That's the news from an 18,000-patient clinical trial comparing Prexige to ibuprofen and naproxen in patients with osteoarthritis. It likely will pave the way for U.S. approval of the newest member of the prescription drug family known as Cox-2 inhibitors. The drugs are also called "coxibs," because their generic names end with "coxib."
Yet the trial results are by no means a total victory either for coxibs in general or for Prexige in particular. As earlier trials show for other coxibs, patients who took Prexige got about the same pain relief as those taking naproxen or ibuprofen, which are sold over-the-counter. Patients on Prexige did have four times fewer ulcer complications than those on naproxen or ibuprofen.
But serious stomach ulcer risk in patients on naproxen or ibuprofen was only 1% over a one-year period. And study participants who took aspirin for heart-disease prevention, as many arthritis patients do, got no significant ulcer protection from Prexige.
"It is not a slam dunk," Michael E. Farkouh, MD, tells WebMD. "[Prexige] is not dropping the risk of ulcers from 20% to 1%, but from 1% to less than that."
"It shows that if you combine a coxib with a low dose of aspirin, the coxib loses its benefit," Gary W. Falk, MD, tells WebMD. "From a clinical point of view, that is a real problem."
The complex study findings appear in two papers and a sharply worded editorial in the Aug. 21 issue of The Lancet. Farkouh, associate director of the cardiovascular clinical research center at New York University, is lead author of a report on the heart disease implications of the study. Falk, director of The Cleveland Clinic's center for swallowing and esophageal disorders, is co-author of the editorial.
Pain, Ulcers, and Heart Disease
Coxibs are pain relievers. They reduce inflammation, the painful reddening and swelling of tissues in response to injury or infection. In this way they act like aspirin, ibuprofen, naproxen, and other nonsteroidal anti-inflammatory drugs, or NSAIDs.
But NSAIDs also increase a person's risk of ulcers. Coxibs are specifically designed to have a much lower ulcer risk. How well they do this is a matter of debate -- especially in patients taking low-dose aspirin to prevent heart disease.
Further complicating the issue is evidence from other coxib trials that the new pain relievers might increase a person's risk of heart disease.
Study co-leader Michael Doherty, MD, professor of rheumatology at the University of Nottingham in England, says the study turned up interesting data about this. He points out that patients taking naproxen had a lower risk of heart disease than those taking either Prexige or ibuprofen. This, he says, suggests that naproxen has an unsuspected heart benefit, not that Prexige is toxic to the heart.
He admits more study is needed. Falk argues that the study included too few heart patients to prove that Prexige is safe for the heart. He also says the study offers little new information about patients at high risk of heart disease and/or digestive system complications.
"We all had great hopes for this coxib class of drugs to eliminate our problems, but they don't," Falk says. "There is a group of people for whom coxib treatment makes sense. ... The million-dollar question is what to do about patients at high risk. These studies don't answer that. We worry about people whose age is over 65. We worry about people with prior ulcers or gastrointestinal complaints. We worry about people on steroids. We worry about people on high doses of NSAIDs or aspirin. All those questions need to be asked."
Thomas J. Schnitzer, MD, PhD, professor of medicine and assistant dean for clinical research at Northwestern University, is the lead researcher of the paper reporting the study's main findings. He says Falk asks excellent questions but that no single study could answer them all.
"I believe this study shows that coxibs can prevent meaningful, serious, gastrointestinal events," Schnitzer tells WebMD. "Even to the extent seen here, it has major clinical meaning in high-risk patients. But this study is not directed to answer every question about these patients. If I have a patient on aspirin at relatively high risk of gastrointestinal complications who requires an analgesic agent, I think the choice of a coxib is arguably a better choice based on these data." But he adds that these patients at high risk of developing an ulcer should consider taking a medication to protect their stomach along with their coxib.
All of the experts who spoke with WebMD about this study agree on several things:
- Patients who are at low risk of heart disease and who don't take aspirin can benefit from coxibs -- if they can afford the high price of these drugs.
- Patients who take low-dose aspirin and also take pain relievers, even coxibs, may need to take other drugs for stomach protection.
- Individual patients need individual treatment. Doctors must look at each patient's risk factors before prescribing any of the medications.
Doherty warns arthritis sufferers and their doctors not to focus solely on the relative merits of drug treatments.
"When talking about managing people with pain due to osteoarthritis, everybody agrees on patient education, exercise, losing weight, mechanical factors -- the lifestyle approach," he says. "When you are down to giving painkillers, everybody agrees that acetaminophen has to be the first tablet for pain relief. In the U.K., we also consider topical creams because they are safe. And there are other things to try before using traditional NSAIDs and coxibs. They come lower down on the list -- they are not the one thing everybody needs."
Prexige is made by Novartis, a WebMD sponsor.