Abatacept
Abatacept Uses, Dosage, Side Effects, Food Interaction and all others data.
Abatacept is a soluble fusion protein, which links the extracellular domain of human cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) to the modified Fc (hinge, CH2, and CH3 domains) portion of human immunoglobulin G1 (IgG1). Structurally, abatacept is a glycosylated fusion protein with a MALDI-MS molecular weight of 92,300 Da and it is a homodimer of two homologous polypeptide chains of 357 amino acids each. It is produced through recombinant DNA technology in mammalian CHO cells. The drug has activity as a selective co-stimulation modulator with inhibitory activity on T lymphocytes. Although approved for the treatment of rheumatoid arthritis, Repligen has entered a slightly different formulation of CTLA4-Ig into clinical trials (RG2077).
Abatacept is the first in a new class of drugs known as Selective Co-stimulation Modulators. 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 CH2 domain, and the CH3 domain of IgG1. 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. Binding of CTLA4-Ig to CD80/86 provides a negative feedback mechanism which results in T-cell deactivation. 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.
| Trade Name | Abatacept |
| Availability | Prescription only |
| Generic | Abatacept |
| Abatacept Other Names | Abatacept, Abatacept recombinant |
| Related Drugs | Humira, Cosentyx, prednisone, methotrexate, hydroxychloroquine, Enbrel, Remicade, Stelara, Xeljanz, adalimumab |
| Weight | 250mg, 125mg/ml, 50mg/0.4ml, 87.5mg/0.7ml, |
| Type | Intravenous Powder For Injection, Subcutaneous Solution, Intravenous |
| Formula | C3498H5458N922O1090S32 |
| Weight | 92300.0 Da (with glycosylation) |
| Groups | Approved |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | United States |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Abatacept is a disease-modifying antirheumatic drug (DMARD) used for the management of moderate-to-severe active rheumatoid arthritis and active polyarticular juvenile idiopathic arthritis as monotherapy or in combination with other DMARDs.
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. It is indicated both as a monotherapy and for use in combination with a continued regimen of DMARDs (not including TNF antagonists). Also used for the management of the signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis in children.
Abatacept is also used to associated treatment for these conditions: Moderate Juvenile idiopathic arthritis, Moderate Rheumatoid arthritis, Severe Juvenile idiopathic arthritis, Severe Rheumatoid arthritis
How Abatacept works
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 implcated in the pathogenesis of rheumatoid arthritis.
Toxicity
Most common adverse events (≥10%) are headache, upper respiratory tract infection, nasopharyngitis, and nausea. Doses up to 50 mg/kg have been administered without apparent toxic effect.
Food Interaction
No interactions found.Abatacept Drug Interaction
Major: adalimumab, adalimumabUnknown: charcoal, charcoal, fluticasone / salmeterol, fluticasone / salmeterol, fluticasone nasal, fluticasone nasal, sodium iodide, sodium iodide, pregabalin, pregabalin, acetaminophen / hydrocodone, acetaminophen / hydrocodone, acetaminophen, acetaminophen, cyanocobalamin, cyanocobalamin, cholecalciferol, cholecalciferol
Abatacept Disease Interaction
Moderate: COPD, diabetes, hepatitis B, infections, tuberculosis
Volume of Distribution
- 0.07 L/kg [RA Patients, IV administration]
- 0.09 L/kg [Healthy Subjects, IV administration]
- 0.11 L/kg [RA patients, subcutaneous administration]
Elimination Route
When a single 10 mg/kg intravenous infusion of abatacept is administered in healthy subjects, the peak plasma concentration (Cmax) was 292 mcg/mL. When multiple doses of 10 mg/kg was given to rheumatoid arthritis (RA) patients, the Cmax was 295 mcg/mL. The bioavailability of abatacept following subcutaneous administration relative to intravenous administration is 78.6%.
Half Life
16.7 (12-23) days in healthy subjects; 13.1 (8-25) days in RA subjects; 14.3 days when subcutaneously administered to adult RA patients.
Clearance
- 0.23 mL/h/kg [Healthy Subjects after 10 mg/kg Intravenous Infusion]
- 0.22 mL/h/kg [RA Patients after multiple 10 mg/kg Intravenous Infusions]
- 0.4 mL/h/kg [juvenile idiopathic arthritis patients]. The mean systemic clearance is 0.28 mL/h/kg when a subcutaneously administered to adult RA patients. The clearance of abatacept increases with increasing body weight.
Elimination Route
kidney and liver
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