Objective: To describe the temporal course of Huntington disease (HD) chorea using the total maximal chorea score of the Unified Huntington Disease Rating Scale – Total Motor Score (UHDRS-TMS) in existing observational and randomized, placebo-controlled clinical trial datasets.

Background: Understanding the temporal course of UHDRS chorea score would provide important insight on motor symptom progression that could inform future trial design and improve patient care.

Methods: Three Huntington Study Group-sponsored, completed clinical trials in adults with mild to moderate HD and one observational study were used to describe the mean change in UHDRS chorea scores over time. Analyses for the clinical trials were limited to participants randomized to receive placebo. The follow-up period was 6 months for TREND-HD (n=156) and HORIZON (n=183) and 3 months for HART (n=56).The COHORT study included 334 participants with clinically manifest HD followed for at least 3 years. Mean changes in chorea scores are described per 3 months to allow comparisons across the various study durations. Separate mixed effects models were used to estimate changes over time for each study. Results are stratified by baseline functional status using quartiles of UHDRS Total Functional Capacity score (<7, 7-9, 10-12, 13).

Results: Of the clinical trials, HORIZON had a mean (SE) chorea score worsening of 0.05 (0.12) points per 3 months while TREND-HD and HART showed chorea score improvements of 0.24 (0.12) and 0.33 (0.46) points per 3 months respectively. The COHORT study demonstrated a UHDRS chorea score worsening of 0.08 (0.02) points per 3 months. A linear relationship between rate of chorea score worsening and Total Functional Capacity was seen in COHORT (p=0.001). However, this relationship was not seen for any clinical trials (all p>0.05).

Conclusions: Chorea score changes over 3 months were modest and highly variable within and between studies. The chorea score improvement evidenced in TREND-HD and HART, both of which were using UHDRS-TMS as a primary outcome measure, may be due to placebo effect and potential effects of participation in a clinical trial relative to routine care. The relationship between chorea score and Total Functional Capacity is worth further exploration in attempts to better understand natural history of chorea and its impact on function.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/temporal-course-of-the-uhdrs-chorea-score-in-huntington-disease/