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Inhaled Levodopa for the Management of OFF Episodes in Parkinson’s Disease: A Cost-Effectiveness Analysis
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DOI：10.1007/s40273-026-01642-z.png)
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Abstract
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OFF episodes in Parkinson’s disease (PD), where symptoms worsen despite symptomatic treatment, are associated with significant burden on patients, carers and healthcare providers. There is an unmet need for an effective, on-demand treatment for OFF episodes that provides fast-acting symptom relief. This study estimated the cost-effectiveness of inhaled levodopa (LD) compared with relevant alternatives from a UK National Health Service and Personal Social Services perspective. A Markov model was developed comparing inhaled LD with subcutaneous (SC) apomorphine, sublingual (SL) apomorphine, dispersible LD and no on-demand treatment (no-ODT) in adults with advanced PD treated with LD and carbidopa and experiencing OFF episodes. A lifetime time horizon was adopted. Within-trial and beyond-trial models were applied for initial treatment and subsequent therapy, respectively. Model structure comprised 12 health states: ten ‘Off’ states, an ‘On’ state and death. Clinical trials and a network meta-analysis informed clinical inputs, with natural history progression applied from year 3. UK national databases and published literature informed costs (2025) and utility data. A 3.5% yearly discount rate is applied to costs and outcomes. Sensitivity analyses and three scenarios exploring alternative progression through health states, caregiver costs and disutilities, as well as subsequent therapy adverse events, were conducted. In base-case analysis, inhaled LD dominated versus dispersible LD and no-ODT and was associated with lower cost and lower quality-adjusted life years (QALYs) versus SC and SL apomorphine. Nevertheless, inhaled LD resulted in net monetary benefit (NMB) of £14,226 and £25,939 compared with SC and SL apomorphine, respectively, at a £25,000 willingness-to-pay threshold. Key model drivers were subsequent therapy costs, discontinuation rates and health state utility values. The probabilistic sensitivity analysis highlighted uncertainty in the model; however, mean probabilistic sensitivity analysis results, along with two scenario analyses, remained consistent with the base case. Inhaled LD may be an economically dominant treatment strategy when compared with dispersible LD and no-ODT. When compared with SC and SL apomorphine, cost-savings with inhaled LD may outweigh potentially fewer QALYs, resulting in an NMB.
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