In a new study using the new videocamera-in-a-capsule diagnostic imaging, investigators demonstrated that Celebrex, Pfizer Inc's leading COX-2 specific inhibitor for treatment of arthritis, is associated with significantly fewer (p<0.001) ulcer-like lesions in the small bowel, compared to a combination of a non-steroidal anti-inflammatory medicine and an acid-reducing agent.
Data from so-called “capsule endoscopies” using videocamera-in-a-capsule technology showed that Celebrex (200 mg taken twice daily) was linked to a nine-fold lower incidence of mucosal lesions developed in the small bowel, compared to treatment with a combination of naproxen (500 mg taken twice daily) and the acid reducing proton pump agent omeprazole (20 mg daily). The findings were presented at the annual meeting of gastroenterologists known as Digestive Disease Week 2003. “These data extend our understanding of the gastrointestinal safety of celecoxib beyond what is already known. They add further evidence that chronic blood loss and development of anemia associated with non-specific nonsteroidal anti-inflammatory drugs may be related to medication-induced damage along the entire length of the small bowel tract, where proton pump inhibitors (PPIs) like omeprazole do not confer protection,” said Dr. Jay Goldstein, Professor of Medicine and Vice Head for Clinical Affairs, Department of Medicine, Section of Digestive and Liver Diseases, University of Illinois, Chicago, Illinois. “They also expand the celecoxib GI safety profile by broadening the concept of GI safety beyond safety in the upper GI tract alone,” Dr Goldstein said.
Additionally, the study highlights an important dimension in gastroenterology that has previously been unrecognized, as it showed a surprisingly high percentage (13.8 per cent) of apparently healthy people with no history of GI symptoms or disease failed initial screening due to the presence of small bowel abnormalities detected by this new capsule technology. “These findings provide us with important new information on the background rate of mucosal abnormalities in the small bowel,” said Dr. Goldstein, the study's lead investigator.
This four-week, prospective, double-blind, placebo-controlled, trial was designed to evaluate the effects of non-specific NSAIDs and COX-2 specific inhibitors on the small bowel mucosa. Participants included healthy subjects between the ages of 18 and 70, whose physical exams revealed no clinically significant findings and no clinically significant abnormal laboratory tests. Potential candidates with any active GI disease or previous history of intestinal surgery were excluded from the trial, as were those taking aspirin or NSAIDs more than three times a week for two weeks prior to screening, or any prescribed medication during the study — (except hormonal replacement). Trial participants entered one of three blinded treatment arms of the study and received either Celebrex 200mg twice daily, naproxen 500 mg twice daily plus omeprazole 20 mg daily, or placebo for a treatment period of two weeks. Results were based on a total of 338 participants who completed the study and were evaluable.
Celebrex is the COX-2 specific inhibitor with the broadest range of approved indications in the U.S., including the relief of signs and symptoms of osteoarthritis (OA), adult rheumatoid arthritis (RA) and the management of acute pain and primary dysmenorrhea in adults. In addition, Celebrex is approved to reduce the number of adenomatous colorectal polyps in familial adenomatous polyposis (FAP)—a rare and devastating genetic disease that may result in colorectal cancer—as an adjunct to usual care. Studies to date have not included a cancer endpoint, and thus Celebrex has not been proven to reduce the risk of GI cancer or the need for any FAP-related surgeries. The recommended dose for OA is 200 mg daily and for RA, 100 mg to 200 mg twice per day. The recommended dose for acute pain and primary dysmenorrhea is 400 mg initially, followed by an additional 200 mg dose if needed on the first day. On subsequent days, the recommended dose is 200 mg twice daily as needed.
Celebrex should not be taken by patients who have aspirin-sensitive asthma or allergic reactions to aspirin or other arthritis medicines or certain sulfa drugs called sulfonamides, or who are in their third trimester of pregnancy. As with all NSAIDs, serious GI tract ulcerations can occur without warning symptoms. Physicians and patients should remain alert to the signs and symptoms of GI bleeding. Celebrex does not affect platelet function and therefore should not be used for cardiovascular prophylaxis. As with all NSAIDs, Celebrex should be used with caution in patients with fluid retention, hypertension, or heart failure. In overall clinical studies the most common side effects of Celebrex were dyspepsia, diarrhea and abdominal pain, which were generally mild to moderate.
There have been infrequent post-marketing reports of increases in prothrombin time, sometimes associated with bleeding events, predominantly in the elderly. Anticoagulant activity should be monitored when therapy with Celebrex is initiated or changed in patients taking warfarin, particularly in the first few days.