Arava, a prescription drug for rheumatoid arthritis, has been linked to at least 12 deaths from liver failure and dozens of serious illnesses and should be banned, says a national consumer group.
Public Citizen filed a petition Thursday with the Food and Drug Administration,asking it to review the unexpected deaths and illnesses attributed to Arava, in use since September 1998.
A Tucson rheumatologist said Thursday that she will continue to prescribe Arava.
“I do not think the drug is dangerous when used appropriately, and I will continue my patients on it,” said Dr. Karen Smith. Appropriate use includes blood tests to monitor patients’ liver function every two to three months, Smith said.
But the director of the University of Arizona Arthritis Center, a former scientific adviser to the FDA, said he supports Public Citizen’s petition, although he still has patients taking Arava.
“I’m very aggressive with rheumatoid arthritis. I’m no shrinking violet,” said Dr. David Yocum, who 12 years ago pioneered another rheumatoid arthritis treatment now widely used.
“But here we have 12 deaths, and these patients died very quickly,” Yocum said. “All I can say is, this needs to be reviewed.”
A spokeswoman for Aventis Pharma, which makes Arava, told The Associated Press Thursday that the company had not seen the petition, and would not comment. The spokeswoman said Arava is “an important therapeutic option” taken by 200,000 patients.
Public Citizen’s petition is not the first warning bell sounded about Arava.
In February 2001, the European Agency for the Evaluation of Medical Products issued a warning to doctors and patients, citing nine deaths from liver failure in patients taking Arava.
Two months later, Aventis Pharma issued a warning letter to physicians. Last August, the American College of Rheumatology published a warning to doctors and patients, urging monthly blood tests in a patient’s first six months on the drug, with follow-up tests every two to three months thereafter.
More than 2 million Americans suffer from rheumatoid arthritis, an auto-immune disease in which a patient’s own immune system attacks his or her joint cartilage, the cushiony material that keeps joints moving smoothly.
Southern Arizona has twice the national incidence of rheumatoid arthritis. About one in 25 people here suffer from it, compared with one in 50 nationally, because so many people crippled by the disease move here for the climate.
The disease strikes children and adults, with women afflicted three times as often as men.
Arava was developed as an alternative to an old rheumatoid arthritis standby, methotrexate – a drug that suppresses the immune system to deter joint destruction. When it approved Arava in 1998, the FDA said it was no better than metho-trexate, but said patients needed options.
Dr. Sidney Wolfe, director of Public Citizen’s Health Research Group, said the FDA has reports of at least 130 cases of severe liver toxicity linked to Arava, including 56 hospitalizations and 12 deaths directly attributed to the drug.
The death rate in Arava users is 33 times higher than in patients taking methotrexate, Wolfe said.
Yocum said Thursday that at least eight other deaths are indirectly related to Arava, including the death two years ago of a 75-year-old woman who was a patient at the UA Arthritis Center.
Another Arthritis Center patient suffered a stroke, Yocum said. And three other patients – two in Phoenix and one in Nevada – died from valley fever, a fungal infection that overwhelmed their immune systems already weakened by Arava, Yocum said.
But valley fever can be easily detected at an early stage by blood test, skin test or chest X-ray, while the liver failure cases were sudden and unpredictable, Yocum said.
In a letter this week to Wolfe supporting Public Citizen’s petition, Yocum bemoaned the fact that most health plans require doctors to prescribe Arava before resorting to two other new drugs, called Enbrel and Remicade, that are far more expensive. Enbrel and Remicade also work on the immune system, but attack only specific cells involved in rheumatoid arthritis’ joint-destroying rampage.
The FDA has required a warning on Remicade packages, stating that it has been linked to about 100 patient deaths worldwide from tuberculosis. Yocum said he has not lost a patient to either drug.
Yocum, who has worked on arthritis drug development for nearly 20 years, said he has never before supported taking a drug off the market. “But it’s kind of scary, what we see,” he said.
Public Citizen, based in Washington, D.C., petitioned the FDA last week to ban another drug, called Meridia, a prescription diet pill that has been linked to severe high blood pressure and heart attack.