title: Gender, body weight, disease activity, and previous radiotherapy influence the response to pegvisomant.
abstract: OBJECTIVE
  To effectively normalize IGF-I in patients with acromegaly, various covariates may affect dosing and plasma concentrations of pegvisomant. We assessed whether sex, age, weight, and previous radiotherapy influence dosing of pegvisomant in patients with active disease.
  
  
  METHODS
  Data from 69 men and 49 women participating in multicenter, open-label trials of pegvisomant were retrospectively evaluated using multiple regression techniques. Sixty-nine subjects (39 men, 30 women) had undergone external beam pituitary radiotherapy. Serum IGF-I was at least 30% above age-related upper limit of normal in all patients at study entry. After a loading dose of pegvisomant (80 mg), patients were commenced on 10 mg/d. Pegvisomant dose was adjusted by 5 mg every eighth week until serum IGF-I was normalized.
  
  
  RESULTS
  At baseline, men had significantly higher mean serum IGF-I levels than women despite similar GH levels. After treatment with pegvisomant, IGF-I levels were similar in men and women. A significant correlation between baseline GH, IGF-I, body weight, and the dose of pegvisomant required to normalize serum IGF-I was observed (all P < 0.001). Women required an average of 0.04 mg/kg more pegvisomant than men and a mean weight-corrected dose of 19.2 mg/d to normalize serum IGF-I [14.5 mg/d (men); P < 0.001]. Patients treated with radiotherapy required less pegvisomant to normalize serum IGF-I despite similar baseline GH/IGF-I levels (15.2 vs. 18.5 mg/d for no previous radiotherapy; P = 0.002).
  
  
  CONCLUSIONS
  Sex, body weight, previous radiotherapy, and baseline GH/IGF-I influence the dose of pegvisomant required to normalize serum IGF-I in patients with active acromegaly.
authors.affiliation: Department of Diabetes and Endocrinology, The Ipswich Hospital National Health Service Trust, Heath Road, Ipswich, Suffolk IP4 5PD, United Kingdom. Craig.Parkinson@ipswichhospital.nhs.uk
authors.forename: Craig
authors.initials: C
authors.lastname: Parkinson
authors.forename: Pia
authors.initials: P
authors.lastname: Burman
authors.forename: Michael
authors.initials: M
authors.lastname: Messig
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Trainer
mesh_terms: D000172:Acromegaly / Q000097:blood / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D001835:Body Weight; D005260:Female; D019382:Human Growth Hormone / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D008875:Middle Aged; D010902:Pituitary Gland / Q000528:radiation effects*; D012189:Retrospective Studies; D012737:Sex Factors
chemical_list: D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; C406545:pegvisomant