EDITOR'S NOTE: The Journal of the American Medical Association has prepared a video news release on this study. It will be fed Tuesday, Nov. 23, from 9-9:30 am EST on Galaxy 3R Transponder 14 (C-Band) and from 2-2:30 pm EST on Telstar 6, Transponder 1 (C-Band). For more information on the satellite feed, contact Barry Cohn, 312-464-4579. For interviews at Beth Israel Deaconess, media must contact communications representatives, below.
BOSTON--A new kind of arthritis drug provides the same relief of pain and inflammation in people with rheumatoid arthritis as a typical nonsteroidal anti-inflammatory drug but with fewer ulcers and other gastrointestinal side effects, according to a 12-week study led by a researcher at Beth Israel Deaconess Medical Center in Boston.
In a randomized, placebo-controlled study of 1,149 people with rheumatoid arthritis, a new kind of drug known as a "COX-2 inhibitor" was as effective as a commonly prescribed nonsteroidal anti-inflammatory drug known as naproxen. Yet, only about 6 percent people taking COX-2 inhibitors developed ulcers compared to 26 percent of people taking an equivalent pain-relieving dose of naproxen. The ulcer rate of people on the COX-2 inhibitors was statistically similar to the 4 percent ulcer rate suffered by people in the placebo group.
The study is published in the Nov. 24 issue of the Journal of the American Medical Association.
"As an advocate for patients with chronic inflammation or pain or both, I believe it is my responsibility to recommend COX-2 specific inhibitors because of their increased safety profile," says Beth Israel Deaconess rheumatologist Lee S. Simon MD, the lead author of the study, which was conducted at 79 hospitals, medical centers and private practices across the country.
Rheumatoid arthritis is one of the most serious and disabling types of arthritis, affecting more than 2.1 million people in this country, or about 1 percent of the population. An autoimmune disease that inflames the lining of the joints, rheumatoid arthritis causes pain, swelling, stiffness, and loss of function. For physicians and patients, managing the symptoms is an ongoing challenge, complicated by the occasional severe gastrointestinal side effects caused by long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs), which are among the most commonly used medications in the world.
Bleeding ulcers pose the most serious gastrointestinal risk in people taking NSAIDs, says Simon, also an associate professor of medicine at Harvard Medical School. In general, younger NSAID users face a three times greater risk of ulcers and their complications than nonusers, while people older than 60 face an even higher risk. Only about one in 1,000 ulcers are likely to develop potentially serious complications, but with 17 million daily users of NSAIDs the complication rate translates into about 170,000 serious cases a year. An estimated excess 7,500-15,000 gastrointestinal deaths related to toxicity of NSAIDs occur annually.
About 20 NSAIDs are available in this country, including aspirin, ibuprofen and acetaminophen, according to Simon. All NSAIDs inhibit both forms of an enzyme that plays an important role in the stomach, intestines and kidney. One form of the enzyme, known as COX-1, protects the lining of the gastrointestinal system. Inhibition of this enzyme is considered to be a major cause of the toxic effects of NSAIDs. However, COX-2 is the form of the enzyme involved in pain and inflammation.
In the past 12 months, two COX-2 inhibitors have been approved by the FDA with a promise of relieving symptoms with fewer dangerous side effects. In this study, researchers used celecoxib, marketed as Celebrex by Searle and approved in December 1998. Another COX-2 inhibitor, rofecoxib (marketed as Vioxx by Merck), was approved in May. Citing a recent cluster of peer-reviewed papers with similar findings in studies of each drug, Simon believes the results of his study apply generally to COX-2 specific inhibitors.
"COX-2 inhibitors have been called 'super aspirins,' but they provide the same pain relief as NSAIDs," says Simon. "What makes them better for patients is increased gastrointestinal safety." Over the past 20 years, Simon has focused on the risks, benefits, actions and toxicities of NSAIDs.
The study was funded by GD Searle & Co., Skokie, Ill. Simon and several co-authors on the paper have received compensation from Searle/Monsanto for serving on speaker's bureaus, serving as consultants, or for clinical trial participation. Two co-authors of the paper are employees of Searle/Monsanto. Simon also has received funding from Merck & Co., Johnson & Johnson, Wyeth-Ayerst, Bristol-Myers Squibb, Amgen, Procter & Gamble, Pfizer Inc., Roche Pharmaceuticals, Forrest, Virtex, Boehringer Ingelheim, and Hoechst Marion Roussel.