April 9, 2007

Letter Concerning Pfizer’s Television Advertisement for Celebrex

Andrew Von Eschenbach, M.D., Commissioner
U.S. Food and Drug Administration
Food and Drug Administration
5600 Fishers Lane 
Rockville,  MD 20857 

Dear Dr. Von Eschenbach:

I urge the Food and Drug Administration to order Pfizer to immediately stop its dangerous, misleading 2 ½ minute television advertisement for Celebrex that began airing on April 2nd.[1]

The overall purpose of the ad is to make it appear, contrary to scientific evidence, that the cardiovascular dangers of Celebrex are not greater than those of any of the other NSAID painkillers. Further, it asserts that certain gastrointestinal problems are, if anything, less frequent with Celebrex than with two popular over-the-counter (OTC) painkillers.

The ad violates FDA law and regulations because it contains several false or misleading statements that will lead many viewers to underestimate the cardiovascular and gastrointestinal risks of Celebrex and use it in preference to equally effective, safer alternatives such as OTC naproxen.

Cardiovascular risks:  

1.  The ad states: “You may think some prescription NSAID pain relievers like ibuprofen and naproxen don’t have any cardiovascular risks. But based on the available research, that’s not clear.”

In a thorough review of all randomized controlled trials of older NSAIDs such as ibuprofen and naproxen, as well as the newer COX-2 NSAIDs such as Vioxx and Celebrex, published almost one year ago,[2] the authors concluded that the COX-2 drugs, including Celebrex,  did have an increased cardiovascular risk, seen most clearly with heart attacks (myocardial infarctions), for which the combined increased risk for all COX-2 drugs, compared to a placebo, was 1.86.

But they also found, in a systematic review of placebo-controlled trials of naproxen, that it did not have an increased cardiovascular risk.

2. The ad also states that “the FDA requires all these NSAID pain relievers, including Celebrex, to have the same cardiovascular warning.”

This statement by Pfizer that all NSAIDs are required “to have the same cardiovascular warning“ is extremely misleading because, as suggested above, the available scientific evidence shows large differences in cardiovascular risk among the various NSAIDs.

A recent statement from the American Heart Association (AHA) acknowledges this and states that “important differences exist between these agents in terms of risk of major thrombotic events.”[3]  Because of these differences, the AHA  recommends a hierarchy for pain treatment of people with known cardiovascular disease or risk factors. Naproxen is the preferred choice among NSAIDs, but the AHA recommendation is that the COX-2 drugs be the last choice, to be used for those people who fail to respond to the older NSAIDs or other drugs. 

Following the withdrawal of both Vioxx and Bextra, in each case involving increased cardiac risks of these COX-2 drugs, the FDA issued a statement requiring boxed warnings of increased cardiovascular risk on the prescription versions of all older (non-selective) NSAIDS and the remaining COX-2 drug, Celebrex. The FDA also explained, however, why the over-the-counter NSAIDS such as naproxen and ibuprofen would be available without such a boxed warning: “We believe that the available data support a conclusion that short-term use of low doses of the available OTC NSAIDs is not associated with any increased serious CV [cardiovascular] risk.”[4]

In addition to the statement (“the FDA requires all these NSAID pain relievers including Celebrex to have the same cardiovascular warning.”) being misleading, it is also false in that OTC NSAIDs such as naproxen and ibuprofen are not required to have the same cardiovascular warning.

Gastrointestinal risks:

3.  The ad correctly states that all NSAIDS are required to include a warning about increased risk of “stomach and intestine problems such as bleeding and ulcers.” But this statement is shortly followed by another statement in the ad making it appear that Celebrex has a gastrointestinal (GI) advantage over prescription naproxen or ibuprofen because “In clinical studies a lower percentage of patients on Celebrex reported indigestion, abdominal pain and nausea versus prescription ibuprofen and naproxen.” This latter statement, explicitly pointing to a Celebrex advantage, is meant to trump the significance of the earlier warning of increased risk of serious stomach and intestinal problems such as bleeding and ulcers that applies equally to all NSAIDS. Considering all studies about GI risk, there is no evidence of a net GI benefit for Celebrex compared to other NSAIDS. The relevance of a lower occurrence of abdominal pain in some studies is meaningless since the more serious problems, ulcers or bleeding, occur equally with all NSAIDS.

Although the company has stated that this ad is the result of long-term consultation with the FDA, it is clear that the final version of the ad was not seen by the agency until very shortly before it started to air last week. Given that this ad is seen by millions of people a day, there is a special urgency to order Pfizer to stop running it before more people are misled into asking their doctors for Celebrex because of the deceptive nature of this ad.

I look forward to a prompt response to this request.

Sincerely,

Sidney M. Wolfe, M.D.
Director
Health Research Group of Public Citizen