Abbott Laboratories' Humira (adalimumab)

Carolyn Soo, PharmD, and Maryellen Dascoli
Published Online: Sunday, January 1, 2006

Rheumatoid arthritis (RA) is an autoimmune disorder of unknown etiology causing inflammation of the joints. It affects approximately 1% of the population, afflicting more women than men.1 RA usually presents with pain, stiffness, and swelling of the joints, although disease progression is highly variable. It may range from mild arthritis to progressive joint destruction and disability.1 RA guidelines, developed in 1996, focused mainly on disease management and drug therapy. Currently, the focus of treatment is on early prevention of disease progression.2 In October 2005, Abbott Laboratories received additional FDA approval for Humira (adalimumab) as a first-line treatment for recent-onset moderate-tosevere RA.3

Pharmacology

Adalimumab is a recombinant human IgG1 monoclonal antibody that binds specifically to tumor necrosis factor (TNF)-alpha. Although TNF-alpha is a naturally occurring cytokine involved in normal inflammatory and immune responses, elevated levels are found in the synovial fluid of patients with RA. By binding to TNF-alpha, adalimumab blocks the interaction of cell surface TNF receptors, therefore inhibiting TNF activity.4

Clinical Trials

A subset analysis of the DE019 adalimumab study found that early treatment might be more efficacious than treatment in later disease progression. The DE019 study evaluated adalimumab 20 mg weekly or 40 mg every other week subcutaneously in combination with methotrexate (MTX) over a 52-week period in a double-blind, randomized, placebo (MTX monotherapy)-controlled trial. The trial included 618 patients with RA who had inadequate response to MTX. A subset analysis of clinical and radiographic response was conducted in patients with early disease (<2 years duration) versus late disease (>2 years duration). When comparing the 74 patients with early disease with the 544 patients with late disease, responses were higher, and health-adjusted quality-of-life scores showed improvement in the early-disease patients.5

Approval for the additional indication for early onset was based on the PREMIER trial. The PREMIER trial compared adalimumab monotherapy, MTX monotherapy, and the combination in a 2-year study involving 799 patients with early-onset moderate-to-severe RA. The primary end points were inhibition of joint damage and improvement in signs and symptoms at 1 year. Inhibition of joint damage was measured using the modified total sharp score (mTSS), which assesses bone erosion and joint space narrowing on x-rays. After 2 years, patients receiving MTX alone had a mean change in mTSS of 10.4, compared with patients receiving combination treatment with a mean change in mTSS of 1.9. Improvement in signs and symptoms was measured using the American College of Rheumatology (ACR)-50 score, which measures a 50% improvement. After 2 years, 59% of patients receiving combination therapy achieved ACR50, compared with 43% receiving MTX alone and 37% receiving adalimumab alone.3

Safety

The most serious adverse reactions include serious infection, neurologic events, and malignancies.4 A trial evaluating the safety of adalimumab in RA found adverse events to include injection-site reaction, rash, and back pain.6 Humira should not be initiated in patients with active infections, and administration with other immunosuppressants increases their risk of infection.4 Humira is in pregnancy category B, has not been studied in patients under 18, and should be used with caution in the elderly because of increased risk of infection.4

Outlook

Humira has been shown to be safe and effective in delaying RA disease progression. Early prevention of RA disease progression is of great importance as joint destruction may occur rapidly. Patients should be closely monitored due to rare cases of severe infections, sepsis, tuberculosis, and hypersensitivity reactions. The recommended dose of Humira for patients with RA is 40 mg subcutaneously every other week. It may be used in combination with MTX, glucocorticoids, salicylates, nonsteroidal anti-inflammatory drugs, analgesics, or other disease-modifying antirheumatic drugs.4

Dr. Soo is a senior research pharmacist with the Investigational Drug Service at Brigham and Women's Hospital, Boston, Mass. Ms. Dascoli is a sixth-year PharmD candidate from Northeastern University currently on clinical clerkship in the Investigational Drug Service at Brigham and Women's Hospital.

For a list of references, send a stamped, self-addressed envelope to: References Department, Attn. A. Stahl, Pharmacy Times, 241 Forsgate Drive, Jamesburg, NJ 08831; or send an e-mail request to: astahl@ascendmedia.com.



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