{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T11:37:02Z","timestamp":1790681822491,"version":"4.1.0"},"reference-count":19,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2024,8,31]],"date-time":"2024-08-31T00:00:00Z","timestamp":1725062400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009857","name":"Regeneron Pharmaceuticals, Inc","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100009857","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,9,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare disorder, characterized by progressive heterotopic ossification (HO) and painful soft-tissue inflammatory flare-ups. This was a post hoc analysis from a phase 2 (NCT03188666) trial in which adults with FOP received intravenous anti-activin A antibody garetosmab 10\u00a0mg\/kg or placebo every 4\u00a0wk over 28\u00a0wk (Period 1), followed by a 28-wk open-label treatment and extension (Periods 2 and 3). Here we describe flare-ups, their relationship to new HO lesions, and the impact of garetosmab on flare-ups. Volume of new HO lesions was measured by CT. Patient-reported flare-ups were defined by any 2 of the following: new onset of pain, swelling, joint stiffness, decrease in movement, or perceived presence of HO. Flare-ups were experienced by 71% (17\/24) of placebo-treated patients, 59% (10\/17) of whom developed a new HO lesion irrespective of flare-up location; 24% of flare-ups location-matched new HO lesions. Twenty-nine new HO lesions occurred in the placebo cohort by week 28, of which 12 (41%) occurred in the same location as new or ongoing flare-ups. A higher volume of newly formed heterotopic bone (week 28) occurred in placebo-treated patients who had experienced a prior flare-up vs those without (median [Q1:Q3] of 16.6 [12.0:31.1] vs 3.2\u00a0cm3). Garetosmab was previously shown to decrease patient-reported flare-up frequency in Period 1; here, garetosmab reduced the median (Q1:Q3) duration of patient-reported flares (15.0 [6.0:82.0] vs 48.0 [15.0:1.00] d) and the severity of flare-ups vs placebo. Frequency of corticosteroid use was numerically reduced in those treated with garetosmab (40.0%) vs placebo (58.3%). In this analysis, 71% of placebo-treated adults with FOP experienced flare-ups over 28\u00a0wk, which were associated with an increased volume of newly formed heterotopic bone. Garetosmab reduced the severity and duration of flare-ups, with effects sustained during the entire trial.<\/jats:p>","DOI":"10.1093\/jbmr\/zjae140","type":"journal-article","created":{"date-parts":[[2024,8,31]],"date-time":"2024-08-31T21:45:23Z","timestamp":1725140723000},"page":"1486-1492","source":"Crossref","is-referenced-by-count":10,"title":["Characterization of flare-ups and impact of garetosmab in adults with fibrodysplasia ossificans progressiva: a post hoc analysis of the randomized, double-blind, placebo-controlled LUMINA-1 trial"],"prefix":"10.1093","volume":"39","author":[{"given":"Richard","family":"Keen","sequence":"first","affiliation":[{"name":"Centre for Metabolic Bone Disease, Royal National Orthopaedic Hospital NHS Trust , London, W1W 5AQ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9980-9138","authenticated-orcid":false,"given":"Kathryn M","family":"Dahir","sequence":"additional","affiliation":[{"name":"Program for Metabolic Bone Disorders, Vanderbilt University Medical Center , Nashville, TN 37232,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"McGinniss","sequence":"additional","affiliation":[{"name":"Medical Affairs , Scientific Communications, , Tarrytown, NY 10591,","place":["United States"]},{"name":"Regeneron Pharmaceuticals, Inc. , Scientific Communications, , Tarrytown, NY 10591,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2998-3202","authenticated-orcid":false,"given":"Robert J","family":"Sanchez","sequence":"additional","affiliation":[{"name":"Medical Affairs , Scientific Communications, , Tarrytown, NY 10591,","place":["United States"]},{"name":"Regeneron Pharmaceuticals, Inc. , Scientific Communications, , Tarrytown, NY 10591,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Mellis","sequence":"additional","affiliation":[{"name":"Medical Affairs , Scientific Communications, , Tarrytown, NY 10591,","place":["United States"]},{"name":"Regeneron Pharmaceuticals, Inc. , Scientific Communications, , Tarrytown, NY 10591,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aris N","family":"Economides","sequence":"additional","affiliation":[{"name":"Medical Affairs , Scientific Communications, , Tarrytown, NY 10591,","place":["United States"]},{"name":"Regeneron Pharmaceuticals, Inc. , Scientific Communications, , Tarrytown, NY 10591,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maja","family":"Di Rocco","sequence":"additional","affiliation":[{"name":"Department of Pediatrics , Unit of Rare Diseases, , Genoa, 16147,","place":["Italy"]},{"name":"IRCCS Istituto Giannina Gaslini , Unit of Rare Diseases, , Genoa, 16147,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Orcel","sequence":"additional","affiliation":[{"name":"Department of Rheumatology - DMU Locomotion, AP-HP Nord - Universit\u00e9 de Paris and INSERM U1132 Bioscar , Paris,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Roux","sequence":"additional","affiliation":[{"name":"Centre d'Evaluation des Maladies Osseuses, Cochin Hospital, Assistance Publique \u2013 H\u00f4pitaux de Paris , 27 Rue du Faubourg Saint-Jacques, Paris, 75014,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacek","family":"Tabarkiewicz","sequence":"additional","affiliation":[{"name":"Centre for Innovative Research in Medical and Natural Sciences, Rzesz\u00f3w University , Rzesz\u00f3w, 35-310,","place":["Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Bachiller-Corral","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Hospital Universitario Ram\u00f3n y Cajal , Madrid, 28034,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela M","family":"Cheung","sequence":"additional","affiliation":[{"name":"Department of Medicine and Joint Department of Medical Imaging , University Health Network, , Toronto, ON, M5S 1A1,","place":["Canada"]},{"name":"University of Toronto , University Health Network, , Toronto, ON, M5S 1A1,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona","family":"Al Mukaddam","sequence":"additional","affiliation":[{"name":"Departments of Orthopaedics , Medicine and the Center for Research in FOP & Related Disorders, , Philadelphia, PA 19104,","place":["United States"]},{"name":"University of Pennsylvania Perelman School of Medicine , Medicine and the Center for Research in FOP & Related Disorders, , Philadelphia, PA 19104,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kusha","family":"Mohammadi","sequence":"additional","affiliation":[{"name":"Medical Affairs , Scientific Communications, , Tarrytown, NY 10591,","place":["United States"]},{"name":"Regeneron Pharmaceuticals, Inc. , Scientific Communications, , Tarrytown, NY 10591,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Gu","sequence":"additional","affiliation":[{"name":"Medical Affairs , Scientific Communications, , Tarrytown, NY 10591,","place":["United States"]},{"name":"Regeneron Pharmaceuticals, Inc. , Scientific Communications, , Tarrytown, NY 10591,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dushyanth","family":"Srinivasan","sequence":"additional","affiliation":[{"name":"Medical Affairs , Scientific Communications, , Tarrytown, NY 10591,","place":["United States"]},{"name":"Regeneron Pharmaceuticals, Inc. , Scientific Communications, , Tarrytown, NY 10591,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5862-403X","authenticated-orcid":false,"given":"Dinko Gonzalez","family":"Trotter","sequence":"additional","affiliation":[{"name":"Medical Affairs , Scientific Communications, , Tarrytown, NY 10591,","place":["United States"]},{"name":"Regeneron Pharmaceuticals, Inc. , Scientific Communications, , Tarrytown, NY 10591,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E Marelise W","family":"Eekhoff","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Amsterdam University Medical Centers (UMC), Vrije Universiteit, Amsterdam UMC Expert Center in Rare Bone Disease, Amsterdam Reproduction & Development , Amsterdam, 1081 HV,","place":["Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederick S","family":"Kaplan","sequence":"additional","affiliation":[{"name":"Departments of Orthopaedics , Medicine and the Center for Research in FOP & Related Disorders, , Philadelphia, PA 19104,","place":["United States"]},{"name":"University of Pennsylvania Perelman School of Medicine , Medicine and the Center for Research in FOP & Related Disorders, , Philadelphia, PA 19104,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J","family":"Pignolo","sequence":"additional","affiliation":[{"name":"Department of Medicine, Mayo Clinic , Rochester, MN 55905,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,8,31]]},"reference":[{"issue":"1","key":"2024101712270723300_ref1","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1186\/s13023-017-0674-5","article-title":"Prevalence of fibrodysplasia ossificans progressiva (FOP) in France: an estimate based on a record linkage of two national databases","volume":"12","author":"Baujat","year":"2017","journal-title":"Orphanet J Rare Dis"},{"issue":"4","key":"2024101712270723300_ref2","doi-asserted-by":"publisher","first-page":"748","DOI":"10.1016\/j.bone.2012.07.002","article-title":"Fibrodysplasia ossificans progressiva in Spain: epidemiological, clinical, and genetic aspects","volume":"51","author":"Morales-Piga","year":"2012","journal-title":"Bone"},{"issue":"2","key":"2024101712270723300_ref3","doi-asserted-by":"publisher","first-page":"31","DOI":"10.29245\/2572-9411\/2020\/2.1196","article-title":"Epidemiology of the 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