{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:22:56Z","timestamp":1791332576886,"version":"4.3.1"},"reference-count":25,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,2,2]],"date-time":"2016-02-02T00:00:00Z","timestamp":1454371200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002491","name":"Bristol-Myers Squibb","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002491","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004323","name":"Amylin Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004323","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UL1TR000433"],"award-info":[{"award-number":["UL1TR000433"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2016,7]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Recombinant human leptin (metreleptin) improves glycaemia and hypertriglyceridaemia in patients with generalized lipodystrophy; antibody development with\n                      <jats:italic>in vitro<\/jats:italic>\n                      neutralizing activity has been reported. We aimed to characterize antimetreleptin antibody development, including\n                      <jats:italic>in vitro<\/jats:italic>\n                      neutralizing activity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>Two randomized controlled studies in patients with obesity (twice\u2010daily metreleptin \u00b1 pramlintide for 20\u201352 weeks; 2006\u20132009); two long\u2010term, open\u2010label studies in patients with lipodystrophy (once\u2010daily or twice\u2010daily metreleptin for 2 months to 12\u00b73 years; 2000\u20132014).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients<\/jats:title>\n                    <jats:p>\n                      A total of 579 metreleptin\u2010treated patients with obesity and 134 metreleptin\u2010treated patients with lipodystrophy (antibody\/neutralizing activity data:\n                      <jats:italic>n<\/jats:italic>\n                      = 105).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements<\/jats:title>\n                    <jats:p>\n                      Antimetreleptin antibodies,\n                      <jats:italic>in vitro<\/jats:italic>\n                      neutralizing activity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Antimetreleptin antibodies developed in most patients (obese: 96\u2013100%; lipodystrophy: 86\u201392%). Peak antibody titers (approximately 1:125 to 1:3125) generally occurred within 4\u20136 months and decreased with continued therapy (lipodystrophy). Antibody development did not adversely impact efficacy or safety (patients with obesity), except for inflammatory injection site reactions, but was associated with elevated leptin concentrations. Three patients with obesity developed\n                      <jats:italic>in vitro<\/jats:italic>\n                      neutralizing activity coincident with weight gain. Weight later returned to baseline in one patient despite persistent neutralizing activity. Four patients with generalized lipodystrophy developed\n                      <jats:italic>in vitro<\/jats:italic>\n                      neutralizing activity concurrent with worsened metabolic control; two with confounding comorbidities had sepsis. One patient with lipodystrophy had resolution of neutralizing activity on metreleptin.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Development of\n                      <jats:italic>in vitro<\/jats:italic>\n                      neutralizing activity could be associated with loss of efficacy but has not been consistently associated with adverse clinical consequences. Whether neutralization of endogenous leptin with clinical consequences occurs remains unclear.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cen.12980","type":"journal-article","created":{"date-parts":[[2015,11,21]],"date-time":"2015-11-21T06:28:41Z","timestamp":1448087321000},"page":"137-149","source":"Crossref","is-referenced-by-count":68,"title":["Immunogenicity associated with metreleptin treatment in patients with obesity or lipodystrophy"],"prefix":"10.1111","volume":"85","author":[{"given":"Jean L.","family":"Chan","sequence":"first","affiliation":[{"name":"Bristol\u2010Myers Squibb Princeton NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joy","family":"Koda","sequence":"additional","affiliation":[{"name":"Bristol\u2010Myers Squibb Princeton NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph S.","family":"Heilig","sequence":"additional","affiliation":[{"name":"AstraZeneca San Diego CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine K.","family":"Cochran","sequence":"additional","affiliation":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip","family":"Gorden","sequence":"additional","affiliation":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elif A.","family":"Oral","sequence":"additional","affiliation":[{"name":"Division of Metabolism, Endocrinology &amp; Diabetes (MEND) University of Michigan Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca J.","family":"Brown","sequence":"additional","affiliation":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,2,2]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/372425a0"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-14-0405"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.282.16.1568"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/oby.2009.184"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0706473105"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.4158\/EP09154.RA"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra025261"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-1159"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.4158\/EP11229.OR"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-009-1502-9"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.54.7.1994"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa012437"},{"key":"e_1_2_9_14_1","unstructured":"AstraZeneca(2014)MYALEPT (metreleptin) prescribing information."},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.4161\/self.1.4.13904"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2006.01.019"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00435-12"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2012.06.018"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.29.18365"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2011.10.012"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0215693"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0308767101"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199602013340503"},{"key":"e_1_2_9_24_1","doi-asserted-by":"crossref","first-page":"2395","DOI":"10.1210\/jcem.87.5.8624","article-title":"Serum adiponectin and leptin levels in patients with lipodystrophies","volume":"87","author":"Haque W.A.","year":"2002","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2006-3165"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-09-1027"}],"container-title":["Clinical Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcen.12980","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cen.12980","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T08:15:55Z","timestamp":1695456955000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cen.12980"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,2,2]]},"references-count":25,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2016,7]]}},"alternative-id":["10.1111\/cen.12980"],"URL":"https:\/\/doi.org\/10.1111\/cen.12980","archive":["Portico"],"relation":{},"ISSN":["0300-0664","1365-2265"],"issn-type":[{"value":"0300-0664","type":"print"},{"value":"1365-2265","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,2,2]]}}}