Treatment stability comparison among different ADD-ON therapies in fluctuating Parkinson’s disease patients: the role of clinical and demographic factors

Introduction: Motor fluctuations represent a major challenge in Parkinson’s disease (PD) management. To address them, ADD-ON therapies with monoamine oxidase type B (MAO-B) and catechol-O-methyl transferase (COMT) inhibitors are used to enhance and prolong dopaminergic effects of levodopa, thereby improving motor fluctuations. Despite widespread use, real-life comparative data remain limited. Methods: We performed a retrospective, longitudinal study including PD patients referred to two Italian tertiary movement disorder centers. Patients with motor fluctuations requiring ADD-ON therapy (selegiline [SL], rasagiline [RS], safinamide [SF], or opicapone [OP]) and ≥ 12 months of follow-up were included. The primary outcome was treatment stability, defined as months without significant therapy modifications or ADD-ON discontinuation. Secondary outcomes included levodopa dosage changes, initiation of other antiparkinsonian therapies, and ADD-ON discontinuation rates. Cox regression models and Kaplan–Meier survival analyses evaluated the influence of ADD-ON type and clinical-demographic variables on treatment stability. Results: We analyzed 169 patients (SL = 20; RS = 26; SF = 78; OP = 45). Groups differed in age at ADD-ON initiation (p = 0.020; RS > OP), disease duration (p = 0.002; OP > RS and SF), and baseline levodopa equivalent daily dose (p = 0.003; SF and OP > RS). No significant differences in treatment stability were found between groups (p = 0.29). SF group showed higher levodopa increases (p = 0.02) and initiation of new therapies (p = 0.02). ADD-ON discontinuation occurred in 23.1% of patients, mainly due to AEs (16.6%). Cox regression showed no significant predictors of treatment stability. Conclusions: All ADD-ON therapies showed comparable treatment stability and tolerability. No statistically significant sex-related differences were observed, although a trend toward more frequent therapy modifications was found in female patients.