Abatacept and arthritis
by Nathan Wei, MD, FACP, FACR
Nathan Wei is a nationally known board-certified rheumatologist and author of the Second Opinion Arthritis Treatment Kit. It's available exclusively at this website... not available in stores.
Click here: Second Opinion Arthritis Treatment Kit
This article was adapted from an excellent review of Orencia. Unfortunately, I don't have the contact information for the author.
Abatacept (CTLA4–Ig) is a novel fusion protein designed to modulate the T cell co-stimulatory signal mediated through the CD28–CD80/86 pathway. In other words, it blocks the ability of the antigen presenting cell to interact fully with the T-cell.Clinical trials showed this compound was effective in the treatment of rheumatoid arthritis.
The failure of anti-TNF drugs to control disease in all patients has led to a search for other approaches to reduce disease activity. T cells are the most abundant inflammatory cells in the RA joint. However, previous treatments involving depletion of peripheral CD4+ T cells, have been less than successful. In contrast to depletion, it is possible that modulation of T cell function, possibly by targeting co-stimulatory molecules, was developed and shown to be effective at controlling the clinical signs and symptoms of RA.
Activation of T cells requires two distinct signals. The first is an antigen-specific interaction between the T cell receptor and antigen presented with the major histocompatibility complex (MHC) on the surface of an antigen-presenting cell. The second signal is provided through a number of different co-stimulatory molecules, an example of which is CD28.
Co-stimulation is especially important for T cell response, and its effects are governed by promoting cell proliferation and survival. Theoretically then, therapies targeting co-stimulatory signals have the potential to target specific T cell responses. Such an approach would be potentially useful in RA.
Abatacept, the fusion protein combining the extracellular portion of human CTLA4 T cell receptor and a blocking antibody, IgG1 Fc, has clearly been shown to be effective at controlling the signs and symptoms of RA, particularly at a dose of 10 mg/kg given monthly. The 2 mg/kg dose has not been shown to be as consistently effective.
Abatacept (Orencia) was approved for use in rheumatoid arthritis by the FDA in January 2006.
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