Oct. 15, 2003 ANN ARBOR, MI – For those who take certain painkiller drugs regularly to help ease arthritis pain or other chronic aches, the relief comes with a tradeoff: a quadrupled chance of developing painful ulcers over the long term, as their digestive systems brim with acid that erodes the lining of their stomachs and upper intestinal tract.
But a new study may offer a promising way to prevent this unwelcome effect.
In an international, multicenter, randomized, placebo-controlled study, a prescription heartburn drug called esomeprazole effectively prevented ulcers among 573 long-term painkiller users. And, it produced few side effects.
"This is a very encouraging result, especially since the participants represented the 'real world' population that faces this ulcer risk," says James Scheiman, M.D., a University of Michigan Health System gastroenterologist who will present the results Tuesday in Baltimore at the annual meeting of the American College of Gastroenterology. "The effect was strong in participants taking over-the-counter painkillers, as well as in those taking prescription Cox-II inhibitor drugs."
Esomeprazole, which is marketed as Nexium® (esomeprazole magnesium) by Astra Zeneca Pharmaceuticals LP, is a member of the class of acid-reducing drugs known as proton pump inhibitors. It blocks the production and secretion of gastric acid.
Astra Zeneca funded the study, and Scheiman is a paid member of the panel that advised the company on the study, as well as presenter of the ACG presentation.
The study results show that ulcers and other effects can be prevented by countering the acid that increases the injury to the gastrointestinal tract that can be caused by use of non-steroidal anti-inflammatory drugs (NSAIDs). NSAIDs include ibuprofen, naproxen, and Cox II inhibitors, all commonly used to treat chronic pain.
The study participants were three-quarters women, and more than 80 percent were taking NSAIDs for some form of arthritis. Although all had screened negative at the study's outset for the bacteria Helicobacter pylori that causes ulcers, they were all at an increased risk of developing ulcers because of their regular painkiller use combined with a history of previous ulcers (about 26 percent), an age over 60 years (about 64 percent), or both (about 10 percent).
The study was done in this group of patients to represent more accurately the "real world" mix of drugs, medical histories and risk factors seen in millions of patients worldwide, says Scheiman, a professor of internal medicine in the U-M Medical School.
All of the participants were taking NSAIDs at least five days a week, either one drug alone or in combination. Around 15 percent were taking Cox II inhibitors (such as celecoxib, marketed as Celebrex, or rofecoxib, marketed as Vioxx). Some were also taking aspirin at doses designed to protect their cardiovascular systems.
Previous studies have shown that about 10 percent to 30 percent of such patients might develop ulcers in a given year. And in fact, among those in the study who received a placebo instead of esomeprazole, 12.3 percent developed either a gastric ulcer or duodenal ulcer in the six months of the study.
But the ulcer rate was 5.2 and 4.4 percent, respectively, for non-Cox II inhibitor NSAID users who received either 20 milligrams or 40 milligrams of esomeprazole daily.
In the small subgroup of patients who were using Cox II inhibitors, 17 percent taking placebo pills developed ulcers. And although the group was not large enough to achieve statistical significance, none of those patients on either dose of esomeprazole developed ulcers during the study.
This last result intrigues Scheiman, who notes that clinicians may want to take note even before further studies are conducted to evaluate whether a Cox II inhibitor-proton pump inhibitor combination might be the best option for such patients.
In addition to being effective at preventing ulcers and other effects, esomeprazole was safe and well-tolerated. Only 6 percent of patients receiving it stopped taking the drug during the study because of any adverse event, compared with 13 percent of placebo patients.
In all, Scheiman notes, the results should give hope to any patient who needs to take painkillers regularly. "With these data, and results from other studies, we can say that we have a way to prevent ulcers and other gastrointestinal effects, in long-term NSAID users," he says. "There doesn't have to be a tradeoff between one kind of pain and another."
The study's main authors include Neville Yeomans of the University of Melbourne, Australia; Christopher J. Hawkey of the University of Nottingham, United Kingdom; Nicholas Talley of the Mayo Clinic, Rochester, Minnesota; Joseph Sung of the Chinese University of Hong Kong; Roger Jones, London, and Lena Gothe and Jorgen Naesdal, Astra Zeneca, Molndal, Sweden.
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