阿达木单抗在临床试验中对银屑病关节炎有效

雅培制药公司宣布，它们的抗关节炎药Humira (阿达木单抗)在一项晚期临床试验中治疗银屑病有关的关节炎有效。Humira已被批准用来治疗类风湿性关节炎。雅培公司说今年年底前它们将使用这些新资料来寻求该药在美国和欧洲用于治疗银屑病关节炎的批准。
 
在美国风湿病学会的圣安东尼奥年会上提交的这项研究中，使用Humira的病人关节和皮肤症状都显著改善（与用安慰剂的相比）。参试的313人以前在用非甾体消炎药治疗时都没改善。该试验的主要目的是关节压痛和肿胀关节数改善20%（ARC20）。到24周时，Humira 组39%的病人达到50%的改善（ARC50），23%达到ARC70，而安慰剂组分别只有6%和1%。在银屑病症状上，前组42% 24周时至少改善90%，而安慰剂组只有1%达到75%的改善，且没人达到90%的改善。

阿达木单抗药品英文资料：

Humira (adalimumab, D2E7)

Christian A. Hartman, BSPharm, RPh, and Claudio Faria, PharmD, RPh

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.5

Pharmacology

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.6

Safety

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.5

Outlook

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.5

For 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。