last updated 20-11-2024

Abatacept

Abatacept

Abatacept inhibits the activation of T-lymphocytes after antigen presentation by the antigen-presenting cell (APC) that plays an important role in the early pathogenesis of rheumatoid arthritis. Activation of a T-cell requires two signals from the APC. The first signal is antigen specific and is given when antigenic peptides are presented to the T-cell through the Major Histocompatibility Complex (MHC). A second signal, the so-called co-stimulation develops from the interaction between the CD80 or CD 86 antigen on the APC and the CD28 antigen on the T-cell.

Abatacept (CTLA4Ig) is a fusion protein of the extracellular domain of the human Cytotoxic T Lymphocyte associated antigen (CTLA-4) linked to a modified Fc of human immunoglobulin 1 (IGG1). Abatacept binds with the extracellular domain of CTLA-4 to the CD 80 or the CD 86 antigen on the APC with a higher affinity than CD28. Abatacept therefore prevents the essential second signal for T-cell activation. The result is that T-cell activation and the production of inflammatory mediators and cytokines (TNF-α, interferon-γ and interleukin-2) is reduced and this has been shown to be beneficial in trials. Trials have shown that progression of joint damage can be slowed and function can be improved after use.

 

Abatacept has been registered for the treatment of rheumatoid arthritis in combination with methotrexate. The indication includes moderate to serious rheumatoid arthritis not responding to other disease modifying antirheumatic drugs (DMARD’s) including TNF-α-blockers.

The occurrence of all kinds of infections as adverse effect of abatacept is explained by its mechanism of suppressing the immune response. Furthermore, headache, hypertension, dizziness, gastrointestinal disorders, and rash are other often noticed adverse effects. A small percentage of the treated patients displays autoimmunity by developing anti-abatacept antibodies.

EPAR of abatacept.

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