Comparative Efficacy Safety and Discontinuation of Inhaled Levodopa for Patients With Parkinson’s Disease: A Network Meta-Analysis
Author(s)
Ubong Silas, MSc1, Omar Madani, MSc2, Chetan Mistry, MSc2, Rushab Shah, BSc2, Grace Chattey, MSc2, Leandro Guerra Primo, MSc3, Stefano Perni, PhD2.
1Merz Therapeutics, Frankfurt, Germany, 2FIECON, a Herspiegel Company, London, United Kingdom, 3FIECON, a Herspiegel Company, Rotterdam, Netherlands.
1Merz Therapeutics, Frankfurt, Germany, 2FIECON, a Herspiegel Company, London, United Kingdom, 3FIECON, a Herspiegel Company, Rotterdam, Netherlands.
OBJECTIVES: Inbrija® (inhaled levodopa) is indicated for the intermittent treatment of OFF episodes in adults with Parkinson’s disease (PD) treated with carbidopa/levodopa. There is no direct clinical evidence comparing inhaled levodopa with other on-demand treatment (ODT) options. This network meta-analysis (NMA) assesses the relative efficacy safety, and discontinuation of inhaled levodopa, apomorphine sublingual (APO-SL), apomorphine subcutaneous (APO-SC), and dispersible levodopa (LD) in patients with PD.
METHODS: An SLR identified 21 RCTs and 11 were included in the network after feasibility assessment. It was not feasible to connect LD to the network. The analysis included the endpoints: change in off-time, UPDRS score, PGI-C, all-cause treatment discontinuation, adverse events (AEs), and AE leading to discontinuation. Vague priors were used for between-study variation, treatment effects, and baseline effects.
RESULTS: Random effects models were selected due to study heterogeneity. Reduction in OFF-time was not significantly different between inhaled levodopa and APO-SC (Standardized mean difference [SMD] = 0.740, 95%CrI [-2.015, 3.484]), while APO-SL could not be included in the network. Changes in UPDRS III were not significantly different between inhaled levodopa and APO-SC (SMD = 1.989, 95%CrI [-0.453, 4.522]) and APO-SL (SMD = 0.963 [-1.664, 3.581]). Inhaled levodopa, APO-SC, and APO-SL showed no significant differences for PGI-C, all-cause treatment discontinuation, and AE. Inhaled levodopa demonstrated significantly lower odds of treatment discontinuation due to AEs (log OR = -20.712, 95% CrI [-55.991, -1.855]) compared to APO-SC, but no significant difference was observed with APO-SL (log OR = -0.734 [-3.201, 1.689]). Scenario analyses confirmed the robustness of the NMA results.
CONCLUSIONS: Inhaled levodopa, APO-SC, and APO-SL have comparable efficacy in reduction in OFF time, change in UPDRS-III score, and improvement in PGI-C score. Although the AE rates are comparable, the probability of treatment discontinuation due to AEs is significantly higher for APO-SC compared to inhaled levodopa.
METHODS: An SLR identified 21 RCTs and 11 were included in the network after feasibility assessment. It was not feasible to connect LD to the network. The analysis included the endpoints: change in off-time, UPDRS score, PGI-C, all-cause treatment discontinuation, adverse events (AEs), and AE leading to discontinuation. Vague priors were used for between-study variation, treatment effects, and baseline effects.
RESULTS: Random effects models were selected due to study heterogeneity. Reduction in OFF-time was not significantly different between inhaled levodopa and APO-SC (Standardized mean difference [SMD] = 0.740, 95%CrI [-2.015, 3.484]), while APO-SL could not be included in the network. Changes in UPDRS III were not significantly different between inhaled levodopa and APO-SC (SMD = 1.989, 95%CrI [-0.453, 4.522]) and APO-SL (SMD = 0.963 [-1.664, 3.581]). Inhaled levodopa, APO-SC, and APO-SL showed no significant differences for PGI-C, all-cause treatment discontinuation, and AE. Inhaled levodopa demonstrated significantly lower odds of treatment discontinuation due to AEs (log OR = -20.712, 95% CrI [-55.991, -1.855]) compared to APO-SC, but no significant difference was observed with APO-SL (log OR = -0.734 [-3.201, 1.689]). Scenario analyses confirmed the robustness of the NMA results.
CONCLUSIONS: Inhaled levodopa, APO-SC, and APO-SL have comparable efficacy in reduction in OFF time, change in UPDRS-III score, and improvement in PGI-C score. Although the AE rates are comparable, the probability of treatment discontinuation due to AEs is significantly higher for APO-SC compared to inhaled levodopa.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
CO59
Topic
Clinical Outcomes
Topic Subcategory
Comparative Effectiveness or Efficacy
Disease
Neurological Disorders