Humira (adalimumab, D2E7)

Background

Rheumatoid arthritis (RA) is a chronic, progressive, inflammatory disease characterized by autoimmune activity presenting as loss of joint function, disabling joint pain, stiffness, swelling, inflammation, warmth of joints, and/or pannus formation.^1,2 While RA affects about 0.5% to 1% of the US population and may decrease life expectancy by 5 to 10 years, treatment strategies have dramatically improved over the past decade.³ This improvement is mainly attributed to new agents known as tumor necrosis factor-a (TNF-a) inhibitors, which have been effective in slowing down the progression of joint deterioration in RA patients. Humira (adalimumab), manufactured by Ab-bott Laboratories, is the first human monoclonal antibody therapy approved for the reduction of signs and symptoms of RA.^4,5 It is indicated for use in adult patients with moderately to severely active RA who have had insufficient response to at least 1 or more disease-modifying antirheumatic drugs (DMARDs). Humira can be used alone or in combination with methotrexate (MTX) or other DMARDs.⁵Pharmacology

TNF-a is a proinflammatory cyto-kine that is overproduced in patients with RA.² By specifically binding to TNF-a, Humira blocks its interaction with the p55 and p75 cell surface TNF receptors, thus neutralizing TNF-a and blocking the inflammatory process.^2,5

Clinical Trials

The Anti-TNF Research Study Program of the Monoclonal Antibody D2E7 in Rheumatoid Arthritis was a 24-week, randomized, double-blind, placebo-controlled trial involving 271 patients with active RA. Patients were assigned to receive 20-, 40-, or 80-mg subcutaneous injections of Humira or placebo every other week simultaneously with a long-term stable dose of MTX. Results were determined by the American College of Rheumatology criteria for 20%, 50%, or 70% improvement responses (defined as ACR20, ACR50, and ACR70, respectively).

At 24 weeks, ACR20 and ACR50 were achieved by a greater percentage of patients in the 20-, 40-, and 80-mg Humira plus MTX treatment groups (47.8%, 67.2%, 65.8% and 31.9%, 55.2%, 42.5%, respectively) than the placebo and MTX group (14.5% for ACR20 and 8.1% for ACR50). Furthermore, the 40- and 80-mg Humira plus MTX groups showed a greater ACR70 response (26.9% and 19.2%, respectively), when compared with placebo plus MTX (4.8%). However, the 20-mg Humira plus MTX group did not show a significant ACR70 response.⁴

The Safety Trial of Adalimumab in Rheumatoid Arthritis was a 24-week, double-blind, placebo-controlled study involving 636 subjects with active RA. This study was designed to mimic clinical practice by evaluating the safety and effectiveness associated with the addition of Humira 40 mg or placebo subcutaneous injection every other week to a preexisting standard of care (DMARDs, corticosteroids, and/or nonsteroidal anti-inflammatory drugs). Results indicated that Humira 40 mg plus standard of care was statistically superior in exhibiting greater ACR20 (51.9% vs 34.6%), ACR50 (28.9% vs 11.3%), and ACR70 (14.8% vs 3.3%) responses, compared with placebo plus standard of care.⁶Safety

In clinical trials, the most common adverse effects were sinusitis, upper respiratory tract infection, pain at the injection site, and headache.⁷ TNF-a blocking agents, including Humira, have been associated with increased cases of tuberculosis, malignancies, opportunistic infections, and exacerbation of demyelinating disease.^2,7 Furthermore, it is recommended that patients be given a tuberculin skin test prior to treatment.⁵Outlook

According to clinical studies, Humira in addition to standard of care has shown to improve signs and symptoms of RA with minimal or mild adverse effects. In addition, with Humira being a human recombinant monoclonal antibody, the risk of hypersensitivity may be less, compared with other synthetic TNF-a inhibitors.² The prescribed dosing of Humira for RA is 40 mg by self-administered subcutaneous injection every other week and is supplied in a prefilled syringe.⁵For a list of references, send a stamped, self-addressed envelope to: References Department, Attn. D. Campagnola, Pharmacy Times, 241 Forsgate Drive, Jamesburg, NJ 08831; or send an e-mail request to: dcampagnola@mwc.com.