Abatacept

For the management of the signs and symptoms of moderate-to-severe active rheumatoid arthritis, inducing major clinical response, slowing the progression of structural damage, and improving physical function in adult patients.

Indications[edit]

It is indicated both as a monotherapy and for use in combination with a continued regimen of DMARDs (not including TNF antagonists).

Other uses[edit]

Also used for the management of the signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis in children.

Associated Conditions[edit]

Moderate juvenile idiopathic arthritis
Moderate rheumatoid arthritis
Severe juvenile idiopathic arthritis
Severe rheumatoid arthritis

Pharmacodynamics[edit]

Abatacept is the first in a new class of drugs known as Selective Co-stimulation Modulators.

Recombinant fusion protein[edit]

Known as a recombinant fusion protein, the drug consists of the extracellular domain of human cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) linked to a modified Fc portion of human immunoglobulin G₁ (IgG₁.
The Fc portion of the drug consists of the hinge region, the C_H2 domain, and the C_H3 domain of IgG₁.

How does it work in RA?[edit]

Although there are multiple pathways and cell types involved in the pathogenesis of rheumatoid arthritis, evidence suggests that T-cell activation may play an important role in the immunopathology of the disease.
Ordinarily, full T-cell activation requires binding of the T-cell receptor to an antigen-MHC complex on the antigen-presenting cell as well as a co-stimulatory signal provided by the binding of the CD28 protein on the surface of the T-cell with the CD80/86 proteins on the surface of the antigen-presenting cell.
CTLA4 is a naturally occurring protein which is expressed on the surface of T-cells some hours or days after full T-cell activation and is capable of binding to CD80/86 on antigen-presenting cells with much greater affinity than CD28.

T-cell deactivation[edit]

Binding of CTLA4-Ig to CD80/86 provides a negative feedback mechanism which results in T-cell deactivation.

Rheumatoid arthritis

Brand name[edit]

Abatacept is marketed as Orencia in the United States and other countries.

Mechanism of action of Abatacept[edit]

Abatacept is a selective costimulation modulator, like CTLA-4, the drug has shown to inhibit T-cell (T lymphocyte) activation by binding to CD80 and CD86, thereby blocking interaction with CD28.
Blockade of this interaction has been shown to inhibit the delivery of the second co-stimulatory signal required for optimal activation of T-cells.
This results in the inhibition of autoimmune T-Cell activation that has been implicated in the pathogenesis of rheumatoid arthritis.

Manufacturer[edit]

Abatacept was developed by Bristol-Myers-Squibb and is licensed in the US for the treatment of Rheumatoid arthritis in the case of inadequate response to anti-TNF-alpha therapy.