Abatacept

Abatacept is a soluble fusion protein of the extracellular domain of cytotoxic T lymphocyte antigen 4 and the Fc portion of IgG1, used in rheumatoid arthritis, psoriatic arthritis, polyarticular juvenile idiopathic arthritis and prophylaxis of acute graft-versus-host disease. It is a selective T cell co-stimulation modulator with a favourable infection profile.

Class. Selective T cell co-stimulation modulator, fusion protein.

Mechanism. It binds CD80 and CD86 on antigen presenting cells, blocking the CD28 signal needed for full T cell activation.

Pharmacokinetics. Intravenous half-life about 13 to 14 days; subcutaneous bioavailability about 79 percent with steady state in about 85 days. Clearance rises with body weight.

Rheumatoid arthritis (intravenous).

• Dose by weight: under 60 kg, 500 mg; 60 to 100 kg, 750 mg; over 100 kg, 1000 mg.

• Schedule: at weeks 0, 2 and 4, then every 4 weeks, infused over 30 minutes.

• Maximum dose: 1000 mg for each infusion.

Rheumatoid arthritis (subcutaneous). 125 mg once weekly, with or without a single intravenous weight-based loading dose.

Psoriatic arthritis. 125 mg subcutaneously once weekly, or the intravenous weight-based regimen.

Polyarticular juvenile idiopathic arthritis (2 years and over).

• Intravenous: 10 mg/kg for under 75 kg, 750 mg for 75 to 100 kg, 1000 mg for over 100 kg, at weeks 0, 2 and 4, then every 4 weeks.

• Subcutaneous weekly: 50 mg for 10 to under 25 kg, 87.5 mg for 25 to under 50 kg, 125 mg for 50 kg and over.

Acute graft-versus-host disease prophylaxis (specialist). 10 mg/kg intravenously (maximum 1000 mg) on the day before transplant and on days 5, 14 and 28 after, with a calcineurin inhibitor and methotrexate.

Concomitant therapy. Methotrexate is continued in rheumatoid arthritis. Do not combine with TNF inhibitors or other biologics.

Contraindications. Hypersensitivity to abatacept or components. Avoid with active serious infection.

Boxed-warning-level risks. No boxed warning. Main hazards are serious infection (more with TNF inhibitor combination), more respiratory adverse events in chronic obstructive pulmonary disease, and malignancy uncertainty.

Adverse effects. Common: headache, nasopharyngitis, upper respiratory infection, nausea, injection site reactions. Serious: serious infection, hypersensitivity, exacerbation of chronic obstructive pulmonary disease, hepatitis B reactivation, possible lung cancer signal in smokers.

Major interactions. TNF inhibitors and anakinra (avoid), live vaccines (avoid for 3 months after the last dose). The intravenous formulation contains maltose and falsely raises glucose readings on strips using glucose dehydrogenase pyrroloquinoline quinone methods, risking missed hypoglycaemia in patients with diabetes.

Common prescribing errors. Using a point-of-care glucose strip that reads maltose as glucose on the infusion day and for 2 days after; combining with TNF inhibitors; not checking hepatitis B status.

Special groups.

• Pregnancy: limited data; avoid if possible, with contraception for up to 14 weeks after the last dose.

• Breastfeeding: limited data; avoid or use with caution.

• Children: from 2 years, intravenous 10 mg/kg (under 75 kg) every 4 weeks after the week 0, 2 and 4 doses, or weekly subcutaneous 50, 87.5 or 125 mg by weight band.

• Older adults: higher infection rate; monitor.

• Kidney impairment: no adjustment.

• Liver impairment: no adjustment; caution.

• Region: tuberculosis and hepatitis B screening before starting; avoid glucose strips that read maltose in diabetic patients.

Formulations. 250 mg lyophilised vials for intravenous use (reconstitute with sterile water and dilute to 100 mL in 0.9 percent sodium chloride; infuse over 30 minutes through a low protein binding filter); 50, 87.5 and 125 mg prefilled syringes and pens for subcutaneous use. Store at 2 to 8 degrees Celsius.

Baseline. Tuberculosis screen, hepatitis B and C and HIV serology, chest radiograph, full blood count, liver enzymes, and vaccination update.

Monitoring. Disease activity and infection symptoms each visit; respiratory symptoms in patients with chronic obstructive pulmonary disease; periodic full blood count and liver enzymes.

Stop or hold thresholds. Serious infection, severe hypersensitivity, or deterioration of respiratory disease.

Referral and escalation. Specialist initiated. Refer for inadequate response at 6 months.