Understanding Anti-CD20 Therapies After Natalizumab for Multiple Sclerosis

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 (MS) is a chronic neurological condition where the immune system attacks the protective covering of nerve fibers. Over the past decade, significant progress has been made in developing disease-modifying therapies (DMTs) that can slow disease progression and reduce relapses.

Natalizumab (sold as Tysabri) is one such highly effective treatment, but it carries a serious risk called progressive multifocal leukoencephalopathy (PML), a rare brain infection caused by the John Cunningham Virus (JCV). For patients who become JCV-positive or develop other safety concerns, switching to another therapy becomes necessary.

This study focused on three anti-CD20 therapies that work by targeting specific immune cells: rituximab (often used off-label for MS), ocrelizumab (Ocrevus), and ofatumumab (Kesimpta). The researchers wanted to understand how effective these treatments are after patients discontinue natalizumab, particularly whether they prevent disease rebound and maintain stability.

Study Methods: How the Research Was Conducted

The research team conducted a retrospective study, meaning they looked back at medical records of patients who had already made the treatment switch. They included 59 patients from a Portuguese medical center who met specific criteria:

• All had confirmed MS diagnosis using McDonald 2017 criteria
• All were at least 18 years old
• All had switched from natalizumab to one of the three anti-CD20 therapies
• All had received at least six months of treatment with the new therapy

The researchers collected detailed information including:

• Demographic data (age, gender)
• Clinical characteristics (disease type, duration)
• Treatment history (how long they took natalizumab, reasons for switching)
• Outcome measures: annualized relapse rate (ARR), Expanded Disability Status Scale (EDSS) scores, and disability progression

They used rigorous statistical methods to analyze whether the treatments showed significant differences in outcomes. The study followed patients for an average of 28.58 months after switching therapies, providing substantial time to observe treatment effects.

Key Findings: Detailed Results with All Numbers

The study included 59 patients with the following distribution: 23 patients (39%) switched to rituximab, 29 patients (49.2%) to ocrelizumab, and 7 patients (11.9%) to ofatumumab. The group was 69.5% female, and 91.5% had relapsing-remitting MS (RRMS).

Key demographic differences emerged between groups:

• Rituximab patients had longer disease duration (11.0 years) compared to ocrelizumab (5.79 years) and ofatumumab (6.29 years)
• Rituximab patients had more active disease before switching, with higher relapse rates (ARR 0.65) compared to ocrelizumab (ARR 0.03) and ofatumumab (ARR 0)
• Rituximab patients also had higher disability scores (EDSS 3.65) before switching compared to ocrelizumab (EDSS 2.4) and ofatumumab (EDSS 2)

Treatment effectiveness results showed:

Rituximab significantly reduced annual relapse rates from 0.65 to 0.08 (p=0.007), meaning patients experienced far fewer relapses after switching. However, these patients also showed a significant increase in disability scores from EDSS 3.65 to 4.15 (p=0.022).

Ocrelizumab and ofatumumab showed no significant changes in either relapse rates or disability scores. Ocrelizumab patients maintained stable relapse rates (0.03 to 0.07, p=0.285) and disability scores (2.40 to 2.52, p=0.058). Ofatumumab patients maintained zero relapses and stable disability scores (2.00 to 2.14, p=0.317).

Disability progression findings revealed:

Overall, 10 patients (16.9%) experienced disability progression during the study. The most significant finding was that 70% of this progression was classified as progression independent of relapse activity (PIRA), meaning it occurred without visible relapses or new MRI lesions.

Safety and treatment changes:

Thirteen patients (22%) had to switch from their anti-CD20 therapy to another treatment. The reasons included:

• Inefficacy (8 patients) - due to relapses, MRI activity, or clinical progression
• Safety concerns (3 patients) - including recurrent infections and other issues
• Adverse events (2 patients) - primarily infections

No significant safety issues were reported for ofatumumab patients during the study period.

Clinical Implications: What This Means for Patients

This research provides reassuring evidence that all three anti-CD20 therapies can be effective options after discontinuing natalizumab. Patients did not experience disease rebound, which was a significant concern when switching from highly effective treatments.

The finding that 70% of disability progression occurred through PIRA (progression independent of relapse activity) is particularly important. This means that even when treatments successfully control visible relapses and new MRI lesions, underlying disease progression can still occur. This highlights the need for treatments that address both inflammatory activity and the smoldering, progressive aspects of MS.

For patients considering switching from natalizumab, this study suggests that anti-CD20 therapies offer a safe transition with maintained disease control. The choice between specific anti-CD20 medications may depend on individual patient factors, including disease duration, current activity level, and personal preferences regarding administration frequency and side effect profiles.

Limitations: What the Study Couldn't Prove

While this study provides valuable insights, several limitations should be considered when interpreting the results:

The sample size was relatively small, particularly for the ofatumumab group which included only 7 patients. This makes it difficult to draw definitive conclusions about this specific treatment.

The groups were not evenly matched at baseline. Rituximab patients had longer disease duration and more active disease before switching, which likely influenced their outcomes. This means we cannot directly compare the effectiveness of the three treatments against each other.

The follow-up period for ofatumumab was shorter (mean 6.86 months) compared to rituximab (48.57 months) and ocrelizumab (17.97 months). Longer observation might reveal different outcomes.

As a retrospective study, researchers could not control for all variables that might influence results. A randomized controlled trial would provide stronger evidence but would be more difficult to conduct given the specific patient population.

Recommendations: Actionable Advice for Patients

Based on this research, patients and providers can consider the following recommendations:

1. Discuss anti-CD20 options if you need to discontinue natalizumab due to JCV positivity or other safety concerns. These therapies appear to prevent disease rebound effectively.
2. Understand that disability progression can occur without relapses. Even with good relapse control, regular monitoring of disability progression remains important.
3. Consider your individual disease history when choosing between anti-CD20 options. Patients with longer disease duration and higher disability might have different responses than those earlier in their disease course.
4. Maintain regular follow-up with your healthcare team. Thirteen patients in this study needed to switch treatments due to inefficacy or side effects, highlighting the importance of ongoing monitoring.
5. Discuss the smoldering aspect of MS with your neurologist. The high rate of PIRA suggests that controlling underlying progression requires attention beyond just preventing relapses.

Source Information

Original Article Title: Effectiveness of anti-CD20 therapies following natalizumab discontinuation: insights from a cohort study

Authors: Carolina Cunha, Sara Matos, Catarina Bernardes, Inês Carvalho, João Cardoso, Isabel Campelo, Carla Nunes, Carmo Macário, Lívia Sousa, Sónia Batista, Inês Correia

Publication: Multiple Sclerosis and Related Disorders, Volume 101, 2025, 106564

Note: This patient-friendly article is based on peer-reviewed research originally published in a scientific journal. It maintains all key findings and data points while making the information accessible to non-medical readers.