New Drug Treats Arthritis, Easy on Stomach But Huge Trial Raises Questions Over Value of Prexige

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New Drug Treats Arthritis, Easy on Stomach

But Huge Trial Raises Questions Over Value of Prexige

By DeNoon

WebMD Medical News Reviewed By , MD

on Thursday, August 19, 2004

Aug. 19, 2004 -- Prexige, like its sister drugs Bextra, Celebrex, and Vioxx,

fights arthritis pain as well as ibuprofen and naproxen, but with less risk

of causing stomach ulcers.

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 -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, " 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, " 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 Northwestern 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

ibs 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. ibs 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 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. "

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.

Perspective

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. "