Reducing therapeutic burden after Safinamide introduction in Parkinson's disease: a longitudinal, retrospective, real-world study
Reducing therapeutic burden after Safinamide introduction in Parkinson's disease: a longitudinal, retrospective, real-world study
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Original abstract
Abstract Background Parkinson's disease (PD) is a progressive neurodegenerative disorder requiring increasing dopaminergic therapy over time. Prolonged levodopa exposure is associated with motor complications. Strategies are needed to limit dopaminergic dose escalation. Safinamide is a selective reversible MAO-B inhibitor with antiglutamatergic properties approved as add-on therapy for fluctuating PD. However, its impact on longitudinal dopaminergic treatment trajectories in real-world practice remains incompletely defined. Objectives To evaluate longitudinal changes in levodopa equivalent daily dose (LEDD) before and after safinamide initiation in a real-world PD cohort. Methods We conducted a monocentric retrospective longitudinal study including 195 PD patients who initiated safinamide between 2016 and 2024. LEDD was collected across four evaluations (~ 24 months) before and after treatment initiation. Longitudinal trajectories were analysed using linear mixed-effects models with piecewise time parameterization. Adjusted analyses included age, sex, Hoehn&Yahr stage, safinamide titration status, and the interaction between titration and post-initiation time. Results Before safinamide initiation, LEDD increased significantly over time, with an estimated slope of 60.9 mg every 6 months (~ 122 mg/year; p < 0.001). After treatment initiation, the slope of LEDD escalation decreased to 46.4 mg every 6 months (~ 93 mg/year). Patients maintained on safinamide 50 mg showed a lower post-initiation rate of dopaminergic dose increase, whereas those requiring titration to 100 mg exhibited a significantly steeper post-initiation trajectory (interaction p < 0.001). Conclusions In routine clinical practice, safinamide introduction was associated with a slower escalation of dopaminergic therapy. Although limited by the retrospective monocentric design, these findings support a potential role of safinamide in reducing cumulative dopaminergic burden during PD progression.