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Humira (Adalimumab) Improves Rheumatoid Arthritis Disease Activity

- Study Published in Arthritis and Rheumatism Highlights Efficacy of New RA Drug -

ABBOTT PARK, IL -- January 30, 2003 -- People with rheumatoid arthritis (RA) who do not respond to traditional treatments may benefit from a new medication, according to a study published in the January issue of Arthritis and Rheumatism. Data from the ARMADA (Anti-TNF Research Study Program of the Monoclonal Antibody D2E7 in Rheumatoid Arthritis) trial show the addition of Humira™ (pronounced Hu-mare-ah) (adalimumab), previously known as D2E7, to methotrexate (MTX) in patients with active RA despite MTX therapy provided significant, rapid, and sustained improvement in disease activity over 24 weeks compared with MTX plus placebo. Humira is the first human monoclonal antibody approved for RA. Humira was created using phage display technology, resulting in an antibody with human-derived heavy and light chains variable regions and human IgG1:K constant regions.

The U.S. Food and Drug Administration recently approved Humira for reducing the signs and symptoms and inhibiting the progression of structural damage in adults with moderately to severely active rheumatoid arthritis (RA) who have had insufficient response to one or more traditional disease modifying antirheumatic drugs (DMARDs).

"A significant number of people with RA have continuing disease activity and progressive joint deterioration even with methotrexate treatment, currently the most commonly prescribed disease modifying agent to treat rheumatoid arthritis," said Charles Birbara, M.D., study co-author and associate professor of medicine, University of Massachusetts Medical School. "Humira clearly offers an effective option to slow the progression of joint damage when added to ongoing methotrexate therapy in these patients."

Trial Design
The ARMADA trial was a pivotal trial included in the regulatory application for Humira. It was designed as a 24-week, randomized, double- blind study of 271 patients with active RA despite current treatment with MTX. Patients were randomly assigned to receive subcutaneous injections of Humira (20mg, 40mg, or 80mg doses) or placebo every other week while continuing to take MTX. The efficacy of Humira was assessed using the American College of Rheumatology ACR 20 response, which represents a 20 percent improvement in clinical measures such as the number of tender and swollen joints. ACR 50 and ACR 70 response rates were also measured, along with a core set of disease activity measures for RA clinical trials, including quality of life (QOL) measurements.

Clinical Results
At 24 weeks, more than half of the patients receiving Humira 40mg every other week achieved an ACR 20 and ACR 50 response (67.2 percent and 55.2 percent), which was significantly greater than the response seen in patients receiving placebo (14.5 and 8.1 percent). Additionally, more than one in four patients achieved the ACR 70 response (26.9 percent vs. 4.8 percent for placebo), which is the closest clinical measure to remission of RA signs and symptoms. Responses were rapid with some patients reaching an ACR 20 response after one week of treatment (25.4 percent of patients receiving Humira 40mg every other week vs. 6.5 percent with placebo).

Patients receiving Humira plus MTX showed a statistically significant improvement at 24 weeks over baseline in each of the seven ACR core components, including tender joint count, swollen joint count, patient pain assessment, and patient global assessment of disease compared to patients receiving MTX plus placebo.

In this study, the most common adverse events seen in patients receiving Humira 40mg compared to placebo were rhinitis (25.4 percent vs. 19.4 percent), upper respiratory tract infection (14.9 percent vs. 9.7 percent), flu syndrome (14.9 percent vs. 8.1 percent), injection site pain (10.4 percent vs. 3.2 percent) and diarrhea (10.4 percent vs. 8.1 percent). Five Humira patients withdrew from the study vs. two placebo patients due to adverse events.

Clinical Measures of Quality of Life
Researchers also measured quality of life outcomes using standard health assessment tools that evaluate the impact of RA on patients. The Medical Outcomes Survey Short-Form 36 (SF-36) questionnaire is a general form used to assess QOL factors relevant to any chronic disease, such as vitality and emotional health. The fatigue scale of the Functional Assessment of Chronic Illness Therapy (FACIT) questionnaire focuses on an assessment of factors related to fatigue. After week 24, improvements in mean SF-36 physical component summary scores and FACIT fatigue scale scores were statistically significantly greater from patients receiving Humira 40 mg than those receiving placebo.

"These data are part of our extensive clinical development program for Humira, which was included in the regulatory application for the recent FDA approval of Humira for RA," said Steven Fischkoff, M.D., global project head for Humira in RA. "These findings provide clinical data evaluating the efficacy and safety of Humira for practitioners who may consider Humira as an option for patients who are living with the debilitating signs and symptoms that are associated with RA."

Important Safety Information
Cases of tuberculosis (TB), frequently disseminated or extra pulmonary at clinical presentation have been observed in patients receiving Humira. Serious infections and sepsis, including fatalities, have been reported with the use of TNF-blocking agents, including Humira. Many of these infections occurred in patients on concomitant immunosuppressive therapy that in addition to their underlying disease could predispose them to infections. Other invasive opportunistic fungal infections have also been observed in patients treated with TNF-blocking agents, including Humira.

TNF-blocking agents, including Humira, have been associated in rare cases with exacerbation of demyelinating disease. The most frequent adverse events seen in the placebo-controlled clinical trials (Humira vs. placebo) were upper respiratory infection (17 percent vs. 13 percent), injection site pain (12 percent vs. 12 percent), headache (12 percent vs. 8 percent), rash (12 percent vs. 6 percent) and sinusitis (11 percent vs. 9 percent). Discontinuations due to adverse events were 7 percent for Humira and 4 percent for placebo. As with any treatment program, the benefits and risks of Humira should be carefully considered before initiating therapy.

About Humira
Humira is available in a pre-filled syringe that was specially designed for use by patients who may have limited use of their hands as a result of the destructive progression of RA. The syringe has unique plastic wings that are easy to hold and will allow those patients who are prescribed Humira in the pre-filled syringe to self-administer their Humira at home without having to mix or measure their medication. This unique design was reviewed by an independent panel of people with arthritis and health professionals and received the Arthritis Foundation Ease of Use Commendation Seal.

Abbott's Humira Medicare Assistance Program ensures that Medicare-eligible seniors in need of a biologic treatment for RA who do not have prescription drug coverage will be able to receive Humira at no cost until a Medicare prescription drug benefit is enacted. Seniors interested in the program should talk with their health care provider. Eligible seniors will receive Humira directly from their health care provider, and access will continue as long as they continue to meet the eligibility criteria. More information is available by calling 1-866-4-Humira.

Humira resembles antibodies normally found in the body. Humira works by specifically blocking tumor necrosis factor alpha (TNF-a), a protein that plays a central role in the inflammatory responses of autoimmune diseases such as RA.

Humira was discovered through a broad scientific collaboration between Abbott and Cambridge Antibody Technology (CAT). As part of the collaboration, Abbott had the right to select several target antigens for which a joint Abbott/CAT research team would discover human antibody therapeutics. Humira was isolated and optimized by Abbott and CAT as part of this collaboration. Abbott owns exclusive worldwide rights to Humira, including responsibility for clinical development, manufacturing, sales and marketing. Abbott will book all revenues for Humira, and CAT will receive a royalty fee based on Humira sales.

The European Agency for the Evaluation of Medicinal Products (EMEA) accepted Abbott's submission for Humira for the treatment of RA in April 2002, and approval is anticipated in mid-2003.

About RA
More than 5 million people worldwide suffer from RA, a chronic autoimmune disease that causes pain, swelling and stiffness in the joints of hands, feet and wrists, and often leads to the destruction of joints. Unlike osteoarthritis, the most common form of arthritis, RA is an autoimmune disease where joints are inflamed, resulting in eventual destruction of the joint's interior and the surrounding bone.

The long-term prognosis for patients with RA is poor, and as a result, many patients face increased disability and premature death. Patients interested in more information about RA can visit the Web site, http://www.RA.com .

Abbott's Commitment to Immunology
Abbott is focused on the discovery and development of innovative treatments for immunologic diseases. Founded in 1989, the Abbott Bioresearch Center in Worcester, Mass., is a world-class discovery and basic research facility committed to finding new treatments for autoimmune diseases.

Abbott Laboratories (NYSE: ABT) is a global, broad-based health care company devoted to the discovery, development, manufacture and marketing of pharmaceuticals, nutritionals, and medical products, including devices and diagnostics. The company employs approximately 70,000 people and markets its products in more than 130 countries.

More information about Abbott Immunology and Humira, including full prescribing information, is available on the Web sites, http://www.abbottimmunology.com and http://www.Humira.com . Abbott's news releases and other information are available on the company's Web site at http://www.abbott.com .


SOURCE: Abbott Laboratories

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