{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T17:40:19Z","timestamp":1791826819237,"version":"4.3.4"},"reference-count":64,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T00:00:00Z","timestamp":1674604800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["asbmr.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Bone &amp; Mineral Res"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Fibrodysplasia ossificans progressiva (FOP) is an ultra\u2010rare, severely disabling genetic disorder of progressive heterotopic ossification (HO). The single\u2010arm, open\u2010label, phase 3 MOVE trial (NCT03312634) assessed efficacy and safety of palovarotene, a selective retinoic acid receptor gamma agonist, in patients with FOP. Findings were compared with FOP natural history study (NHS; NCT02322255) participants untreated beyond standard of care. Patients aged \u22654\u2009years received palovarotene once daily (chronic: 5\u00a0mg; flare\u2010up: 20\u2009mg for 4\u2009weeks, then 10\u2009mg for \u22658\u2009weeks; weight\u2010adjusted if skeletally immature). The primary endpoint was annualized change in new HO volume versus NHS participants (by low\u2010dose whole\u2010body computed tomography [WBCT]), analyzed using a Bayesian compound Poisson model (BcPM) with square\u2010root transformation. Twelve\u2010month interim analyses met futility criteria; dosing was paused. An independent Data Monitoring Committee recommended trial continuation. Post hoc 18\u2010month interim analyses utilized BcPM with square\u2010root transformation and HO data collapsed to equalize MOVE and NHS visit schedules, BcPM without transformation, and weighted linear mixed\u2010effects (wLME) models, alongside prespecified analysis. Safety was assessed throughout. Eighteen\u2010month interim analyses included 97 MOVE and 101 NHS individuals with post\u2010baseline WBCT. BcPM analyses without transformation showed 99.4% probability of any reduction in new HO with palovarotene versus NHS participants (with transformation: 65.4%). Mean annualized new HO volume was 60% lower in MOVE versus the NHS. wLME results were similar (54% reduction fitted; nominal\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0=\u00a00.039). All palovarotene\u2010treated patients reported \u22651 adverse event (AE); 97.0% reported \u22651 retinoid\u2010associated AE; 29.3% reported \u22651 serious AE, including premature physeal closure (PPC)\/epiphyseal disorder in 21\/57 (36.8%) patients aged &lt;14\u2009years. Post hoc computational analyses using WBCT showed decreased vertebral bone mineral density, content, and strength, and increased vertebral fracture risk in palovarotene\u2010treated patients. Thus, post hoc analyses showed evidence for efficacy of palovarotene in reducing new HO in FOP, but high risk of PPC in skeletally immature patients. \u00a9 2022 The Authors.\n                    <jats:italic>Journal of Bone and Mineral Research<\/jats:italic>\n                    published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).\n                  <\/jats:p>","DOI":"10.1002\/jbmr.4762","type":"journal-article","created":{"date-parts":[[2022,12,30]],"date-time":"2022-12-30T07:51:56Z","timestamp":1672386716000},"page":"381-394","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":70,"title":["Reduction of New Heterotopic Ossification (\n                    <scp>HO<\/scp>\n                    ) in the\n                    <scp>Open\u2010Label<\/scp>\n                    , Phase 3\n                    <scp>MOVE<\/scp>\n                    Trial of Palovarotene for Fibrodysplasia Ossificans Progressiva (\n                    <scp>FOP<\/scp>\n                    )"],"prefix":"10.1093","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8533-9438","authenticated-orcid":false,"given":"Robert J.","family":"Pignolo","sequence":"first","affiliation":[{"name":"Department of Medicine Mayo Clinic  Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward C.","family":"Hsiao","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, the UCSF Metabolic Bone Clinic, the Eli and Edythe Broad Institute for Regeneration Medicine, and the Institute of Human Genetics, Department of Medicine, and the UCSF Program in Craniofacial Biology University of California\u2010San Francisco  San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona","family":"Al Mukaddam","sequence":"additional","affiliation":[{"name":"Departments of Orthopaedic Surgery &amp; Medicine, The Center for Research in FOP and Related Disorders, Perelman School of Medicine University of Pennsylvania  Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genevi\u00e8ve","family":"Baujat","sequence":"additional","affiliation":[{"name":"D\u00e9partement de G\u00e9n\u00e9tique Institut IMAGINE and H\u00f4pital Universitaire Necker\u2010Enfants Malades  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Staffan K.","family":"Berglund","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Pediatrics Ume\u00e5 University  Ume\u00e5 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew A.","family":"Brown","sequence":"additional","affiliation":[{"name":"Faculty of Life Sciences and Medicine King's College London  London UK"},{"name":"Genomics England Ltd  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8332-0744","authenticated-orcid":false,"given":"Angela M.","family":"Cheung","sequence":"additional","affiliation":[{"name":"Department of Medicine and Joint Department of Medical Imaging, University Health Network University of Toronto  Toronto ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"De Cunto","sequence":"additional","affiliation":[{"name":"Pediatric Rheumatology Section, Department of Pediatrics Hospital Italiano de Buenos Aires  Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Delai","sequence":"additional","affiliation":[{"name":"Centro de Pesquisa Clinica Hospital Israelita Albert Einstein  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuhiko","family":"Haga","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine The University of Tokyo Hospital  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Kannu","sequence":"additional","affiliation":[{"name":"Hospital for Sick Children  Toronto ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Keen","sequence":"additional","affiliation":[{"name":"Centre for Metabolic Bone Disease Royal National Orthopaedic Hospital  Stanmore UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim\u2010Hanh","family":"Le Quan Sang","sequence":"additional","affiliation":[{"name":"D\u00e9partement de G\u00e9n\u00e9tique Institut IMAGINE and H\u00f4pital Universitaire Necker\u2010Enfants Malades  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edna E.","family":"Mancilla","sequence":"additional","affiliation":[{"name":"Children's Hospital of Philadelphia, Perelman School of Medicine University of Pennsylvania  Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rose","family":"Marino","sequence":"additional","affiliation":[{"name":"Ipsen  Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Strahs","sequence":"additional","affiliation":[{"name":"Ipsen  Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederick S.","family":"Kaplan","sequence":"additional","affiliation":[{"name":"Departments of Orthopaedic Surgery &amp; 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