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FDA advisory committees back CV safety of celecoxib
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During a joint meeting of the FDA Arthritis Advisory Committee and the Drug Safety and Risk Management Advisory Committee, members voted 15 to 5 that the cardiovascular risk of celecoxib was no worse than the risk associated with naproxen or ibuprofen among patients with osteoarthritis or rheumatoid arthritis.
The vote, prompted by a supplemental new drug application submitted by Pfizer, clears the way for the FDA to issue a final decision on an update of CV safety information on the labeling of celecoxib (Celebrex), as requested by the company.
“Within the context of what is currently approved for prescribed indications, I am confident that there is little chance that this drug is more harmful than the others in the study, despite the limitations of the trial,” Yves D. Rosenberg, MD, MPH, a member of the Drug Safety and Risk Management Advisory Committee, said following the vote. “The consistency of the results with previous science, and within the trial, is fairly strong.”
Pfizer is seeking modifications to the CV safety section of celecoxib’s labeling based on results from the sponsored 2016 PRECISION trial.
Previously, the FDA has approved updates to the label indicating an increased risk for MI and stroke and had recommended consultation with a doctor before use, especially in those with high BP, heart disease or a history of stroke, liver cirrhosis and kidney disease.
However, according to the PRECISION study, among patients with rheumatoid arthritis and osteoarthritis who were at increased CV risk, celecoxib 100 mg was noninferior to the nonselective nonsteroidal anti-inflammatory drugs ibuprofen and naproxen with regard to CV safety. In addition, celecoxib demonstrated fewer gastrointestinal and renal events.
In a subsequent analysis from PRECISION, celecoxib exhibited a superior CV safety profile than ibuprofen and naproxen in patients not taking aspirin, and a similar CV safety profile in those taking aspirin.
However, several members of the committee expressed reservations about being asked to comment on the CV safety of the drug, as well as several of the PRECISION study limitations, particularly that the dosage amounts used in the trial and those used in medical practice did not appear to be equivalent.
“My major concern is the word ‘safety,’ and the fact that I do not think the study proved safety, even if it demonstrated noninferiority,” Neil J. Faber, MD, a member of the Drug Safety and Risk Management Advisory Committee, said. “Even apart from that, if I were reviewing the study for a paper as a peer reviewer, I would have a lot of comments and I would send it back saying you need to address these before we could publish.”
A majority of the joint committee also voted to recommend updating the labeling for nonprescription naproxen to include a warning regarding interactions with aspirin. A total of 12 members voted in favor of the updated labeling, basing their decision partly on findings from the Kontakt study, which assessed whether concurrent administration of naproxen resulted in a pharmacodynamic interaction when combined with chewable aspirin. Committee members also expressed a desire to make the label consistent with that of ibuprofen, which carries a similar aspirin warning.
“There is no difference in the data we have seen for naproxen and ibuprofen,” Christopher H. Schmid, PhD, a member of the Drug Safety and Risk Management Advisory Committee, said. “Since we have a warning label on ibuprofen, I believe there should be a label for naproxen.”
A minority of seven members voted to make no change to the label, while two were in favor of including a contraindication of use for naproxen when taken with aspirin.
The two committees later voted down a recommendation to amend the labeling of nonprescription ibuprofen, with 17 members determining that there was no new data that would justify a change. A minority of four members voted to recommend a contraindication of use for the drug when taken with aspirin.
“I think the current warning for ibuprofen is about as clear as you could get already,” Richard A. Neill, MD, acting chairperson of the Drug Safety and Risk Management Advisory Committee, said. “I think some of the other elements of labeling need some work, but for this question, I think it is as clear as day.” – by Jason Laday
Disclosures: One panel member reports her spouse holds equity in two health care sector mutual funds. The other panel members report no relevant financial disclosures.