{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T00:20:05Z","timestamp":1793146805425,"version":"4.5.0"},"reference-count":31,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,9,10]],"date-time":"2023-09-10T00:00:00Z","timestamp":1694304000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>The natural history of Friedreich ataxia is being investigated in a multi\u2010center 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\u2010matched comparison of data from the open\u2010label MOXIe extension (omaveloxolone) to that from FACOMS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Data from the MOXIe extension show that omaveloxolone provided persistent benefit over 3\u2009years 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\u2009=\u2009\u22123.6; nominal <jats:italic>p<\/jats:italic> value\u2009=\u20090.0001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>These results suggest a meaningful slowing of Friedreich ataxia progression with omaveloxolone, and consequently detail how propensity\u2010matched analysis may contribute to understanding of effects of therapeutic agents. This demonstrates the direct value of natural history studies in clinical trial evaluations.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.51897","type":"journal-article","created":{"date-parts":[[2023,9,11]],"date-time":"2023-09-11T05:30:40Z","timestamp":1694410240000},"page":"4-16","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["Propensity matched comparison of omaveloxolone treatment to Friedreich ataxia natural history data"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7168-214X","authenticated-orcid":false,"given":"David R.","family":"Lynch","sequence":"first","affiliation":[{"name":"Departments of Pediatrics and Neurology The Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"},{"name":"Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angie","family":"Goldsberry","sequence":"additional","affiliation":[{"name":"Reata Pharmaceuticals  Dallas Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4911-911X","authenticated-orcid":false,"given":"Christian","family":"Rummey","sequence":"additional","affiliation":[{"name":"Clinical Data Science GmbH  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Farmer","sequence":"additional","affiliation":[{"name":"Friedreich Ataxia Research Alliance  Downingtown Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia","family":"Boesch","sequence":"additional","affiliation":[{"name":"Department of Neurology Medical University Innsbruck  Innsbruck Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin B.","family":"Delatycki","sequence":"additional","affiliation":[{"name":"Victorian Clinical Genetics Services Murdoch Children's Research Institute  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Giunti","sequence":"additional","affiliation":[{"name":"University College London Hospital  Bloomsbury London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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