Category: Huntington's Disease
Objective: To establish a minimal clinically important difference (MCID) for the Unified Huntington Disease Rating Scale (UHDRS®) Total Maximal Chorea (TMC) score as a measure of chorea severity in Huntington disease (HD), using data from KINECTTM-HD (NCT04102579), a 12-week, phase 3 trial of valbenazine (VBZ) in adults with HD-related chorea.
Background: In KINECT-HD, the efficacy of VBZ was demonstrated by the least squares mean (LSM) change from screening/baseline in TMC score, which was significantly better with VBZ versus placebo (PBO) at Wk10/12 (prespecified primary endpoint). Currently, no MCID has been established for the TMC score in patients with HD-related chorea.
Method: Anchor-based analyses were performed to identify MCID thresholds for TMC score (range, 0 to 28). MCID was defined as the mean of within-subject TMC score change that corresponded to a 1-point improvement in the Clinical Global Impression of Severity (CGI-S: range, 1 [normal, not at all ill] to 7 [extremely ill]) or Patient Global Impression of Severity (PGI-S: range, 1 [none] to 5 [very severe]). MCID analyses included all assessment data regardless of treatment. Results are presented for responders, defined as participants who had a CGI-S or PGI-S score change <0 at Wk12.
Results: 46 participants (VBZ=30, PBO=16) had a CGI-S score change <0 at Wk12 and were considered responders for analysis; 63 (VBZ=26, PBO=37) were considered non-responders. Based on 34 responders who had a 1-point reduction on the CGI-S, the MCID for TMC was -4.0. 33 participants (VBZ=22, PBO=11) had a PGI-S score <0 at Wk12 and were considered responders; 76 (VBZ=34, PBO=42) were non-responders. Based on 22 responders who had a 1-point reduction on the PGI-S, the MCID for TMC was ‑4.3. Per these anchor-based results, the LSM change of -4.6 found for VBZ on the primary endpoint exceeded the MCID. In addition, 57% of participants in the VBZ group had ≥4-point reduction in TMC compared to 20% in the PBO group.
Conclusion: Data from KINECT-HD suggest that a change in UHDRS® TMC score of -4.0 (CGI-S anchor) or -4.3 (PGI-S anchor) corresponds to a minimal clinically meaningful TMC improvement in patients with HD-related chorea. These MCID thresholds were exceeded by the LSM change of -4.6 for VBZ in the primary endpoint, and substantially more VBZ-treated participants had a ≥4-point change in TMC (57% vs 20% for PBO).
To cite this abstract in AMA style:
E. Furr Stimming, D. Claassen, E. Kayson, J. Goldstein, H. Zhang, O. Klepitskaya, G. Liang, D. Haubenberger. A minimal clinically important difference for UHDRS® Total Maximal Chorea score as a measure of chorea severity in Huntington disease [abstract]. Mov Disord. 2023; 38 (suppl 1). https://www.mdsabstracts.org/abstract/a-minimal-clinically-important-difference-for-uhdrs-total-maximal-chorea-score-as-a-measure-of-chorea-severity-in-huntington-disease/. Accessed May 14, 2025.« Back to 2023 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/a-minimal-clinically-important-difference-for-uhdrs-total-maximal-chorea-score-as-a-measure-of-chorea-severity-in-huntington-disease/