Cost-effectiveness of nonsteroidal anti-inflammatory drugs and opioids in the treatment of knee osteoarthritis in older patients with multiple comorbidities

Abstract

Objective: To evaluate long-term clinical and economic outcomes of naproxen, ibuprofen, celecoxib or tramadol for OA patients with cardiovascular disease (CVD) and diabetes.

Design: We used the Osteoarthritis Policy Model to examine treatment with these analgesics after standard of care (SOC) - acetaminophen and corticosteroid injections - failed to control pain. NSAID regimens were evaluated with and without proton pump inhibitors (PPIs). We evaluated over-the-counter (OTC) regimens where available. Estimates of treatment efficacy (pain reduction, occurring in ∼57% of patients on all regimens) and toxicity (major cardiac or gastrointestinal toxicity or fractures, risk ranging from 1.09% with celecoxib to 5.62% with tramadol) were derived from published literature. Annual costs came from Red Book Online(®). Outcomes were discounted at 3%/year and included costs, quality-adjusted life expectancy, and incremental cost-effectiveness ratios (ICERs). Key input parameters were varied in sensitivity analyses.

Results: Adding ibuprofen to SOC was cost saving, increasing QALYs by 0.07 while decreasing cost by $800. Incorporating OTC naproxen rather than ibuprofen added 0.01 QALYs and increased costs by $300, resulting in an ICER of $54,800/QALY. Using prescription naproxen with OTC PPIs led to an ICER of $76,700/QALY, while use of prescription naproxen with prescription PPIs resulted in an ICER of $252,300/QALY. Regimens including tramadol or celecoxib cost more but added fewer QALYs and thus were dominated by several of the naproxen-containing regimens.

Conclusions: In patients with multiple comorbidities, naproxen- and ibuprofen-containing regimens are more effective and cost-effective in managing OA pain than opioids, celecoxib or SOC.

Keywords: Cost-effectiveness; NSAIDS; Nonsteroidal anti-inflammatory drugs; Opioids; Osteoarthritis.

Figure 1. Treatment Sequences for OA Management

This figure depicts the treatment sequences evaluated. Shaded cells indicate a contrast to the standard of care sequence. For each regimen assessing NSAIDs (naproxen, ibuprofen, and celecoxib), an additional regimen incorporating PPIs was evaluated. Further, for naproxen and ibuprofen regimens, over-the-counter based sequences were assessed.

Figure 2. Cost-effectiveness of all treatment strategies

This figure portrays the cost-effectiveness of alternative prescription- and over-the-counter-based treatment strategies for OA patients with multiple comorbidities. The efficiency frontier (solid line) defines the greatest QALE that can be achieved for any given outlay. Strategies that lie along this frontier are termed ‘efficient.’

Figure 3. Incremental Cost-Effectiveness Ratios of Over-the-Counter Regimens of (a) Naproxen and (b) Naproxen + PPI

Figure 3 shows the results of a “two-way sensitivity analysis.” This figure illustrates the ICERs calculated for (a) the naproxen over-the-counter (OTC) regimen and (b) OTC naproxen with PPIs regimens, under a range of values for regimen efficacy and toxicity. The purpose of the analysis is to examine the effect on cost-effectiveness (measured in ICERs) of differences in efficacy and toxicity of OTC vs. prescription naproxen. The horizontal axis shows changes in efficacy of OTC naproxen as compared with prescription naproxen. The vertical axis shows changes (increases or reductions) in toxicity of the regimen compared to prescription naproxen. The shading denotes the ICER, ranging from light yellow (ICERs < $25,000/QALY) to black (dominated, indicating greater cost and lower efficacy than the comparator). In panel (a) the OTC naproxen regimen is compared to prescription ibuprofen. In panel (b) OTC naproxen with PPIs is compared to OTC naproxen (without PPIs). In both instances, the base case, using the initial input assumptions, is marked with an asterisk.

Figure 4. Probability of cost-effectiveness of alternative treatment strategies at each WTP threshold

The probability of cost-effectiveness of prescription naproxen with either prescription or OTC PPIs is shown. These results are based on 100 iterations, varying the efficacy of all regimens, probability of prescription naproxen major toxicity, and the toxicity of OTC agents. The probability of cost-effectiveness of prescription naproxen with OTC PPIs reaches 60% if the WTP threshold is $150,000/QALY.