Long-Term Ocrelizumab Treatment Shows Sustained Benefits for Relapsing-Remitting MS Patients Over 10 Years

Table of Contents

• Introduction: Why This Research Matters
• Study Methods: How the Research Was Conducted
• Safety Findings: Treatment Side Effects and Risks
• Effectiveness Results: How Well Ocrelizumab Worked
• B-Cell Monitoring: What Happens to Immune Cells
• Clinical Implications: What This Means for Patients
• Study Limitations: What the Research Couldn't Prove
• Patient Recommendations: Actionable Advice
• Source Information

Introduction: Why This Research Matters

Multiple sclerosis is a lifelong condition that requires long-term treatment strategies. Ocrelizumab (brand name Ocrevus) is an approved medication for both relapsing and primary progressive forms of MS. This anti-CD20 monoclonal antibody works by targeting specific immune cells called B-cells that contribute to MS inflammation.

While earlier studies showed ocrelizumab's effectiveness over shorter periods, this research provides the longest follow-up data ever reported—tracking patients for over a decade from 2008 to 2020. Understanding long-term safety and effectiveness is crucial because MS patients may need treatment for decades, and both patients and doctors need to know what to expect from prolonged therapy.

The study specifically examines what happens when treatment is interrupted, which is important real-world information since patients may need to pause treatment for various reasons. The research also provides valuable insights into how quickly MS activity returns after stopping medication and whether there's any rebound effect—where disease activity worsens beyond pre-treatment levels.

Study Methods: How the Research Was Conducted

This international study involved 220 participants with relapsing-remitting MS recruited from 79 medical centers across 20 countries. To qualify, patients needed to be between 18-55 years old with definite RRMS diagnosis, at least two relapses within three years (with one occurring within the previous year), and an EDSS disability score between 1-6.

The study had four distinct phases conducted over more than a decade. The initial 96-week primary treatment period randomly assigned patients to one of four groups: ocrelizumab 2000mg, ocrelizumab 600mg, placebo, or interferon beta-1a. After the first 24-week cycle, all patients received ocrelizumab for the remaining three cycles.

Following the treatment period, patients entered a treatment-free phase that included both an assessed period (where patients were monitored every 12 weeks until their B-cells returned to normal levels) and an unassessed period. Finally, 103 patients entered the open-label extension phase where everyone received ocrelizumab 600mg every 24 weeks.

Researchers measured multiple outcomes including:

• MRI activity (gadolinium-enhancing lesions and new T2 lesions)
• Annualized relapse rates
• Disability progression measured by EDSS scores
• Safety monitoring for adverse events and serious side effects
• B-cell counts and immune system markers

Safety Findings: Treatment Side Effects and Risks

The safety data from over a decade of observation provides reassuring information for patients considering long-term ocrelizumab treatment. The most common side effects across all study periods were infusion-related reactions, infections, headache, and back pain.

During the primary treatment period, exposure-adjusted rates of adverse events were comparable across treatment groups. The overall rate of adverse events was 401.1 per 100 patient-years in the ocrelizumab groups versus 375.3 in the interferon group. Serious adverse events occurred at a rate of 24.6 per 100 patient-years with ocrelizumab versus 33.8 with interferon.

Infusion reactions were most common with the first infusion (occurring in 25-35% of patients) but became rare after the fourth infusion. The study reported no cases of progressive multifocal leukoencephalopathy (PML), a serious brain infection that can occur with some MS treatments.

Infection rates were slightly higher during the treatment periods compared to the treatment-free period, as expected with any immune-modulating therapy. Serious infections remained low throughout the study at 1.5-5.5 events per 100 patient-years during ocrelizumab treatment.

There were two deaths during the study period. One occurred during the assessed treatment-free period from systemic inflammatory response syndrome in a patient who had received ocrelizumab. Another death occurred in the interferon group during the primary treatment period.

Effectiveness Results: How Well Ocrelizumab Worked

The effectiveness results demonstrate impressive long-term control of MS disease activity. During the open-label extension period, which had a median follow-up of 6.5 years, patients maintained excellent disease control.

The annualized relapse rate remained remarkably low at 0.15 throughout the entire open-label extension period. This means patients experienced on average only one relapse every 6-7 years while on treatment.

Disability progression was also well-controlled. The percentage of patients with confirmed disability progression (sustained for 24 weeks) remained low throughout the study. Even during the treatment-free period, disability progression rates were minimal.

MRI measures showed outstanding disease control. The number of gadolinium-enhancing lesions (indicating active inflammation) was reduced by 89-96% compared to placebo in the initial treatment period. This suppression of inflammatory activity was maintained throughout the long-term extension.

Perhaps most importantly, when patients stopped treatment during the treatment-free period, there was no evidence of disease rebound. The earliest signs of MRI activity reappeared at 24 weeks after the last dose, and only 16.3% of patients showed any MRI activity during the assessed treatment-free period.

B-Cell Monitoring: What Happens to Immune Cells

Ocrelizumab works by depleting CD20-positive B-cells, and this study provides important insights into how long this effect lasts and how quickly these cells recover after stopping treatment.

CD19+ B-cell counts declined rapidly after ocrelizumab treatment began and remained mostly undetectable during treatment periods. During the treatment-free period, these cells gradually repopulated.

Researchers observed a trend toward slower B-cell recovery in patients who had initially received ocrelizumab compared to those who started on placebo or interferon. The median time to B-cell repletion (reaching 80 cells/µL) was longer in the ocrelizumab groups.

At the start of the open-label extension period, the median CD19+ B-cell count was 204.0 cells/µL (range 6.0-646.0), showing that immune cells had largely recovered after the treatment break. Memory B-cells (CD19+ CD38lo CD27+) also repopulated but to a lesser extent, with a median of only 5.0 cells/µL at OLE baseline.

Once patients restarted ocrelizumab in the extension phase, B-cell counts again dropped below detection levels and remained there throughout treatment, demonstrating the medication's consistent effect on its target cells.

Clinical Implications: What This Means for Patients

This long-term study provides several important insights for MS patients considering or currently using ocrelizumab. The decade-long data shows that ocrelizumab maintains its effectiveness over many years without any loss of benefit.

For patients who need to temporarily interrupt treatment—whether due to pregnancy, surgery, insurance issues, or other reasons—the findings are particularly reassuring. The study shows that disease activity doesn't immediately return after stopping treatment, and there's no rebound effect where MS becomes worse than before treatment.

The safety profile remained consistent over time with no new emerging risks identified with prolonged use. This is important for patients who may need decades of treatment. The most common side effects (infusion reactions) typically decrease after the first few treatments.

The B-cell monitoring data helps patients understand what's happening at the immune system level. The slow return of B-cells after stopping treatment explains why disease control persists for several months after the last infusion.

Study Limitations: What the Research Couldn't Prove

While this study provides valuable long-term data, it's important to understand its limitations. The open-label extension phase wasn't randomized or controlled, meaning all participants received ocrelizumab, so we can't compare it to other treatments or no treatment during this period.

The number of patients decreased over time, which is common in long-term studies. Only 103 of the original 220 patients entered the open-label extension, and 86 remained on treatment at the data cutoff. This attrition means the results might not represent all patients who start ocrelizumab.

The study population was relatively homogeneous—all had active relapsing-remitting MS at baseline. The results might not apply to patients with less active disease or different MS subtypes.

As an exploratory analysis, the statistical comparisons weren't powered to detect differences between groups, so we must be cautious about drawing firm conclusions from numerical differences that weren't statistically tested.

Patient Recommendations: Actionable Advice

Based on this long-term study, patients using or considering ocrelizumab should:

1. Discuss long-term treatment planning with your neurologist, as this study supports ocrelizumab's safety and effectiveness over many years
2. Be aware that infusion reactions are most common with the first infusion and typically decrease with subsequent treatments
3. Understand that if treatment needs to be paused, disease protection may persist for several months due to slow B-cell recovery
4. Continue regular monitoring as recommended by your healthcare team, including routine blood tests and infection vigilance
5. Report any new symptoms to your medical team, especially signs of infection, as with any immune-modulating therapy

This research reinforces that ocrelizumab can be a long-term treatment option for RRMS with sustained benefits and a consistent safety profile. However, treatment decisions should always be made individually in consultation with your healthcare provider.

Source Information

Original Article Title: Ocrelizumab exposure in relapsing–remitting multiple sclerosis: 10-year analysis of the phase 2 randomized clinical trial and its extension

Authors: Ludwig Kappos, Anthony Traboulsee, David K. B. Li, Amit Bar-Or, Frederik Barkhof, Xavier Montalban, David Leppert, Anna Baldinotti, Hans-Martin Schneble, Harold Koendgen, Annette Sauter, Qing Wang, Stephen L. Hauser

Publication: Journal of Neurology (2023) 271:642–657

Note: This patient-friendly article is based on peer-reviewed research originally published in the Journal of Neurology. It aims to translate the scientific findings into accessible language while preserving all key data and information from the original study.