Abatacept, marketed as Orencia appears to offer pain relief and increased mobility to rheumatoid arthritis patients

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Abatacept, marketed as Orencia appears to offer pain relief and

increased mobility to rheumatoid arthritis patients

Medical Study News

Published: Wednesday, 21-Sep-2005

A new drug appears to offer pain relief and increased mobility to

rheumatoid arthritis patients who have exhausted their other medical

treatment options.

A researcher at the Stanford University School of Medicine led a six-

month, multicenter clinical trial that found patients were more than

twice as likely to have significant improvement with the new drug

than with standard therapy. The findings are reported in the current

issue of the New England Journal of Medicine.

The study was a phase-III trial, the final stage of human testing

normally required by the U.S. Food and Drug Administration before it

will consider approving a drug. Based on the results, an FDA advisory

panel met on Sept. 6 and recommended the drug's approval for the

treatment of rheumatoid arthritis in cases in which standard therapy

has failed.

Abatacept, marketed as Orencia, is made by Bristol-Myers Squibb,

which sponsored the study. The lead author, Mark Genovese, MD,

Stanford associate professor of medicine (immunology and

rheumatology), is a paid consultant for the company.

" This drug works where others haven't, " said Genovese, who is also

the associate chief of the medical school's Division of Immunology

and Rheumatology. " These patients had tried and failed the best

therapies to date, and they could still have a very good response to

this drug. "

Autoimmune diseases such as rheumatoid arthritis are characterized by

an overactive immune system that turns its attack to body tissues

instead of invading microbes. T cells are immune cells thought to

play a major role in the development of rheumatoid arthritis.

Abatacept is the first of a class of drugs, called co-stimulation

blockers, that selectively impede one of the two signals needed to

activate T cells.

" It's exciting to have a therapy with a new mechanism of action, "

said Genovese. " In the next few years we are going to get an

increasing sense of who the best patients are for this therapy and

even whether patients with other autoimmune diseases might benefit. "

Bristol-Myers Squibb is also testing the drug for use in lupus.

Stuart Levine, MD, assistant professor of medicine in the division of

rheumatology at s Hopkins University School of Medicine,

expressed optimism about the new drug. " This would likely be a useful

addition to our armamentarium for patients who are failing or have

failed first-line therapy, " said Levine, who has no financial

connections with Bristol-Myers Squibb and was not part of the study.

Rheumatoid arthritis is a disease of the joints that affects more

than 2 million Americans. The disease is characterized by an

infiltration of the joints with immune cells aimed against the cells

lining the joint. The immune system attack causes pain, stiffness and

swelling of the joints and can eventually lead to cartilage

breakdown, bone loss and weakness of the joints. Without effective

therapy, approximately 15 percent of patients will be crippled by

their disfigured joints.

Nonsteroidal anti-inflammatory drugs can provide pain relief for

rheumatoid arthritis but do not treat the underlying disease.

Standard therapy currently includes other agents that suppress the

immune system and can actually modify the course of disease. In

addition, new medications that block the immune system's response

have become available in recent years. Still, many patients don't

benefit from these medications.

Bristol-Myers Squibb conferred with Genovese and others to design an

international trial to test whether abatacept could benefit these

rheumatoid arthritis sufferers who hadn't responded to existing

therapy. At 89 sites around the world, 258 of these patients received

abatacept as an intravenous injection seven times over the course of

the study, and 133 patients received a placebo. Neither the patients

nor the physicians knew who received active drug.

After six months of treatment, half of the patients taking abatacept

achieved at least 20 percent improvement compared with one of every

five taking the placebo. The FDA requires that a majority of patients

benefit by this degree before a drug can be approved for treating

rheumatoid arthritis.

A 20 percent improvement means a lot, Genovese said, particularly for

the severely affected patients in this study, who had an average of

30 tender joints each. " For many of these patients, it means a

significant increase in their ability to function, " he said. " That

means turning on the shower, opening a car door, using the toilet --

little actions that make a huge change in their quality of life. "

One in five patients taking abatacept achieved at least 50 percent

improvement and one in 10 achieved the definition for remission -- a

difficult hurdle to clear for a group that failed to see significant

improvement from all other therapies.

According to the trial results, abatacept appears to be safe, with

few side effects. About 2 percent of both groups experienced serious

infections. Mild to moderate infections such as bronchitis and upper

respiratory tract infections were slightly higher in the group taking

the drug -- 38 percent compared with 32 percent in the placebo group.

" It " s a fine line between trying to modulate the immune system and

suppressing it to an extent that you are at an increased risk for

infections, " said Genovese. The higher risk of less serious

infections is something to keep in mind with abatacept.

" Any time you modulate the immune system you are at a potential

risk, " he said, " but you just have carefully weigh the risks and the

benefits. "

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