{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T06:08:27Z","timestamp":1793858907721,"version":"4.6.1"},"reference-count":33,"publisher":"BMJ","issue":"7","license":[{"start":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T00:00:00Z","timestamp":1671580800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015362","name":"Amicus Therapeutics","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015362","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2022,11,11]]},"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Fabry disease is a rare, multisystemic disorder caused by\n                      <jats:italic>GLA<\/jats:italic>\n                      gene variants that lead to alpha galactosidase A deficiency, resulting in accumulation of glycosphingolipids and cellular dysfunction. Fabry-associated clinical events (FACEs) cause significant morbidity and mortality, yet the long-term effect of Fabry therapies on FACE incidence remains unclear.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This\n                      <jats:italic>posthoc<\/jats:italic>\n                      analysis evaluated incidence of FACEs (as a composite outcome and separately for renal, cardiac and cerebrovascular events) in 97 enzyme replacement therapy (ERT)-na\u00efve and ERT-experienced adults with Fabry disease and amenable\n                      <jats:italic>GLA<\/jats:italic>\n                      variants who were treated with migalastat for up to 8.6 years (median: 5 years) in Phase III clinical trials of migalastat. Associations between baseline characteristics and incidence of FACEs were also evaluated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>During long-term migalastat treatment, 17 patients (17.5%) experienced 22 FACEs and there were no deaths. The incidence rate of FACEs was 48.3 events per 1000 patient-years overall. Numerically higher incidence rates were observed in men versus women, patients aged &gt;40 years versus younger patients, ERT-na\u00efve versus ERT-experienced patients and men with the classic phenotype versus men and women with all other phenotypes. There was no statistically significant difference in time to first FACE when analysed by patient sex, phenotype, prior treatment status or age. Lower baseline estimated glomerular filtration rate (eGFR) was associated with an increased risk of FACEs across patient populations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The overall incidence of FACEs for patients during long-term treatment with migalastat compared favourably with historic reports involving ERT. Lower baseline eGFR was a significant predictor of FACEs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jmg-2022-108669","type":"journal-article","created":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T13:20:20Z","timestamp":1671628820000},"page":"722-731","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":37,"title":["Long-term multisystemic efficacy of migalastat on Fabry-associated clinical events, including renal, cardiac and cerebrovascular outcomes"],"prefix":"10.1136","volume":"60","clinical-trial-number":[{"clinical-trial-number":"nct01218659","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct00925301","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct00925301","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct01218659","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct01458119","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct02194985","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4531-9173","authenticated-orcid":false,"given":"Derralynn A","family":"Hughes","sequence":"first","affiliation":[{"name":"Lysosomal Storage Disorders Unit, Royal Free London NHS Foundation Trust and University College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel G","family":"Bichet","sequence":"additional","affiliation":[{"name":"H\u00f4pital du Sacr\u00e9 Coeur, University of Montr\u00e9al, Montr\u00e9al, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Giugliani","sequence":"additional","affiliation":[{"name":"Medical Genetics Service, HCPA, Department of Genetics, UFRGS, DASA and INAGEMP, Porto Alegre, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J","family":"Hopkin","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, College of Medicine, Department of Pediatrics, Cincinnati Children\u2019s Hospital and University of Cincinnati, Cincinnati, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Krusinska","sequence":"additional","affiliation":[{"name":"Clinical Development, Amicus Therapeutics Inc, Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"Nicholls","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iacopo","family":"Olivotto","sequence":"additional","affiliation":[{"name":"Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5903-3355","authenticated-orcid":false,"given":"Ulla","family":"Feldt-Rasmussen","sequence":"additional","affiliation":[{"name":"Department of Medical Endocrinology and Metabolism, Rigshospitalet, National University Hospital, Copenhagen University, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norio","family":"Sakai","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Osaka 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