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April 10, 2000
Already Celebrexing?
Hold the party: The alternatives to traditional NSAIDs need more study
By Christopher Chaput, M.D.

illustration: Jason Stout

Mrs. Harriet said she was in my office because the weather had changed. "These old knees are aching me something terrible," she lamented as she showed me her bowed legs, typical of advanced osteoarthritis. "I've got to have something to help me get around when my arthritis flares up like this." Mrs. Harriet was living alone and wanted to continue her independent lifestyle. "Listen to these things," she said, bending her knees. "Have you ever heard such creaking?"

While Mrs. Harriet told me about her pain, I flipped through her chart and saw she was more frail than she looked. She had congestive heart failure, coronary artery disease, and diabetes. She had been in and out of the hospital a couple of times for chronic bronchitis that bloomed into pneumonia. She still smoked "a cigarette or two" a day and somehow managed to keep track of her ten or so prescription medications well enough to hold her medical conditions under fair control.

I saw some notes from other orthopedists. Mrs. Harriet had tried most of the standard therapies for arthritis -- including steroid injections into the knees, nonsteroidal anti-inflammatory drugs, canes, and bracing -- as well as the alternative treatment glucosamine. "Did anything help?" I asked.

"That big pill helped some. But it almost killed me," she said, smiling. She meant her pain reliever; about a year ago Mrs. Harriet was admitted for a three-week stay in the intensive-care unit after vomiting up a significant amount of blood. The most likely cause of the bleeding was the prolonged use of nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, naproxen, or ketoprofen. She had been taking these medications for more than a year.

I began to offer Mrs. Harriet alternatives: "There is always joint replacement, but I'm not sure your heart and lungs would be able to take it. It's a big surgery." She wasn't interested in surgery, but she was interested in a new drug called celecoxib, known by the brand name Celebrex. She had heard, as had I, that this new breed of NSAID was supposed to be much easier on the stomach.

NSAIDs: Over 30 million served

Nonsteroidal anti-inflammatories are relatively safe when taken for limited periods of time and under the supervision of a physician. The most common serious problems linked to NSAIDs include ulcers, gastrointestinal bleeding, and intestinal perforation. These drugs can have more serious side-effects, however, such as kidney failure, bleeding and clotting problems during surgery, and quite a list of less common complications. Every treatment comes at a price, and with NSAIDs, that price can be rather steep.

Thirty million patients a day use NSAIDs, making them the most commonly prescribed type of medication in the world. Perhaps as a result, they (by some estimates) cause the highest number of reported serious complications of all medications. Every year, nearly four billion dollars a year are spent treating these complications and about 7,600 people actually die from them.

Patients like Mrs. Harriet are at significant risk; the elderly and those with chronic health problems who must take these drugs for long periods of time to control pain often end up with NSAID-related complications. According to one study, up to 40 percent of elderly patients receive prescriptions for NSAIDs.

Celebrex is among a new class of NSAIDs called COX-2 inhibitors, which were developed in response to the potentially serious side effects of common anti-inflammatories. COX-2 inhibitors are much more "selective" than traditional NSAIDS; whereas drugs like ibuprofen medicate generally, COX-2 inhibitors target specific receptors involved in pain and inflammation.

When Celebrex came out in December of 1998, it quickly surpassed Viagra (the "male potency pill") as the number-one prescription drug in the nation. Patients, like Mrs. Harriet, heard Celebrex was easier on the stomach and began requesting it from me within months of its release. This put me in an awkward position. I'm never comfortable prescribing a medication that has just hit the market, no matter how many free pens I get with the drug's name emblazoned on it. The potential complications of new medications are rarely known until long after their release.

Alternatives still understudied

The short-term studies on Celebrex and other COX-2 inhibitors, such as Vioxx (rofecoxib), support the claim that they are safer than standard NSAIDs. In studies, they've been shown to cause fewer ulcers and bleeding problems; unlike standard NSAIDs, they do not affect the receptors on the lining of the stomach or on platelets (blood cells that are important in clot formation).

Despite the positive reviews from early studies, there hasn't been enough time to determine the drugs' long-term effects. Will COX-2 inhibitors harm the kidneys over several years? What side effects can we expect in patients who have a history of ulcers or other medical problems that make them more susceptible to gastrointestinal bleeding?

One very recent study from the University of Calgary shows that COX-2 inhibitors may delay the healing of ulcers or other internal bleeding tissue by blocking the pathway for prostaglandins that are needed to stimulate the gastrointestinal tract. This means that if you have ulcers from using traditional NSAIDs, there is a possibility that switching to Celebrex or Vioxx may slow their healing. Although this study was performed on laboratory rats, not on humans, the results call for more research on the subject.

This brings me back to Mrs. Harriet. During her appointment, she told me she was hopeful that this new medication would offer a little relief. I carefully scanned her medication list for possible interactions with one of the COX-2 inhibitors and asked her if she had any allergies. I reviewed her kidney function and saw that, like her knees, her kidneys had seen better days. Then I gave her a small sample of Celebrex and told her to let her primary physician closely monitor her on it. I also reminded her that although her stomach ulcers had healed, there was no guarantee she wouldn't have another bleeding episode or that her kidney function wouldn't be affected.

Mrs. Harriet thanked me for my time, took hold of her four-poster cane, and slowly walked down the exam room hallway. Her knees thrust to the side when she planted her weight on them. I felt a sympathetic twinge in my own knee as I watched her go.

Related links:

Rx.magazine feature article: Nature's cure for Osteoarthritis?

Arthritis Foundation's review of new arthritis drugs

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