Inhaled Levodopa for the Management of OFF Episodes in Patients with Parkinson's Disease: A Network Meta-analysis

In the course of their disease, most patients with Parkinson's disease (PD) will experience OFF episodes, during which symptoms worsen despite symptomatic treatment. Current on-demand treatments for OFF episodes include inhaled levodopa and subcutaneous and sublingual apomorphine, however no head-to-head comparison of these treatments is available. We performed a network meta-analysis (NMA) to provide robust comparative evidence for on-demand OFF episode treatments.

Randomized controlled trials assessing OFF episode treatments in patients with PD were identified in a systematic literature review. A feasibility assessment was conducted considering OFF time, Unified Parkinson's Disease Rating Scale (UPDRS) Part III scores, Patient Global Impression of Change score (PGI-C), and safety outcomes. An NMA was carried out using a random effects model.

Twenty-one trials were identified in the systematic literature review, 11 of which were included in the feasibility assessment and deemed suitable to be included in the NMA. No statistically significant difference in OFF time was observed between patients receiving inhaled levodopa and those receiving subcutaneous apomorphine, and no statistically significant difference in UPDRS Part III scores or probability of PGI-C score improvements, all-cause discontinuation, or adverse events (AEs) were observed between patients receiving inhaled levodopa, subcutaneous apomorphine, or sublingual apomorphine. Subcutaneous apomorphine had significantly higher probability of treatment discontinuation due to adverse events compared to inhaled levodopa (Log odds ratio 20.712; 95% credible interval 1.855, 55.991).

Inhaled levodopa demonstrated no statistically significant difference in efficacy with subcutaneous or sublingual apomorphine, however inhaled levodopa had a lower probability of treatment discontinuation due to AEs than subcutaneous apomorphine. These data highlight that inhaled levodopa is a suitable non-invasive and well-tolerated treatment for OFF episodes.