Celebrex Gets Passing Grades for Gastric and Cardiac Safety

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Celebrex Gets Passing Grades for Gastric and Cardiac Safety



By Jeff Minerd, MedPage Today Staff Writer

Reviewed by Zalman S. Agus, MD; Emeritus Professor at the University

of Pennsylvania School of Medicine.

February 23, 2006



MedPage Today Action Points

Carefully weigh the potential risks versus benefits when considering

prescribing an NSAID or -2 inhibitor for treating osteoarthritis

pain.

Explain to patients who ask that the lack of detection of a

significant thromboembolic risk may have been due to the short

duration of the study and the fact that this study was not

sufficiently powered to detect these differences.

Review

PALO ALTO, Calif., Feb. 23 - Here is yet another chapter in the epic

story of the safety and efficacy of -2 inhibitors.

A Stanford group reported in the March issue of the American Journal

of Medicine that Celebrex (celecoxib) may be as effective as non-

specific non-steroidal anti-inflammatory drugs (NSAIDs) in treating

osteoarthritis and carries less risk of serious gastric events.

In addition, the number of cardiovascular thromboembolic events was

not significantly different between patients taking Celebrex and

those on NSAIDs, reported Gurkirpal Singh, M.D., and colleagues.

While -2 inhibitors were promoted as an alternative to traditional

NSAIDs that would be safer for the gastrointestinal tract, the

Celecoxib Long-term Arthritis Safety Study (CLASS), published in

2000, did not conclusively demonstrate gastric safety, Dr. Singh and

colleagues noted.

A case for GI safety was made in the Vioxx Gastrointestinal Outcomes

Research (VIGOR) trial. It found that 50 mg of Vioxx (rofecoxib)

daily caused less GI toxicity than 500 mg of Naprosyn (naproxen)

twice a day. But that study has been faulted because it allegedly

presented a misleading picture of cardiovascular risks associated

with Vioxx.

Vioxx was voluntarily withdrawn from the market in September 2004

when the data safety monitoring board of a colon cancer prevention

trial reported an increase in thromboembolic events among patients

who took Vioxx daily for 18 months or longer. A year ago, Bextra

(valdecoxib), another -2 inhibitor, was also withdrawn amid

reports that it, too, increased the risk of heart attack and stroke.

Celebrex is the only -2 inhibitor still available.

The current study, termed the Successive Celecoxib Efficacy and

Safety Study-1 (SUCCESS-1), evaluated the overall safety, efficacy,

and tolerability of Celebrex compared with the NSAIDs Voltaren

(diclofenac) and Naprosyn. The study included more than 13,000

osteoarthritis patients in community-based, outpatient clinical

practices in 39 countries.

Patients were randomly assigned to double-blind, twice-daily

treatment with Celebrex at 100 mg, Celebrex at 200 mg, Voltaren at 50

mg, or Naprosyn at 500 mg. Follow-up was 12 weeks.

Both dosages of Celebrex were as effective as the NSAIDs in treating

osteoarthritis symptoms, as assessed by the Patient's Assessment of

Pain Visual Analog Scale and other standard assessment tools, the

investigators reported.

However, compared with the Celebrex group, the NSAID group was seven

times more likely to have ulcer complications (odds ratio=7.02; 95%

confidence interval=1.46-33.8; P=.008).

In addition, patients in the NSAID group were six times more likely

to experience an upper gastrointestinal event compared with the

Celebrex group (OR=6.02; 95% CI=1.50-34.57; P=.004).

There were no significant differences between Celebrex and the NSAIDs

in any cardiovascular adverse event rate, with the exception of

cardiac failure, which was significantly higher in the NSAID group

(OR=4.51; 95% CI=1.26-20.06; P=.01).

The study found reduced risk for myocardial infarction in the NSAID

group compared with Celebrex, but this did not reach statistical

significance (OR=.20; 95% CI=0.03-1.56; P=.11). The authors, however,

pointed out that the study was not powered to detect such differences.

Overall, a significantly smaller proportion of patients treated with

Celebrex had an adverse event compared with those treated with the

NSAIDs (37% versus 40%; P<.001).

" In summary, our study shows that the -2 specific inhibitor

celecoxib is as effective as the non-specific NSAIDs naproxen and

diclofenac but has significantly fewer serious upper gastrointestinal

events, " the authors said. " The number of cardiovascular

thromboembolic events in our study was low, and, although numeric

differences were noted, these did not reach statistical significance. "

They added, " Because current clinical osteoarthritis treatment

guidelines vary in their recommendations regarding the appropriate

therapeutic role of -2-specific inhibitors, clinicians should

consider a number of factors, including the risk for upper

gastrointestinal events, duration of therapy, as well as costs,

before deciding upon individual patient treatment. "

While essentially confirming the results of earlier studies upon

which the approval of Celebrex was based, rather than adding anything

new, this study's chief strength is its large size, said Arthur

Kavanaugh, M.D., a professor of medicine at the University of

California in San Diego and member of the American College of

Rheumatology.

The study may be useful to physicians trying to reassure patients

about the safety of -2 inhibitors, he said. However, the chief

weaknesses of the study were its failure to present safety data

broken down by dosage of Celebrex and its lack of a clear definition

of what constituted a myocardial infarction, he added. Another

limitation noted by the authors was the short duration of the study,

limiting extrapolation of the results to long-term therapy.

The study was supported by Pfizer, which makes Celebrex.



Primary source: The American Journal of Medicine

Source reference:

Singh G et al. Celecoxib versus naproxen and diclofenac in

osteoarthritis patients: SUCCESS-1 study. The American Journal of

Medicine. 2006; 119:255-266.

http://www.medpagetoday.com/Rheumatology/Arthritis/dh/2735