{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T03:53:06Z","timestamp":1792641186894,"version":"4.5.0"},"reference-count":17,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2017,10,3]],"date-time":"2017-10-03T00:00:00Z","timestamp":1506988800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100013995","name":"Sanofi Genzyme","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100013995","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2017,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Eliglustat, an oral substrate reduction therapy, is a first\u2010line treatment for adults with Gaucher disease type 1 (GD1) who are poor, intermediate, or extensive CYP2D6 metabolizers (&gt;90% of patients). In the primary analysis of the Phase 3 ENGAGE trial (NCT00891202), eliglustat treatment for 9 months resulted in significant reductions in spleen and liver volumes and increases in hemoglobin concentration and platelet count compared with placebo. We report 18\u2010month outcomes of patients who entered the trial extension period, in which all patients received eliglustat. Of 40 trial patients, 39 entered the extension period, and 38 completed 18 months. Absolute values and percent change over time were determined for spleen and liver volume, hemoglobin concentration, platelet count, bone mineral density, bone marrow burden, and Gaucher disease biomarkers. For patients randomized to eliglustat in the double\u2010blind period, continuing treatment with eliglustat for 9 more months resulted in incremental improvement of all disease parameters. For patients randomized to placebo in the double\u2010blind period, eliglustat treatment during the 9\u2010month, open\u2010label period resulted in significant decrease of spleen and liver volumes and significant increase of hemoglobin and platelets, with a similar rate of change to patients who had received eliglustat in the double\u2010blind period. Eliglustat treatment was also associated with improvement in bone marrow burden score, bone mineral density, and established biomarkers of Gaucher disease, including reduction of the bioactive lipid, glucosylsphingosine. These findings underscore the efficacy of eliglustat in treatment\u2010na\u00efve patients. Eliglustat was well\u2010tolerated, and there were no new safety concerns with longer\u2010term exposure.<\/jats:p>","DOI":"10.1002\/ajh.24877","type":"journal-article","created":{"date-parts":[[2017,8,1]],"date-time":"2017-08-01T09:44:36Z","timestamp":1501580676000},"page":"1170-1176","source":"Crossref","is-referenced-by-count":89,"title":["Outcomes after 18 months of eliglustat therapy in treatment\u2010na\u00efve adults with <scp>G<\/scp>aucher disease type 1: The phase 3 ENGAGE trial"],"prefix":"10.1002","volume":"92","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3447-6421","authenticated-orcid":false,"given":"Pramod K.","family":"Mistry","sequence":"first","affiliation":[{"name":"Department of Internal Medicine and Pediatrics Yale University School of Medicine New Haven CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Lukina","sequence":"additional","affiliation":[{"name":"Department of Orphan Diseases National Research Center for Hematology Moscow Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hadhami","family":"Ben Turkia","sequence":"additional","affiliation":[{"name":"Department of Pediatrics H\u00f4pital La Rabta Tunis Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suma P.","family":"Shankar","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Emory University School of Medicine Atlanta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hagit","family":"Baris","sequence":"additional","affiliation":[{"name":"Raphael Recanati Genetic Institute Rabin Medical Center Petach Tikvah Israel"},{"name":"Sackler Faculty of Medicine Tel Aviv University Tel Aviv Israel"},{"name":"The Genetics Institute, Rambam Health Care Campus and The Ruth and Bruce Rappaport Faculty of Medicine Technion \u2013 Israel Institute of Technology Haifa Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwan","family":"Ghosn","sequence":"additional","affiliation":[{"name":"Department of Hematology\u2010Oncology H\u00f4tel\u2010Dieu de France University Hospital Beirut Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atul","family":"Mehta","sequence":"additional","affiliation":[{"name":"Department of Haematology, The Royal Free Hospital University College London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seymour","family":"Packman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics UCSF School of Medicine San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Pastores","sequence":"additional","affiliation":[{"name":"Department of Neurology and Pediatrics New York University School of Medicine New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milan","family":"Petakov","sequence":"additional","affiliation":[{"name":"Department of Neuroendocrinology, Clinical Center of Serbia Belgrade University Medical School  Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarit","family":"Assouline","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Hematology Jewish General Hospital Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manisha","family":"Balwani","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomic Sciences Icahn School of Medicine at Mt. Sinai Hospital New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumita","family":"Danda","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Christian Medical College Vellore Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evgueniy","family":"Hadjiev","sequence":"additional","affiliation":[{"name":"Medical University \u2010 Sofia, Faculty of Medicine, Department of Internal diseases UMHAT \u201cAlexandrovska\u201d\u2010 Clinic of Hematology Sofia Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andres","family":"Ortega","sequence":"additional","affiliation":[{"name":"OCA Hospital Monterrey Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastiaan J. M.","family":"Gaemers","sequence":"additional","affiliation":[{"name":"Global Pharmacovigilance Sanofi Genzyme Naarden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regina","family":"Tayag","sequence":"additional","affiliation":[{"name":"Prometrika Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Judith","family":"Peterschmitt","sequence":"additional","affiliation":[{"name":"Rare Diseases Clinical Development Sanofi Genzyme Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,10,3]]},"reference":[{"key":"e_1_2_9_2_1","volume-title":"OMMBID: The Online Metabolic and Molecular Bases of Inherited Disease","author":"Grabowski GA","year":"2013"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature21368"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1003308107"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1358\/dof.2010.035.08.1505566"},{"key":"e_1_2_9_6_1","unstructured":"CERDELGA (eliglustat) [package insert]. 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