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

Background: The UHDRS-TMS is a widely used outcome measure for motor function in HD studies. Understanding the temporal course of the UHDRS-TMS is critical for clinical care and future trial design.

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-TMS over time. Analyses for the clinical trials were limited to participants randomized to receive placebo. The follow-up period for TREND-HD (n=156) and HORIZON (n=183) was 6 months, and for HART (n=56) was 3 months. The COHORT study included 334 participants with clinically manifest HD followed for at least 3 years. Mean changes in UHDRS-TMS 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 Total Functional Capacity score (<7, 7-9, 10-12, 13).

Results: Rates based on clinical trial data ranged from a mean (SE) worsening in UHDRS-TMS of 0.51 (0.33) to 0.68 (0.29) points (TREND-HD and HORIZON) to an improvement of 1.45 (1.03) points (HART) per 3 months. The COHORT study demonstrated a mean (SE) worsening in UHDRS-TMS of 0.74 (0.06) points per 3 months. UHDRS-TMS scores by Total Functional Capacity quartile generally worsened monotonically over time, except within the HART study which showed monotonic improvement within each quartile.

Conclusions: The degree of UHDRS-TMS worsening in the clinical trials was comparable to that observed in the observational study, although the HART study demonstrated an improvement over a 3 month period. This improvement may be attributable to placebo effect, the shorter duration of the trial, and the smaller sample size. This analysis adds to the existing natural history information about the UHDRS-TMS in HD and may be used to support future study designs, especially study duration and sample size estimates.

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