{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T10:31:41Z","timestamp":1794047501130,"version":"4.8.0"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2022,3,31]],"date-time":"2022-03-31T00:00:00Z","timestamp":1648684800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,3,31]],"date-time":"2022-03-31T00:00:00Z","timestamp":1648684800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Endocrinol Invest"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Objective<\/jats:title>\n                <jats:p>A comprehensive picture of pegvisomant use for treating acromegaly in routine clinical practice in different countries is lacking. We aimed, therefore, to document country-specific behaviors in real-life pegvisomant use, and the main safety and effectiveness outcomes in the ACROSTUDY.\n<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Design<\/jats:title>\n                <jats:p>ACROSTUDY is an open-label, non-interventional, post-marketing safety surveillance study.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>A descriptive analysis was performed using data from the six top-recruiter ACROSTUDY countries, i.e., Germany (<jats:italic>n<\/jats:italic>\u2009=\u2009548 patients), Italy (<jats:italic>n<\/jats:italic>\u2009=\u2009466), France (<jats:italic>n<\/jats:italic>\u2009=\u2009312), USA (<jats:italic>n<\/jats:italic>\u2009=\u2009207), Spain (<jats:italic>n<\/jats:italic>\u2009=\u2009200) and the Netherlands (<jats:italic>n<\/jats:italic>\u2009=\u2009175). These nations accounted for\u2009&gt;\u200985% of the ACROSTUDY cases.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The mean pegvisomant dose at treatment start was lowest in the Netherlands (9.4\u00a0mg\/day), whereas it ranged between 10.9 and 12.6\u00a0mg\/day in the other countries. At year 5, the mean pegvisomant dose was around 15\u00a0mg\/day in all countries, except France (18.1\u00a0mg\/day). At starting pegvisomant, patients treated with monotherapy ranged between 15% in the Netherlands and 72% in Spain. Monotherapy remained lowest over time in the Netherlands. In all countries, the percentage of patients with normal IGF-1 increased steeply from\u2009&lt;\u200920% at baseline to 43\u201358% at month 6 and 51\u201367% at year 1. After that, we observed minor changes in the rate of acromegaly control in all countries. The Netherlands peaked in disease control at year 2 (72%). The proportion of patients reporting changes in pituitary tumor size was generally low. Serious treatment-related adverse events were\u2009&lt;\u20095% in all countries.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Our study provided a detailed summary of real-life use of pegvisomant in the six top-recruiter ACROSTUDY nations.\n<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s40618-022-01789-4","type":"journal-article","created":{"date-parts":[[2022,3,31]],"date-time":"2022-03-31T19:03:10Z","timestamp":1648753390000},"page":"1535-1545","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Are there country-specific differences in the use of pegvisomant for acromegaly in clinical practice? An analysis from ACROSTUDY"],"prefix":"10.1007","volume":"45","author":[{"given":"S.","family":"Grottoli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Bianchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Bogazzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Bona","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. O.","family":"Carlsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Colao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Dassie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Giampietro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Gomez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Granato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Maffei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Pivonello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Prencipe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Ragonese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Urbani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Cannav\u00f2","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,3,31]]},"reference":[{"issue":"1","key":"1789_CR1","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1007\/s11102-016-0754-x","volume":"20","author":"A Lavrentaki","year":"2017","unstructured":"Lavrentaki A, Paluzzi A, Wass JA, Karavitaki N (2017) Epidemiology of acromegaly: review of population studies. Pituitary 20(1):4\u20139","journal-title":"Pituitary"},{"issue":"2","key":"1789_CR2","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1210\/jc.2003-031199","volume":"89","author":"IM Holdaway","year":"2004","unstructured":"Holdaway IM, Rajasoorya RC, Gamble GD (2004) Factors influencing mortality in acromegaly. J Clin Endocrinol Metab 89(2):667\u2013674","journal-title":"J Clin Endocrinol Metab"},{"issue":"4","key":"1789_CR3","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1038\/nrendo.2014.21","volume":"10","author":"A Giustina","year":"2014","unstructured":"Giustina A, Chanson P, Kleinberg D, Bronstein MD, Clemmons DR, Klibanski A et al (2014) Expert consensus document: A consensus on the medical treatment of acromegaly. Nat Rev Endocrinol 10(4):243\u2013248","journal-title":"Nat Rev Endocrinol"},{"issue":"9","key":"1789_CR4","doi-asserted-by":"publisher","first-page":"552","DOI":"10.1038\/s41574-018-0058-5","volume":"14","author":"S Melmed","year":"2018","unstructured":"Melmed S, Bronstein MD, Chanson P, Klibanski A, Casanueva FF, Wass JAH et al (2018) A Consensus Statement on acromegaly therapeutic outcomes. Nat Rev Endocrinol 14(9):552\u2013561","journal-title":"Nat Rev Endocrinol"},{"issue":"3","key":"1789_CR5","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1530\/EJE-13-0166","volume":"169","author":"F Bogazzi","year":"2013","unstructured":"Bogazzi F, Colao A, Rossi G, Lombardi M, Urbani C, Sardella C et al (2013) Comparison of the effects of primary somatostatin analogue therapy and pituitary adenomectomy on survival in patients with acromegaly: a retrospective cohort study. Eur J Endocrinol 169(3):367\u2013376","journal-title":"Eur J Endocrinol"},{"issue":"1","key":"1789_CR6","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1530\/EJE-18-0255","volume":"179","author":"F Bolfi","year":"2018","unstructured":"Bolfi F, Neves AF, Boguszewski CL, Nunes-Nogueira VS (2018) Mortality in acromegaly decreased in the last decade: a systematic review and meta-analysis. Eur J Endocrinol 179(1):59\u201371","journal-title":"Eur J Endocrinol"},{"issue":"16","key":"1789_CR7","doi-asserted-by":"publisher","first-page":"1171","DOI":"10.1056\/NEJM200004203421604","volume":"342","author":"PJ Trainer","year":"2000","unstructured":"Trainer PJ, Drake WM, Katznelson L, Freda PU, Herman-Bonert V, van der Lely AJ et al (2000) Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant. N Engl J Med 342(16):1171\u20131177","journal-title":"N Engl J Med"},{"issue":"9295","key":"1789_CR8","doi-asserted-by":"publisher","first-page":"1754","DOI":"10.1016\/S0140-6736(01)06844-1","volume":"358","author":"AJ van der Lely","year":"2001","unstructured":"van der Lely AJ, Hutson RK, Trainer PJ, Besser GM, Barkan AL, Katznelson L et al (2001) Long-term treatment of acromegaly with pegvisomant, a growth hormone receptor antagonist. Lancet 358(9295):1754\u20131759","journal-title":"Lancet"},{"issue":"Suppl 5","key":"1789_CR9","first-page":"68","volume":"68","author":"PJ Trainer","year":"2007","unstructured":"Trainer PJ (2007) ACROSTUDY: an overview. Horm Res 68(Suppl 5):68\u201369","journal-title":"Horm Res"},{"issue":"10","key":"1789_CR10","doi-asserted-by":"publisher","first-page":"1099","DOI":"10.1007\/s40618-015-0289-4","volume":"38","author":"S Cannavo","year":"2015","unstructured":"Cannavo S, Bogazzi F, Colao A, De Marinis L, Maffei P, Gomez R et al (2015) Does pegvisomant treatment expertise improve control of resistant acromegaly? The Italian ACROSTUDY experience. J Endocrinol Invest 38(10):1099\u20131109","journal-title":"J Endocrinol Invest"},{"issue":"1","key":"1789_CR11","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1007\/s12020-014-0393-9","volume":"48","author":"S Grottoli","year":"2015","unstructured":"Grottoli S, Maffei P, Bogazzi F, Cannavo S, Colao A, Ghigo E et al (2015) ACROSTUDY: the Italian experience. Endocrine 48(1):334\u2013341","journal-title":"Endocrine"},{"issue":"6","key":"1789_CR12","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1530\/EJE-18-0616","volume":"179","author":"M Buchfelder","year":"2018","unstructured":"Buchfelder M, van der Lely AJ, Biller BMK, Webb SM, Brue T, Strasburger CJ et al (2018) Long-term treatment with pegvisomant: observations from 2090 acromegaly patients in ACROSTUDY. Eur J Endocrinol 179(6):419\u2013427","journal-title":"Eur J Endocrinol"},{"issue":"1","key":"1789_CR13","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1007\/s12020-020-02501-3","volume":"71","author":"E Kuhn","year":"2021","unstructured":"Kuhn E, Caron P, Delemer B, Raingeard I, Lefebvre H, Raverot G et al (2021) Pegvisomant in combination or pegvisomant alone after failure of somatostatin analogs in acromegaly patients: an observational French ACROSTUDY cohort study. Endocrine 71(1):158\u2013167","journal-title":"Endocrine"},{"issue":"2","key":"1789_CR14","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1530\/EJE-16-0697","volume":"176","author":"NA Tritos","year":"2017","unstructured":"Tritos NA, Chanson P, Jimenez C, King D, Jonsson PJ, Klibanski A et al (2017) Effectiveness of first-line pegvisomant monotherapy in acromegaly: an ACROSTUDY analysis. Eur J Endocrinol 176(2):213\u2013220","journal-title":"Eur J Endocrinol"},{"issue":"4","key":"1789_CR15","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1111\/cen.12993","volume":"84","author":"AM Ramos-Levi","year":"2016","unstructured":"Ramos-Levi AM, Bernabeu I, Alvarez-Escola C, Aller J, Lucas T, de Miguel P et al (2016) Long-term treatment with pegvisomant for acromegaly: a 10-year experience. Clin Endocrinol (Oxf) 84(4):540\u2013550","journal-title":"Clin Endocrinol (Oxf)"},{"issue":"Suppl 1","key":"1789_CR16","doi-asserted-by":"publisher","first-page":"S3","DOI":"10.1530\/EJE-09-0350","volume":"161","author":"M Buchfelder","year":"2009","unstructured":"Buchfelder M, Schlaffer S, Droste M, Mann K, Saller B, Brubach K et al (2009) The German ACROSTUDY: past and present. Eur J Endocrinol 161(Suppl 1):S3\u2013S10","journal-title":"Eur J Endocrinol"},{"issue":"Suppl 1","key":"1789_CR17","doi-asserted-by":"publisher","first-page":"S11","DOI":"10.1530\/EJE-09-0333","volume":"161","author":"T Brue","year":"2009","unstructured":"Brue T, Castinetti F, Lundgren F, Koltowska-Haggstrom M, Petrossians P, investigators A (2009) Which patients with acromegaly are treated with pegvisomant? An overview of methodology and baseline data in ACROSTUDY. Eur J Endocrinol 161(Suppl 1):S11\u2013S17","journal-title":"Eur J Endocrinol"},{"issue":"5","key":"1789_CR18","doi-asserted-by":"publisher","first-page":"1589","DOI":"10.1210\/jc.2011-2508","volume":"97","author":"AJ van der Lely","year":"2012","unstructured":"van der Lely AJ, Biller BM, Brue T, Buchfelder M, Ghigo E, Gomez R et al (2012) Long-term safety of pegvisomant in patients with acromegaly: comprehensive review of 1288 subjects in ACROSTUDY. J Clin Endocrinol Metab 97(5):1589\u20131597","journal-title":"J Clin Endocrinol Metab"},{"issue":"4","key":"1789_CR19","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1530\/EJE-21-0239","volume":"185","author":"M Fleseriu","year":"2021","unstructured":"Fleseriu M, Fuhrer-Sakel D, van der Lely AJ, De Marinis L, Brue T, van der Lans-Bussemaker J et al (2021) More than a decade of real-world experience of pegvisomant for acromegaly: ACROSTUDY. Eur J Endocrinol 185(4):525\u2013538","journal-title":"Eur J Endocrinol"},{"issue":"1","key":"1789_CR20","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1007\/s12020-018-1729-7","volume":"63","author":"LP Leonart","year":"2019","unstructured":"Leonart LP, Tonin FS, Ferreira VL, Fernandez-Llimos F, Pontarolo R (2019) Effectiveness and safety of pegvisomant: a systematic review and meta-analysis of observational longitudinal studies. Endocrine 63(1):18\u201326","journal-title":"Endocrine"},{"issue":"10","key":"1789_CR21","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.1007\/s40618-014-0146-x","volume":"37","author":"A Giustina","year":"2014","unstructured":"Giustina A, Ambrosio MR, Beck Peccoz P, Bogazzi F, Cannavo S, De Marinis L et al (2014) Use of Pegvisomant in acromegaly. An Italian Society of Endocrinology guideline. J Endocrinol Invest 37(10):1017\u20131030","journal-title":"J Endocrinol Invest"},{"key":"1789_CR22","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1186\/1756-9966-32-40","volume":"32","author":"A Bianchi","year":"2013","unstructured":"Bianchi A, Valentini F, Iuorio R, Poggi M, Baldelli R, Passeri M et al (2013) Long-term treatment of somatostatin analog-refractory growth hormone-secreting pituitary tumors with pegvisomant alone or combined with long-acting somatostatin analogs: a retrospective analysis of clinical practice and outcomes. J Exp Clin Cancer Res 32:40","journal-title":"J Exp Clin Cancer Res"},{"issue":"4","key":"1789_CR23","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1530\/EJE-17-0996","volume":"178","author":"CJ Strasburger","year":"2018","unstructured":"Strasburger CJ, Mattsson A, Wilton P, Aydin F, Hey-Hadavi J, Biller BMK (2018) Increasing frequency of combination medical therapy in the treatment of acromegaly with the GH receptor antagonist pegvisomant. Eur J Endocrinol 178(4):321\u2013329","journal-title":"Eur J Endocrinol"},{"issue":"4","key":"1789_CR24","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1530\/EJE-16-0008","volume":"175","author":"AJ van der Lely","year":"2016","unstructured":"van der Lely AJ, Jonsson P, Wilton P, Akerblad AC, Cara J, Ghigo E (2016) Treatment with high doses of pegvisomant in 56 patients with acromegaly: experience from ACROSTUDY. Eur J Endocrinol 175(4):239\u2013245","journal-title":"Eur J Endocrinol"},{"issue":"3","key":"1789_CR25","doi-asserted-by":"publisher","first-page":"264","DOI":"10.4158\/EP14330.OR","volume":"21","author":"PU Freda","year":"2015","unstructured":"Freda PU, Gordon MB, Kelepouris N, Jonsson P, Koltowska-Haggstrom M, van der Lely AJ (2015) Long-term treatment with pegvisomant as monotherapy in patients with acromegaly: experience from ACROSTUDY. Endocr Pract 21(3):264\u2013274","journal-title":"Endocr Pract"},{"issue":"5","key":"1789_CR26","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1007\/s40618-017-0773-0","volume":"41","author":"M Ragonese","year":"2018","unstructured":"Ragonese M, Grottoli S, Maffei P, Alibrandi A, Ambrosio MR, Arnaldi G et al (2018) How to improve effectiveness of pegvisomant treatment in acromegalic patients. J Endocrinol Invest 41(5):575\u2013581","journal-title":"J Endocrinol Invest"},{"issue":"1","key":"1789_CR27","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1210\/jc.2006-1412","volume":"92","author":"C Parkinson","year":"2007","unstructured":"Parkinson C, Burman P, Messig M, Trainer PJ (2007) Gender, body weight, disease activity, and previous radiotherapy influence the response to pegvisomant. J Clin Endocrinol Metab 92(1):190\u2013195","journal-title":"J Clin Endocrinol Metab"},{"issue":"1","key":"1789_CR28","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.jval.2015.09.2938","volume":"19","author":"C Nordon","year":"2016","unstructured":"Nordon C, Karcher H, Groenwold RH, Ankarfeldt MZ, Pichler F, Chevrou-Severac H et al (2016) The \u201cEfficacy-Effectiveness Gap\u201d: historical background and current conceptualization. Value Health 19(1):75\u201381","journal-title":"Value Health"},{"issue":"6","key":"1789_CR29","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1007\/s40618-017-0614-1","volume":"40","author":"A Giustina","year":"2017","unstructured":"Giustina A, Arnaldi G, Bogazzi F, Cannavo S, Colao A, De Marinis L et al (2017) Pegvisomant in acromegaly: an update. J Endocrinol Invest 40(6):577\u2013589","journal-title":"J Endocrinol Invest"}],"container-title":["Journal of Endocrinological Investigation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40618-022-01789-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s40618-022-01789-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40618-022-01789-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,23]],"date-time":"2022-07-23T11:17:26Z","timestamp":1658575046000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s40618-022-01789-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,31]]},"references-count":29,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2022,8]]}},"alternative-id":["1789"],"URL":"https:\/\/doi.org\/10.1007\/s40618-022-01789-4","relation":{},"ISSN":["1720-8386"],"issn-type":[{"value":"1720-8386","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,31]]},"assertion":[{"value":"24 November 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 March 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 March 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Silvia Grottoli received research grants from Pfizer, Ipsen and Novartis and is a consultant for Pfizer. Martin Ove Carlsson, Roy Gomez and Simona Granato are employees and stockholders of Pfizer. Other authors have no conflicts of interest to declare.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Prof. Nunzia Prencipe is among the Members of the Editorial Board of the Journal of Endocrinological Investigation.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical statements"}},{"value":"Ethical approval was obtained from the Comitato Etico dell\u2019Universit\u00e0 Cattolica del Sacro Cuore \u2013 Policlinico Universitario Agostino Gemelli di Roma, Rome, for the Italian coordinating center (i.e., Universit\u00e0 Cattolica del Sacro Cuore, Rome, Italy) and from local Boards or Ethical Committees for all study centers.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Research involving human participants and\/or animals"}},{"value":"All patients provided written informed consent before enrollment in the study.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}