RESEARCH - Study suggesting no GI advantage puts COX-2s back in the limelight

[Guest guest]

New study suggesting no GI advantage puts coxibs back in the limelight

Rheumawire

Dec 6, 2005

Gandey

Nottingham, UK - A new observational study from the UK showing no real

safety advantage of selective nonsteroidal anti-inflammatory drugs is

sparking renewed debate over the coxibs [1]. Writing in the December 3, 2005

issue of the BMJ, Dr Hippisley- (University of Nottingham, UK) and

colleagues report finding " no consistent evidence " of enhanced safety

against gastrointestinal events with any of the new COX-2 inhibitors

compared with nonselective NSAIDs.

But the study has received severe criticism by experts such as Dr

Abramson (NYU Medical Center and Hospital for Joint Diseases, New York).

Abramson told rheumawire that the BMJ paper is " editorially slanted and

irresponsible. " He adds: " The authors are very unfair to celecoxib. Based on

these results, celecoxib actually looked pretty good. "

During an interview, Abramson said that among the study's faults are its

significant channeling bias and inadequate detailing of concomitant

medications and comorbidities. " What is most disturbing about this paper is

the inadequate description of the patient population. Was aspirin preventing

the gastrointestinal protection of the COX-2 inhibitors? There are many

questions that we will be unable to answer until we analyze the data not

provided by the authors. "

As previously reported by rheumawire, coxib prescribing in the UK was

limited by recommendations issued by the National Institute of Clinical

Excellence encouraging that these drugs be reserved for patients at high

risk of gastrointestinal damage. This alone may represent an important

confounder of subsequent studies.

But despite the many challenges, other experts say this study is a useful

addition to a growing body of research. " There is a consistent message

emerging, " Dr Matteson (Mayo Clinic College of Medicine, Rochester, MN

and an editorial consultant to www.jointandbone.org) said during an

interview. " For most patients, the cost/benefit ratio of the COX-2

inhibitors is simply not worth it. While the coxibs do have a role to play

for specific patients, this is not the case for most. "

He adds, " The authors of this study found a slight decrease in risk for

celecoxib, but even this selective agent didn't eliminate the risk. The

argument that coxibs are GI safe has always been incorrect. At the best of

times, you could say there is somewhat less risk. "

Not as safe as originally thought?

In their nested case-control study, Hippisley- and her team looked at

more than 360 general practices covering every health authority and each

board in England, Wales, and Scotland. They sought to determine the risk of

an adverse upper gastrointestinal event in patients taking various coxibs

compared with nonselective NSAIDs.

The participants were aged 25 or older with a first diagnosis of an upper-GI

event (peptic ulcer or hematemesis). The researchers identified more than

9400 cases and over 88 800 matched controls. About 45% of the cases had been

prescribed a conventional NSAID in the previous three years, and 10% had

been prescribed a COX-2 inhibitor.

The investigators found that the overall incidence of adverse upper-GI

events was 1.36 per 1000 person-years (95% CI 1.34-1.39).

Hippisley- and her team found that ulcer-healing drugs reduced the

increased risk of adverse gastrointestinal outcomes with all NSAID groups

except diclofenac users. " That ulcer-healing drugs were associated with a

reduction in risk of adverse events for COX-2 inhibitors as a whole suggests

that there is some risk to protect against and that these drugs may not be

as safe as originally thought, " the researchers comment.

Their findings are triggering renewed discussion of this hot-button issue.

Since this paper was published, the BMJ website has received a flurry of

rapid responses from readers. Among them, Underhill, assistant

director of education and development at the National Prescribing Centre in

the UK: " It is important to note that this was an observational study, which

we all know occupies a lower place on the hierarchy of evidence than large,

prospective, randomized controlled trials measuring outcomes that are

important to patients. "

He adds, " The regulators in the US and in Europe have concluded that the

data from the CLASS study [2] do not show a meaningful benefit for

celecoxib. It is disappointing that the prescribing of this drug continues

to increase despite the lack of good-quality evidence for its usefulness in

providing a benefit to our patients. "

Underhill concludes, " Perhaps we should stick to the facts rather than argue

about the wording of the conclusions of hypothesis-generating data like the

Hippisley- paper. Although such data are interesting, they do not inform

our practice in the same way as a negative prospective randomized controlled

trial does. "

Dr Enrique Sánchez-Delgado (Hospital Metropolitano Vivian Pellas, Managua,

Nicaragua) writes that a clear picture is coming to light. NSAIDs, in

addition to their analgesic and anti-inflammatory effects, increase

cardiovascular, renal, and gastrointestinal risks, and as such should be

initiated at the lowest dose for the shortest period of time. He notes that

the risks and benefits of individual medications are determined by their

potencies-a point foreseen by Paracelsus 500 years ago.

Sources

1. Hippisley- J, Coupland C, Logan R. Risk of adverse

gastrointestinal outcomes in patients taking cyclooxygenase-2 inhibitors or

conventional nonsteroidal anti-inflammatory drugs: Population based nested

case-control analysis. BMJ 2005; 331:1310-1312.

2. Silverstein FE, Faich G, Goldstein JL, et al.

Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory

drugs for osteoarthritis and rheumatoid arthritis: The CLASS study: A

randomized controlled trial. Celecoxib Long-term Arthritis Safety Study.

JAMA 2000; 284:1247-1255.

Not an MD

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org