Celebrex (celecoxib) arthritis drug fails

Millions suffering the crippling disease will be left wondering if it is safe to take pills for pain relief.

Bad news for the drug industry came in a double dose yesterday as a leading arthritis drug was linked with heart problems and a promising cancer drug flopped in a clinical trial.

For patients, the more alarming of the two announcements came from Pfizer, which revealed that its arthritis drug Celebrex (celecoxib) had more than doubled the risk of heart attacks and strokes in one trial.

The second blow to the industry came from AstraZeneca, which revealed that its cancer drug Iressa had turned out to be no better than a placebo in treating lung cancer (see below).

Millions of people take the Pfizer drug Celebrex, whose market share has been boosted by the withdrawal by Merck of its principal rival, Vioxx, over identical fears.

The new data suggest that all cyclooxygenase-2 (COX-2) inhibitors (the class to which these drugs belong) may share a tendency to cause muscle weakening, principally shown by the heart, which consists largely of muscle.

Bayers COX-2 drug - marketed as Baycol or Lipobay - was the first to show up the problem, and billion-dollar lawsuits followed its withdrawal. Vioxx was withdrawn in October and most of the 400,000 British patients who were taking it are likely to have switched to Celebrex.

So far, however, the findings are contradictory and a flight from Celebrex is not justified. Pfizer had launched two long-term trials of the drug in cancer prevention, hoping to find a new market. One of these trials shows an increased cardiovascular risk, while the other does not, Pfizer said.

These clinical trial results are new,? Hank McKinnell, the chief executive officer, said.

The cardiovascular findings in one of the studies are unexpected and not consistent with the reported findings in the second study.

Pfizer is taking immediate steps fully to understand the results and rapidly communicate new information to regulators, physicians and patients around the world.?

Both trials used large doses, typically double those used for arthritis patients, and some patients in the trials had been taking the drug for four years.

In the Adenoma Prevention with Celecoxib (APC) trial, Pfizer said, patients taking 400mg and 800mg of Celebrex daily more than doubled their risk of experiencing a fatal or non-fatal heart attack or stroke compared with patients taking a placebo.

The US National Cancer Institute, which was conducting the study for Pfizer, has suspended the use of Celebrex in the trial. But in the Prevention of Spontaneous Adenomatous Polyps (PreSAP) trial, there was no increase in risk for patients taking 400mg a day compared with those taking a placebo. This month, the US Food and Drug Administration said that it was adding a warning to the labels of another Pfizer COX-2 inhibitor, Bextra, giving warning of potential heart problems associated with the use of that drug in people who have recently had heart bypass surgery.

These results, taken together, suggest that the problems with COX-2 inhibitors may be common to all members of the class. If so, what will arthritis sufferers do? Doctors will be reluctant to put them back on an earlier class of painkillers known as non-steroidal antiinflammatory drugs (NSAIDs). These drugs, which include ibuprofen and naproxen, have side-effects that are almost certainly worse.

In a proportion of patients they cause stomach ulcers and bleeding that can be fatal. In the UK, NSAIDs are believed to cause about 12,000 hospital admissions a year, and 2,600 deaths. One US study suggested that they caused more deaths than asthma, cervical cancer or malignant melanoma, and nearly as many as leukaemia. COX-2 inhibitors were developed to reduce this risk, and trials suggest that they do, although they do not eliminate it as had been hoped. They also have life-enhancing benefits in relieving pain from arthritis.

On balance, the benefits of the COX-2 inhibitors may comfortably exceed the heart risks. The British drug regulatory agency was surprised by Merck's decision to pull Vioxx from the market, as it did not believe the cardiovascular risks justified such action. That remains true in even greater degree for Celebrex. Nobody yesterday was recommending patients to stop taking the drug.

The Times, Saturday 18th December,2004

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