Arthritis runs in Laura Arden’s family. She has osteoarthritis, as do both of her parents. Her sister has rheumatoid arthritis, which can be even more debilitating. A bottle of aspirin or other pain reliever is part of everyday life for the Chicago family, as it is for millions of others.
During the last century, Americans have reached for the modest white aspirin tablet as the remedy for everything from infant teething to menstrual cramps to fever to you-name-the-ache-or-pain.
Even though aspirin is the world’s most popular drug, it is not a panacea. Not only is it limited in effectiveness for treating severe pain, but it also can have unwanted side effects, including stomach upset. Same goes for most other pain relievers on the market, except for acetaminophen (Tylenol is a common brand), which doesn’t cause upset stomachs but is limited in use because it does not treat inflammation.
But a revolution in pain relievers is likely to rearrange the family medicine cabinet, with a newcomer about to muscle aside or assign different roles to the bottles of pills now on the shelf. Beginning this month, a new class of medications known by scientists as COX-2 inhibitors will start changing what we reach for first — depending on what the ailment is and who’s taking it. These drugs are being hailed as “super aspirin” because they have all the power of pain relievers — targeting fever, pain and inflammation — without any of the unpleasant side effects, such as heartburn or ulcers, associated with aspirin, ibuprofen, naproxen and other non-steroidal anti-inflammatory drugs (NSAIDs).
Skokie-based G.D. Searle is on the market with its Celebrex brand (doctors have written a staggering one million prescriptions for it since the Jan. 1 approval), while another pharmaceutical giant, Merck, will likely be selling its Vioxx brand by summer.
For now, and probably for at least the next five years, COX-2 inhibitors will be available by prescription only. But that doesn’t figure to dissuade the Arden family and some of the 40 million Americans with arthritis, as well as millions of others who have chronic pain. What’s more, there is also preliminary evidence that preventive doses of COX-2 inhibitors might help block colon cancer and perhaps dramatically slow Alzheimer’s disease.
So what does this mean for other pain relievers? For one thing, it means that we’ll be more carefully choosing our uses of medicines that once were universal aids for just about every member of the family and every situation.
With an active ingredient from white willow bark that dates back to Hippocrates in 200 B.C., aspirin is unlikely to vanish. Its future is connected to heart disease and stroke, which research shows it can help prevent in a dose that is usually called “baby aspirin” (though aspirin is no longer recommended for children under 18, especially babies), or 81 milligrams. Aspirin remains the only over-the-counter drug that can help reduce clotting in the blood and keep arteries flowing freely.
“Research is strong enough to recommend cardio doses of 81 milligrams per day for any man older than 40 with risk factors, including family history,” said Dr. Joan Briller, a University of Illinois at Chicago cardiologist and spokeswoman for the American Heart Association. “I recommend the same for post-menopausal women.”
A major study published in February showed an added protective benefit of taking a regular 325-milligram tablet twice each month along with daily 81-milligram doses. What’s more, the American Heart Association now recommends chewing a regular aspirin or two baby aspirins during a heart attack to help get its action to the bloodstream as soon as possible.
Acetaminophen stays in the family medicine cabinet because it is the choice among pediatricians (and nurses who handle many of the phone calls) to reduce a child’s fever without any chance of a rare but serious disorder called Reye’s Syndrome, which has been tied to aspirin use in children. Acetaminophen is the new baby non-aspirin.
In contrast, the future of once cutting-edge pain relievers such as ibuprofen (brands such as Motrin and Advil) or naproxen (Aleve) is less clear. Many doctors figure it is only a matter of time, appropriate research submitted to the Food and Drug Administration and acceptable price points before COX-2 products are sold over the counter. It’s logical to assume consumers will select similar-acting medications with fewer side effects if the cost is competitive.
COX stands for cyclooxygenase. It is an enzyme in the body that helps make hormonelike substances called prostaglandins. COX-1 enzymes produce prostaglandins that actually protect the stomach lining. COX-2 enzymes are involved with creating pain and swelling in the body, especially joints. Where the newly available Celebrex, Vioxx and others will succeed is by blocking only COX-2 enzymes.
Aspirin, ibuprofen, naproxen and other non-steroidal anti-inflammatory drugs stop both COX-1 and COX-2, leaving too many patients susceptible to digestive problems and even greater potential risks when overused.
Americans filled some 77 million prescriptions for NSAIDs last year, and added about as many over-the-counter purchases. It is conservatively estimated 80,000 people are hospitalized each year from complications using such drugs, and about 8,000 died as a result. About 2 to 4 percent of 17 million NSAID users develop complications, or somewhere between 340,000 and 680,000 people.
“The most susceptible groups are the elderly and patients with coexisting diseases in the liver or heart,” said Dr. Jay Goldstein, a gastroenterologist at the University of Illinois at Chicago Medical Center who has enrolled more than 200 patient in COX-2 trials. “Plus, the longer you take them, the more likely you will suffer consequences.”
One of the problems with inflammation is that the process frequently becomes a vicious cycle. In cases such as arthritis, one bout actually causes more inflammatory response to the area. It’s tempting to try anything that halts the cycling.
“We’re talking about medications that help people greatly reduce pain while increasing the ability to walk and enjoy life,” said Goldstein.
Goldstein has long worried about patients who assumed that if they didn’t have any stomach discomfort, they couldn’t be having any complications from the drug.
“About 80 percent of people have no symptoms until they start bleeding in the stomach or get diagnosed with an ulcer,” he said. “There’s always been a false sense of security there. With COX-2 inhibitors, which I like to call `COX-1 sparing drugs,’ the sense of security is real.”
Enthusiasm seems contagious among both doctors and patients.
Arden, 37, was diagnosed with osteoarthritis more than a decade ago. Journals she kept as a young girl noted severe pain in her legs as early as 11 years old. She has worked as a secretary for temporary agencies mostly because it afforded her more flexibility for off-days when the pain was so bad she couldn’t sit in a chair.
For years, Arden took Naproxen two to three times daily in 550-milligram doses, which is a prescription-only dose. Most days her pain was manageable, but with an unwelcome constant reminder.
“I had a burning stomach, especially if I didn’t eat a full meal every time I took the medication,” said Arden. “Antacids didn’t help. My stomach felt like it was twisting slowly in knots.”
Arden untangled her symptoms by enrolling in a trial for Celebrex.
“I have all of the pain relief without any of the stomach stuff,” said Arden.
That’s an important point here, said Dr. Eric Ruderman, a rheumatologist at Rush-Presbyterian-St. Luke’s Medical Center who has treated more than 100 patients in Celebrex clinical trials.
“The COX-2 inhibitors are not more effective, but they are safer,” Ruderman explained.
Safety comes in these numbers: More than 13,000 people have used Celebrex in clincal trials. Side effects such as indigestion, diarrhea and abdominal pain were minor and caused less than 1 percent of participants to drop out. No ulcers, no stomach bleeding and minimal lesions were noticed by doctors such as Ruderman who have actually slid tubing into the upper digestive tracts of patients. Arthritis sufferers previously not able to use non-steroidal anti-inflammatory drugs because of stomach problems or adverse drug interactions (blood thinners are one example) are now booking appointments with their doctors.
“I’m prescribing it daily to patients,” said Ruderman. “People are experiencing fewer side effects already. The reports of heartburn are much less. I expect a big shift among chronic users now and plenty more changes in the years ahead.”
