Weeks before pharmaceutical giant Merck & Co. sent seismic waves through the medical community, pulling its painkiller Vioxx off the market, it announced the drug had been approved for children.
Few drugs are available for those younger than 18 with debilitating rheumatoid disorders. And Merck announced with some fanfare on Sept. 8 that the federal Food and Drug Administration had approved Vioxx for pediatric use, based on research that ran three months. A longer Merck-sponsored study in adults showed the drug increases the risk of heart attacks and strokes, a finding that ended the five-year pharmaceutical run of Vioxx late last monthThe little pill was a multibillion-dollar earner for the company, bringing in $2.5 billion last year alone.But Merck and the FDA had strong hints about the drug’s cardiovascular risks as early as 1999. And even as product liability lawyers were advertising for Vioxx victims on the radio and Internet, the company went ahead with the pediatric test.”The information [about heart risks] was on the label, and it was for all dosing levels,” said Anita Larsen, a spokeswoman for Merck, referring to the fine-print package insert that accompanies all prescription drugs, which, studies have shown, are rarely read.Larsen said the label information was based on scientific data reported in 2001. Still, had the company not withdrawn the drug, it is likely that youngsters could have been taking it for years.No signs in pediatric studyOfficials at the Arthritis Foundation, the nation’s leading advocacy group for people with rheumatoid diseases, did not fault the FDA’s approval of Vioxx for children. Dr. John Klippel, a rheumatologist and president of the foundation, said that FDA approval of Vioxx for children was based solely on the three-month pediatric study and that nothing in it hinted at heart problems.”Vioxx wasn’t approved long enough for children so that it would have caused a problem in kids,” he said.The study that doomed Vioxx was aimed at determining how well the medication prevented colon polyps, intestinal growths that can sometimes flare into full-blown tumors.The study began in November 2000 and was halted prematurely last month when researchers discovered that patients on the medication had double the risk of cardiovascular disorders compared with people on placebos. Merck’s Larsen said an additional reason for that study was to examine the drug’s potential for heart attack and stroke.Yet the company embarked on the pediatric study two years later already aware it was researching cardiovascular problems – as well as polyps – in adults.”This was something we really wanted to examine,” Larsen said of the drug’s potential to cause cardiovascular problems. Still, evidence against Vioxx began arriving from numerous quarters.Dr. Garret FitzGerald, a cardiologist at the University of Pennsylvania, underscored that heart risks related to Vioxx were evident as early as 1999, the year Vioxx was federally approved. He published a scientific paper about the dangers in 2001. And last week, in a study released early by the New England Journal of Medicine, he said the entire class of drugs – COX-2 inhibitors – are potentially lethal.Dr. Steven Nissen, the Cleveland Clinic’s vice chairman of cardiology, told Newsday that Merck and the FDA knew about the risks again in 2001 because he had pointed to them as a member of an FDA heart and kidney advisory panel.Nissen had discovered a higher risk of cardiovascular problems in a group of arthritis patients on Vioxx compared with another on naproxen, a non-steroidal anti-inflammatory drug, or NSAID. Vioxx, unlike older NSAIDs, was designed to act only on pain and inflammation – and not cause stomach problems, for which NSAIDs are notorious.”What we were saying to the medical community is that we see a problem, and we think it needs more study,” Nissen said. “But it was very controversial, and we got a lot of flak for it.”Merck revised the Vioxx label in 2001, warning patients of increased cardiovascular risks.Results out before approvalThe FDA’s Dr. David Graham examined the medical records of more than 1 million adults on Vioxx and also found evidence of cardiovascular disorders. His results were reported at a medical conference in August, just weeks before the agency approved Vioxx for juvenile rheumatoid arthritis.Graham’s study “is what is known in the industry as observational, epidemiological, which is not considered the gold standard by the pharmaceutical industry,” Merck’s Larsen said. In short, the study wasn’t considered strong enough to dissuade Merck from pursuing pediatric approval.The Vioxx debacle has underscored other crises facing children with rheumatoid diseases, Klippel said, including that there is only one other approved medication for them, Enbrel, which also has risks.A rare Enbrel complication is lymphoma, cancer of the lymphatic system. Enbrel is considered a breakthrough because it acts directly on the biological processes of rheumatoid arthritis. A second drug not yet approved for children, Remicade, was shown last week to cause the same cancer in very rare instances.”The medical condition itself is a serious problem,” Klippel said of juvenile arthritis. “If you’re faced with a child who has juvenile arthritis or lupus, you have to think about taking risks with medications. And with many kids, you can get the disease in remission.”More than 300,000 children in the United States have some form of rheumatoid disease, which can transform an ordinary childhood into one with extraordinary challenges.”We are in favor of testing drugs for children, so is the FDA. That’s probably one reason there were no questions about Vioxx” from rheumatologists, Klippel said.Klippel underscored that no potent medication is trouble-free. (Source: Newsday Health News, Oct 2004)