{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T22:05:02Z","timestamp":1791669902921,"version":"4.3.4"},"reference-count":16,"publisher":"American Medical Association (AMA)","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Neurol"],"published-print":{"date-parts":[[2022,10,1]]},"abstract":"\n Importance<\/jats:title>\n Corticosteroidal anti-inflammatory drugs are widely prescribed but long-term use shows adverse effects that detract from patient quality of life.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To determine if vamorolone, a structurally unique dissociative steroidal anti-inflammatory drug, is able to retain efficacy while reducing safety concerns with use in Duchenne muscular dystrophy (DMD).<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n Randomized, double-blind, placebo- and prednisone-controlled 24-week clinical trial, conducted from June 29, 2018, to February 24, 2021, with 24 weeks of follow-up. This was a multicenter study (33 referral centers in 11 countries) and included boys 4 to younger than 7 years of age with genetically confirmed DMD not previously treated with corticosteroids.<\/jats:p>\n <\/jats:sec>\n \n Interventions<\/jats:title>\n The study included 4 groups: placebo; prednisone, 0.75 mg\/kg per day; vamorolone, 2 mg\/kg per day; and vamorolone, 6 mg\/kg per day.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n Study outcomes monitored (1) efficacy, which included motor outcomes (primary: time to stand from supine velocity in the vamorolone, 6 mg\/kg per day, group vs placebo; secondary: time to stand from supine velocity [vamorolone, 2 mg\/kg per day], 6-minute walk distance, time to run\/walk 10 m [vamorolone, 2 and 6 mg\/kg per day]; exploratory: NorthStar Ambulatory Assessment, time to climb 4 stairs) and (2) safety, which included growth, bone biomarkers, and a corticotropin (ACTH)\u2013challenge test.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Among the 133 boys with DMD enrolled in the study (mean [SD] age, 5.4 [0.9] years), 121 were randomly assigned to treatment groups, and 114 completed the 24-week treatment period. The trial met the primary end point for change from baseline to week 24 time to stand velocity for vamorolone, 6 mg\/kg per day (least-squares mean [SE] velocity, 0.05 [0.01] m\/s vs placebo \u22120.01 [0.01] m\/s; 95% CI, 0.02-0.10;\n P<\/jats:italic>\n \u2009=\u2009.002) and the first 4 sequential secondary end points: time to stand velocity, vamorolone, 2 mg\/kg per day, vs placebo; 6-minute walk test, vamorolone, 6 mg\/kg per day, vs placebo; 6-minute walk test, vamorolone, 2 mg\/kg per day, vs placebo; and time to run\/walk 10 m velocity, vamorolone, 6 mg\/kg per day, vs placebo. Height percentile declined in prednisone-treated (not vamorolone-treated) participants (change from baseline [SD]: prednisone, \u22121.88 [8.81] percentile vs vamorolone, 6 mg\/kg per day, +3.86 [6.16] percentile;\n P<\/jats:italic>\n \u2009=\u2009.02). Bone turnover markers declined with prednisone but not with vamorolone. Boys with DMD at baseline showed low ACTH-stimulated cortisol and high incidence of adrenal insufficiency. All 3 treatment groups led to increased adrenal insufficiency.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n In this pivotal randomized clinical trial, vamorolone was shown to be effective and safe in the treatment of boys with DMD over a 24-week treatment period. Vamorolone may be a safer alternative than prednisone in this disease, in which long-term corticosteroid use is the standard of care.<\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n ClinicalTrials.gov Identifier:\n NCT03439670<\/jats:ext-link>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamaneurol.2022.2480","type":"journal-article","created":{"date-parts":[[2022,8,29]],"date-time":"2022-08-29T11:32:00Z","timestamp":1661772720000},"page":"1005","source":"Crossref","is-referenced-by-count":145,"title":["Efficacy and Safety of Vamorolone vs Placebo and Prednisone Among Boys With Duchenne Muscular Dystrophy"],"prefix":"10.1001","volume":"79","author":[{"given":"Michela","family":"Guglieri","sequence":"first","affiliation":[{"name":"John Walton Muscular Dystrophy Research Centre, Newcastle Hospitals NHS Foundation Trust and Newcastle University, Newcastle, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula R.","family":"Clemens","sequence":"additional","affiliation":[{"name":"University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seth J.","family":"Perlman","sequence":"additional","affiliation":[{"name":"University of Washington School of Medicine, Seattle"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward C.","family":"Smith","sequence":"additional","affiliation":[{"name":"Duke University School of Medicine, Durham, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iain","family":"Horrocks","sequence":"additional","affiliation":[{"name":"Royal Hospital for Children, Glasgow, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard S.","family":"Finkel","sequence":"additional","affiliation":[{"name":"Nemours Children\u2019s Hospital, Orlando, Florida"},{"name":"St Jude Children\u2019s Research Hospital, Memphis, 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