Abstract
Objective: To enhance interpretation of change on the composite Unified Huntington’s Disease Rating Scale (cUHDRS).
Background: The cUHDRS was developed to assess disease progression in early-to-moderate manifest Huntington’s disease (HD). It consists of four assessments: Total Functional Capacity, Total Motor Score, Symbol Digit Modalities Test and Stroop Word Reading. Composite endpoints can be difficult to interpret; thus, qualitative and quantitative evidence was generated to aid interpretation of cUHDRS clinically meaningful change.
Design/Methods: Qualitative evidence was reviewed to identify the importance of the concepts measured by each individual scale. This included a targeted literature review and patient/caregiver interviews. To better understand the relative contribution of each scale, meaningful change estimates were produced for each constituent measure, using a 1-category worsening on the CGI-S over 12 months (REGISTRY), and was compared to the denominators of the z-scores used in the cUHDRS scoring algorithm. To demonstrate how the cUHDRS score relates to daily functional ability, cUHDRS scores across manifest HD patients were split into deciles and the proportion of patients achieving each item on the Functional Assessment was calculated (ENROLL-HD). Finally, meaningful within-patient change estimates (over 12 months) were produced for the cUHDRS using 1-category worsening on CGI-S (REGISTRY) and a decline of 10 points on Independence Scale (ENROLL-HD) as anchors.
Results: Qualitative evidence highlights the importance to patients and their families of cognitive and motor impairments, and loss of daily functional ability resulting from HD. Meaningful change estimates for the individual scales have a similar ratio to the denominators used to create z-scores. A strong relationship between cUHDRS and functional ability was demonstrated. Triangulation of meaningful change estimates produced a value of 1.2.
Conclusions: The cUHDRS score uses logical weighting for its constituent scales and produces a score that associates strongly with functional ability. A worsening of 1.2 points can be considered clinically meaningful.
Disclosure: Dr. Trundell has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Roche Products Ltd. Dr. Palermo has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with F. Hoffmann–LaRoche. Dr. Schobel has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with F. Hoffmann-La Roche Ltd. Dr. Schobel holds stock and/or stock options in F. Hoffmann-La Roche Ltd. Dr. Long has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with: Wave Life Sciences USA Inc, Vaccinex Inc., Azevan Pharmaceuticals Inc., F. Hoffmann-La Roche Ltd, HSG (for uniQure biopharma B.V.), and Mitoconix Bio Limited.. Dr. Leavitt has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Roche, Teva, uniQure, Nuredis, PTC, sRNAlytics, and Ionis Pharmaceuticals. Dr. Leavitt has received personal compensation in an editorial capacity for Journal of Huntington’s Disease. Dr. Leavitt has received research support from Teva Pharmaceuticals, uniQure, and Nuredis Pharmaceuticals . Dr. Tabrizi has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Through the offices of UCL Consultants Ltd, a wholly owned subsidiary of University College London, Sarah has undertaken advisory board consultancy services for Teva pharmaceuticals to assess PRIDE-HD study results and the Pridopidine Phase 3 trial design. Dr. Tabrizi has received research support from Through the offices of UCL Consultants Ltd, a wholly owned subsidiary of University College London, Sarah has undertaken consultancy services for Ixitech Limited a company subcontracted by Teva to perform imaging analysis of the LEGATO-HD Trial.
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