A Breakthrough for Victims of Arthritis

BETHESDA, Md. —  The first new drug in more than a decade for rheumatoid arthritis won the backing of government advisors Friday, with a warning that it must be taken very carefully by women who have not gone through menopause.

Arava, made by Hoechst Marion Roussel, does not cure crippling rheumatoid arthritis. But it appears to work as well as the gold-standard treatment--the cancer drug methotrexate--at treating swollen, painful joints. And it appears to slow the progression of the debilitating disease.

“This drug does good things in joints,” said Dr. Kenneth Brandt of Indiana University, before fellow advisors to the Food and Drug Administration recommended unanimously that Arava be approved for sale.

The FDA is not bound by its advisors’ recommendations, but typically follows them.

Rheumatoid arthritis affects about 2 million Americans, the vast majority of them women.

It is not the kind of arthritis that plagues the elderly as their joints essentially wear out. Instead, rheumatoid arthritis is an autoimmune disease: The immune system goes awry and attacks patients’ own cartilage. It typically strikes between ages 25 to 50.

Although the best treatment to date has been methotrexate, it causes troublesome side effects and its effectiveness wears off over a period of time, which leaves patients with few options.

Arava, which is known chemically as leflunomide, is the first in a series of promising new treatments approaching the market for general use, after decades of no new alternatives. Arava works by blocking the overproduction of immune cells that are responsible for most of the inflammation caused by arthritis.

Hoechst studied 480 Americans with moderate disease. About 41% of Arava patients saw their arthritis improve, compared to 19% of patients taking dummy pills. Methotrexate patients improved at about the same rate as Arava patients.

Then Hoechst took X-rays of patients’ hands and feet, studying bone erosion and cartilage disappearance to track the progress of the arthritis. Arava patients did get worse, but over the course of a year of study, the placebo patients worsened four times more quickly than did the Arava patients. Methotrexate also slowed the progression of the disease, but not as much as Arava did.

Arava caused side effects in more than one-fourth of all patients, including diarrhea and hair loss. But Arava did not seem as prone to causing the serious problems that methotrexate sometimes can, such as kidney failure, said Dr. Marc Hochberg of the University of Maryland, who monitored the study’s safety. Methotrexate also works by blocking immune cells, but targets a different enzyme than Arava to do the job.

But Arava does have a significant problem: Unlike most drugs that dissipate shortly after patients take the last dose, Arava can take at least six months to clear out of the body. Also, animal studies suggest it can cause numerous birth defects.

The FDA advisors warned that pregnant women should never take Arava and pre-menopausal women should use effective birth control to guard against becoming pregnant.

More troublesome was what to tell women who have already taken Arava and then decide they want to have a baby.

Hoechst has discovered that a longtime anti-cholesterol drug called cholestyramine can help flush Arava out of the body. Ten days of cholestyramine treatment can reduce blood levels of Arava a thousandfold, Hoechst scientists said.

So the FDA advisors recommended that women who use Arava also take cholestyramine and birth control until lab tests determine that Arava is no longer detectable in their blood.

The panel also recommended regular liver-monitoring, because just like methotrexate, Arava can cause liver damage.