Many options remain for former Vioxx patients
By John Gever
For the Dominion Post
When the first "super aspirin" drugs came on the market in the late 1990s, they were hailed as breakthroughs. Clinical studies suggested the agents -- Celebrex, Vioxx, Bextra -- were as effective as aspirin, ibuprofen and similar over-the-counter drugs, but with much less likelihood of causing stomach ulcers. The drugs looked like a godsend for people with arthritis and other chronically painful conditions.
Companies producing the drugs put their marketing machines in high gear, and soon the airwaves and the pages of popular magazines were saturated with ads that hinted at life-changing powers for the agents.
All that came to a crashing halt in September for one of those pharma firms, Merck & Co. The company had sponsored an ambitious clinical study with its product, Vioxx. Merck hoped the trial, which involved thousands of patients, would prove that Vioxx prevents colon cancer in susceptible individuals. (Many earlier studies have suggested that some painkillers, for reasons that are still uncertain, have this effect.)
Instead, the scientists running the trial noticed that the subjects taking Vioxx were experiencing heart attacks and strokes at roughly double the rate of those assigned to get a regular painkiller. The rate was low -- about 1 percent of patients who'd been taking the drug at least 18 months -- but Vioxx doesn't save lives, it only makes people feel better, and such drugs demand high safety standards. The researchers ended the study immediately and gave the bad news to Merck executives. The company consulted with officials at the federal Food and Drug Administration and agreed to "voluntarily" remove Vioxx from the market altogether.
After announcing the decision, Merck said more than 100 million prescriptions for Vioxx were written in the U.S. during the five years it was on the market. Some 20 million people took the drug, it said.
What went wrong with what once seemed a wonder drug? And what are patients who were taking it, and happy with it, going to do now?
The second question is easy to answer. "There are lots of different options" for arthritis patients and others with chronic pain and inflammation, said Tara Whetsel, clinical assistant professor in the WVU School of Pharmacy. Patients will need to sort through them with their doctors, she said, but nearly all patients should be able to find another drug, or drug combination, that will control their pain and swelling.
Before going further, it will be helpful to understand what made Vioxx and the other "super aspirins" different from regular painkillers.
Aspirin, ibuprofen, naproxen and other over-the-counter painkillers work by interrupting the inflammation process, blocking an enzyme called cyclo-oxygenase, or COX for short. Some people may find that one works better for them than another, but collectively, this group of drugs -- scientists call them NSAIDs, for non-steroidal anti-inflammatory drugs -- is very effective at alleviating pain and reducing swelling and joint stiffness. In arthritis, they don't do anything to halt the underlying joint disease, but they make people feel better. There's a problem, though -- taking the drugs for any length of time often leads to stomach ulcers, which can be painful and even life-threatening.
About 15 years ago, scientists discovered that there are actually two COX enzymes, almost but not quite identical. One, dubbed COX-1, helps maintain the lining of the gastrointestinal tract. The other, COX-2, mediates the inflammatory process elsewhere in the body. Standard NSAIDs inhibit both versions more or less equally. Scientists, and especially the pharma industry, reasoned that if drugs could be designed to block only COX-2, and leave COX-1 alone, the result would be painkillers that don't damage the gastrointestinal tract.
By the late 1990s, efforts to develop so-called selective COX-2 inhibitors paid off, with Celebrex, Vioxx and Bextra winning FDA approval in rapid succession. Initially, though, the FDA wouldn't allow the companies to claim that these drugs were less likely to cause ulcers than regular NSAIDs. In order to persuade the agency to allow that claim, the manufacturers undertook new and larger studies to document the reduced ulcer risk. Eventually they succeeded, but careful review of the studies suggested that the reduction was not complete. Whetsel said the upshot was that the ulcer reduction was real, but small. In fact, in some patient groups, there was no advantage at all.
For example, according to Whetsel, people taking low-dose aspirin for its heart-protective value along with a COX-2 inhibitor are just as likely to get an ulcer as someone taking a regular painkiller like ibuprofen. That's a fair-sized chunk of the population likely to be eligible for a COX-2 inhibitor.
So Whetsel thinks most former Vioxx patients would probably do fine on a standard NSAID such as ibuprofen or naproxen. (There are several others as well.) For patients at heightened risk for ulcers -- over age 60 or 65, needing high doses, also taking steroids or blood-thinning medications, or with other chronic diseases like emphysema or diabetes -- a doctor might want to add an anti-ulcer drug like Prilosec.
"It's an individual answer," echoed Jo Ann Hornsby, a WVU rheumatologist who said she had prescribed Vioxx to some of her patients. "It depends on what other meds they've tried, what they're allergic to."
Hornsby said she was sorry to see Vioxx taken off the market, though she agreed that it was the right thing to do. "The more options we have (available), the more options we can offer our patients," she said. Hornsby explained that some patients have trouble finding a drug that suppressed their pain adequately without causing nasty side effects. It's not uncommon for a person to try three or four different products before hitting on one that works. For some patients, that may have been Vioxx.
Hornsby also noted that every drug has side effects, and that patients should take them seriously yet not get too wigged out by the fact of them. She likened it to driving a car.
"If we knew ever single thing that could happen to us before we got in the car, we probably wouldn't drive," she said. "Is it worth it to drive the car and take a risk that you're going to get a flat tire, which is a minor complication? Or that you're going to get in a serious wreck? You've got to think about your side effects the same way."
Still, some consumer groups and critics of the pharma industry said the drug should have been pulled long before. They noted that a Vioxx study conducted four years ago reached much the same conclusion about the increased heart attack risk. At the time, the FDA ordered Merck to warn doctors and patients about the risk, but let Vioxx stay on the market.
And in the aftermath of the Vioxx debacle, some drug safety advocates said that questions also lingered over Celebrex and Bextra. "We advise patients not to use any of these 'super aspirin'" drugs, said Sidney Wolfe, director of the consumer group Public Citizen's health arm.
The drug firm Pfizer, which markets both Celebrex and Bextra, defended the drugs' safety record.
The FDA said it would establish a special expert panel to review the cardiovascular risks for the COX-2 inhibitor class. The panel may recommend additional actions that FDA could take, such as additional label warnings.
If they were all removed from the market, Whetsel suggested it wouldn't be a great loss. "In my opinion, they're probably overused," she said. She blamed the companies' marketing for helping to create a "misconception" that the COX-2 inhibitors are better painkillers. They're not, she said.
There are, however, "a lot of unknowns as far as this group of medications is concerned."
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