{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T03:08:56Z","timestamp":1772680136949,"version":"3.50.1"},"reference-count":40,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2022,7,11]],"date-time":"2022-07-11T00:00:00Z","timestamp":1657497600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006483","name":"AbbVie","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006483","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:sec><jats:title>Aim<\/jats:title><jats:p>Elagolix, a gonadotropin\u2010releasing hormone receptor antagonist, was recently approved for heavy menstrual bleeding associated with uterine fibroids (UF, Oriahnn) at a dose of 300\u2009mg twice daily (BID) in combination with add\u2010back therapy (oestradiol 1\u00a0mg\/norethindrone acetate 0.5\u00a0mg [E2\/NETA] once daily) for 24\u2009months use. The limited duration of treatment is related to elagolix dose\u2010 and duration\u2010dependent decrease in oestrogen that is mechanistically linked to changes in bone mineral density (BMD). The work herein supported the extended treatment duration of 24\u2009months.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>An integrated exposure\u2010response and epidemiological modelling framework of elagolix effects on femoral neck BMD (FN\u2010BMD), informed by real\u2010world data and phase 3 clinical trials data, was developed to predict the time course and magnitude of changes in BMD and its relation to risk of bone fracture in women with UF.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Model results indicated that women treated with elagolix 300\u2009mg BID\u2009+\u2009E2\/NETA in the long term (ie, &gt;24\u2009months) may experience less than 1% loss in FN\u2010BMD per year, relative to placebo. The exposure\u2010response model simulations and clinical risk factors were used to estimate 10\u2010year risk of fractures using the clinically validated Fracture Risk Assessment Tool (FRAX). The impact of elagolix 300\u2009mg BID\u2009+\u2009E2\/NETA treatment on the 10\u2010year risk of hip or major osteoporotic fractures estimated from the FRAX model was minimal compared to that of placebo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The elagolix integrated exposure\u2010BMD analysis and translation to fracture risk provided an interdisciplinary model\u2010informed drug development framework for clinical benefit\u2010risk evaluation and enabled approval of longer treatment duration to benefit the patient.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.15440","type":"journal-article","created":{"date-parts":[[2022,6,13]],"date-time":"2022-06-13T13:54:29Z","timestamp":1655128469000},"page":"5257-5268","source":"Crossref","is-referenced-by-count":6,"title":["Interdisciplinary model\u2010informed drug development for extending duration of elagolix treatment in patients with uterine fibroids"],"prefix":"10.1111","volume":"88","author":[{"given":"Denise","family":"Beck","sequence":"first","affiliation":[{"name":"Clinical Pharmacology and Pharmacometrics AbbVie Deutschland GmbH &amp; Co. 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Boston USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nael M.","family":"Mostafa","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Pharmacometrics, AbbVie  North Chicago IL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie E.","family":"Chiuve","sequence":"additional","affiliation":[{"name":"Global Epidemiology, AbbVie  North Chicago IL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charlotte","family":"Owens","sequence":"additional","affiliation":[{"name":"Clinical Development, General Medicine, AbbVie  North Chicago IL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0147-8933","authenticated-orcid":false,"given":"Mohamad","family":"Shebley","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Pharmacometrics, AbbVie  North Chicago IL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,7,11]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2013.07.017"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychores.2014.12.016"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2019.11.1255"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(00)03622\u20109"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0000000000002675"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002\u20109378(95)90077\u20102"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1055\/s\u20102007\u20101016336"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002\u20109378(92)91706\u2010g"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0378\u20105122(96)01015\u20108"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/14712598.2019.1581761"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(01)06797\u20106"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2016\u20103845"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262\u2010019\u201000840\u20107"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00198\u2010005\u20100027\u20104"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.i6755"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2008.08.106"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0000000000000964"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/00042192\u2010200207000\u201000004"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0015\u20100282(98)00500\u20107"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0000000000002933"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00404\u2010014\u20103230\u20108"},{"key":"e_1_2_13_23_1","unstructured":"Orilissa\u2122 (elagolix) [United States package insert]. 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