Future hope for patients with Rheumatoid Arthritis, Targeting 'B-Cells' a new approach to RA treatment

Main Category: Arthritis / Rheumatology
Article Date: 18 Jun 2004 - 10:00 PDT


New data in New England Journal of Medicine show MabThera(reg) (rituximab) is effective in rheumatoid arthritis patients that have failed current therapy.

The New England Journal of Medicine (NEJM) today publishes a study which offers future hope for the thousands of rheumatoid arthritis (RA) patients who are not responding to currently available treatments (Disease Modifying Anti-Rheumatic Drugs (DMARDs)).

The multicentre study demonstrated that just two doses of MabThera(reg) (rituximab) two weeks apart, in combination with methotrexate (MTX), significantly improved symptoms in patients with severe RA by up to 70%, with response rates sustained for up to one year.

Unlike other RA treatments, MabThera is a targeted treatment that selectively seeks and destroys particular B cells (also known as B-lymphocytes).

"At the National Rheumatoid Arthritis Society we are excited and encouraged by this data. It looks as if MabThera could be an important new option in the future for patients living with Rheumatoid Arthritis in the UK.

Knowing there are other new drugs in the pipeline gives patients who are failing on current therapies hope." Ailsa Bosworth, Chief Executive National Rheumatoid Arthritis Society.

B-cells - a new approach to RA

As research advances into the causes of RA a new approach is emerging. Historically, B cells were considered to contribute to RA - however for much of the past 20 years, it has generally been considered a T-cell mediated disease.

However, new scientific evidence has rekindled a strong interest in B cells, which appear to play an important role in the pathogenesis of RA, suggesting B cells are a promising target for the development of successful treatments.

"The study provides strong support for the idea that B lymphocytes play a central role in rheumatoid arthritis and suggests that B lymphocyte targeted therapy has significant potential", said Professor Jonathan Edwards, University College of London, UK, lead investigator for the study.

MabThera is the only treatment for RA that specifically targets B-Cells.

About the study

In this Phase II study, investigators followed patients for 6 months, with a further observation at 12 months assessing the response with MabThera(reg) alone or in combination with cyclophosphamide or MTX, compared to MTX alone.

The results at 24 weeks showed that the proportion of patients reaching at least a 50% improvement in disease scores (ACR 50 - the primary endpoint) was significantly greater in the MabThera(reg) treated groups compared with the control. Moreover, a significantly higher percentage of patients treated with MabThera(reg) plus MTX achieved a 70% improvement in symptoms (ACR 70).

According to the investigators, the study's safety profile indicates that all three MabThera(reg) regimens were well tolerated with similar levels and type of adverse events compared to MTX alone. Most adverse events were reported during the initial 15 days, with most more likely to occur with the first infusion of MabThera(reg).

The majority of events were of mild to moderate intensity. At week 48, the incidence and types of events, including infections, were evenly balanced across all groups.

About MabThera(reg)

MabThera(reg) (rituximab) is a genetically engineered, therapeutic monoclonal antibody that binds specifically to the CD20 protein found on the surface of B cells.

By selectively targeting B cells, MabThera(reg) breaks the inflammatory cascade of RA - a series of reactions inflaming the joints and leading to the cartilage loss and bone erosion that is characteristic of the disease, the new theory is that B cells play a key role in this inflammatory cascade.

MabThera, known as the 'magic bullet for cancer' has been widely used in clinical practice in the UK for over 6 years for treatment of a form of lymphatic cancer called non-Hodgkin's lymphoma (NHL). More than 370,000 patients worldwide have been treated with MabThera(reg) to date.

Rheumatoid Arthritis

RA affects over 400,000 people in the UK, which is a debilitating disease that hinders the daily activities of sufferers. Although primarily RA affects persons over 64 a significant proportion are aged between 45 and 64.

RA is characterized by inflammation of multiple joints, cartilage loss and bone erosion, which leads to joint destruction and ultimately, reduced joint function. Additionally, since RA is a systemic disease, it can have effects on other tissues, such as lungs, eyes and bone marrow. After ten years of RA, fewer than 50% of patients can continue to work or function normally on a day to day basis. In the UK alone this results in a loss of £833 million in production costs.

MabThera is not currently licensed for use in rheumatoid arthritis in the United Kingdom

- Ends -

For further information:
Denise Reid-Bashir / Joanna Dixon
Cohn and Wolfe
Tel: +44 20 7331 5337 / +44 20 7331 5321
Mobile: +44 7947 259 41

Rebecca Hunt/Helen Brown
Roche UK
(UK) 01707 367 551/01707 366 805
(UK) 07786 171 214

Notes to editors - results of the NEJM Publication

Response rates at 24 weeks, when using MabThera� / Rituxan� in combination with MTX included:

-- 73% of patients showed at least a 20% improvement in symptoms (ACR 20, p=0.003 vs. MTX alone)

-- 43% showed at least a 50% improvement in symptoms (ACR 50 p=0.005 vs MTX alone)

-- 23% showed at least a 70% improvement in symptoms (ACR 70 p=0.048 vs MTX alone)

-- Peripheral blood immunoglobulin levels remained within the normal range throughout and MabThera� / Rituxan� was well tolerated with a favorable safety profile

In a further analysis, similar response rates were maintained up to at least 48 weeks without further MabThera� / Rituxan� treatment, in the MabThera� / Rituxan� plus MTX group, with ACR 20 in 65%, ACR 50 in 35% and ACR 70 in 15%.

Results from the other three arms of the study at 48 weeks include:

-- MTX alone: 20% of patients experienced a 20% improvement in symptoms and 5% experienced a 50% improvement; none experienced 70% improvement

-- MabThera� / Rituxan� alone: 33% experienced a 20% improvement, 15% experienced a 50% improvement and 10% experienced a 70% improvement

-- MabThera� / Rituxan� and cyclophosphamide: 49% experienced a 20% improvement, 27% experienced a 50% improvement and 10% experienced a 70% improvement

Carrie Rosenstone
Cohn & Wolfe Healthcare
30 Orange Street, London WC2H 7LZ
Tel: +44 (0)20 7331 5449
Fax: +44 (0)20 7331 9084

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