Vioxx Causes Fewer Endoscopic Ulcers Than Ibuprofen, Study Shows

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Doctor's Guide
October 25, 1999

WEST POINT, PA. -- October 25, 1999 -- Results of a new study published this month in the journal Gastroenterology show that osteoarthritis patients taking Vioxx® (rofecoxib) developed significantly fewer endoscopic ulcers than patients taking ibuprofen, a commonly used arthritis medicine.

"In this study, there was a marked difference between the groups taking rofecoxib and the group taking ibuprofen in the incidence rate of endoscopic ulcers," said Loren Laine, M.D., a study author and professor of medicine, University of Southern California. "In this study rofecoxib 25 mg and 50 mg caused significantly less gastroduodenal ulceration than ibuprofen."

Vioxx, which was approved by the U.S. Food and Drug Administration (FDA) in May, is the new once-a-day medicine developed by Merck & Co., Inc. for the relief of the signs and symptoms of osteoarthritis, management of acute pain in adults, and treatment of menstrual pain (primary dysmenorrhea).

The recommended dose for the treatment of osteoarthritis is 12.5 mg once daily. Some patients may receive additional benefit by increasing the dose to 25 mg once daily. People who have had an allergic reaction to Vioxx, aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) should not take Vioxx.

The study published in Gastroenterology was designed to assess whether patients treated with Vioxx developed fewer endoscopic ulcers than those treated with a comparably effective dose of ibuprofen. In the study, which was supported by a grant from Merck & Co., Inc., 742 osteoarthritis patients were randomly assigned to receive either Vioxx (25 mg or 50 mg once daily), ibuprofen (800 mg three times per day) or placebo. Neither patients nor physicians knew which treatment was being received, and none of the patients who participated in the study had active ulcers at the start of the study.

The study used endoscopes, medical instruments that allow physicians to view the esophagus, stomach and a small part of the upper intestine, to measure the incidence of gastroduodenal ulcers of 3 mm or greater. Patients were examined when they enrolled in the study and after six, 12 and 24 weeks of treatment.

The incidences of ulcers between Vioxx 25 mg and 50 mg and ibuprofen were significantly lower (p<0.001) than in the ibuprofen group at the 12 and 24-week measurements. At 12 weeks, the endoscopies showed that 4.1 percent and 7.3 percent of patients taking Vioxx 25 mg and 50 mg, respectively, developed ulcers greater than 3 mm, compared to 27.7 percent in patients taking ibuprofen and 9.9 percent in the placebo group. At 24 weeks, the endoscopies showed that 9.6 percent and 14.7 percent of patients taking Vioxx 25 mg and 50 mg, respectively, developed ulcers greater than 3 mm, compared to 45.8 percent in patients taking ibuprofen. (The group of patients treated with placebo was discontinued at week 16 by design.)

Important considerations for endoscopy studies

The correlation between ulcers detected with endoscopes and the relative incidence of clinically serious upper gastrointestinal (GI) events that may be observed with different products has not been fully established. Serious clinically significant upper GI bleeding has been observed in patients taking Vioxx in controlled clinical trials, although infrequently. Studies like the one published this month cannot rule out at least some increase in the rate of endoscopic gastroduodenal ulcers when comparing Vioxx with placebo. Prospective, long-term studies required to compare the incidence of serious, clinically significant upper GI adverse events in patients taking Vioxx versus comparator NSAID products have not been performed.

In this study, the most commonly reported side effects were similar in each treatment group and included upper respiratory infection, diarrhea and abdominal pain.

Important information about Vioxx

Serious stomach problems, such as bleeding, can occur with or without warning symptoms. Physicians and patients should remain alert for signs and symptoms of GI bleeding. Safety and effectiveness in children below the age of 18 has not been studied.

In other studies, the most common side effects reported in clinical trials with Vioxx were upper-respiratory infection, diarrhea, nausea and high blood pressure.

Scientists believe that Vioxx works by inhibiting an enzyme called COX-2, which plays a role in pain and inflammation. However, Vioxx, at therapeutic doses, does not inhibit the COX-1 enzyme, which helps maintain the normal stomach lining. In general, NSAIDs inhibit both COX enzymes, so they treat pain and inflammation but may damage the stomach lining, potentially leading to ulcers in some patients.

Since its approval by the FDA in May, more than 2.2 million prescriptions have been written for Vioxx in the United States, making it one of the most successful product introductions in the pharmaceutical industry's history.