FDA Drug Safety & Risk Management Advisory Committee member Curt Furberg advocates limiting use of COX-2 inhibitors to the lowest dose for the shortest duration possible.

Furberg, an epidemiologist at Wake Forest, and University of Washington epidemiologist Bruce Psaty co-authored an editorial, "COX-2 Inhibitors - Lessons in Drug Safety," that will appear in the Feb. 17 New England Journal of Medicine.

NEJM released the editorial Feb. 15, on the eve of the Feb. 16-18 advisory committee meeting on the safety of the COX-2 class. [ Editors' Note: To ¹ watch a webcast or order a video/DVD of this meeting, visit FDAAdvisoryCommittee.com.]

"If a COX-2 were necessary, patients would have to be informed of the potential risks, and the lowest possible dose should be used for the shortest possible time," the authors state.

In December, FDA issued a similar cautionary statement, urging physicians to consider using the lowest effective dose for the shortest possible duration in patients who require a COX-2 inhibitor. For other patients, FDA advised physicians to consider alternative therapies.

FDA's recommendation came after the National Cancer Institute-sponsored Adenoma Prevention with Celecoxib trial demonstrated 2.5-fold and 3.4-fold increases in cardiovascular risk compared to placebo at the 400 mg and 800 mg doses of Pfizer's Celebrex , respectively (² Also see "Pfizer Celebrex Polyp Trial Shows Increase In Cardiovascular Events" - Pink Sheet, 17 December, 2004.).

The results of the APC study are among the five studies and editorials on COX-2 inhibitors that will appear in the Feb. 17 NEJM (see ³ [A#PS061546] ).

Furberg's recommendation appears to stop short of suggesting that FDA withdraw COX-2 inhibitors from the market.

Furberg has been critical of both COX-2 inhibitors and Pfizer. Nevertheless, his recommendations on limited use of the drugs may suggest that the advisory committee will not have widespread support for recommending that FDA pull the COX-2 class off the market.

Furberg is slated to attend the three-day advisory committee review, although his participation in the meeting had been in question.

Furberg said his invitation to attend the meeting was rescinded after his meta-analyses of Pfizer's Bextra (valdecoxib) demonstrating an increased risk of cardiovascular events were presented at an American Heart Association meeting in November (⁴ Also see "Bextra Meta-Analyses Could Be Taken Up At February COX-2 Advisory Cmte." - Pink Sheet, 12 November, 2004.).

Furberg was not formally re-invited by FDA to participate in the meeting as a member of the drug safety advisory committee until the beginning of February (⁵ Also see "FDA COX-2 Review Will Include Input From Furberg, Full Rx Safety Advisory Cmte." - Pink Sheet, 8 February, 2005.).

[Editor's note: Furberg and FDA Drug Safety Advisory Committee Chairman Peter Gross will discuss the outcome of the COX-2 committee meeting at a Feb. 23 Drug & Device Dialogue audio conference. To register, visit ⁶ www.drugdevicedialogue.com or call 800-332-2181. ]

The editorial also calls for an independent drug safety center.

"We believe that to protect the health of the public, Congress needs to provide the FDA with the necessary authority and also to create an independent Center for Drug Safety with new authority and funding," the authors state.

On Feb. 15, HHS announced a drug safety initiative that includes creation of an independent Drug Safety Oversight Board (see ⁷ Also see "FDA Drug Safety Oversight Board Will Include VA, Other Agencies" - Pink Sheet, 15 February, 2005.).

- Lee Kalowski

COX-2 Use Should Be Limited, FDA Advisory Cmte. Member Furberg Says In NEJM

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