RESEARCH - COX-2 inhibitors may be a better bet than the older NSAIDs

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COX-2 inhibitors may be a better bet than the older NSAIDs

Rheumawire

Jan 31, 2006

Zosia Chustecka

London, UK - Although they have come in for a tremendous amount of criticism

over the past year, the selective COX-2 inhibitors may turn out to be a

better bet overall than the older nonselective nonsteroidal

anti-inflammatory drugs (NSAIDs) for many patients, argue two UK researchers

[1]. In a detailed review of both science and the clinical data in the

January 1, 2006 issue of Nature Reviews Drug Discovery, they comment that

further analysis may eventually lead to the conclusion that COX-2-selective

drugs carry a similar risk to NSAIDs when it comes to cardiovascular events

but that they have a lower gastrointestinal risk. If this does transpire,

" we would be back to where the COX-2 field started-the possibility of newer

drugs with improved overall safety. "

In fact, the evidence so far suggests that the cardiovascular risks are very

similar for selective COX-2 inhibitors and nonselective NSAIDs, lead author

Prof Tim Warner ( Harvey Research Institute, London, UK) tells

rheumawire. There's been a lot of focus on selectivity and on how the newer

drugs differ from the older drugs, and " as scientists we've been very

interested in this, but with regard to clinical use, COX-2 selectivity in a

test-tube is much less important. In the way these drugs are used, it must

be realized that once in the body, they all inhibit the COX-2 enzyme, " he

says. " If, as many people hold, it is the inhibition of the COX-2 enzyme

that underlies the cardiovascular risk, then there wouldn't be much

difference in this adverse effect between the selective COX-2 inhibitors and

the nonselective NSAIDs, because they all inhibit the COX-2 enzyme. "

In the review, Warner and his coauthor Dr Jane (Royal Brompton

Hospital, London, UK), suggest that the newer drugs would be more accurately

described as being " COX-1 sparing " rather than COX-2 selective and speculate

that it is this COX-1 sparing that underlines the crucial differences

between the two groups of drugs. They also argue against the use of the term

" coxib, " which has been loosely used for these newer agents, pointing out

that this is neither a chemical nor pharmacological class.

" Overall, we should remember that COX-2-selective inhibitors are members of

the NSAID class, and all produce their therapeutic effects through the

common mechanism of inhibiting COX-2, " the authors write.

" I think that many people haven't really got this point, " Warner comments to

rheumawire. " People seem to think that the selective COX-2 inhibitors are

doing something different, but in fact the difference between them and

traditional NSAIDs doesn't lie in what the newer drugs do, it lies in what

they don't do. " He believes that general physicians would have a better

understanding of these drugs if they had been called COX-1 sparing and

recalls that his group did suggest this name quite early on in the

development of these products in a letter to the Lancet, but it " wasn't

early enough, as the other name had already been widely used. "

The review also notes that recent regulatory announcements made on this

class of compounds have highlighted the fact that the cardiovascular risks

associated with selective COX-2 inhibitors appear to be similar to those

associated also with the nonselective NSAIDS. In the US, the FDA concluded

that the available data are best interpreted as being consistent with a

class effect of an increased risk of serious adverse CV events for both and

ruled that all these drugs should carry a boxed warning. European and

Canadian regulators have also reached similar conclusions, the review notes.

It also points out that Health Canada's expert panel voted overwhelmingly in

July 2005 that the benefits of rofecoxib outweigh its potential

cardiovascular harm (although by this time, the drug was already off the

market).

Source

1. JA and Warner TD. COX isoforms in the

cardiovascular system: understanding the activities of nonsteroidal

anti-inflammatory drugs. Nat Rev Drug Discov 2006; 5:75-86.

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Mayo Clinic in Rochester

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