Editor note: On 09/30/2004, Merck the maker of Vioxx, issued a worldwide recall, halting sales of the drug. On 04/07/2005, Following scrutiny of the class of arthritis drugs known as NSAIDs and COX-2 inhibitors, the FDA announced planned regulatory actions. See: Questions & Answers: FDA Actions On COX-2 Inhibitors & NSAIDs Fallout from the Vioxx recall will continue for years to come.
Dateline: December 1, 1999
COX-2 Inhibitor Safety
As new drugs become available assurance of their safety is of utmost importance to consumers. When reports appear which boast about the safety profile of a specific class of drugs, only to be followed up a week later with other reports which question their safety, confusion abounds. Conflicting reports have recently appeared in two medical journals about the safety of the COX-2 inhibitors, Celebrex and Vioxx.
In the November 24, 1999 issue of the Journal of the American Medical Association, it was reported that the new COX-2 drugs are comparable in effectiveness to older NSAIDS (nonsteroidal anti-inflammatory drugs) but much less likely to cause stomach ulcers, bleeding, or intestinal obstructions. One study involving 1,149 patients with rheumatoid arthritis revealed that Celebrex, though comparable for pain relief, had a significantly reduced incidence (4%) of small ulcers which could be detected by an endoscope, compared to naproxen (26%). Another study, which was actually an analysis of eight other studies involving 5,435 osteoarthritis patients, established that Vioxx was 50 percent less likely to cause perforations, ulcers, and bleeding.
The new COX-2 drugs have been viewed as an improvement over older NSAIDS because they act by selectively inhibiting COX-2, the enzyme involved in the pain and inflammation pathway, while not inhibiting COX-1, the enzyme involved in protecting the stomach. Older NSAIDS affect both COX-1 and COX-2 enzymes.
That all sounds great, right? It would seem from those reports that COX-2 drugs are obviously better than older NSAIDS. Except, consider this. A report just released in the December issue of Nature Medicine claims that blocking the COX-2 enzyme interferes with angiogenesis (the formation of new blood vessels). New blood vessels are imperative to wound and ulcer healing. Cited laboratory study results revealed reduced angiogenesis when rat or human blood cells were treated with either indomethacin (an older NSAID) or by NS-398 (a COX-2 inhibitor). COX-2 and COX-1 are required for healing of the stomach and intestinal lining. This new data raises questions concerning whether selective COX-2 drugs are safer for the gastrointestinal tract than older NSAIDS after all since inhibiting angiogenesis may result in ulcer complications.
The new report in Nature Medicine points to caution and the need for more studies. Reportedly, in response to the findings in Nature Medicine, Merck is standing behind their own clinical trial results and claims about the safety of Vioxx.
Sources: Painkillers Questioned, 11/30/99, CNN; New Painkillers May Not Protect Stomach After All, 11/29/99, Reuters Health; Stomach-Friendly Arthritis Drugs, 11/24/99, Intelihealth;
Studies Back New Class Of Arthritis Pain Killers, 11/23/99, Reuters
First published: 12/01/1999