Patient-reported disease burden in the Accelerate Clinical Trials in Charcot-Marie-Tooth Disease Study

T Rehbein; J Purks; N Dilek; S Behrens-Spraggins; J E Sowden; K J Eichinger; ACT‐CMT Study Group; J Burns; D Pareyson; S S Scherer; M M Reilly; M E Shy; M P McDermott; C R Heatwole; D N Herrmann

doi:10.1111/jns.12662

Patient-reported disease burden in the Accelerate Clinical Trials in Charcot-Marie-Tooth Disease Study

J Peripher Nerv Syst. 2024 Oct 10. doi: 10.1111/jns.12662. Online ahead of print.

Authors

T Rehbein¹, J Purks¹, N Dilek¹, S Behrens-Spraggins¹, J E Sowden¹, K J Eichinger¹; ACT‐CMT Study Group; J Burns², D Pareyson³, S S Scherer⁴, M M Reilly⁵, M E Shy⁶, M P McDermott^{1

7

8}, C R Heatwole^{1

8}, D N Herrmann¹

Collaborators

Affiliations

¹ Department of Neurology, University of Rochester School of Medicine, Rochester, New York, USA.
² Sydney School of Health Sciences, University of Sydney, Sydney, Australia.
³ Unit of Rare Neurological Diseases, Department of Clinical Neurosciences, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
⁴ Department of Neurology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
⁵ Centre for Neuromuscular Diseases, Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, University College of London, London, UK.
⁶ Department of Neurology, University of Iowa, Carver School of Medicine, Iowa City, Iowa, USA.
⁷ Department of Biostatistics and Computational Biology, University of Rochester School of Medicine, Rochester, New York, USA.
⁸ The Center for Health and Technology, University of Rochester School of Medicine, Rochester, New York, USA.

PMID: 39390667
DOI: 10.1111/jns.12662

Abstract

Background and aims: The Charcot-Marie-Tooth Disease Health Index (CMT-HI) is a disease-specific, patient-reported disease burden measure. As part of an international clinical trial readiness study, individuals with CMT1A (ages 18-75 years) underwent clinical outcome assessments (COAs), including the CMT-HI, to capture their longitudinal perspective on the disease burden.

Methods: Two hundred and fifteen participants underwent serial COAs including the CMT-HI, CMT Functional Outcome Measure (CMT-FOM), CMT Neuropathy Score (CMTNSv2R), and CMT Exam Score (CMTES/CMTES-R). Correlations between the total and subscale scores for the CMT-HI and other COAs were determined. Changes in the CMT-HI scores over 12 months were assessed using paired t-tests. The minimum clinically important difference (MCID) for the CMT-HI and its subscales were calculated by anchoring to a participant global impression of change scale.

Results: At baseline, CMT1A participants were 44.5 ± 15 years old (range: 18-75) and 58% were women. The mean CMT-HI was 25.7 ± 18.8 (range: 0-91.9; 100 reflecting maximal disease burden). The CMT-HI correlated with the CMT-FOM (r = .54, p < .0001), CMTNSv2R (r = .48, p < .0001), and CMTES/CMTES-R (r = .52/r = .54, p < .0001). Disease burden was greater in women than in men (CMT-HI 29.1 ± 19.1 vs. 21.2 ± 17.3, p = .001). Over 12 months, there was a nonsignificant mean increase in CMT-HI of 0.40 ± 10.0 (n = 189, p = .89). The MCID for the CMT-HI total score was 3.8 points (95% CI: 1.7-5.9).

Discussion: Patient-reported disease burden in CMT1A as measured by the CMT-HI is associated with measures of neurologic impairment and physical functioning. Women reported a higher disease burden than men. These data will inform the design of clinical trials in CMT1A.

Keywords: CMT; CMT HI; CMT Health Index; CMT1A; Charcot–Marie–tooth disease; MCID; clinical trial design; patient‐reported outcomes; quality of life; sex differences.

Grants and funding

#NIH 1U01 NS109403/NH/NIH HHS/United States