Humira (Adalimumab) Improves Rheumatoid Arthritis Disease Activity

[Guest guest]

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 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 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