AbataceptRx

Trade Names: Orencia

Drug Class: Biologic DMARD, co-stimulation modulator

Preparations: 250 mg vial for IV, 125 mg single dose pre-filled syringe for subQ injection

Dose: For RA: IV over 30 minutes in a dose of 500 mg for patients <60 kg, 750 mg for 60-100 kg, 1000 mg for > 100 kg. Dose is repeated at 2 and 4 weeks and then every 4 weeks thereafter. Or subQ injection 125 mg weekly; can be started without an IV loading dose or can load with one infusion of IV preparation (dose above) followed immediately by 125 mg subQ.

Indications: RA with inadequate response to one or more DMARDs, polyarticular juvenile idiopathic arthritis

Mechanism of Action: A soluble fusion protein of the extracellular domain of human cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) joined to the modified Fc portion of human IgG1. Inhibits T-cell activation by binding to CD80 and CD86 blocking interaction with CD28.

Contraindications: Hypersensitivity, untreated tuberculosis and other opportunistic infections, sepsis, active infection, chronic localized or recurrent infections

Precautions: Increased risk of serious infections including TB and fungal. Exclude latent or active TB with a skin test or TB blood test (interferon-gamma release assays or IGRAs) before starting therapy. The risk of opportunistic infections is increased. Caution if used in the debilitated or in those at high risk of infection. Avoid live virus vaccines. Should not be used in combination with other biologics (increased risk of serious infection). Exclude hepatitis B infection.

Monitoring: Monitor clinically for infection. After therapy started, additional TB testing may be indicated for individuals likely to have exposure to TB.

Pregnancy Risk: C

Adverse Effects
Common: Upper respiratory infections
Less common: Allergy, infusion reactions, injection site reactions (subQ), exacerbation of COPD, infection (viral, bacterial and opportunistic infections such as tuberculosis, listeriosis, and histoplasmosis), falsely elevated blood glucose on test strips on day of IV infusion (contains maltose) with certain blood glucose strips
Rare: Anaphylaxis, reactivation of hepatitis B, cancer

Drug Interactions: Concurrent use of high-dose steroids and other immunosuppressants may increase risk of infection. Avoid concurrent biologics.

Patient Instructions: Avoid live virus vaccines; avoid pregnancy; stop injections and call your doctor if an infection or fever develops that lasts more than a few days.

Comments: Response rates to abatacept and TNF antagonists appear similar but some patients who do not respond to an anti-TNF respond to abatacept (and vice versa). Patients start to respond quickly, usually within 4–6 weeks although maximum response may not occur until after 4-6 months of treatment. However, not all patients respond. Combined therapy with methotrexate is more effective than  methotrexate alone.

Clinical Pharmacology: Half-life is 13 days; is not metabolized and thus few drug-drug interactions

Cost: $$$$$

BIBLIOGRAPHY

Weinblatt ME, Schiff M, Valente R, van der Heijde D, Citera G, Zhao C, Maldonado M, Fleischmann R. Head-to-head comparison of subcutaneous abatacept versus adalimumab for rheumatoid arthritis: findings of a phase IIIb, multinational, prospective, randomized study. Arthritis Rheum 2013;65:28-38. PMID: 23169319.