ocrelizumab, it would be considered noninferior.

Treatment protocols followed real-world practices: ocrelizumab was typically administered as 300mg doses two weeks apart, then 600mg every six months. Rituximab was usually given as 1000mg doses two weeks apart, followed by 500-1000mg every six months, though dosing varied by treatment center.

Patient Characteristics

From an initial pool of 6,027 patients treated with either medication, 1,613 met the strict inclusion criteria for analysis. The study population had these characteristics:

• Mean age: 42.0 years (±10.8 years standard deviation)
• Gender distribution: 68% female (1,089 patients), 32% male (524 patients)
• Source: 898 patients from MSBase registry, 715 from Danish registry

After matching patients with similar baseline characteristics, the final comparison included 710 ocrelizumab-treated patients matched with 186 rituximab-treated patients. Before matching, rituximab patients tended to have more severe disease:

• Higher disability scores (mean EDSS 3.5 vs 3.0)
• More relapses in the previous year (0.7 vs 0.5)
• More active MRI scans (41% vs 32% had gadolinium-enhancing lesions)
• More previous MS therapies (median 2.0 vs 2.0, but with different distributions)

The matching process successfully balanced these differences, creating comparable groups for analysis with a mean follow-up of 1.4 years (±0.7 years).

Key Findings: Relapse Rates and Disability Outcomes

The study revealed significant differences in relapse prevention between the two treatments:

Annualized Relapse Rates (ARR): Patients taking rituximab experienced nearly twice as many relapses: • Rituximab ARR: 0.20 (±0.49) • Ocrelizumab ARR: 0.09 (±0.28) • This difference was statistically significant (p < 0.001)

Relapse Risk Comparison: The rate ratio was 1.8 (95% CI: 1.4-2.4), meaning rituximab patients had 1.8 times higher relapse rates than ocrelizumab patients. Since the upper bound of the confidence interval (2.4) exceeded the predefined noninferiority margin of 1.63, rituximab failed to demonstrate noninferiority.

Cumulative Relapse Hazard: Patients taking rituximab had 2.1 times higher risk of experiencing relapses over time (Hazard Ratio: 2.1; 95% CI: 1.5-3.0). This means that at any point during the study, rituximab patients were more than twice as likely to have a relapse compared to ocrelizumab patients.

Disability Outcomes: Interestingly, despite the difference in relapse prevention, both treatments showed similar effectiveness in preventing disability progression: • Disability accumulation: Hazard Ratio 1.51 (95% CI: 0.86-2.64) - not statistically significant • Disability improvement: Hazard Ratio 0.80 (95% CI: 0.49-1.31) - not statistically significant

This suggests that while rituximab was less effective at preventing relapses, it provided similar protection against long-term disability progression during the study period.

Treatment Persistence and Discontinuation

The study also examined how long patients remained on each treatment:

Patients were significantly more likely to discontinue rituximab than ocrelizumab (Hazard Ratio: 3.11; 95% CI: 2.36-4.11). This means rituximab patients were over three times more likely to stop treatment during the study period.

Available data on discontinuation reasons (available for 66% of ocrelizumab and 49% of rituximab discontinuations) showed:

• Most common reasons for rituximab discontinuation: patient/clinician decision (33%) and other/unknown reasons (48%)
• 69% of patients who stopped rituximab switched to ocrelizumab
• Very few discontinuations due to intolerance: 16 ocrelizumab patients, 9 rituximab patients

The high switch rate from rituximab to ocrelizumab likely reflects the latter's regulatory approval for MS during the study period, making it more accessible and potentially preferred by clinicians and insurers.

Clinical Implications for Patients

These findings have important implications for MS treatment decisions:

For patients considering B-cell therapy options, this study suggests that ocrelizumab may provide better relapse prevention than rituximab. The nearly doubled relapse rate with rituximab represents a clinically meaningful difference that could impact quality of life and disease management.

However, the similar disability outcomes between treatments suggest that both medications provide substantial protection against long-term progression. This is an important consideration since preventing disability accumulation is ultimately the primary goal of MS therapy.

The higher discontinuation rate with rituximab may reflect various factors including insurance coverage changes, clinician preference after ocrelizumab approval, or patient decisions based on perceived efficacy differences. The similar low intolerance rates suggest both medications are generally well-tolerated.

Patients should discuss these findings with their neurologists in the context of their individual disease characteristics, treatment history, and personal preferences. The choice between these medications involves considering efficacy, safety, cost, insurance coverage, and administration logistics.

Study Limitations

While this study provides valuable real-world evidence, several limitations should be considered:

This was an observational study rather than a randomized controlled trial, meaning treatment decisions were made by clinicians rather than randomly assigned. Although researchers used sophisticated statistical methods to match patients, unmeasured factors could still influence results.

The follow-up period averaged 1.4 years, which is relatively short for evaluating MS outcomes. Longer-term data might reveal different patterns in disability progression or safety profiles.

Dosing of rituximab varied between treatment centers (500-1000mg every 6 months), while ocrelizumab dosing was more standardized. This variability might have influenced the results, though sensitivity analysis excluding patients with non-standard dosing confirmed the main findings.

The study couldn't comprehensively compare side effects or safety profiles due to insufficient adverse event data in the registries. Safety considerations remain important in treatment decisions.

Finally, the high rate of switching from rituximab to ocrelizumab during the study period might have influenced the results, particularly the persistence analysis.

Recommendations for Patients

Based on this research, patients with RRMS should consider the following:

1. Discuss both options with your neurologist: Have an informed conversation about the relative benefits and limitations of ocrelizumab versus rituximab for your specific situation.
2. Consider relapse prevention priorities: If preventing relapses is your primary concern, ocrelizumab may offer better protection based on this study.
3. Evaluate disability protection: Both medications showed similar effectiveness in preventing disability progression, which is ultimately the long-term goal of MS therapy.
4. Consider practical factors: Insurance coverage, out-of-pocket costs, infusion center availability, and dosing schedules may influence your decision.
5. Stay informed about ongoing research: Several randomized clinical trials are currently comparing these medications directly, which may provide more definitive answers in the future.
6. Monitor your response: Regardless of which treatment you choose, careful monitoring of disease activity through clinical assessments and regular MRI scans is essential.

Remember that treatment decisions should be individualized based on your specific disease characteristics, treatment history, lifestyle factors, and personal preferences. This study provides important evidence but shouldn't be the sole factor in your treatment decisions.

Source Information

Original Article Title: Rituximab vs Ocrelizumab in Relapsing-Remitting Multiple Sclerosis

Authors: Izanne Roos, MBChB, PhD; Stella Hughes, MD; Gavin McDonnell, MD, PhD; et al

Publication: JAMA Neurology

Publication Date: June 12, 2023 (online); August 2023 (print)

Volume and Issue: Vol. 80, No. 8

Pages: 789-797

DOI: 10.1001/jamaneurol.2023.1625

This patient-friendly article is based on peer-reviewed research published in JAMA Neurology. It maintains all key findings, statistics, and methodological details from the original study while making the information accessible to patients and caregivers.