The blockbuster arthritis drug Celebrex doesn't protect the stomach from dangerous bleeding ulcers as well as thought, a study suggests.
Celebrex and two similar new anti-inflammatory drugs are heavily advertised as being safer for arthritis patients based on earlier research that found they caused fewer ulcers and other gastrointestinal complications than older anti-inflammatory medicines. Together, the three new drugs have annual sales exceeding $6 billion.
But their safety has been called into question recently. The new study, which focused on arthritis patients at high risk of recurrent ulcers, escalates the controversy involving Celebrex, showing nearly 10 percent each year would develop another bleeding ulcer.
The study found the same thing for an older anti-inflammatory drug combined with ulcer medicine Prilosec, which doctors often give arthritis patients to protect their stomachs. In addition, neither treatment protected as many patients from dangerous kidney complications as past studies showed, the researchers said.
The Hong Kong researchers and some other experts said the results, while showing the treatments work the same, indicate more study is needed on preventing bleeding stomach ulcers in vulnerable older people who for years ease joint pain with nonsteroidal anti-inflammatory drugs, or NSAIDs.
``I think patients and doctors need to be aware ... there is a risk of gastrointestinal bleeding and there is a risk of renal toxicity,'' so high-risk patients should be monitored closely by their doctor, said Dr. John H. Klippel, medical director of the Arthritis Foundation.
A spokesman for Pharmacia Corp., which makes Celebrex, said the company interprets the findings as showing Celebrex as reducing the risk of gastrointestinal complications in high-risk patients.
``It is our feeling that these findings should guide future research in the area,'' spokesman Paul Fitzhenry said Wednesday.
Representatives of AstraZeneca Pharmceuticals LP, which sells Prilosec, did not return calls seeking comment Wednesday.
The study, reported in Thursday's New England Journal of Medicine, included 287 patients who had a previous bleeding ulcer and so were at very high risk of developing another, potentially life-threatening ulcer.
Half took the anti-inflammatory diclofenac together with Prilosec; half received Celebrex. It is one of three brand-name NSAIDs in a newer class called cox-2 inhibitors because they block the cox-2 enzyme. It produces chemicals called prostaglandins that cause pain and inflammation in the stomach as part of the body's repair process.
These drugs, which also include Vioxx and Bextra, do not block action of the cox-1 enzyme, which protects the lining of the stomach. Older NSAIDs such as diclofenac block both cox enzymes, and so can cause stomach irritation and exacerbate ulcers.
Complications from taking older anti-inflammatory drugs hospitalize about 107,000 Americans, and ulcer complications kill an estimated 16,500 each year.
Of the study patients receiving Celebrex, about 5 percent had recurrent bleeding during the six months of research, compared with about 6.5 percent for those getting diclofenac and Prilosec.
However, that equates to annual rates of about 9 percent and 11 percent, respectively, Dr. David Y. Graham of the Veterans Affairs Medical Center in Houston wrote in an accompanying editorial.
``The results were unexpected: Neither regimen provided a good or even acceptable level of protection from recurrent bleeding,'' Graham wrote.
Both treatments did a good job in reducing pain and enabling patients to perform daily activities over the six-month experiment.
But about 25 percent of those in the Celebrex group and 31 percent in the diclofenac/Prilosec group suffered kidney complications, including high blood pressure and swollen ankles; about 6 percent in each group suffered life-threatening kidney failure.
Klippel said that shows doctors must monitor high-risk patients on these anti-inflammatory drugs for increased pain and bloody stools indicating an ulcer flareup. They also should watch for swelling in the extremities and elevated blood pressure _ signs the kidneys can't excrete enough fluid.
``Physicians should avoid prescribing these drugs to patients with known kidney diseases, poorly controlled hypertension and heart failure,'' said the lead researcher, Dr. Francis K.L. Chan. ``Previous studies reported a very low incidence of kidney side effects because they excluded patients with major medical illnesses.''
Still, the study backs up the American College of Rheumatology's current guidelines for treating arthritis and gives doctors options, said Dr. Todd Stitik, associate professor of physical medicine and rehabilitation at University of Medicine and Dentistry of New Jersey in Newark.
For patients whose prescription plan covers the pricey cox-2 inhibitors, one less pill is more convenient and reduces chances of interactions with their other medicines, he said. For others, numerous generic anti-inflammatory and ulcer drugs are available.
Some arthritis patients can limit or avoid pain medications, Stitik noted, through treatments ranging from stretching and other exercise to weight loss, hot or cold packs and braces or splints.