Motor and Non-motor Complications Following Different Early Therapies in Parkinson's Disease: Longitudinal Analysis of Real-Life Clinical and Therapeutic Data from the French NS-PARK Cohort.

Background: Levodopa, dopamine agonists (DA) and monoamine oxidase inhibitors (MAOI) are all approved first-line therapies for Parkinson's disease (PD), as monotherapy or in combination. Data on their use in the early management of patients with PD in real-life are lacking. Our objective was to assess the impact of early therapeutic strategies on the development of motor and neuropsychiatric complications using a nationwide PD cohort.

Methods: NS-PARK is a cohort of patients with PD recruited between 2011 and 2021 from 26 expert centres for PD in France. We analysed the patients with less than 5-years disease duration and no motor complications at inclusion. We used interval censoring survival models to assess the associations between therapeutic strategies (levodopa monotherapy, levodopa alternative therapies or levodopa combinations) and motor fluctuations, dyskinesia, impulse control and related behaviours (ICRBs), apathy, psychosis/hallucination and daytime sleepiness. Analyses were adjusted for sex, age, disease duration, dopaminergic dose and disease severity.

Results: We included 1722 patients (38.4% female, median age 67.7 years). At inclusion, 41% received levodopa monotherapy, 31% received levodopa alternative therapies and 28% received levodopa combinations. Compared with levodopa monotherapy, levodopa alternative therapies were associated with a lower dyskinesia risk (hazard ratio (HR) 0.48, 95% confidence interval (CI)[0.28-0.84]), but there was no significant difference in motor fluctuations. Both levodopa alternative and combinations therapies increased ICRBs risk (HR 4.06, 95% CI [2.48-6.67]; HR 5.16, 95% CI [3.00-8.86]) and decreased apathy risk (HR 0.36, 95% CI [0.26-0.49]; HR 0.52, 95% CI [0.39-0.69]). No association was found with psychosis/hallucination or daytime sleepiness.

Conclusions: In this real-life cohort, our data supported an association between levodopa alternative therapies and a lower risk of dyskinesia and apathy, but a higher risk of ICRBs compared with levodopa monotherapy. Results: null NCT04888364. Registered June 2021.