Abatacept

Indications

Abatacept is used for: 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.

Adult Dose

Rheumatoid arthritis: Intravenous Adult: As monotherapy or in combination with methotrexate or other DMARDs: Initially, <60 kg: 500 mg; 60-100 kg: 750 mg; >100 kg: 1 g. Dose is given via infusion over 30 minutes, repeated at 2 and 4 weeks after 1st infusion, then every 4 weeks thereafter. Subcutaneous Adult: 125 mg once weekly. If initiated with single IV infusion, administer 125 mg within the day of infusion followed by 125 mg once weekly.

Child Dose

Juvenile idiopathic arthritis: Intravenous Child: As monotherapy or in combination with methotrexate or other DMARDs: 6-17 yr <75 kg: 10 mg/kg via infusion over 30 minutes, repeated at 2 and 4 weeks after 1st infusion, then every 4 weeks thereafter; ≥75 kg Same as adult dose.

Renal Dose

Administration

Contra Indications

- Hypersensitivity. - Lactation. - Severe and uncontrolled infections (e.g. sepsis, active TB, hepatitis B, opportunistic infection). - Concomitant use w/ tumour necrosis factor (TNF) inhibitors and biologic immunosuppressive agents.

Precautions

Patient w/ COPD, history of recurrent infections, underlying conditions that may predispose to infections, or chronic, latent, or localised infections. Childn. Pregnancy. Admin of live vaccines.

Pregnancy-Lactation

Interactions

May diminish the therapeutic effect of live vaccines. Potentially Fatal: Increased risk of serious infection w/ TNF inhibitors (e.g. adalimumab, etanercept, infliximab). Enhanced toxicity w/ biologic immunosuppressive agents (e.g. anakinra, rituximab).

Adverse Effects

Side effects of Abatacept : Significant: Viral reactivation (i.e. hepatitis B), exacerbation of COPD. Nervous: Dizziness, headache, fatigue, paraesthesia, depression, anxiety, vertigo. GI: Nausea, dyspepsia, diarrhea, mouth ulcers. CV: HTN, hypotension, flushing, arrhythmias. Resp: Wheezing, nasopharyngitis, dyspnoea, cough, bronchitis. Haematologic: Leucopenia, Thrombocytopenia. Hepatic: Abnormal liver function values. Musculoskeletal: Back pain, pain in extremities. Ophthalmologic: Conjunctivitis. Dermatologic: Pruritus, rash, cellulitis, alopecia, psoriasis. Others: Inj site reactions (e.g. haematoma, erythema, itch), infusion-related reactions. Potentially Fatal: Serious infections (e.g. pneumonia, sepsis). Rarely, hypersensitivity, anaphylaxis, or anaphylactoid reactions.

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 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.