Increased “Off” Time is Associated with Poorer Clinical and Humanistic Outcomes in Patients with Advancing Parkinson’s Disease: Results From the PROSPECT Observational Study
Pilar Sanchez Alonso1, David Houghton2, Fabienne Ory3, Tomoko Oeda4, Delaram Safarpour5, Lars Bergmann6, Pavnit Kukreja6, Koray Onuk6, siting wang6, Connie Yan6, David Standaert7
1Hospital U. Puerta de Hierro, 2Ochsner Health, 3University Hospital of Toulouse, 4National Hospital Organization Unato, 5Oregon Health and Science University School of Medicine, 6AbbVie, Inc., 7Univ of Alabama - Dept of Neurology
Objective:
Evaluate association of increased “Off” time with clinical and humanistic outcomes in people with advanced Parkinson’s disease (PwP) inadequately managed by oral PD therapies.
Background:
As PD progresses, managing symptoms with oral regimens becomes more challenging. Real-world evidence linking increased “Off” time with worsened motor and non-motor symptoms (NMS) and diminished quality of life (QoL) is limited.
Design/Methods:
The 24-month international, prospective observational PROSPECT study enrolled levodopa-responsive adults (≥30 years) with ≥2.5 “Off” hours/day despite optimized oral PD therapies. Normalized “Off” hours/day were calculated from PD Hauser diaries. Clinical outcomes included morning akinesia, fall incidence, episodes of motor fluctuations/day, NMS, and sleep disturbance. Humanistic outcomes included QoL, activities of daily living, activity impairment, and treatment satisfaction. “Off” time and outcomes were assessed at baseline and every 6 months with data pooled across visits. Associations were analyzed by adjusted logistic and robust linear regressions.
Results:
There were 842 observation visits across 229 PwP, with baseline mean (SD) age of 67.8 (9.4) years, Hoehn & Yahr stage score of 2.3 (0.9), PD duration of 8.7 (5.4) years, and motor fluctuation duration of 6.0 (5.2) years. Mean (SD) “Off” time was 4.4 (2.6) hours, with 74% of observations ≥3 hours/day, suggesting poorly managed PD. Each 1-hour increase in “Off” time raised morning akinesia odds by 37.7% (P<.001). Hourly increases in “Off” time were significantly associated with higher NMSS (worsening NMS), PDSS-2 (poorer sleep quality), PDQ-39 (poorer PD-related QoL), and WPAI (greater activity impairment) scores; more motor fluctuation episodes/day; and lower scores for EQ‑5D‑5L/EQ-VAS (poorer QoL) and TSQM-9 in 2 domains (reduced treatment global satisfaction and perceived treatment effectiveness) (all P<.05).
Conclusions:
Increased “Off” hours/day was associated with worse clinical and humanistic outcomes in a real-world setting of PwP on oral regimens. This highlights the critical need for earlier optimization of PD treatment strategies, including regimens beyond oral therapies.
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