Abatacept; Uses, Dosage, Side Effects, Drug Interactions

Abatacept

Abatacept is the first in a new class of biologics known as selective costimulation modulators. It inhibits full activation of T cells and interacts with other cell types to affect additional mediators of the drug used to treat autoimmune diseases like rheumatoid arthritis, by interfering with the immune activity of T cells.  It is a fusion protein composed of the Fc region of the immunoglobulin IgG1 fused to the extracellular domain of CTLA-4. In order for a T cell to be activated and produce an immune response, an antigen presenting cell must present two signals to the T cell. One of those signals is the major histocompatibility complex (MHC), combined with the antigen, and the other signal is the CD80 or CD86 molecule (also known as B7-1 and B7-2). Abatacept binds to the CD80 and CD86 molecule and prevents the second signal. Without the second signal, the T cell can’t be activated.

Mechanism of action of Abatacept

Abatacept prevents antigen-presenting cells (APCs) from delivering the co-stimulatory signal. This prevents the T cells from being fully activated, and even downregulates them. Simple signaling without co-stimulation allows the cell to recognize the primary signal as “self” and not ramp-up responses for future responses as well. In order for T cells to be activated and attack an antigen, that antigen must be presented to the T cell by an antigen-presenting cell (APC). That activation requires two signals (one of which is called the co-stimulatory signal or signal 2). For signal 1, the APC must bind the antigen to a major histocompatibility complex (MHC) molecule, bring that complex to its surface, and present it to the T cell receptor on the surface of the T cell. For signal 2, the APC must present a B7 protein on its cell surface to a CD28 protein on the surface of the T cell. These two signals activate the T cell. Without signal 2, the T cell will not be activated and will become anergic. Abatacept consists of a fusion protein of the extracellular domain of CTLA-4 and human IgG1, binds to the B7 protein on the APC and prevents it from delivering the co-stimulatory signal to the T cell. 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.

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Indications of Abatacept

Contra-Indications of Abatacept

Dosage of Abatacept

Strengths: 250 mg; 125 mg/mL; 50 mg/0.4 mg/mL

Rheumatoid Arthritis

IV

  • Less than 60 kg, give 500 mg
  • If 60 to 100 kg, give 750 mg
  • If greater than 100 kg, give 1000 mg
  • Administer as a 30-minute IV infusion; repeat the dose 2 and 4 weeks after the initial dose, then every 4 weeks thereafter.

Subcutaneous

  • 125 mg subcutaneously once a week with or without an IV loading dose
  • For patients initiating therapy with an IV loading dose, begin therapy with a single IV infusion followed by the first 125 mg subcutaneous injection administered within a day of the IV infusion.

Psoriatic Arthritis

IV

  • Less than 60 kg, give 500 mg
  • If 60 to 100 kg, give 750 mg
  • If greater than 100 kg, give 1000 mg
  • Administer as a 30-minute IV infusion; repeat the dose 2 and 4 weeks after the initial dose, then every 4 weeks thereafter.
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Subcutaneous

  • 125 mg subcutaneously once a week (without an IV loading dose)

Pediatric Juvenile Idiopathic Arthritis

IV ,6 years and older

  • fast breathing
  • If less than 75 kg: 10 mg/kg IV
  • If 75 kg to 100 kg: 750 mg IV
  • If greater than 100 kg: 1000 mg IV
  • Maximum dose: 1000 mg
  • Administer once as a 30-minute IV infusion; repeat at 2 and 4 weeks after the initial dose, then every 4 weeks thereafter

Subcutaneous
2 years and older; The subcutaneous injection should be given without an IV loading dose

  • If 10 kg to less than 25 kg: 50 mg subcutaneously once a week
  • If 25 kg to less than 50 kg: 87.5 mg subcutaneously once a week
  • If 50 kg or more: 125 mg subcutaneously once a week

Side Effects of Abatacept

The most common

More common

Rare

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Drug Interactions of Abatacept

Abatacept  may interact with the following drugs, supplements, & may change the efficacy of the drug

  • adalimumab
  • bacillus Calmette-Guérin (BCG)
  • belimumab
  • canakinumab
  • certolizumab pegol
  • live vaccines (e.g., measles, mumps, and rubella (MMR), tuberculosis (BCG), yellow fever)
  • cyclophosphamide
  • denosumab
  • fingolimod
  • leflunomide
  • nivolumab
  • natalizumab
  • pimecrolimus
  • roflumilast
  • sulfasalazine
  • tacrolimus
  • tocilizumab
  • tofacitinib
  • trastuzumab
  • vaccines (e.g., yellow fever, BCG, cholera, typhoid, varicella, meningococcal, diphtheria)

Pregnancy Catagory of Abatacept

FDA Pregnancy Category C

Pregnancy

There have been no studies on the use of abatacept by pregnant women. This medication should not be used during pregnancy unless the benefits outweigh the risks. If you become pregnant while taking this medication, contact your doctor immediately.

Lactation

It is not known if abatacept passes into breast milk. If you are a breastfeeding mother and are taking this medication, it may affect your baby. Talk to your doctor about whether you should continue breastfeeding. The safety and effectiveness of the intravenous form of abatacept have not been established for children less than 6 years of age. The subcutaneous form of this medication has not been studied for use by children and adolescents. It is not recommended for this age group.

References

abatacept