COX-2: aspirin by any other name

In the heady world of the pharmaceutical industry, the most profitable industry in the world – where world sales doubled in the last five years – the pressure is always intense to develop new product. New products represent nearly a fifth of all sales by drug companies and nearly a third of all prescriptions written. In this highly competitive marketplace, the search is always on for the new innovative breakthrough, the new Viagra, that will revolutionise treatment in a particular area and redefine the marketplace.

No area offers the potential for a major moneyspinner than something that will take away the pain of arthritis, a market possibly bigger than any, excluding vaccination. Such is the desperation of medicine to find a breakthrough for arthritis that they are currently experimenting with chemotherapy that was originally developed to combat non-Hodgkin’s lymphoma – a drug so toxic that it can cause acute respiratory failure within an hour of taking it (Hoffmann-LaRoche, Rituxan product monograph, 21 June 2000).

Although non-steroidal anti-inflammatory drugs (NSAIDs) had firmly staked out the arthritis market as their own, there was a long list of problems with this class of drugs. Patients might enjoy relief from the pain of arthritis, but were then beset with gastrointestinal ulcers. A good number of patients with arthritis were in the situation of having to take ‘chaser’ drugs to alleviate the pain and side-effects caused by the original drugs they were taking for their condition.

Enter the COX-2 inhibitors. These are the fair-haired boys in arthritis treatment at the moment – the ‘super-aspirins’, drugs that have been marketed as a pain reliever with no strings attached. Indeed, the first two to be marketed – Celebrex and Vioxx (virtually all of these drugs have an ‘x’ incorporated into their names, making them the weirdest drug names of all time) – were, virtually overnight, the most successful drugs in medical history, snatching the mantle from Viagra.

As is usually the case in modern medicine, much of the fanfare over the COX-2s has been seriously overplayed. For one thing, as the postmarketing evidence begins pouring in, it seems that COX-2 inhibitors cause the same side-effects as their predecessors. Numerous trials show that many of these drugs can cause ulcers (BMJ, 1999; 319: 1518). Indeed, a recent Norwegian study concluded that COX-2s were actually more dangerous than NSAIDs and caused more side-effects (Tidsskr Nor Laegefor, 2002; 122: 476-80). In fact, Bextra (valdecoxib), among the latest of the COX-2s, was approved less than a year ago and has already been linked to many life-threatening skin conditions, such as Stevens-Johnson syndrome, as well as anaphylactic shock. Other drugs, such as Celebrex (celecoxib), were linked to deaths from gastrointestinal ulcers and heart problems. Studies have emerged showing that patients taking Vioxx (rofecoxib) are twice as likely to suffer a cardiovascular problem, such as a heart attack, than those given an NSAID (JAMA, 2001, 286: 954-9). Such are the questions lingering over the heart dangers with COX-2s that the Food and Drug Administration in America is considering the use of a warning.

As is so often the case with a modern ‘miracle’ drug, the hype was premature and the testing was inadequate. The COX-2 inhibitors are not super-aspirins – they are just aspirin in a more dangerous suit of clothes. If I were trying to come up with a clever drug name for this batch of beauties, I’d be inclined toward ‘Nothanx.’
Lynne McTaggart