title: Long-term safety of pegvisomant in patients with acromegaly: comprehensive review of 1288 subjects in ACROSTUDY.
abstract: BACKGROUND
  Pegvisomant is a GH receptor antagonist. The ACROSTUDY is a global safety surveillance study of long-term treatment of acromegaly with pegvisomant.
  
  
  OBJECTIVE
  The objective of the study was to monitor long-term safety and treatment outcomes.
  
  
  METHODS
  ACROSTUDY is open to all patients with acromegaly who are treated with pegvisomant. We report an interim analysis of data captured from 1288 subjects enrolled before a database freeze of December 31, 2009.
  
  
  METHODS
  This was a global noninterventional surveillance study.
  
  
  METHODS
  Long-term monitoring of safety, including central magnetic resonance imaging (MRI) reading and treatment outcomes, was measured.
  
  
  RESULTS
  Subjects (n = 1288) were treated with pegvisomant for a mean of 3.7 yr and followed up in ACROSTUDY for a mean of 2.1 yr. A total of 1147 adverse events (AE) were recorded in 477 subjects (37%), among which 192 AE in 124 subjects (9.6%) were considered to be related to pegvisomant. Serious AE were recorded in 159 subjects (12.3%), whereas pegvisomant-related Serious AE were recorded in 26 subjects (2%). No deaths (15 subjects; 1.2%) were attributed to pegvisomant use. The incidence of increase in pituitary tumor size in the subset with confirmed MRI increases on central reading represented 3.2% of the overall cohort with at least two available MRI (n = 936). Injection-site reactions were reported in 28 cases (2.2%). In 30 patients (2.5%), an elevated aspartate aminotransferase or alanine aminotransferase of more than 3 times the upper level of normality was reported. There were no reports of liver failure. After 5 yr of pegvisomant treatment, 63.2% of subjects had normal IGF-I levels at a mean dose of 18 mg/d.
  
  
  CONCLUSIONS
  Data entered and evaluated in ACROSTUDY indicate that pegvisomant is an effective and safe medical treatment in patients with acromegaly. The reported low incidence of pituitary tumor size increase, liver enzyme elevations, and lipodystrophy at the injection site are reassuring.
authors.affiliation: Department of Medicine, Erasmus University Medical Center, 3000 CA Rotterdam, The Netherlands. a.vanderlelij@erasmusmc.nl
authors.forename: A J
authors.initials: AJ
authors.lastname: van der Lely
authors.forename: Beverly M K
authors.initials: BM
authors.lastname: Biller
authors.forename: Thierry
authors.initials: T
authors.lastname: Brue
authors.forename: Michael
authors.initials: M
authors.lastname: Buchfelder
authors.forename: Ezio
authors.initials: E
authors.lastname: Ghigo
authors.forename: Roy
authors.initials: R
authors.lastname: Gomez
authors.forename: Judith
authors.initials: J
authors.lastname: Hey-Hadavi
authors.forename: Frida
authors.initials: F
authors.lastname: Lundgren
authors.forename: Natasa
authors.initials: N
authors.lastname: Rajicic
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Strasburger
authors.forename: Susan M
authors.initials: SM
authors.lastname: Webb
authors.forename: Maria
authors.initials: M
authors.lastname: Koltowska-Häggström
mesh_terms: D000172:Acromegaly / Q000188:drug therapy* / Q000209:etiology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006727:Hormone Antagonists / Q000009:adverse effects* / Q000627:therapeutic use; D019382:Human Growth Hormone / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D007223:Infant; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D010911:Pituitary Neoplasms / Q000150:complications / Q000188:drug therapy*; D011358:Product Surveillance, Postmarketing; D011986:Receptors, Somatotropin / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome
chemical_list: D006727:Hormone Antagonists; D011986:Receptors, Somatotropin; D019382:Human Growth Hormone; C406545:pegvisomant