Journal article
Propensity matched comparison of omaveloxolone treatment to Friedreich ataxia natural history data
Annals of clinical and translational neurology, Vol.11(1), pp.4-16
01/2024
DOI: 10.1002/acn3.51897
PMCID: PMC10791025
PMID: 37691319
Abstract
Abstract Objective The natural history of Friedreich ataxia is being investigated in a multi‐center longitudinal study designated the Friedreich ataxia Clinical Outcome Measures Study (FACOMS). To understand the utility of this study in analysis of clinical trials, we performed a propensity‐matched comparison of data from the open‐label MOXIe extension (omaveloxolone) to that from FACOMS. Methods MOXIe extension patients were matched to FACOMS patients using logistic regression to estimate propensity scores based on multiple covariates: sex, baseline age, age of onset, baseline modified Friedreich Ataxia Rating scale (mFARS) score, and baseline gait score. The change from baseline in mFARS at Year 3 for the MOXIe extension patients compared to the matched FACOMS patients was analyzed as the primary efficacy endpoint using mixed model repeated measures analysis. Results Data from the MOXIe extension show that omaveloxolone provided persistent benefit over 3 years when compared to an untreated, matched cohort from FACOMS. At each year, in all analysis populations, patients in the MOXIe extension experienced a smaller change from baseline in mFARS score than matched FACOMS patients. In the primary pooled population (136 patients in each group) by Year 3, patients in the FACOMS matched set progressed 6.6 points whereas patients treated with omaveloxolone in MOXIe extension progressed 3 points (difference = −3.6; nominal p value = 0.0001). Interpretation These results suggest a meaningful slowing of Friedreich ataxia progression with omaveloxolone, and consequently detail how propensity‐matched analysis may contribute to understanding of effects of therapeutic agents. This demonstrates the direct value of natural history studies in clinical trial evaluations.
Details
- Title: Subtitle
- Propensity matched comparison of omaveloxolone treatment to Friedreich ataxia natural history data
- Creators
- David R. Lynch - Children's Hospital of PhiladelphiaAngie Goldsberry - Reata Pharmaceuticals (United States)Christian Rummey - Swiss Data Science CenterJennifer Farmer - Friedreich's Ataxia Research AllianceSylvia Boesch - Innsbruck Medical UniversityMartin B. Delatycki - Victorian Clinical Genetics ServicesPaola Giunti - Royal London HospitalJ. Chad Hoyle - The Ohio State UniversityCaterina Mariotti - Fondazione IRCCS Istituto Neurologico Carlo BestaKatherine D. Mathews - University of IowaWolfgang Nachbauer - Innsbruck Medical UniversitySusan Perlman - University of California, Los AngelesS.H. Subramony - University of Florida Health Science CenterGeorge Wilmot - Emory UniversityTheresa Zesiewicz - University of South FloridaLisa Weissfeld - Statistics CollaborativeColin Meyer - Reata Pharmaceuticals (United States)
- Resource Type
- Journal article
- Publication Details
- Annals of clinical and translational neurology, Vol.11(1), pp.4-16
- DOI
- 10.1002/acn3.51897
- PMID
- 37691319
- PMCID
- PMC10791025
- NLM abbreviation
- Ann Clin Transl Neurol
- ISSN
- 2328-9503
- eISSN
- 2328-9503
- Language
- English
- Electronic publication date
- 09/10/2023
- Date published
- 01/2024
- Academic Unit
- Neurology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Neurology (Pediatrics)
- Record Identifier
- 9984464480702771
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