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

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

Other uses

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

Associated Conditions

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

Pharmacodynamics

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

Recombinant fusion protein

• 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?

• 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

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

Rheumatoid arthritis

Brand name

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

Mechanism of action of Abatacept

• 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

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.

Prescriber info

• label info

Cost

The annual drug cost is estimated to be about $18,663 per patient in the United States.

Frequently asked questions

• Is abatacept an immunosuppressant?

• What are the side effects of abatacept?

• Does Orencia weaken the immune system?

• How does abatacept work in rheumatoid arthritis?

• What to avoid while on immunosuppressants?

• What is the best medicine for autoimmune disease?

• How long does it take for abatacept to work?

• What is the best pain medication for rheumatoid arthritis?

• Can you live normal life with RA?

• What happens if you stop taking Orencia?

• What is the difference between Orencia and Humira?

• Does Orencia affect the liver?

• Does abatacept cause weight gain?

• How does Orencia work in the body?

• Is Orencia an anti inflammatory?

• What is the safest drug for rheumatoid arthritis?

• Why are biologics so expensive?

• What is the best biologic for rheumatoid arthritis?

• Dailymed label info on Abatacept
• FDA Abatacept

Antirheumatic Agents

• Gold Preparations

• • Auranofin, Gold salts, Gold sodium thiomalate

• Interleukin receptor antagonists

• • Anakinira, Canakinumab, Rilonacept, Sarilumab, Tocilizumab

• Major immunosuppressive agents

• • Cyclosporine, Mycophenylate, Sirolimus, Tacrolimus

• Monoclonal antibodies

• • Adalimumab, Canakinumab, Certolizumab, Golimumab, Infliximab, Rituximab, Sarilumab, Tocilizumab, Ustekinumab

• Thiopurines

• • Azathioprine, Mercaptopurine, Thioguanine

• Tumor necrosis factor antagonists

• • Adalimumab, Certolizumab, Etanercept, Golimumab, Infliximab

• Tyrosine kinase inhibitors

• • Baricitinib, Tofacitinib

• Miscellaneous

• • Abatacept, Flavocoxid, Hydroxychloroquine, Leflunomide, Methotrexate, Penicillamine