Adalimumab (D2E7)

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Conference Presentations to Show Effectiveness of Adalimumab (D2E7) for

Rheumatoid Arthritis

http://www.acurian.com/diseases/disease_news.jsp?id=0900744b8000f3a1 & cond=S0104

Research to be presented June 15, 2001, at the annual European Congress

of Rheumatology (EULAR 2001) in Prague, Czech Republic, suggests that

adalimumab (D2E7) continues to show promise in treating the debilitating

effects of rheumatoid arthritis (RA). Rheumatoid arthritis is one of the

most severe forms of arthritis, affecting more than seven million people

in Western Europe, Japan and North America. Two thirds of the patients

are women.

Adalimumab is an investigational drug that is the first fully human

anti- tumor necrosis factor (TNF) alpha monoclonal antibody. As such, it

differs from other " chimeric " anti-TNF antibodies, which include varying

amounts of genetic material from other species, often from mice. Studies

show that adalimumab selectively binds TNF alpha in patients with RA and

therefore turns off the inflammation signal.

According to Dr. W. Baumgartner from the Department of Medicine,

University of Washington School of Medicine, who was not involved in the

trial of adalimumab, the rationale for this type of treatment lies in

the understanding of the processes that cause chronic inflammation.

Various chemical messengers regulate the body's natural immune defenses.

Tumor necrosis factor is one of them. Investigations that focused on the

rheumatoid synovium -- the protective sac that surrounds a joint -- have

been essential in understanding that blocking TNF might be an effective

treatment.

The rheumatoid synovium is filled with lubricating liquid called

synovial fluid. In RA, continuous inflammation of the synovium gradually

destroys cartilage and eventually damages bone. In progressive RA,

destruction of cartilage accelerates when inflammatory cells, directed

by TNF, accumulate in the synovium. This accumulation produces a pannus

-- a growth composed of thickened synovial tissue -- that causes

debilitating pain and further joint damage that can result in long-term

disability.

The ARMADA Trial, led by Dr. Keystone at the Center for Advanced

Therapeutics, Mount Sinai Hospital in Toronto, included 271 patients who

had active RA despite treatments with methotrexate, another medication

used in RA to prevent inflammation by suppressing the body's immune

response. The patients randomly received either an inactive substance

know as a placebo or one of three doses (20-, 40-, or 80-mg doses) of

adalimumab in addition to methotrexate. The patients were also

instructed on how to administer adalimumab, which is injected

subcutaneously (under the skin) every 2 weeks, and continued the

treatments for 24 weeks.

The researchers determined that 53.7 percent of patients receiving the

40-mg dose (52.7 percent among patients receiving the 80-mg dose)

experienced a 50 percent reduction of RA symptoms, compared to 8.1

percent among the patients receiving a placebo. Likewise, 26.9 percent

of patients receiving the 40-mg dose (19.2 percent among patients

receiving the 80-mg dose) experienced a 70 percent reduction of RA

symptoms, compared to 4.8 percent among the placebo patients.

An injection site reaction was experienced by 14.8 percent of patients

receiving adalimumab. The same side effect also occurred in 3.2 percent

of patients receiving the placebo.

Two other European trials of adalimumab, which included fewer patients

but were longer-term, are also scheduled to be presented during the same

session as the ARMADA Trial results at EULAR 2001.

Adalimumab was initially isolated and developed as part of a research

collaboration between Knoll Pharmaceutical Company, a division of BASF

Corporation that was purchased by Abbott Laboratories in late 2000, and

Cambridge Antibody Technology, a U.K.-based biotechnology company. Abbot

Laboratories plans to file an application for marketing approval of

adalimumab with the U.S. Food and Drug Administration in early 2002.