2024 American Academy of Neurology Abstract Website

Anika Varma¹, Shaweta Khosa¹, Jennifer Weinstein¹, Jamison Seabury¹, Spencer Rosero², Charlotte Engebrecht¹, Nuran Dilek³, John Heatwole⁴, Charlotte Irwin¹, Christina Shupe¹, Kaitlin Chung¹, Eileen Sawyer⁵, Asif M Paker⁶, Gregory Brooks⁷, Chan Beals⁷, Rohan Gandhi⁷, Chad Heatwole¹
¹University of Rochester Center for Health + Technology, ²The University of Utah Spencer Fox Eccles School of Medicine, ³Neurology, University of Rochester, ⁴Cornell University, ⁵SwanBio Therapeutics Ltd., ⁶Vertex Pharmaceuticals, ⁷Autobahn Therapeutics

Objective:

To develop and validate the Adrenoleukodystrophy-Health Index (ALD-HI) and Adrenomyeloneuropathy-Health Index (AMN-HI); two novel, patient-reported outcome (PRO) measures designed to measure clinically relevant changes during therapeutic trials for individuals with adrenoleukodystrophy (ALD) and adrenomyeloneuropathy (AMN).

Background:

ALD and AMN are X-linked, neurodegenerative disorders that impact the physical, emotional, social, and disease-specific domains in the patients. The ALD-HI and AMN-HI were developed and validated using large-scale patient-reported data and FDA published guidelines to quantify meaningful changes in disease burden in response to therapeutic intervention in domains of health deemed significant to individuals with ALD and AMN.

Design/Methods:

Semi-structured, qualitative interviews were followed by an international cross-sectional study in adults diagnosed with ALD and/or AMN to identify the most prevalent and impactful symptoms. Following cross-sectional analysis revealing notable differences in symptoms between general ALD and the AMN subtype and expert review, we developed the first versions of ALD-HI and AMN-HI. Beta testing, test-retest reliability evaluations, and factor analysis were conducted to further optimize clarity, usability, meaningfulness, and responsiveness of the ALD-HI and AMN-HI.

Results:

Seventeen individuals with ALD and/or AMN participated in initial qualitative interviews and 109 participants completed the cross-sectional survey. Beta interviews with 31 individuals with ALD and AMN indicated that ALD-HI and AMN-HI were clear, relevant, and easy to use. Test-retest evaluations with 41 participants demonstrated high reliability of the ALD-HI and AMN-HI (ICC = 0.95 and 0.97). The final ALD-HI and AMN-HI yielded high internal consistency scores (Cronbach’s α = 0.98). The ALD-HI contains 20 symptomatic themes and takes an average of 7 minutes to complete. The AMN-HI contains 15 symptomatic themes and takes an average of 9 minutes to complete.

Conclusions:

The ALD-HI and AMN-HI are sensitive, reliable, disease-specific PROs which comprehensively measure patient-reported disease burden for use in clinical monitoring and drug-labeling claims in ALD and AMN.