There are now enough data for clinical guidelines on the use of COX-2 specific inhibitors to be evidence based, according to Professor Paul Emery (professor of rhematology, University of Leeds).
Speaking on May 9 at a session of the British Society of Rheumatology meeting, in Brighton, Profesor Emery said that there was no doubt that the two drugs (rofecoxib and celecoxib) were safer than standard non-steroidal anti-inflammatory drugs (NSAIDs) in terms of gastrotoxicity. The COX-2 hypothesis - that specific inhibition of COX-2 would have the analgesic and anti-inflammatory effects of typical NSAIDs without the troublesome, and on occasion fatal, side effects - had been confirmed. The new drugs had no effect on prostaglandin synthesis in the gastric mucosa, produced no faecal blood loss, and were associated with a low incidence of ulceration in endoscopy studies. Of particular interest, long-term safety data were now becoming available from two "landmark" studies with the drugs: the CLASS study for celecoxib and the VIGOR study for rofecoxib (see Panel).
Emphasising that the CLASS and VIGOR data were, so far, "very preliminary", Professor Emery explained that this type of outcome data was needed for the manufacturers to be able to put "clear blue water" between the COX-2 selective drugs and conventional NSAIDs. In both studies there was a reduced incidence of symptomatic ulceration and ulcer complications (eg, bleeding, perforation) with the COX-2 specific drugs. In CLASS, the reduction in complications was statistically significant only when patients taking aspirin (given for cardiovascular protection) were excluded. Professor Emery said that the impact on the gastrointestinal tract of COX-2 inhibition in patients taking aspirin was unclear. "The message, I think, is that COX-2 inhibitors do not reduce the risk of aspirin taking, but they do not increase it," he said.
Cardiovascular mortality was lower in the naproxen group in VIGOR. This was likely to be an indication that patients should have been on aspirin. (Aspirin's antiplatelet action is a COX-1 effect.) "Until we know more, patients who need aspirin should still be getting aspirin," said Professor Emery.
In terms of other side effects of the COX-2 specific drugs, Professor Emery said that dyspepsia was reduced but not abolished. Early concerns that, because COX-2 was expressed in the brain, there might be central side effects were unfounded and headache, for example, was reduced with the newer drugs. Sodium retention could occur, as with standard NSAIDs. "We were wrong in thinking that there would be no renal effects," said Professor Emery. Lower extremity oedema did occur (probably no more than with standard NSAIDs).
Professor Emery added that there was intruiging data suggesting that COX-2 specific drugs might be effective in patients with aspirin-induced asthma.

Outcome trials

CLASS study
8,000 patients (with OA or RA)
Trial drug: Celecoxib
Comparator drugs: Ibuprofen or diclofenac
Aspirin allowed (for cardiovascular purposes)

VIGOR study
8,000 patients (mostly RA)
Trial drug: Rofecoxib
Comparator drug: Naproxen
No aspirin allowed