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| |  ACG MEETING: Studies Show Vioxx Does Not Damage Gastrointestinal Tract BOSTON, MA -- Oct. 13, 1998 -- Merck & Co.’s Vioxx(TM)(rofecoxib), an investigational medicine for pain and arthritis, showed no significant differences from placebo in effects on the mucosal integrity of the gastrointestinal (GI) tract, while the NSAIDs ibuprofen and indomethacin produced damage, in two new safety studies presented today during the annual meeting of the American College of Gastroenterology. NSAIDs (non-steroidal anti-inflammatory drugs) are the most commonly used therapy available today for arthritis and pain. The results were consistent at doses of Vioxx of up to 50 mg -- two to four times higher than doses that have reduced the signs and symptoms of osteoarthritis in previous studies, according to Dr. Thomas Simon, M.D., executive director, Merck Research Laboratories. "NSAIDs can cause GI damage that may be detected using specialised, non-invasive tests," Dr. Simon said. "These sensitive tests can help physicians obtain a complete picture of the type of damage NSAIDs cause along the entire GI tract, even in the absence of symptoms." The Merck studies used two such tests to evaluate GI blood loss and permeability -- indicators of subtle and sometimes more serious GI damage -- along the GI tract, including the stomach and both the upper and lower intestine. Chronic treatment with NSAIDs results in more than 76,000 hospitalisations and 7,600 deaths each year in the United States due to GI side effects such as ulcers and bleeding, according to published estimates. The first study evaluated GI blood loss among 67 healthy volunteers aged 19 to 37 years old. One week prior to the start of the 28-day study, volunteers were injected with radioactive 51Cr, a substance that binds to red blood cells. Study participants were randomised to either 25 mg or 50 mg of Vioxx once a day, placebo, or 800 mg of ibuprofen three times a day (2,400 mg). "Ibuprofen and other NSAIDs have been well-established in studies and in practice as causing small amounts of gastrointestinal blood loss, an indicator of microerosions or ulcers," said lead study author Richard Hunt, M.D., professor of medicine and gastroenterology, McMaster University Medical Center, Hamilton, ON. All fecal samples, collected daily for four weeks, were monitored for the presence of radioactivity. The amount of radioactivity found is a measure of the amount of intestinal blood loss along the whole GI tract, Dr. Hunt explained. Findings showed that volunteers in both treatment groups of Vioxx had results similar to those taking placebo, showing no significant differences in blood loss. Study participants given ibuprofen had twice as much blood loss as those taking Vioxx or placebo. In a second study, volunteers given 25 mg or 50 mg of Vioxx once a day had no significant difference from placebo in measures of intestinal permeability, while those given 50 mg of indomethacin three times a day had significant increases -- up to 58 percent -- in permeability. Increases in intestinal permeability are believed to be a harbinger of GI toxicity, particularly low-grade inflammation, bleeding and intestinal protein loss. Permeability is a measure of the leakiness of the protective linings of the stomach and intestine. "A healthy and functional GI tract allows sugar, for example, to be absorbed and acts as a barrier to toxic agents, preventing them from being absorbed," said lead author Ingvar Bjarnason, M.D., reader in medicine and gastroenterology at King's College School of Medicine, London. The seven-day study involved 39 healthy volunteers aged 18 to 39 years who drank a mixture of agents, some that are normally absorbed through the lining of the intestine and others that are not. Urine samples were evaluated for the presence and ratio of these agents to determine increases in intestinal permeability to those agents that are normally not absorbed. A common procedure to assess the effects of medicine on the GI system uses an instrument called an endoscope that allows for visualisation of the esophagus, stomach and a small part of the upper intestine. Endoscopy is usually performed after a patient complains of signs and symptoms of an ulcer or other GI problem. "Although not often used in practice, specialised non-invasive tests, such as those measuring blood loss and GI permeability, may be useful in identifying patients who are experiencing damage in the GI tract even in areas that are beyond the reach of the endoscope," Dr. Simon said. However, precise correlation between the results of these types of studies and clinically important adverse events, such as symptomatic ulcers and serious GI bleeding, has not been established. Vioxx is a member of an investigational class of medicines called COX-2 specific inhibitors. Phase III studies evaluating the clinical efficacy and safety of Vioxx for the treatment of the signs and symptoms of osteoarthritis and for the relief of pain have been completed.
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