Clinical
Study questions greater GI safety of COX-2 inhibitors
Last Updated: 2005-12-01 19:01:18 -0400 (Reuters Health)
By Anthony J. Brown, MD
NEW YORK (Reuters Health) - COX-2 selective inhibitors, such as rofecoxib (Vioxx) or celecoxib (Celebrex), have been billed as pain relievers with a lower risk of upper gastrointestinal side effects than conventional NSAIDs, but new research suggests that this may not be the case.
In a study of data from 367 general practices in the UK, Dr. Julia Hippisley-Cox, from the University of Nottingham in the UK, and colleagues found no consistent evidence that the COX-2 selective inhibitors were less likely to cause upper GI side effects than the standard NSAIDs.
The one possible exception: celecoxib. After adjusting for potential confounders, celecoxib use was not associated with a significantly increased risk of upper GI side effects. However, the authors believe that this may have been because relatively few patients in the study were taking celecoxib and thus statistical power was lacking.
The report also indicates that with the exception of diclofenac, the risk of adverse GI effects with both NSAIDs and COX-2 inhibitors can be largely eliminated through the use of ulcer healing drugs. This, the authors claim, supports their contention that there is an elevated risk of GI side effects with COX-2 inhibitors as a whole and that these agents "may not be as safe as originally thought."
The study, which is reported in the British Medical Journal for December 3, involved a comparison of COX-2 and general NSAID use among 9407 subjects who experienced a peptic ulcer or hematemesis during a 5-year period and 88,867 matched controls who did not.
The overall rate of upper GI events was 1.36 per 1000 person-years, the report indicates. Compared with nonuse, current use of either COX-2 selective or conventional NSAIDs was associated with an increased risk of such events.
After adjustment for confounders, use of naproxen, diclofenac, and rofecoxib remained significantly linked to GI events, whereas celecoxib use was not. As noted, these elevated risks largely disappeared when ulcer healing drugs were also used, except for diclofenac, which continued to raise the risk of events by 49%.
"Evidence of enhanced GI safety with any of the new COX-2 inhibitors compared with the non-selective NSAIDs is lacking," the researchers conclude.
"We think that these findings are consistent with prior information in that they show an advantage for Celebrex" in terms of GI safety, Dr. Gail Cawkwell, medical director for Celebrex at Pfizer, Inc., told Reuters Health. "But, we are very disappointed that (the researchers) chose to present the information in a manner that is not helpful for doctors and patients who are trying to make important health decisions."
Dr. Cawkwell agreed that the low patient numbers in the current study make it impossible to reach definitive conclusions about the GI safety of Celebrex, but she said that several previous studies have found the drug to be safer than conventional NSAIDs. She also noted that of the drugs evaluated, only Celebrex had a GI risk that was not significantly altered by the use of ulcer healing drugs, further supporting the drug's greater safety.
Representatives from Merck, the embattled maker of the recently withdrawn Vioxx, could not be reached for direct comment, but left this statement: "Results from observational or epidemiological studies should be interpreted within the context of all available data, particularly results from randomized, controlled clinical trials. In a large, outcome trial (VIGOR), VIOXX 50 mg, twice the maximum dose recommended for chronic use, was associated with a significantly reduced risk of clinical upper GI events and complicated events compared to a common clinical dose of naproxen."
