AdalimumabRx

Trade Names: Humira

Drug Class: Biologic DMARD, TNF antagonist

Preparations: 40 mg injection

Dose: For RA 40 mg subQ injection every 2 weeks. Some other indications have a loading dose.

Indications: RA, psoriatic arthritis, plaque psoriasis, ankylosing spondylitis, juvenile idiopathic arthritis, Crohn’s disease, ulcerative colitis

Mechanism of Action: A human IgG1 antibody against TNF-alpha that blocks the effects of the cytokine

Contraindications: Hypersensitivity, untreated tuberculosis and other opportunistic infections, sepsis, active infection, chronic localized or recurrent infections, demyelinating disease, optic neuritis, moderate-to-severe heart failure

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 IGRA). Caution in debilitated or high risk of infection.  Exclude active hepatitis B infection or carriage.  Avoid live virus vaccines and BCG. Do not use with other biologics. May exacerbate pre-exisiting demyelinating disease and heart  failure.

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

Pregnancy Risk: B

Adverse Effects
Common: Injection site reactions, positive antinuclear and double stranded DNA antibodies
Less common: Allergy, infection (bacterial, but particularly opportunistic infections such as tuberculosis, listeriosis, and histoplasmosis)
Rare: Lymphoma (including fatal hepatosplenic T-cell lymphoma), hepatitis, demyelinating CNS disorders, optic neuritis, seizures, pancytopenia, drug-induced lupus, reactivation of hepatitis B, new onset psoriasis

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

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: TNF antagonists are among the most effective treatments for RA. Patients start to respond quickly, usually within 4–6 weeks but maximum response may take 4-6 months.  In RA, combined therapy with an anti-TNF drug and MTX is more effective than either drug alone. TNF antagonists are being explored in a range of diseases such as sarcoidosis and inflammatory eye disease. Risk of tuberculosis may be lower with etanercept than other TNF antagonists; comparative risk of adverse effects among individual TNF antagonists is not clear and side effects likely a class effect. Patients may form antibodies to anti-TNF drugs that decrease their effect. Concurrent treatment with MTX may reduce the frequency of this.

Clinical Pharmacology: Half-life is 14 days. Biologic agents are not metabolized and thus have few drug interactions.

Cost: $$$$$

BIBLIOGRAPHY

Bombardier C, Hazlewood GS, Akhavan P, et al. Canadian Rheumatology Association recommendations for the
pharmacological management of rheumatoid arthritis with traditional and biologic disease-modifying antirheumatic drugs: part II safety. J Rheumatol 2012;39:1583-602. PMID: 22707613.

Weinblatt ME, Keystone EC, Furst DE, et al. Adalimumab, a fully human anti-tumor necrosis factor alpha monoclonal antibody,for the treatmentof rheumatoid arthritis in patients taking concomitant MTX: The ARMADA trial. Arthritis Rheum 2003; 48:35–45. PMID:12528101 Singh JA, Furst DE, Bharat A. et al.2012 Update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis.Arthritis Care Res 2012;64(5):625-39. PMID:22473917