Economic evaluation of therapies for the treatment of motor fluctuations in advanced stage Parkinson's disease

Abstract

Background: Up to half of all patients with Parkinson’s Disease (PD) will progress to its advanced stage, when quality of life is severely hampered and treatment costs escalate. Advanced, device-assisted therapies are usually considered in these patients. Existing surgical interventions, including deep brain stimulation (DBS) and levodopa-carbidopa intestinal gel (LCIG), are invasive and difficult to access in the United States. Subcutaneous infusion therapies, namely continuous subcutaneous apomorphine infusion (CSAI) and continuous subcutaneous foslevodopa-foscarbidopa infusion (LDp/CDp) are the latest advanced therapies approved by the US Food and Drug Administration in October 2024 and February 2025, respectively. They promise to be minimally invasive alternatives to existing surgical interventions and alleviate access issues plaguing the advanced PD treatment landscape in the US. However, there is no direct efficacy comparison between subcutaneous infusions and surgical interventions. These new therapies are also costly, raising questions about their cost-effectiveness. My thesis provides the first evidence to address these questions. Methods: First, we conducted a systematic review and Bayesian network meta-analysis of randomized clinical trials studying advanced therapies to estimate the comparative efficacy and safety of these treatments. We further evaluated whether the differences between the treatments, if there are any, are clinically meaningful. Next, we performed a cost-effective analysis to assess whether the new subcutaneous infusions offer good value for money and whether they are more economically efficient than surgical interventions. Results: In the systematic review and network meta-analysis, we identified and analyzed 13 randomized controlled trials with a combined 2,069 participants. We found that the newly approved therapies generally fall behind existing treatments, most notably DBS. Foslevodopa-foscarbidopa is less effective than DBS at improving OFF time [mean difference (MD) vs. DBS, +1.13 hours (95% CrI: −0.01 to +2.29)] and clinical motor functions [UPDRS-III, MD vs. DBS, +2.36 points (95% CrI: −0.10 to +4.89)]. Similarly, CSAI is less effective than DBS at improving quality of life [PDQ-39, MD vs. DBS, +5.09 points (95% CrI: −0.37 to +10.67)]. However, the differences between therapies at improving OFF time and motor functions are not clinically important. In terms of safety, the risk of serious adverse effects is elevated with DBS. In the cost-effective analysis, we found that the newly approved subcutaneous infusions are not cost-effective compared with existing surgical therapies. DBS is the optimal therapy from a cost-effectiveness perspective, costing less but providing more quality-adjusted life years (QALYs) compared to all other treatments. Infusion therapies are not cost-effective versus best medical therapy (BMT) at a willingness-to-pay threshold of $100,000/QALY. LDp/CDp and CSAI have incremental cost-effectiveness ratios of $1.69 million and $1.98 million per QALY compared to BMT, respectively. Their prices would have to be reduced by 82-83% for them to be cost-effective versus BMT. However, in cases where infusion therapies are used as intermediate treatment before DBS, the novel therapies only need price reductions of 4-20% to be the best infusion option. Conclusion: The findings of my thesis provide the first evidence on the economic value of LDp/CDp. It, also provides evidence on the value of subcutaneous infusions vs existing treatments for advanced PD in the United States. The systematic review and network meta-analysis highlighted the lower efficacy of subcutaneous infusions but also the small comparative differences between therapies. Furthermore, the cost-effectiveness analysis indicated that using DBS is cost-saving, while LDp/CDp and CSAI are not cost-effective, mainly due to high drug acquisition prices. At the same time, a modest price reduction can make subcutaneous infusions valuable options amidst limited DBS access. Altogether, the findings provided insights into the worth of eliminating barriers to accessing DBS, the economic value of novel infusion therapies as bridging treatments, and the need to negotiate price discounts for these therapies.