Does Ocrevus reduce disability progression? Examining the evidence

Over 2.8 million people worldwide are affected by Multiple Sclerosis (MS), a chronic disease where a central treatment goal is to slow or prevent disability progression. For many with the condition, a key question is: Does Ocrevus reduce disability progression? Evidence from major clinical trials and over a decade of follow-up demonstrates that this B-cell targeting therapy has a significant and sustained effect in delaying disability worsening in both relapsing and primary progressive forms of the disease.

Quick Summary

Clinical trial evidence and real-world data confirm that ocrelizumab significantly reduces confirmed disability progression in individuals with both relapsing multiple sclerosis (RMS) and primary progressive multiple sclerosis (PPMS) by targeting specific immune cells.

Key Points

• Reduces Disability in Relapsing MS (RMS): Clinical trials (OPERA I & II) showed a 40% lower risk of 12-week and 24-week confirmed disability progression (CDP) for Ocrevus compared to interferon beta-1a.

• Reduces Disability in Primary Progressive MS (PPMS): In the ORATORIO trial, Ocrevus was the first therapy to demonstrate a significant slowing of disability progression in PPMS, with a 24% lower risk of 12-week CDP versus placebo.

• Long-term Efficacy Confirmed: Open-label extension studies show the benefit of Ocrevus in reducing disability progression is sustained over 10 years for both RMS and PPMS patients.

• Early Treatment is Crucial: Long-term data highlights that initiating Ocrevus earlier is associated with a lower risk of disability events compared to delaying treatment.

• Targets B-Cells to Slow Progression: Ocrevus's mechanism of targeting CD20-positive B-cells is central to its ability to slow disability progression by controlling both relapses and progression independent of relapse activity (PIRA).

• Correlates with Drug Exposure: Higher serum levels of Ocrevus have been consistently linked to a greater reduction in the risk of confirmed disability progression.

Understanding Ocrevus and its mechanism

Ocrevus (ocrelizumab) is a humanized monoclonal antibody designed to selectively target CD20-positive B-cells. These immune cells are thought to contribute to the inflammation and nerve damage characteristic of MS. By depleting these B-cells, Ocrevus aims to modulate the immune response, potentially slowing disease activity and progression.

Evidence for reducing disability progression in relapsing MS

Studies have demonstrated Ocrevus's efficacy in relapsing forms of MS (RMS), including relapsing-remitting MS (RRMS) and active secondary progressive MS (SPMS). In major clinical trials comparing Ocrevus to interferon beta-1a, key findings indicated a significantly lower risk of confirmed disability progression (CDP) at both 12 and 24 weeks in patients treated with Ocrevus. Long-term follow-up data, extending over 10 years, further supports the sustained benefit of continuous Ocrevus treatment in preventing disability accumulation and reaching disability milestones.

Evidence for reducing disability progression in primary progressive MS

Ocrevus is the first approved treatment for primary progressive MS (PPMS), a form of MS characterized by steady symptom worsening. Evidence from clinical trials shows that Ocrevus treatment is associated with a reduced risk of 12-week confirmed disability progression compared to placebo. Studies have also indicated a slower worsening of walking ability and a reduction in brain lesion volume. Further research in patients with more advanced PPMS has also shown a reduction in the risk of composite confirmed disability progression.

Higher exposure and early treatment matter

Analyses from trials suggest that greater exposure to ocrelizumab is linked to a more significant reduction in the risk of confirmed disability progression, particularly in RMS. This highlights the potential importance of consistent dosing for optimal effect. Additionally, long-term data emphasizes the benefit of starting Ocrevus treatment early to help prevent irreversible disability accumulation.

How is disability progression measured?

Disability progression in clinical trials is assessed using several methods, including:

• Expanded Disability Status Scale (EDSS): A clinician-rated scale for neurological function. A sustained increase in the EDSS score is considered confirmed disability progression (CDP).
• Timed 25-Foot Walk (T25FW): Measures walking speed.
• 9-Hole Peg Test (9HPT): Assesses manual dexterity.
• Brain imaging (MRI): Used to track disease activity and progression through measures like lesion volume.

Comparison of Ocrevus's effect on disability progression

Parameter	Ocrevus vs. IFNβ-1a (Relapsing MS)	Ocrevus vs. Placebo (Primary Progressive MS)
Trial Name	OPERA I & II	ORATORIO
Risk of 12-week CDP	40% reduction (pooled analysis)	24% reduction
Risk of 24-week CDP	40% reduction (pooled analysis)	25% reduction
Effect on Brain Lesions	94–95% lower number of T1 Gd+ lesions	7.4% average increase vs. 3.4% decrease in T2 lesion volume
Long-term Freedom from Progression (10 years)	77% of patients free from disability progression	36% of patients free from disability progression

The importance of PIRA vs. RAW

Disability in MS can worsen due to relapses (Relapse-Associated Worsening or RAW) or independent of relapses (Progression Independent of Relapse Activity or PIRA). Studies suggest that PIRA is a significant contributor to disability accumulation even with therapies that control relapses. Clinical trial data indicates that Ocrevus is effective against both RAW and PIRA, though its impact on RAW may be more pronounced.

Conclusion: a proven effect on disability progression

Clinical trial and long-term evidence supports that Ocrevus reduces the risk of disability progression in both relapsing and primary progressive multiple sclerosis. It helps manage inflammatory activity and measurably slows the long-term accumulation of disability, which is important for patient quality of life. Starting treatment early and consistently appears to be key to maximizing this benefit. For more details on the ORATORIO trial for PPMS, you can refer to the original publication.

Frequently Asked Questions

How is disability progression measured in clinical trials for Ocrevus?

Disability progression in Ocrevus trials is measured using the Expanded Disability Status Scale (EDSS) and functional tests like the Timed 25-Foot Walk (T25FW) and 9-Hole Peg Test (9HPT). A sustained increase in the EDSS score, or worsening on functional tests, is documented as confirmed disability progression (CDP) over a period of 12 or 24 weeks.

Does Ocrevus help with both relapsing and progressive forms of MS?

Yes, Ocrevus is approved for and has shown efficacy in treating both relapsing forms of MS (including RRMS and active SPMS) and primary progressive MS (PPMS). Clinical trials have demonstrated its ability to reduce disability progression in both patient populations.

What is the difference in effect between Ocrevus and interferon beta-1a on disability progression?

In comparative trials for relapsing MS, Ocrevus demonstrated superior efficacy by reducing the risk of confirmed disability progression by 40% compared to interferon beta-1a. It also led to a greater proportion of patients showing disability improvement.

Is there long-term evidence that Ocrevus reduces disability progression?

Yes, long-term open-label extension (OLE) studies following the initial trials have provided up to 10 years of data. These studies show a sustained reduction in disability progression for patients continuously treated with Ocrevus, especially those who started early.

How does higher drug exposure of Ocrevus relate to disability progression?

Post hoc analyses of trial data have shown a consistent trend where higher ocrelizumab serum levels correlate with a greater reduction in the risk of confirmed disability progression. This supports the consistent every-six-month dosing schedule to maintain optimal drug levels and efficacy.

Can Ocrevus prevent disability progression that is independent of relapses (PIRA)?

Yes, real-world data and analyses of clinical trials indicate that Ocrevus helps control progression independent of relapse activity (PIRA), which is a major contributor to disability accumulation in MS. While it may be more effective against relapses, it also provides a measurable benefit against PIRA.

Are there any patient factors that might affect Ocrevus's impact on disability progression?

Some analyses have shown that the magnitude of Ocrevus's effect on disability progression might be influenced by factors such as body weight and baseline MRI activity. Patients with MRI lesion activity at baseline, for example, showed a greater reduction in the risk of disability progression in recent PPMS trial data.