Arava is linked to 22 deaths in its first three years of approval, according to FDA data obtained by the watchdog group Public Citizen. Twelve of the deaths appear directly due to liver damage from the drug. And that's just the tip of the iceberg -- the deaths were among 130 severe liver reactions, including 56 hospitalizations.
That's not all, says Sidney M. Wolfe, MD, director of the Public Citizen Health Research Group. The drug also is linked to severe high blood pressure resulting in stroke and can cause birth defects. These effects can persist long after a person stops taking the drug, as it stays in the body for months. And normal "wash-out" procedures that remove the drug from the body don't seem to work when patients suffer toxic effects.
"If this were a breakthrough drug that is really saving lives, that would be one thing -- but this is a drug that is no better than safer alternatives," Wolfe tells WebMD.
Wolfe notes that several studies show another drug, methotrexate, to be as effective as Arava.
Yocum, an internationally recognized expert in arthritis treatment, says there is no way to predict which patients will suffer ill effects from Arava.
"Given the information on such serious adverse events, the apparent inability to predict patients who might suffer from the severe and potentially life-threatening complications, and the apparent ineffectiveness of a wash-out procedure, I support [Wolfe's] view that this agent should be withdrawn from the market," he writes.
Wolfe notes that during the first three years after Arava approval, there were five-and-a-half times more prescriptions written for methotrexate than for Arava. Yet Arava had six times more reports of fatal liver damage and 13 times more reports of high blood pressure. There also were 12 reports of a life-threatening autoimmune disease with Arava, but none with methotrexate.
"We have really understated how prevalent these problems are," Wolfe says. "This drug will come off the market. Unfortunately it will be too late for many people who had liver damage or strokes from taking it."
Arava is manufactured by Aventis.
"Aventis continues to believe that the benefit-to-risk profile for Arava is positive," Aventis spokeswoman Susan Brooks tells WebMD. "We encourage all physicians to closely follow all warnings and recommendations in the product labeling."
Brooks says that the company is aware of reports of adverse events and is already working with the FDA to put stronger warnings on the Aventis label. This might include the so-called "black-box" warning that FDA uses for particularly dangerous drugs.
Wolfe and Yocum say this isn't enough.
"Providing a black box warning concerning these issues may not be effective since no one can predict who will suffer from these complications," Yocum writes. "In addition, I am not sure that frequent monitoring of the patients with blood chemistries and a complete blood profile would be effective at preventing them."