Abatacept

ABATACEPT

Mechanism of Action

Abatacept is a co-stimulation modulator biologic that inhibits the activation of T cells. After a T cell has engaged an antigen-presenting cell (APC), a second signal is produced by CD28 on the T cell that interacts with CD80 or CD86 on the APC, leading to T-cell activation. Abatacept (which contains the endogenous ligand CTLA-4) binds to CD80 and 86, thereby inhibiting the binding to CD28 and preventing the activation of T cells.

Pharmacokinetics

Abatacept is given as three intravenous infusion “induction” doses (day 0, week 2, and week 4), followed by monthly infusions. The dose is based on body weight; patients weighing less than 60 kg receiving 500 mg, those 60–100 kg receiving 750 mg, and those more than 100 kg receiving 1000 mg. Dosing regimens in any adult group can be increased if needed. The terminal serum half-life is 13–16 days. Co-administration with methotrexate, NSAIDs, and corticosteroids does not influence abatacept clearance.

Indications

Abatacept can be used as monotherapy or in combination with other DMARDs in patients with moderate to severe rheumatoid arthritis who have had an inadequate response to other DMARDs. It reduces the clinical signs and symptoms of rheumatoid arthritis, including slowing of radiographic progression. It is also being tested in early rheumatoid arthritis.

Adverse Effects

There is a slightly increased risk of infection (as with other biologic DMARDs), predominantly of the upper respiratory tract. Concomitant use with TNF-α antagonists is not recommended due to the increased incidence of serious infection. Infusion-related reactions and hypersensitivity reactions, including anaphylaxis, have been reported but are rare. Anti-abatacept antibody forma-tion is infrequent (<5%) and has no effect on clinical outcomes. There is a possible increase in lymphomas but not in other malig-nancies when using abatacept.