Description

Simple

A medication used to treat inflammatory conditions in the muscles and joints, such as rheumatoid arthritis, in children and adults.

Clinical

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.

Overview

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).

Pharmacology

Indication

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 c... Read more

Pharmacodynamic

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 G Read more

Mechanism of action

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 r... Read more

Absorption

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 subc... Read more

Protein binding

Information currently not available.

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]

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 clea... Read more

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.

Route of elimination

kidney and liver

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.

Adverse Effects

Effect Regions Age Groups Incidences Evidence Type

Contraindications

Information currently not available.

Food Interactions

Information currently not available.