Impact of Uncontrolled Motor Fluctuations in Parkinson’s Disease: Real-World Insights from the PROSPECT Observational Study

Limited real-world data exist around the long-term impact of uncontrolled motor fluctuations in Parkinson’s disease (PD). With this first-ever, prospective, observational study, we sought to describe real-world treatment patterns and longitudinal outcomes of patients with PD and motor fluctuations inadequately controlled by oral medications. PROSPECT was a 24-month multicountry observational study that included 229 adults with idiopathic PD and uncontrolled motor fluctuations (≥ 2.5 h/day “off” time) on optimized oral PD medications who were device-aided therapy-naive. Treatment modifications, including adding device-aided therapy, were made as part of routine clinical care and were not assigned by the study. Assessments included change from baseline (CFB) in motor and non-motor symptoms, activities of daily living (ADL; MDS-UPDRS Part II), and quality of life (QoL; EQ-5D-5L, PDQ-39). Outcomes were adjusted for baseline differences using linear regression. Subgroup analyses were performed among those who remained on oral PD medications only and those who initiated device-aided therapy. Most patients (80.3%, n = 184) remained solely on oral PD medications due to clinician not offering or patient refusal, and showed a small reduction in "off" time (CFB − 0.7 h/day, p = .006) at 24 months, with nominal decline in ADL (CFB = 1.5, p = .010) and QoL (PDQ-39 CFB = 2.6, p = .010; EQ-5D-5L CFB = − 0.04, p = .017). Approximately half (49.8%, n = 114) were offered device-aided therapy, of whom 44.7% ( n = 51/114) declined, mainly citing needing time to decide or perception as unnecessary. Patients who initiated device-aided therapy (19.7%, n = 45) showed a meaningful "off" time reduction (CFB = − 2.2 h/day, p < .0001) and no change in ADL and QoL at 24 months, versus slight worsening with oral medications only. Despite device-aided therapy eligibility, most patients with PD remained exclusively on oral medications. Device-aided therapy initiation was associated with improved motor symptoms, while those who remained on oral medications showed no meaningful change.