Abstract Details

Title Re-weighting MDS-UPDRS Motor Items for Optimal Sensitivity to Parkinson’s Disease Progression in Untreated Patients Using Parkinson’s Progression Markers Initiative Data

Topic Movement Disorders

Presentation(s) S2 - Movement Disorders: Epidemiology and Clinical Aspects (1:36 PM-1:48 PM)

Poster/Presentation
Number 004

Background As a complex degenerative disease, Parkinson’s disease (PD) affects motor abilities across diverse domains, even prior to initiation of dopaminergic therapy (DT). This work demonstrates how CS consisting of re-weighted combinations of the items from MDS-UPDRS Parts II and III can better detect meaningful changes in motor progression.

Objective Examine composite scores (CS) of re-weighted combinations the MDS-UPDRS items as a more sensitive measure of meaningful changes in motor progression.

Design/Methods

This study analyzed the Parkinson’s Progression Markers Initiative MDS-UPDRS data Parts II and III in subjects with confirmed PD naïve to DT. Patients were censored from the analysis once DT was initiated. The sensitivity of individual items to disease progression was assessed using partial least square regression. Selected items were weighted using the model coefficients and summed to create the CS. CS responsiveness to change was assessed using a 1-year mean-to-standard-deviation ratio (MSDR).

Results

CS were generated for untreated subjects (n=428) across items from Parts II and III individually, and as a combined motor composite score (MCS). The three most responsive items (with their combined weights) were: turning in bed, getting out of bed/car/chair, and tremor (45%) for Part II, and leg agility (left) and rest tremor amplitude – left and right (34%) for Part III. The MSDRs increased from 0.5431 to 0.5647, and 0.6341 to 0.7040, which increases power 3% and 8%, respectively. Items from Part II and III contributed to 37.4% and 62.6% of the weighed MCS. Similar items were retained in the MCS as in the individual CSs, and the MSDR increased from 0.7615 to 0.8591, increasing power 8%.

Conclusions Endpoints derived from the CS reflecting items from combined domains can measure clinically meaningful progression of motor symptoms and the impacts with greater sensitivity compared to using the totality of items from existing tools.

Authors/Disclosures
Gilbert J. L'Italien PRESENTER	Gilbert J. L'Italien has received personal compensation for serving as an employee of Biohaven Pharmaceuticals. Gilbert J. L'Italien has stock in biohaven pharmaceuticals.
Samuel Dickson (Pentara)	No disclosure on file
Basia Rogula	No disclosure on file
Jordan S. Dubow, MD	Dr. Dubow has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Avadel Pharmaceuticals.
Nick Kozauer (Biohaven Pharmaceuticals)	No disclosure on file
Lauren Powell (Broadstreet HEOR)	No disclosure on file
Michele Potashman, PhD (Biohaven)	Dr. Potashman has received personal compensation for serving as an employee of Biohaven Pharmaceuticals.
Kim Crimin	No disclosure on file
Patrick O'Keefe (Pentara)	No disclosure on file
Ellen Korol (Broadstreet HEOR)	No disclosure on file
Madeleine Crabtree (Broadstreet HEOR)	No disclosure on file
Fernanda Nagase (Broadstreet HEOR)	No disclosure on file
Vladimir Coric	Vladimir Coric has received personal compensation for serving as an employee of Biohaven. Vladimir Coric has received personal compensation in the range of $1,000,000+ for serving as an officer or member of the Board of Directors for Bioahven. Vladimir Coric has stock in Biohaven. Vladimir Coric has received intellectual property interests from a discovery or technology relating to health care.
Suzanne Hendrix, PhD	Dr. Hendrix has received personal compensation for serving as an employee of Pentara Corporation. Dr. Hendrix has received personal compensation in the range of $50,000-$99,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pentara Corporation. Dr. Hendrix has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Pentara Corporation. The institution of Dr. Hendrix has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Pentara Corporation. Dr. Hendrix has stock in Pentara.