RESEARCH = Evidence mounting for NSAID plus proton pump inhibitor over coxibs

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Evidence mounting for NSAID plus proton pump inhibitor over coxibs

Rheumawire

May 9, 2005

Gandey

Los Angeles, CA - New cost-effectiveness and cost-utility analyses reveal

that coxibs are inferior to a nonsteroidal anti-inflammatory drug plus

proton pump inhibitor approach. In a recent issue of Arthritis and

Rheumatism, investigators report that their findings emerged despite

explicitly biasing their model in favor of the coxibs [1]. " Our research

shows that under no circumstances is it cost-effective to administer a COX-2

inhibitor, " lead author Dr Brennan Spiegel (University of California, Los

Angeles) told rheumawire. " The COX-2 inhibitors really lose ground because

they are so expensive, using them in combination with aspirin reduces their

effectiveness, and there are concerns over cardiovascular risks. " Spiegel

and his team found that for high-risk patients, the combination of a NSAID

taken with an acid-lowering drug is not only less expensive, but also safer

and more effective.

Spiegel says the study took baseline CV risks of traditional NSAIDs into

account. " But I can tell you that even if we had increased the risk of

traditional NSAIDs, it wouldn't have changed the results of our study. "

In their paper, the researchers report that NSAIDs are the most commonly

used medications for chronic arthritis accounting for 111 million

prescriptions annually and 3% of the American prescription drug market. The

economic impact of these adverse events is significant resulting in more

than 100 000 hospitalizations annually at a cost of $1.6 billion. The group

adds that each year there are 17 000 deaths in the United States as a result

of NSAID-related GI complications. " In light of the substantial human and

economic costs of NSAID-related adverse events, the decision to use NSAIDs

requires a delicate balance between effective pain relief on the one hand

and GI complications on the other, " the researchers write.

Emerging data suggest that alternative therapies equal or preferable to

coxibs

Spiegel and his team write that despite enthusiasm for the coxibs, a number

of recent findings cast doubt on the endorsement of coxibs in favor of

alternative therapies:

1. Despite the significant relative risk reduction in GI complications

afforded by coxibs, their absolute risk reduction compared with NSAIDs is

less than 1% for significant ulcer complications.

2. Recent economic models show that the small degree of risk reduction is

insufficient to offset the increased cost of coxibs versus generic NSAIDs

for average-risk patients.

3. Prospective studies in high-risk patients indicate that coxibs do not

provide an additional risk reduction when compared with the NSAID plus

proton pump inhibitor combination.

4. Data reveal that the use of concurrent aspirin attenuates the relative

GI protective effects of coxibs versus NSAIDs.

5. One randomized controlled trialthe Vioxx Gastrointestinal Outcomes

Research (VIGOR) trial revealed a significantly increased risk for

cardiovascular events with rofecoxib versus naproxen.

In light of these new data and uncertainties, Spiegel and colleagues sought

to reappraise the initial treatment of choice for arthritis patients with

varying risk factors. Their work was funded by Tap Pharmaceutical Products

Inc, the maker of the proton pump inhibitor lansoprazole. Spiegel told

rheumawire that the company's involvement was investigator initiated and

involved no participation in the study's design, management or writing.

In their cost-effectiveness and cost-utility analyses, the researchers

evaluated 3 competing strategies. They reviewed a generic nonsteroidal

anti-inflammatory drug, a NSAID plus a proton pump inhibitor (PPI), and a

COX-2 inhibitor. Cost estimates were from a third-party payer perspective.

The outcomes were incremental cost per ulcer complication avoided and

incremental cost per quality-adjusted life year gained. They performed a

sensitivity analysis to evaluate the impact of varying patient GI risks and

aspirin use.

ib strategy found to be less effective and more expensive

Spiegel and his team found that in average-risk patients, the NSAID and PPI

strategy cost an incremental $45 350 per additional ulcer complication

avoided and $309 666 per quality-adjusted life year gained compared with the

NSAID alone. They found that the coxib strategy was less effective and more

expensive than the NSAID plus PPI strategy. Sensitivity analysis revealed

that the NSAID with PPI became the dominant approach in patients at high

risk for a NSAID adverse event such as in those on aspirin with risk factors

for a GI complication. " Previous studies of COX-2 inhibitors looked at

dramatic bleeds and perforations, " Spiegel said during an interview. " But we

found that the coxibs led to more dyspepsia compared to other drugs. "

Spiegel and colleagues calculate that substituting either a coxib or a NSAID

with PPI combination instead of a generic naproxen may cost over $300 000

more per quality-adjusted life year gained in average-risk patientsa cost

that is significantly higher than most accepted interventions in medicine.

The researchers say their findings emerged despite biasing the model in

favor of the coxibs. Four assumptions exemplify this bias. One, rather than

assume that PPIs reduce clinically significant ulcer complications by up to

80%, as suggested by the literature, the group adopted a 50% risk reduction

as their base-case estimate. Two, rather than assume that PPIs reduce

non-ulcer dyspepsia by 50%, as suggested by a recent meta-analysis, they

chose an 18% risk reduction (representing the lower 95% confidence interval

from the meta-analysis). Also, rather than assume that up to 50% of the

hypothetical 60-year-old cohort was eligible for cardioprophylaxis, as

suggested by current guidelines, they assumed that only 20% received

aspirin. And finally, rather than assume that the incidence of overall

serious adverse events is lower with nonselective NSAIDs than coxibs, as

indicated by a US Food and Drug Administration review measuring outcomes

across all organ systems, this analysis only included GI adverse events.

The investigators also point out several limitations to their study. They

note that because their base case point estimates are largely derived from

randomized controlled trials and expert opinion, the findings may not be

generalizable to all relevant arthritis populations. " Moreover, several of

our estimates are based on studies of varying design, patient population,

follow-up, and quality, " they write. " However, we attempted to guard against

inaccurate base case results by systematically reviewing the literature,

relying on pre-existing meta-analyses when available, and conducting our own

meta-analyses when necessary to develop precise point estimates. In

addition, we relied upon an expert panel of physicians to provide estimates

in areas in which data are lacking. "

Spiegel and colleagues conclude, " This analysis reveals that the

cost-effectiveness of competing NSAID strategies in chronic arthritis is

highly dependent on individual risk factors. Our analysis suggests that

generic nonselective NSAIDs are most cost-effective in patients at low risk

for an adverse event. However, as both the GI and cardiovascular risk

increase, the addition of a PPI to a nonselective NSAID may be preferable to

coxib-based strategies. "

Source

a. Spiegel BM, Chiou CF, Ofman JJ. Minimizing complications

from nonsteroidal anti-inflammatory drugs: cost-effectiveness of competing

strategies in varying risk groups. Arthritis Rheum 2005; 53:185-197.

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