——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。

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 ofjointdeterioration 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

Humira

Generic name: Adalimumab

What is Humira?

Humira is type of drug called a tumor necrosis factor (TNF) blocker. It is used to treat moderate-to-severe rheumatoid arthritis (RA) or psoriatic arthritis (PsA). RA is an inflammatory disease of the joints; PsA is an inflammatory disease of the joints and skin. Humira is also used to treat juvenile idiopathic arthritis (JIA), ankylosing spondylitis (a chronic, degenerative inflammatory arthritis, causing eventual fusion of the spine), Crohn's disease (a type of inflammatory bowel disease), and plaque psoriasis. People with these conditions have too much of a protein called TNF in the affected areas of the body.

What is the most important information I should know about Humira?

Humira can lower your immune system's ability to fight infection. There is a risk of getting serious infections such as tuberculosis or other infections caused by viruses, fungi, and bacteria. You should be tested and, if positive, treated for tuberculosis before beginning treatment with Humira.

Who should not take Humira?

Do not begin treatment with Humira if you have an allergy to any of its ingredients. The needle cover on the prefilled syringe contains dry natural rubber, so tell your doctor if you have any allergies to rubber or latex.

What should I tell my doctor before I take the first dose of Humira?

Tell your doctor about all prescription, over-the-counter, and herbal medications you are taking before beginning treatment with Humira. Also, talk to your doctor about your complete medical history, especially if you have or have had any kind of infection (including an open cut or sore) or a systemic infection (such as the flu); if you have ever had tuberculosis (TB), or if you have been in close contact with someone who has had it; or if you experience any numbness or tingling or have ever had a disease that affects your nervous system such as multiple sclerosis. Your doctor should know if you are scheduled to have surgery or have a vaccination.

What is the usual dosage?

The information below is based on the dosage guidelines your doctor uses. Depending on your condition and medical history, your doctor may prescribe a different regimen. Do not change the dosage or stop taking your medication without your doctor's approval.

Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis

Adults: The recommended dose of Humira is one 40-milligram (mg) injection every other week.

Crohn's Disease

Adults: The recommended starting dose of Humira is a 160-mg injection at Day 1 (given as 4 separate 40-mg injections in 1 day or as two 40-mg injections per day for 2 consecutive days), followed by 80 mg 2 weeks later (Day 15). After 4 weeks (Day 29), start maintenance dose of a 40-mg injection every other week.

Plaque Psoriasis

Adults: The recommended starting dose of Humira is one 80-mg injection, then 1 week after the initial dose, you'll receive a maintenance dose of 40 mg every other week.

Juvenile Idiopathic Arthritis

Children 4 to 17 years: The recommended dose of Humira (children >66 pounds) is one 40-mg injection every other week.

The recommended dose of Humira (children 33 to 66 pounds) is one 20-mg injection every other week.

If your child is <33 pounds, speak to your doctor about an appropriate Humira dosage.

How should I take Humira?

Your doctor will administer your first injection of Humira in your front thigh or abdomen. If you would like to self-administer, or have a caregiver administer your injection, have the doctor explain the proper injection and discarding technique.

What are possible food and drug interactions associated with Humira?

If Humira is taken with certain other drugs, the effects of either could be increased, decreased, or altered. It is especially important to check with your doctor before combining Humira with anakinra

What are the possible side effects of Humira?

Side effects cannot be anticipated. If any develop or change in intensity, tell your doctor as soon as possible. Only your doctor can determine if it is safe for you to continue taking this drug.

Side effects may include: reaction at site of injection (bruising, itching, rash, redness, swelling)

Usually, the rash will go away within a few days. If the skin around the area where you injected Humira still hurts or is swollen, try using a towel soaked with cold water on the injection site. If you have pain, redness or swelling around the injection site that doesn't go away within a few days or gets worse, call your doctor right away.

Can I receive Humira if I am pregnant or breastfeeding?

The effects of Humira during pregnancy and breastfeeding are unknown. Talk with your doctor before taking this drug if you are pregnant, plan to become pregnant, or are breastfeeding.

What should I do if I miss a dose of Humira?

If you forget to take Humira on time, inject the next dose right away. Then, take the following dose when your next scheduled dose is due.

How should I store Humira?

Store Humira in a refrigerator in the original container until it is used. Protect from light. Do not freeze Humira; if it has been frozen, do not use. Humira remains safe to use until the expiration date printed on the prefilled syringe or pen. If traveling, store Humira in a cool carrier with an ice pack and protect from light. Do not use if liquid is cloudy, discolored, or has flakes or particles in it.