The Theory Behind B-Cell Depletion
Antibody-forming white blood cells, called B-lymphocytes, create abnormal antibodies that cause rheumatoid arthritis symptoms and keep the disease trapped in a vicious cycle. In the vicious cycle, autoreactive B-lymphocytes generate their own antigen, facilitating the autoimmune response whereby the B-cells attack healthy tissue and cause inflammation of the joints.
Dr. Edwards theorized that if the B-cells were removed, normal cells which make normal antibodies would return after a few months. By removing the B-cells, the immune system would "reboot" and essentially forget that it had rheumatoid arthritis, breaking out of the vicious cycle.
How Does B-Cell Depletion Work?
Removal of the B-lymphocytes was achieved by using a combination of the drugs:
- rituximab (a monoclonal anti-CD20 antibody also known as Mabthera or Rituxan)
- prednisoline (a corticosteroid)
- cyclophosphamide (also known as Cytoxan)
The drugs were administered by intravenous infusion during two short hospital stays.
Results of B-Cell Depletion
Twenty patients had been treated, at one point, ranging in age from 40 to 70 years old. The twenty patients had suffered with rheumatoid arthritis for an average of 22 years.
The first five patients treated were 70% improved after 18 months. Two of the five did require further treatment during that time. A second group of five people experienced significant improvement six months after treatment.
Some of the responsive patients have been able to stop their other arthritis medications and resume normal lives. One of the patients has been able to resume gardening for the first time in 20 years.
Two of the 20 patients treated have shown no improvement. It was also reported that only two patients experienced adverse effects from the treatment, respiratory tract infection and mild thrombocytopenia (low platelet count).
The Future of B-Cell Depletion
Dr. Edwards conducted a larger, controlled, two-year study which involved 160 rheumatoid arthritis patients in Europe, Australia, and Canada. For the study, Hoffman la Roche contributed 30% of the cost of the drugs.
It is thought that B-cell depletion therapy has the potential to also benefit patients with other autoimmune diseases such as:
B-Cell Depletion Promising But Not A "Cure"
This latest development in the area of rheumatoid arthritis research appears so promising that the word "cure" has been tossed around in news reports. Realistically, however, much work lies ahead to confirm the positive results already seen. Dr. John Klippel, medical director of the Arthritis Foundation, was quoted as saying that the improvement and duration of response is much greater than what is usually seen. But, even if results are confirmed, it is likely to take from 5 to 7 years before the treatment would become available.
Editor note: On 3/01/2006, Rituxan (rituximab) was FDA approved to be used in combination with methotrexate to treat rheumatoid arthritis by reducing the signs and symptoms in adult patients who have moderately-to-severely active rheumatoid arthritis and have failed one or more anti-TNF drugs e.g. Enbrel (etanercept), Remicade (infliximab), or Humira (adalimumab). See: Facts About Rituxan
UK Researcher Targeting Arthritis, AP Wire, 10/30/00
B Lymphocyte Depletion May Cure RA, ReutersHealth, 10/31/00
Scientists Closer to Arthritis "Cure", BBC News, 10/29/00.
Arthritis Relief, ABCNEWS.com, 10/31/00.
Sustained Improvement in RA Following B Lymphocyte Depletion, Abstract Preview, ACR.