title: Effectiveness of first-line pegvisomant monotherapy in acromegaly: an ACROSTUDY analysis.
abstract: OBJECTIVE
  To examine the effectiveness and safety of primary pegvisomant monotherapy.
  
  
  METHODS
  Retrospective analysis of data extracted from ACROSTUDY (global observational outcomes study of patients with acromegaly treated with pegvisomant).
  
  
  METHODS
  The earliest time to insulin-like growth factor 1 (IGF-1) normalization on pegvisomant monotherapy was determined. Both the proportion of patients who achieved IGF-1 normalization and the time to IGF-1 normalization on pegvisomant monotherapy were assessed.
  
  
  RESULTS
  Eligible patients included 28 subjects on primary medical therapy (PT) and 176 controls on adjunctive pegvisomant therapy treated postoperatively, including 43 who were naïve to medical therapy (NMT) and 133 who were previously treated medically and were washed out (WASH). IGF-1 normalization occurred in 76.9% (PT), 85.2% (NMT) and 78.3% (WASH) patients (P = NS). Median times to IGF-1 normalization were 0.5 year (PT), 0.7 year (NMT) and 0.6 year (WASH), P = NS. On survival analysis, the fraction of patients controlled on pegvisomant monotherapy was not different between groups. Higher baseline IGF-1 levels, obtained at study entry, predicted a lower likelihood of IGF-1 normalization on monotherapy (P = 0.012). Safety data include low prevalence of skin rashes, injection site reactions and reversible transaminase elevations. There was one patient (NMT) with a verified increase in tumor size.
  
  
  CONCLUSIONS
  Pegvisomant monotherapy, administered either as primary medical therapy or as adjunctive therapy according to local practice, led to IGF-1 normalization in >75% of patients. Pegvisomant monotherapy had a favorable safety profile, consistent with previous observations. Prospective data are needed to further evaluate the role of primary pegvisomant monotherapy in acromegaly.
authors.affiliation: Neuroendocrine UnitMassachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA ntritos@mgh.harvard.edu.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Tritos
authors.affiliation: Assistance Publique-Hôpitaux de ParisHôpitaux Universitaires Paris-Sud, Hôpital de Bicêtre, Service d'Endocrinologie et des Maladies de la Reproduction, Le Kremlin Bicêtre, France.|Institut National de la Santé et de la Recherche Médicale U1185Fac Med Paris Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Chanson
authors.affiliation: Endocrine Neoplasia and Hormonal DisordersThe University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Camilo
authors.initials: C
authors.lastname: Jimenez
authors.affiliation: Endocrine CarePfizer, Inc, Lawrenceville, New Jersey, USA.
authors.forename: Donna
authors.initials: D
authors.lastname: King
authors.affiliation: Pfizer Health ABSollentuna, Sweden.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Jönsson
authors.affiliation: Neuroendocrine UnitMassachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Anne
authors.initials: A
authors.lastname: Klibanski
authors.affiliation: Neuroendocrine UnitMassachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Beverly M K
authors.initials: BM
authors.lastname: Biller
mesh_terms: D000172:Acromegaly / Q000188:drug therapy* / Q000378:metabolism; D000328:Adult; D000368:Aged; D005260:Female; D019382:Human Growth Hormone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; C406545:pegvisomant