Since Vioxx was withdrawn from the market in September, Olga Morales has been feeling the pain. Without medication, she said, her osteoarthritis feels like "having a constant toothache all over your body."
Since the heavily promoted pain medication was pulled by its manufacturer, Merck & Co., Morales has tried several different drugs.
Taking eight daily doses of Advil — a nonsteroidal anti-inflammatory drug, or NSAID — gave her no relief. Several prescription NSAIDs caused flare-ups of her acid reflux disease and "chest pains like I was having heart attack," she said.
She now takes Daypro, another prescription NSAID. It doesn't make her ill, she said, but it doesn't work as well as Vioxx.
Vioxx "was great," said the 58-year-old Falls Church resident, who had taken the drug daily for three years. "It didn't make all of the pain go away. It just took the edge off, so I could function."
Search for alternatives
Morales is one of the millions of people with chronic osteoarthritis pain trying to figure out what to do in a post-Vioxx world. About 20 million people in the United States have taken Vioxx since 1999. Merck pulled the drug from the market after a study found heightened risk of cardiovascular side effects, including heart attack and stroke, among people taking the drug for at least 18 months. Previous studies had shown similar dangers as early as 2000.
Like Morales, most patients took Vioxx, in a class of drug known as COX-2 inhibitors, to treat osteoarthritis, the most common form of arthritis. About 20 million people have osteoarthritis — characterized by erosion of surface cartilage (tissue that covers the ends of bones in a joint), which causes joint pain and limited movement. It is the most frequent cause of disability in adults, according to the National Institute of Arthritis and Musculoskeletal and Skin Diseases.
There is no cure for osteoarthritis. Some cases are so severe that joint replacement surgery is warranted, doctors said. Many drugs and other treatments remain available for the condition's short-term pain. But the many people who, like Morales, seek relief from its daily pain and stiffness do not have a clear alternative.
A new meta-analysis in the British Medical Journal (BMJ) recommends "only limited use" of NSAIDs for long-term treatment of knee osteoarthritis, citing questions about their effectiveness and safety. Of the 23 trials analyzed, all but one was short-term, evaluating the drugs' effects after two to 13 weeks. (The only longer-term study involved a drug not available in the United States.) A meeting of the Food and Drug Administration (FDA) drug safety advisory committee is planned for February to discuss the safety of the two other COX-2 drugs remaining on the U.S. market — Bextra and Celebrex.
Balancing act
For some patients, doctors said, the benefits of taking those drugs may outweigh any risks.
"Arthritis hurts every day. These people have a problem every day," said David Borenstein, a rheumatologist at Arthritis and Rheumatism Associates, which has several locations in Maryland and the District. For them, Borenstein said, the possibility of long-term side effects needs to be weighed against greatly reduced pain today. His practice has switched some former Vioxx patients to Celebrex or Bextra.
Clinicians agree that drugs should not be seen as the only, or even the most effective, pain management tool. Exercise, physical therapy and pool exercise classes should be a key part of most osteoarthritis patients' regular routines. In many cases these measures can reduce or even eliminate the need for pain medications.
"The most important intervention people can have are exercise and maintaining their weight at a reasonable level," said Joan M. Bathon, a professor of medicine and the director of the Johns Hopkins Arthritis Center. Bathon said that the most common osteoarthritis patients are overweight women.
Morales, who works out six days a week and takes Pilates, yoga, spinning and dance classes, said exercise is an integral part of the management of her arthritis. "The biggest thing is to keep moving," she said, "because you feel better if you're moving."
Pained and confused
Arthritis and Rheumatism Associates' phones started ringing within 15 minutes of the first news reports of Vioxx's withdrawal. Not all patients wanted to stop taking the drug.
"I have had patients who called and said, 'I will never take another one of these [COX-2 inhibitor] medicines again,' " said Borenstein. "On the other hand, there were other patients who said, 'This is the only medicine that has been helpful to me. . . . Is there a black market for this stuff?' "
COX-2 inhibitors were developed as alternatives to NSAIDs, which offer equivalent pain relief but carry risks of side effects including stomach pain, severe heartburn, ulcers and bleeding, doctors said. Studies have shown that COX-2 drugs offer protection from those side effects.
NSAIDs — including ibuprofen (sold as Advil and Motrin), naproxen (Aleve) and aspirin — are often used to reduce pain and inflammation and to treat headaches and fevers. But regular use may lead to gastrointestinal problems.
Another option, acetaminophen (Tylenol), does not have gastrointestinal side effects but it lacks the anti-inflammatory effects of an NSAID. It is often used for fevers and aches and pains.
Some doctors said they are mostly prescribing NSAIDs until the FDA can evaluate the safety of the other COX-2s. Some prescribe an additional drug, such as Prilosec or Xantec, to manage the gastrointestinal side effects.
John Dombrowski, director of pain medicine at Georgetown University Hospital's Pain Management Clinic, said most patients seen there who had been taking Vioxx have been switched to other COX-2 drugs. Others are now using NSAIDs.
Eric Matteson, a consultant in rheumatology and a professor of medicine at the Mayo Medical Center's pain management center in Rochester, Minn., said some Vioxx patients there were switched to other COX-2 drugs, but the clinic is "strongly limiting" their use due to concerns about cardiovascular effects.
Caution urged
In an article published this month in the Journal of Managed Care, A. Mark Fendrick, a professor of internal medicine at the University of Michigan Medical School, wrote that doctors should consider therapies other than COX-2 drugs and NSAIDs.
John Abramson, a Harvard Medical School professor and family practitioner, wrote "Overdosed America : The Broken Promise of American Medicine" (HarperCollins, 2004), which contains a chapter on Vioxx. "I would go Tylenol first, and then Aleve or Advil," he said. "And then if the relief were unsatisfactory, then I would consider trying one of the prescription drugs."
Patients should use the lowest dosage possible to control symptoms, Abramson said. Because high dosages of acetaminophen can cause liver damage, patients should stay in close contact with their doctors, he said.
Morales is happy to have found Daypro. She also takes glucosamine, an over-the-counter dietary supplement that some patients report has helped ease their arthritis pain.
If she could, she'd continue to take Vioxx, Morales said. She has no history of heart disease, is very active and takes good care of her health.
"I'm concerned" about risks, she said. "But you [also] have to talk about quality of life. . . . I probably would've stayed on it."