The makers of Celebrex (celecoxib) do
not have enough evidence to claim their popular arthritis drug
is safer for the stomach than traditional non-steroidal anti-inflammatory
drugs (NSAIDs) like ibuprofen.
The Arthritis Advisory Committee to the FDA met to
discuss whether findings from Celebrex-maker Pharmacia's "CLASS"
study proved that Celebrex is safer on the stomach than two NSAIDs,
ibuprofen and diclofenac.
Celebrex, like Merck's Vioxx, is a selective
COX-2 inhibitor. Other anti-inflammatory drugs also inhibit COX-2, which
is an enzyme involved in inflammation, in addition to COX-1, which is
thought to protect the lining of the stomach. Based on current estimates,
there about 16,500 deaths per year
in the US due to serious NSAID toxicity, according to the company.
Clinical trials that led to the approval of the COX-2
inhibitors suggested they were safer on the stomach, but regulators said
the companies needed to conduct larger studies
before they could drop a warning about gastrointestinal risks that all
NSAIDS carry on their packaging.
The panel agreed that Pharmacia had
not established a "clinically meaningful"
safety advantage over
NSAIDs and that data from the CLASS study would not support a superiority
claim.
Although the trial showed an overall 2-fold reduction
in gastrointestinal complications, that trend was reversed
among subjects who also took low-dose aspirin. Many older people take
low-dose aspirin daily to protect against heart attack.
Among aspirin takers, Pharmacia was unable to demonstrate
safety superiority over ibuprofen or pooled NSAID data, including ibuprofen
and diclofenac, FDA official Dr. James Witter told Reuters Health.
The CLASS study also did not establish a safety advantage
over NSAIDs among patients with ulcer complications.
The panel advised that further studies should be done
to better asses the risk of COX-2 specific inhibitors and NSAIDS when
taken with aspirin but did not advise any labeling changes
for Celebrex for the time being.
The product's labeling currently warns that the drug
is not to be used as an aspirin substitute for cardiac protection.
Celebrex, approved in December 1998 to treat
osteoarthritis and rheumatoid arthritis, was the first COX-2 specific
inhibitor on the market.
Celebrex's approval was followed by the FDA's
May 1999 clearance of Merck's Vioxx (rofecoxib), indicated to treat
osteoarthritis, acute pain and painful menstruation.
Pharmacia's CLASS trial involved 8,000 mostly female
patients who averaged 60 years of age and who had osteoarthritis or rheumatoid
arthritis. The trial compared Celebrex at an "exaggerated"
dose of 800 milligrams (mg) per day, or 4 times the recommended dose to
treat osteoarthritis and twice the usual dose for rheumatoid arthritis,
against normal doses of both ibuprofen and diclofenac.
Advisory Panel to the
US Food and Drug Administration (FDA) Gaithersburg, MD, February 8, 2001
