Latest on Arthritis Painkillers: Glucosamine, Celebrex, and Vioxx

Healthfacts, March, 2001 by Maryann Napoli

Glucosamine has been proven in several clinical trials to be an effective pain reliever for people with osteoarthritis. The popular over-the-counter dietary supplement is also much safer than the standard painkillers, known as non-steroidal, anti-inflammatory drugs (NSAIDs), such as aspirin, ibuprofen, and acetaminophen. NSAIDs cause about 15,000 deaths and about 70,000 hospitalizations yearly due to gastrointestinal bleeding. A newly published clinical trial suggests another advantage over NSAIDs; glucosamine appears to slow the progression of osteoarthritis (The Lancet, 1/27/01).

The trial involved 212 people with mild to moderate knee osteoarthritis who were randomly assigned to take 1,500 mg of glucosamine daily or a placebo (inactive pill) for three years. Before and after knee x-rays were given to all participants. Those who had been taking the placebo showed a progressive joint-space narrowing that did not occur among those taking glucosamine. Symptoms worsened slightly in the placebo group, but the significant lessoning of pain and disability was sustained for three years among those taking glucosamine. There was no substantial difference in adverse events between the two groups. The three-year duration of this trial is significant because two months is the usual length of a clinical trial for prescription drugs awaiting approval by the Food and Drug Administration (FDA). Because it is classified as a dietary supplement, glucosamine did not have go through the pre-approval safety and efficacy testing required of prescription drugs.

Celebrex and Vioxx

Last month an FDA panel of experts made recommendations concerning Celebrex and Vioxx, two very expensive NSAIDs marketed to people with arthritis. Both belong to a new class of drugs known as selective COX-2 inhibitors. Though the ads for Celebrex and Vioxx tend to emphasize power and strength, neither has been proven to be more effective than the older NSAIDs. The FDA panel's rulings centered on the purported ability of the COX-2 inhibitors' to relieve pain without the gastrointestinal risk posed by the older NSAIDs.

Pharmacia, the manufacturer of Celebrex, submitted the results of a new study in which its drug was compared with two other NSAIDs, ibuprofen and diclofenac. The FDA panel concluded that the company had not proven a meaningful safety advantage over the other NSAIDs and rejected Pharmacia's request to remove the warning about gastrointestinal risks that Celebrex and all other NSAIDs must have on their packaging and in their ads ("serious stomach problems, such as bleeding, can occur without warning"). These drugs can still cause ulcers. Significantly, many of the participants in this study were also taking low doses of aspirin to prevent heart attack, thereby canceling any stomach-protective benefit offered by Celebrex. The target population for Celebrex, older people, is most likely to be on aspirin therapy.

In a separate decision, the FDA issued its fourth warning letter to Pharmacia because its marketing of Celebrex is "false, lacking in balance." The company was minimizing the potentially serious risk of using Celebrex with blood-thinning drugs like aspirin. Of all the NSAIDs, ibuprofen and diclofenac have the most evidence of safety for aspirin users.

Merck, manufacturer of Vioxx, fared better, albeit slightly, at the hands of the FDA panel. The company submitted a new study that had compared its drug against naproxen. There was a lower rate of stomach ulcers, but the drop wasnt large enough to remove the warning about bleeding risks from the Vioxx label. The FDA panel, however, did accede to Merck's request to have these results described in the drug's label information. Alarmingly, the Vioxx users showed twice the rate of heart attack and other cardiovascular side effects as those taking naproxen. Doctors and patients must be warned accordingly, advised the panel, whose recommendations are usually followed by the FDA.

A month's supply of Celebrex or Vioxx is about $72-85 and about $10-20 for glucosamine.