SUMMARY: A study geared towards assessing the overall long-term safety of Celebrex® (celecoxib capsules) resulted in positive findings. Arthritis patients taking four times the recommended osteoarthritis (OA) dose of the drug experienced fewer symptomatic gastrointestinal (GI) ulcers and ulcer complications than patients taking ibuprofen and diclofenac.
ABSTRACT: Chicago, IL — In a landmark study to assess the overall long-term safety of the COX-2 specific inhibitor Celebrex(R) (celecoxib capsules), arthritis patients taking four times the recommended osteoarthritis (OA) dose of the drug experienced fewer symptomatic gastrointestinal (GI) ulcers and ulcer complications than patients taking ibuprofen and diclofenac – a difference that was statistically significant based on a combined analysis of Celebrex versus these two traditional nonsteroidal anti-inflammatory drugs (NSAIDs). The findings, presented at the American College of Physicians annual meeting, also demonstrated differences on a variety of measures in renal and liver toxicity among those taking Celebrex or the NSAID comparators, two of the world’s most widely prescribed drugs of this kind. Importantly, Celebrex showed no increase in thromboembolic or other cardiovascular-related events, even among non-aspirin users.
Also, in comparison to Celebrex, ibuprofen and diclofenac were associated with a significantly greater GI blood loss – equivalent to two pints or more – over the course of the study, even in patients not experiencing bleeding ulcers. Such blood loss can often signal serious hidden damage throughout the GI tract.
The Celecoxib Long-term Arthritis Safety Study, an approximately 13-month, multi-center, randomized, double-blind outcomes trial of about 8,000 arthritis patients – 5,800 with OA and 2,200 with rheumatoid arthritis (RA) – was designed to mirror everyday clinical practice by enrolling a broad spectrum of patients, including adult patients of all ages and disease severity, and patients taking low-dose aspirin for cardioprotection. The study, designed to obtain a rigorous assessment of Celebrex safety, compared four times the recommended OA dose of Celebrex (800 mg daily) to typical daily doses of ibuprofen (2400 mg/daily) and diclofenac (150 mg/daily). The Celebrex study dose is twice the highest recommended RA dose.
“No previous study has examined such a broad range of GI side effects – which encompass events ranging from serious and often devastating GI ulcers and ulcer complications, to silent but medically important damage to the lining of the intestine, to symptoms like abdominal pain,” said Lee S. Simon, M.D., associate professor of medicine, Harvard Medical School. “We’ve known the serious risks of traditional NSAIDs for some time, but these long-term findings show that patients taking Celebrex, in contrast to those on ibuprofen or diclofenac, experienced fewer treatment-related side effects in a number of important areas. These side effects often limit patients’ ability to maintain their therapy and get the arthritis pain relief they require.”
Researchers estimate that up to 30 percent of patients taking traditional NSAIDs develop persistent GI symptoms, and more than 10 percent of all patients discontinue treatment. An estimated 33 million people take traditional NSAIDs regularly.
The study, funded by Searle and Pfizer Inc, found that Celebrex patients experienced significantly fewer symptomatic GI ulcers and ulcer complications compared with ibuprofen or diclofenac. Celebrex was also associated with numerically fewer ulcer complications than the NSAID comparators among all patients, and 64 percent fewer of these serious events among non-aspirin users – a statistically significant difference. It is well known that aspirin is an independent risk factor for GI complications. Ulcer complications typically lead to hospitalization, and in some cases, death. Further, patients in the study reported Celebrex to be well tolerated, with dyspepsia, nausea and abdominal pain occurring at a significantly lower rate than with diclofenac.
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“This rigorous outcomes trial set the bar higher than any previous study of its kind. It included a large number of patients who received four times the recommended OA dose of Celebrex for up to 13 months. It also compared Celebrex with commonly used traditional NSAIDs – ibuprofen, one of the most well tolerated; and diclofenac, extensively used throughout the world,” said Fred Silverstein, M.D., chairperson of the study’s external review board. “Even at these very high doses, Celebrex showed sustained safety and tolerability in organ systems often affected by NSAIDs. As such, these are compelling findings for physicians to consider when treating arthritis patients.”
In addition, the study examined the renal, liver and cardiovascular safety profile of Celebrex. Observed rates of various renal abnormalities and renal complications among Celebrex-treated patients were significantly lower as compared with diclofenac and ibuprofen, respectively. Moreover, in this study, significantly more patients developed hypertension or edema on ibuprofen, and kidney or liver abnormalities on diclofenac, compared to the Celebrex group. Furthermore, Celebrex showed no increases in thromboembolic events (such as myocardial infarctions and stroke) or other cardiovascular adverse events compared with the traditional NSAID comparators. This is an important finding in light of the fact that about 40 percent of patients in each arm of the study had a history of cardiovascular disease, and about half of these patients were taking low-dose aspirin.
The incidence of skin rash was significantly higher with Celebrex – at four times the recommended OA dose – compared with both of the traditional NSAIDs. No serious rashes were observed. Other adverse events most commonly reported with Celebrex in these studies, at approximately the same rate as the comparators, included colds and sinusitis.
Many of the estimated 43 million Americans with OA and RA use NSAIDs, which can lead to stomach ulcers and other serious complications, and are the greatest source of serious adverse drug reactions reported to the U.S. Food and Drug Administration. These GI side effects often show no obvious signs or symptoms and go undiagnosed until patients are admitted to the hospital emergency room. Typically 60 to 80 percent of GI complications resulting from NSAIDs occur without previous symptoms.
Patients who have a known allergic reaction to celecoxib, certain sulfa drugs called sulfonamides, aspirin or NSAIDs should not use Celebrex. 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. Concomitant administration of aspirin with Celebrex may result in an increased risk of GI ulceration or other complications, compared to Celebrex alone. 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 studies, the most common side effects of Celebrex were dyspepsia, diarrhea and abdominal pain, which were generally mild to moderate.
Celebrex is co-promoted by Searle, now part of Pharmacia Corporation, and Pfizer Inc.
Pharmacia Corporation is a leading global pharmaceutical company created through the merger of Pharmacia & Upjohn with Monsanto Company and its G.D. Searle unit. Pharmacia has a broad product portfolio, a robust pipeline of new medicines, and an annual investment of more than $2 billion in pharmaceutical research and development.
Pfizer Inc is a research-based, global pharmaceutical company that discovers, develops, manufactures and markets innovative medicines for humans and animals. The company reported revenues of more than $16 billion in 1999 and expects to spend about $3.2 billion on research and development this year.
Source: Pfizer Inc.