Category: Parkinson’s Disease: Clinical Trials
Objective: We used Parkinson Progression Marker Initiative (PPMI) data to assess the frequency of clinically meaningful disease milestones and examine baseline predictors of reaching these milestones.
Background: Assessment of time to clinically relevant milestones could serve as a composite endpoint in clinical trials, and could be implemented in trials including patients receiving dopaminergic treatment.
Method: We measured milestones across six domains – “Walking & Balance”, “Motor Complications”, “Cognitive”, “Autonomic”, “Functional Independence”, & “Functional Activities”. Milestones reflected severe manifestations of a given problem (i.e. a score of 3-4 on relevant UPDRS items). We explored whether metrics within any of the above criteria were met at any visit. Then, we conducted a time-to-event analysis to explore whether baseline factors including demographic factors, clinical features of PD and CSF and imaging biomarkers were associated with progression.
Results: At least one milestone was reached by 44.1% (166/376) of evaluable subjects over 5 years of follow up. The cognitive domain was reached most often (14.1%; 53/376). The functional independence (12.0% 45/376) and autonomic domains (10.9%; 41/376) were the next highest. 82% of subjects who reached a milestone continued to meet outcome criteria at one or more subsequent visits, demonstrating the stability of the milestone-based approach. Clinical features at baseline that predicted reaching at least one milestone included increasing age (p<0.001), greater UPDRS total score (p<0.001) and greater depression score on the GDS-15 (p=0.03). Biomarker predictors of reaching a milestone included decreasing DAT SPECT binding (p=0.0043) and CSF lower total alpha-synuclein (p=0.0033). Dopaminergic treatment was not significantly associated with the likelihood of reaching a milestone (p= 0.16).
Conclusion: Clinically relevant milestones occur frequently within 5 years of follow-up, and are associated with baseline clinical and biological markers, but not significantly associated with dopaminergic treatment. The milestone based outcome could serve as an endpoint in clinical trials.
To cite this abstract in AMA style:
M. Brumm, A. Siderowf, T. Simuni, C. Caspell-Garcia, L. Chahine, T. Foroud, V. Arnedo, A. Reimer, C. Tanner, K. Poston, D. Weintraub, S. Hutten, K. Kieburtz, K. Marek, C. Coffey. A Milestone-based approach to monitoring disease progression in Parkinson’s disease [abstract]. Mov Disord. 2021; 36 (suppl 1). https://www.mdsabstracts.org/abstract/a-milestone-based-approach-to-monitoring-disease-progression-in-parkinsons-disease/. Accessed June 15, 2025.« Back to MDS Virtual Congress 2021
MDS Abstracts - https://www.mdsabstracts.org/abstract/a-milestone-based-approach-to-monitoring-disease-progression-in-parkinsons-disease/