How does abatacept really work in rheumatoid arthritis?

The purpose of this review is to summarize the current knowledge concerning the mechanisms of action of Abatacept in patients with rheumatoid arthritis.Abatacept (CTLA-4Ig) represents a soluble, recombinant, fully humanized fusion protein, comprising the extracellular domain of CTLA-4 and the Fc portion of IgG1. Abatacept binds to the costimulatory molecules CD80 and CD86 on antigen-presenting cells (APC), thereby blocking interaction with CD28 on T cells. In humans, Abatacept treatment was shown to be effective in patients with various autoinflammatory diseases including rheumatoid arthritis. Although the prevention of T-cell activation by interfering with signaling via CD28 still represents the main mechanism of action Abatacept acts on additional cell populations including regulatory T cells (Treg), monocytes/macrophages, osteoclasts, and B cells.Effects of Abatacept on other cell populations besides T cells have to be taken into account and might represent a valuable contribution to the therapeutic success.