Background/Purpose: Weight-loss has been shown to alleviate knee osteoarthritis (OA) symptoms in persons with OA and obesity. Utilization of GLP1RA medications has increased rapidly. These agents result in average weight-loss of 10-25%. We sought to determine the cost-effectiveness of adding a GLP1RA (semaglutide or tirzepatide) to usual OA care (UC) for patients with obesity and symptomatic knee OA.

Methods: We used the Osteoarthritis Policy (OAPol) Model, a widely published and validated microsimulation of knee OA, to estimate the long-term clinical benefits and costs of GLP1RA treatments compared to three other weight-loss strategies and UC alone: 1) UC (NSAIDs, corticosteroid injections, opioids and total knee replacement); 2) UC + diet and exercise (D+E); 3) UC + 2.4 mg weekly semaglutide; 4) UC + 15 mg weekly tirzepatide; 5) UC + laparoscopic sleeve gastrectomy (LSG); 6) UC + Roux-en-Y gastric bypass (RYGB).We derived weight reduction associated with semaglutide and tirzepatide from the STEP-1 and SURMOUNT-4 trials, respectively. We modeled a 20% reduction in major cardiovascular events based on the SELECT trial. We used a 12% GLP1RA annual discontinuation rate derived from observational studies. In the base case analysis, we assumed a maximum GLP1RA use of 5 years. We used published literature to determine the pain reduction associated with weight-loss and the BMI reduction from other strategies. The annual costs of GLP1RA regimens include the wholesale acquisition cost of the medication itself plus monthly lifestyle coaching ($17,000 for semaglutide; $13,500 for tirzepatide). We initiated a cohort with a mean age of 55 years, WOMAC pain (0-100, 100 worst) of 38, mean BMI of 38 kg/m² and 50% KL grade 2/50% KL grade 3. We calculated incremental cost-effectiveness ratios (ICERs) as the ratio of the difference in lifetime costs (2024 USD) to the difference in quality-adjusted life years (QALYs) between two adjacent, competing strategies. We conducted the analysis from a modified societal perspective and discounted QALYs and costs at 3% annually. We performed sensitivity analyses to examine the robustness of our findings given the uncertainty in input parameters.

Results: GLP1RA-based strategies were dominated (increased costs and decreased QALYs) by LSG and RYGB (Table 1). The ICERs for LSG and RYGB were $18,100/QALY and $158,400, respectively. In the absence of surgical options, D+E had an ICER of $25,800/QALY, and tirzepatide’s ICER was $91,200. Medication cost, years on treatment, and starting BMI had the greatest impact on tirzepatide’s ICER: when the price of tirzepatide was lowered to its federal supply schedule cost ($9,840), its ICER fell to $56,800. D+E was cost-effective in 87% of scenarios if willingness to pay (WTP) was $50,000/QALY; tirzepatide was cost-effective in 53% if WTP was $100,000.

Conclusion: In the absence of surgical options, tirzepatide could be cost-effective if WTP < $100,000/QALY. Semaglutide was dominated by tirzepatide due to its higher costs and lower weight-loss efficacy. For WTP < $50,000, D+E could offer good value. LSG could offer high value in clinical OA management for patients with OA and obesity who are willing to undergo bariatric surgery.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-cost-effectiveness-of-glucagon-like-peptide-1-receptor-agonists-glp1ras-for-patients-with-knee-osteoarthritis-and-obesity/