A clear result from this analysis is it is cost effective to co-prescribe a proton pump inhibitor when either a COX 2 selective inhibitor or a traditional NSAID is given, even for patients at relatively low risk of gastrointestinal adverse events. This result is driven by recent improvements in the evidence base for proton pump inhibitors and reductions in their price.6 7
In the past it has not been considered usual to co-prescribe a proton pump inhibitor with a COX 2 selective inhibitor, thus this recommendation represents a change in current practice. Assuming a class effect for proton pump inhibitors, the cheapest of these agents will always be cost effective. At current prices the relative risk of gastrointestinal adverse events could be as high as 0.98 before the addition of a proton pump inhibitor becomes cost ineffective at a cost effectiveness threshold of £20
000 per additional quality adjusted life year.
Another key finding of this analysis is that the co-prescription of a proton pump inhibitor with a COX 2 selective inhibitor rather than a traditional NSAID might be a cost effective treatment option for younger patients without specific gastrointestinal risk factors. Previously, the use of a COX 2 selective inhibitor would have been considered only in patients at high risk of gastrointestinal adverse events. There is uncertainty over this finding, though, primarily owing to uncertainties over the adverse event data, some of which are based on low event numbers.
The relative cost effectiveness of the traditional NSAIDs depended on the adverse event data used. The sensitivity analyses showed that there is high uncertainty over which specific NSAID or COX 2 selective inhibitor is most cost effective—the results were sensitive to most of the analyses run. It is, therefore, difficult to make a firm conclusion. The same is true for the relative cost effectiveness of the two currently available COX 2 selective inhibitors. For patients at increased risk of cardiovascular or gastrointestinal events (that is, equivalent to the risk of an average 65 year old), paracetamol results in fewer adverse events and is more cost effective than any of the traditional NSAIDs co-prescribed with a proton pump inhibitor, but is not superior a COX 2 selective inhibitor with a proton pump inhibitor. For lower risk patients, prescribing a traditional NSAID or a COX 2 selective inhibitor with a proton pump inhibitor is likely to be cost effective compared with paracetamol.
The relatively high rates of side effects with all of the traditional NSAIDs and COX 2 selective agents studied, as well as questions over their long term efficacy,46 47 48
suggest that these drugs should only be prescribed to control symptoms of osteoarthritis as and when required and should be used at the lowest effective dose for the shortest possible period of time. Our results are based on the lowest licensed dose considered to be effective for osteoarthritis.
Previous studies have determined a wide range of cost effectiveness estimates for COX 2 selective inhibitors compared with NSAIDs for people with osteoarthritis—some have indicated that COX 2 selective inhibitors provide cost savings and health gains, whereas others found that COX 2 selective inhibitors increase costs and result in health losses.9 12 49
Our analysis differs because it is based on the most recent data and includes a range of gastrointestinal and cardiovascular adverse events. Despite this, we found that the difference between individual NSAIDs and COX 2 selective inhibitors remains uncertain. Unlike previous analyses, however, we found that the addition of a proton pump inhibitor to both traditional NSAIDs and COX 2 selective inhibitors was likely to be cost effective on the basis of the latest data and prices.
Our analysis also indicates that for people with osteoarthritis and a low risk of cardiovascular adverse events, a COX 2 selective inhibitor in combination with a proton pump inhibitor might be the most cost effective treatment option. It should be noted that in our economic model we assessed three months of continuous use of treatments. This treatment schedule might not reflect real world use of these agents, which might be infrequent and for shorter durations in people with intermittently symptomatic osteoarthritis. Most people with osteoarthritis are elderly and have multiple comorbidities, especially cardiovascular disease, which will ultimately limit the use of COX 2 selective inhibitors. This fact might be reflected in current prescribing patterns, given that prescriptions of COX 2 selective inhibitors form a low proportion of total NSAID prescriptions.2
Our analysis also shows that traditional NSAIDs are not likely to be more cost effective than COX 2 selective inhibitors for people with osteoarthritis who are at high risk of cardiovascular adverse events, thus both traditional NSAIDs and COX 2 selective inhibitors should be avoided in such patients.4
The limitations of this evaluation are associated with the small number of large randomised controlled trials available for inclusion, which restricted the number of agents that could be compared. Ideally, a large trial that directly compared the available NSAIDs and COX 2 selective inhibitors with and without co-prescription of a proton pump inhibitor and collected data on a range of gastrointestinal and cardiovascular adverse events would be used to populate our model. Unfortunately such data are not available.
The assumptions that we made regarding the relation between dose and efficacy also represent a limitation of our analysis. We were unable to identify a relation between dose and efficacy with the trials that we used, and thus we assumed that the utility scores associated with each treatment in the absence of adverse events were independent of dose. This presumption might not be realistic; however, we are confident that the adverse events included in the model are the main drivers behind the results and that our dose-efficacy assumption does not undermine our findings.
Additionally, the difficulties associated with amalgamating randomised controlled trial data and observational data meant that in the base case a large amount of informative observational adverse event data were not used.
Finally, we were aware of new data suggesting that long term proton pump inhibitor use may be linked to hip fractures50 51
; thus we tested the impact of this possibility in a sensitivity analysis. We found that hip fractures were so rare that they made no difference to the results of the economic analysis.