Cost-Effectiveness of Cyclooxygenase-2 Inhibitors in Chronic Arthritis

IN RESPONSE:

We thank Pellissier and colleagues for their interest in our study. Whereas we estimated that it costs more than $275 000 per quality-adjusted life-year gained to prescribe a coxib in lieu of naproxen in average-risk patients with arthritis, Pellissier and colleagues came to very different conclusions. Specifically, the authors estimated that it costs only $4738 more per ulcer complication avoided to use a coxib instead of a nonselective NSAID when clinical data are incorporated, and further concluded that coxibs dominate when endoscopic data are considered (1). Our statement that Pellissier and colleagues found that rofecoxib was “more effective and cost-saving when compared with nonselective NSAIDs” is precisely in line with their latter conclusion and in fact is the very definition of dominance. We did not specify whether the conclusion arose from their base-case analysis or their sensitivity analysis.

When we compared our analyses, several potential biases were apparent in the work by Pellissier and colleagues. First, although the paper was published in 2001, the authors relied on the 1998 Red Book to adopt their cost estimates. In doing so, they determined that the average wholesale price of a coxib was $2.42 per pill, whereas the current cost is closer to $2.70 (2). Similarly, using an undisclosed recipe of weighted averages (by market share) of NSAIDs, the authors estimated that nonselective NSAIDs cost $1.47 per pill, compared with average wholesale prices of $0.18 for naproxen and $0.10 for ibuprofen (2). Moreover, by failing to report sensitivity analyses on either of these key estimates, the authors failed to demonstrate the degree to which they affected the model results. The net effect of these cost assumptions is to improve the relative cost-effectiveness of coxibs versus nonselective NSAIDs.

Second, rather than compare the head-to-head cost-effectiveness of coxibs and nonselective NSAIDs, the authors instead assumed that a proportion in each arm received co-prescribed GI prophylaxis. On the basis of the “input of an expert panel,” the authors estimated that the co-prescription of prophylactic agents was “75% less than with nonselective NSAIDs.” They further assumed that 25.5% of the nonselective NSAID group received co-prescriptions. Where we reported that all 25.5% received omeprazole, Pellissier and colleagues noted that their analysis allowed for a combination of gastroprotective agents, including misoprostol and H₂-receptor antagonists. However, the authors did not report the relative proportion of PPI use (that is, did PPIs account for all, half, or none of the 25.5%?). Moreover, because misoprostol is rarely used for GI prophylaxis because of side effects and H₂-receptor blockers are proven ineffective for this indication, there is little doubt that PPIs are the drug class of choice for NSAID gastropathy. The more important issue is whether co-prescribed therapy should be modeled in the first place. The use of nonselective NSAIDs with co-therapy is a very different strategy from the use of NSAIDs alone and should therefore be the subject of a different analysis. Moreover, co-prescribing therapy is an explicit choice and should emanate from the “decision node” of a decision tree, not a “probability node” as modeled by Pellissier and colleagues. The notion that our hands are tied and that co-prescribing practices are a matter of probability (as determined by an expert panel) serves only to reify current practice rather than to test the real issue: whether coxibs alone are cost-effective versus nonselective NSAIDs alone.

Third, Pellissier and colleagues assumed that PPIs reduce the risk for NSAID-related ulcer complications by 40% versus NSAIDs alone. However, the authors also adopted data from studies indicating that coxibs reduce complications by 50% versus NSAIDs alone. Therefore, the analysis assumes that the combination of an NSAID and a PPI is less effective than a coxib. This is not borne out by recent data indicating that the competing strategies are equally effective (3). Pellissier and colleagues suggested that we failed to test the full range of possible costs for nonselective NSAIDs, since “the range . . . extends well beyond the $0.04 to $0.50 range described.” However, Table 5 of our study shows that we extended the range well beyond these constraints. Specifically, we found that the coxib strategy became dominant only when the cost of the NSAID comparator exceeded $2.17, 12 times the average wholesale price of naproxen.