Abstract Details

Title The Impact of Antidopaminergic Medication on Longitudinal Clinical Progression in Huntington Disease

Topic Movement Disorders

Presentation(s) P6 - Poster Session 6 (8:00 AM-9:00 AM)

Poster/Presentation
Number 3-003

Objective

To evaluate the association between common concomitant medication use and global clinical progression in early manifest Huntington Disease (HD).

Background

To date, no double-blind clinical trial has assessed the long-term effect of antidopaminergic medications (ADMs) (neuroleptics and VMAT2 inhibitors) on disease progression in HD. Observational studies suggest that these ADMs may adversely affect the rate of HD decline (Harris et al. 2020; Huntington Study Group 2006; and Tedroff et al. 2015).

Design/Methods Rates of progression up to six years were assessed in an early manifest population (TFC >7) from the Enroll-HD database that were either exposed to ADMs or antidepressants at all visits (treatment) or not exposed at any visit (control). Four groups (ADMs n=1706, neuroleptics n=930, VMAT2 inhibitors n=396, and antidepressants n=662) were propensity score matched to their respective control at study entry across 12 covariates.

Results

Participants on ADMs had significantly faster disease progression compared to the control group off ADMs, across multiple measures including total functional capacity (TFC) (p<0.001), symbol digit modalities test (SDMT) (p<0.001), Stroop Word test (SWR) (p<0.001), and the composite UHDRS (cUHDRS) (p<0.001). However, there was no difference in participants using ADMs in progression on total motor score (TMS). Similar results were observed with a 3-year duration, and when assessing the effect of neuroleptics and VMAT2 inhibitors alone, VMAT2 had a larger effect. On TMS subscales, ADM use was associated with improvement on the chorea subscale, however it was also associated with faster progression on bradykinesia (p=0.001) and gate-balance (p<0.001) subscales. Participants on antidepressants showed no difference in progression rate across all outcome measures evaluated.

Conclusions ADM use was associated with accelerated HD progression across multiple measures in this analysis. These results should be considered in the design, conduct and analysis of clinical trials in HD.

Authors/Disclosures
Randal Hand (Prilenia Therapeutics) PRESENTER	Dr. Hand has received personal compensation for serving as an employee of Prilenia Therapeutics.
Michal Geva (Prilenia Therapeutics)	Michal Geva has received personal compensation for serving as an employee of Prilenia Therapeutics. Michal Geva has received intellectual property interests from a discovery or technology relating to health care.
Paul Goldberg	Paul Goldberg has received personal compensation for serving as an employee of Prilenia. Paul Goldberg has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Ionis Pharmaceuticals. Paul Goldberg has stock in Prilenia.
Michael Hayden	Michael Hayden has received personal compensation for serving as an employee of Prilenia Therapeutics. Michael Hayden has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for CAMP4. Michael Hayden has received personal compensation in the range of $50,000-$99,999 for serving as an officer or member of the Board of Directors for AbCellera Biologics Inc.. Michael Hayden has received personal compensation in the range of $50,000-$99,999 for serving as an officer or member of the Board of Directors for Ionis Pharmaceuticals . Michael Hayden has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for 89 Bio. Michael Hayden has received personal compensation in the range of $50,000-$99,999 for serving as an officer or member of the Board of Directors for Oxford Biomedica . Michael Hayden has stock in Ionis Pharmaceuticals. Michael Hayden has stock in AbCellera Biologics Inc.. Michael Hayden has stock in 89 Bio. The institution of Michael Hayden has received research support from Canadian Institutes of Health Research. The institution of Michael Hayden has received research support from National Research Council Canada. The institution of Michael Hayden has received research support from Huntington Society of Canada. The institution of Michael Hayden has received research support from Bev Hartig Huntington Disease Foundation. Michael Hayden has received intellectual property interests from a discovery or technology relating to health care. Michael Hayden has received intellectual property interests from a discovery or technology relating to health care. Michael Hayden has received intellectual property interests from a discovery or technology relating to health care. Michael Hayden has received intellectual property interests from a discovery or technology relating to health care. Michael Hayden has received intellectual property interests from a discovery or technology relating to health care. Michael Hayden has received intellectual property interests from a discovery or technology relating to health care. Michael Hayden has received intellectual property interests from a discovery or technology relating to health care. Michael Hayden has received intellectual property interests from a discovery or technology relating to health care. Michael Hayden has received intellectual property interests from a discovery or technology relating to health care. Michael Hayden has received intellectual property interests from a discovery or technology relating to health care.

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