{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T20:47:58Z","timestamp":1765486078539},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"4","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2017,4]]},"abstract":"<jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>Effective treatment of acromegaly with pegvisomant (PEGV), a growth hormone receptor antagonist, requires an appropriate dose titration. PEGV doses vary widely among individual patients, and various covariates may affect its dosing and pharmacokinetics.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Objective<\/jats:title>\n<jats:p>To identify predictors of the PEGV dose required to normalize insulin-like growth factor I (IGF-I) levels during PEGV monotherapy and in combination with long-acting somatostatin analogues (LA-SSAs).<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Design<\/jats:title>\n<jats:p>Two retrospective cohorts (Rotterdam\u2009+\u2009Li\u00e8ge Acromegaly Survey (LAS), total <jats:italic>n<\/jats:italic>\u2009=\u2009188) were meta-analyzed as a form of external replication to study the predictors of PEGV dosing in addition to LA-SSA, the LAS (<jats:italic>n<\/jats:italic>\u2009=\u200983) was used to study the predictors of PEGV monotherapy dosing. Multivariable regression models were used to identify predictors of the PEGV dose required to normalize IGF-I levels.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>For PEGV dosing in combination with LA-SSA, IGF-I levels, weight, height and age, were associated with the PEGV normalization dosage (<jats:italic>P<\/jats:italic>\u2009\u2264\u20090.001, <jats:italic>P<\/jats:italic>\u2009\u2264\u20090.001, <jats:italic>P<\/jats:italic>\u2009=\u20090.028 and <jats:italic>P<\/jats:italic>\u2009=\u20090.047 respectively). Taken together, these characteristics predicted the PEGV normalization dose correctly in 63.3% of all patients within a range of \u00b160\u2009mg\/week (21.3% within a range of \u00b120\u2009mg\/week). For monotherapy, only weight was associated with the PEGV normalization dose (<jats:italic>P<\/jats:italic>\u2009\u2264\u20090.001) and predicted this dosage correctly in 77.1% of all patients within a range of \u00b160\u2009mg\/week (31.3% within a range of \u00b120\u2009mg\/week).<\/jats:p><\/jats:sec>\n<jats:sec>\n<jats:title>Conclusion<\/jats:title>\n<jats:p>In this study, we show that IGF-I levels, weight, height and age can contribute to define the optimal PEGV dose to normalize IGF-I levels in addition to LA-SSA. For PEGV monotherapy, only the patient\u2019s weight was associated with the IGF-I normalization PEGV dosage.<\/jats:p>\n<\/jats:sec>","DOI":"10.1530\/eje-16-0956","type":"journal-article","created":{"date-parts":[[2017,1,19]],"date-time":"2017-01-19T01:50:34Z","timestamp":1484790634000},"page":"421-431","update-policy":"http:\/\/dx.doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":20,"title":["A multivariable prediction model for pegvisomant dosing: monotherapy and in combination with long-acting somatostatin analogues"],"prefix":"10.1093","volume":"176","author":[{"given":"S E","family":"Franck","sequence":"first","affiliation":[{"name":"1Department of Internal MedicineEndocrinology Section, Erasmus University Medical Center, Rotterdam, The Netherlands"}]},{"given":"T I M","family":"Korevaar","sequence":"additional","affiliation":[{"name":"1Department of Internal MedicineEndocrinology Section, Erasmus University Medical Center, Rotterdam, The Netherlands"}]},{"given":"P","family":"Petrossians","sequence":"additional","affiliation":[{"name":"2Department of Internal MedicineEndocrinology Section, Centre Hospitalier Universitaire de Li\u00e8ge, University of Li\u00e8ge, Domaine Universitaire du Sart\u2010Tilman, Li\u00e8ge, Belgium"}]},{"given":"A F","family":"Daly","sequence":"additional","affiliation":[{"name":"2Department of Internal MedicineEndocrinology Section, Centre Hospitalier Universitaire de Li\u00e8ge, University of Li\u00e8ge, Domaine Universitaire du Sart\u2010Tilman, Li\u00e8ge, Belgium"}]},{"given":"P","family":"Chanson","sequence":"additional","affiliation":[{"name":"3Assistance Publique-H\u00f4pitaux de ParisH\u00f4pitaux Universitaires Paris-Sud, H\u00f4pital de Bic\u00eatre, Service d\u2019Endocrinologie et des Maladies de la Reproduction, Le Kremlin Bic\u00eatre, France"},{"name":"4Inserm 1185Fac Med Paris Sud, Univ Paris-Sud, Universit\u00e9 Paris-Saclay, Le Kremlin-Bic\u00eatre, France"}]},{"given":"M L","family":"Jaffrain-R\u00e9a","sequence":"additional","affiliation":[{"name":"5Department of Biotechnological and Applied Clinical SciencesUniversity of L\u2019Aquila, L\u2019Aquila and Neuromed, IRCCS, Pozzilli, Italy"}]},{"given":"T","family":"Brue","sequence":"additional","affiliation":[{"name":"6Aix-Marseille Universit\u00e9CNRS, CRN2M UMR 7286, Marseille, France"},{"name":"7APHMH\u00f4pital Conception, Service d\u2019Endocrinologie, Diab\u00e8te et Maladies M\u00e9taboliques, Centre de R\u00e9f\u00e9rence des Maladies Rares d\u2019Origine Hypophysaire, Marseille, France"}]},{"given":"G K","family":"Stalla","sequence":"additional","affiliation":[{"name":"8Clinical NeuroendocrinologyMax-Planck-Institute of Psychiatry, Munich, Germany"}]},{"given":"D","family":"Carvalho","sequence":"additional","affiliation":[{"name":"9Department of EndocrinologyDiabetes and Metabolism Section and Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, University of Porto, Centro Hospitalar S. Jo\u00e3o , Porto, Portugal"}]},{"given":"A","family":"Colao","sequence":"additional","affiliation":[{"name":"10Dipartimento di Medicina Clinica e ChirurgiaUniversit\u00e0 Federico II di Napoli, Naples, Italy"}]},{"given":"V","family":"H\u00e1na","sequence":"additional","affiliation":[{"name":"113rd Department of Internal MedicineFirst Medical Faculty, Charles University, Prague, Czech Republic"}]},{"given":"B","family":"Delemer","sequence":"additional","affiliation":[{"name":"12Department of EndocrinologyDiabetes, and Nutrition, University Hospital of Reims, Reims, France"}]},{"given":"C","family":"Fajardo","sequence":"additional","affiliation":[{"name":"13Servicio de Endocrinolog\u00edaHospital Universitario La Ribera, Valencia, Spain"}]},{"given":"A J","family":"van der Lely","sequence":"additional","affiliation":[{"name":"1Department of Internal MedicineEndocrinology Section, Erasmus University Medical Center, Rotterdam, The Netherlands"}]},{"given":"A","family":"Beckers","sequence":"additional","affiliation":[{"name":"2Department of Internal MedicineEndocrinology Section, Centre Hospitalier Universitaire de Li\u00e8ge, University of Li\u00e8ge, Domaine Universitaire du Sart\u2010Tilman, Li\u00e8ge, Belgium"}]},{"given":"S J C M M","family":"Neggers","sequence":"additional","affiliation":[{"name":"1Department of Internal MedicineEndocrinology Section, Erasmus University Medical Center, Rotterdam, The Netherlands"}]}],"member":"286","reference":[{"key":"2017020917401821000_176.4.421.1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI39375"},{"key":"2017020917401821000_176.4.421.2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra062453"},{"key":"2017020917401821000_176.4.421.3","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-08-0267"},{"key":"2017020917401821000_176.4.421.4","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.2007.03012.x"},{"key":"2017020917401821000_176.4.421.5","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1159\/000080505","article-title":"Treatment of acromegaly","volume":"62","author":"Holdaway","year":"2004","journal-title":"Hormone Research"},{"key":"2017020917401821000_176.4.421.6","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012-3072"},{"key":"2017020917401821000_176.4.421.7","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013-3318"},{"key":"2017020917401821000_176.4.421.8","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2014-2032"},{"key":"2017020917401821000_176.4.421.9","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200004203421604"},{"key":"2017020917401821000_176.4.421.10","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.2009.03620.x"},{"key":"2017020917401821000_176.4.421.11","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-10-0867"},{"key":"2017020917401821000_176.4.421.12","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(01)06844-1"},{"key":"2017020917401821000_176.4.421.13","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.mce.2013.09.004","article-title":"Evaluation of growth hormone (GH) action in mice: discovery of GH receptor antagonists and clinical indications","volume":"386","author":"Kopchick","year":"2014","journal-title":"Molecular and Cellular Endocrinology"},{"key":"2017020917401821000_176.4.421.14","doi-asserted-by":"publisher","DOI":"10.1210\/jc.86.4.1716"},{"key":"2017020917401821000_176.4.421.15","unstructured":"Farmacotherapeutisch Kompas. 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