title: Treatment of acromegaly with the GH receptor antagonist pegvisomant in clinical practice: safety and efficacy evaluation from the German Pegvisomant Observational Study.
abstract: OBJECTIVE
  The GH receptor antagonist pegvisomant is a highly effective new treatment option in acromegaly. The German Pegvisomant Observational Study (GPOS) was started to monitor long-term safety and efficacy of pegvisomant as prescribed in clinical practice.
  
  
  METHODS
  GPOS is an observational, multi-center, surveillance study, which comprises non-interventional data collection.
  
  
  METHODS
  Of the 229 patients included in the study, 90.4% had previous pituitary surgery, 43.2% were treated by radiation therapy, and 94.3% had previous medical therapy for acromegaly that had been discontinued mainly due to persistent IGF-I elevation or side effects. The intention-to-treat population included 177 patients with at least one post-baseline efficacy measurement.
  
  
  RESULTS
  IGF-I levels decreased from 1.75+/-0.91-fold the upper limit of normal at baseline to 1.05+/- 0.62 at the 6-month visit, 0.96+/-0.60 at the 12-month visit, and to 0.89+/-0.41-fold after 24 months (P<0.0001). Mean duration of pegvisomant therapy was 51.8+/-35.8 weeks (median=51.9 weeks). IGF-I was normalized in 64.4% at 6 months with a median dose of 15.0 mg/day, in 70.9% at 12 months, and in 76.3% at 24 months. Fasting glucose levels improved from 114.4+/-45.9 to 101.5+/- 42.8 mg/dl after 6 months (P<0.01) and to 100.6+/-33.2 mg/ml after 12 months (P<0.01). General physical condition measured by specific signs and symptoms score improved significantly. Adverse events occurring in >1% were injection site reactions in 7.4%, elevated liver enzymes (>3 times of normal) in 5.2% (3.1% spontaneously normalized during continued treatment), reported increase of pituitary tumor volume in 5.2% (which was verified in 3.1%), and headache in 1.7%.
  
  
  CONCLUSIONS
  Pegvisomant is generally well tolerated with a safety profile similar to that reported in clinical trials and can effectively reduce IGF-I in patients with acromegaly refractory to conventional therapy.
authors.affiliation: Pfizer Pharma GmbH, Karlsruhe, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Schreiber
authors.forename: M
authors.initials: M
authors.lastname: Buchfelder
authors.forename: M
authors.initials: M
authors.lastname: Droste
authors.forename: K
authors.initials: K
authors.lastname: Forssmann
authors.forename: K
authors.initials: K
authors.lastname: Mann
authors.forename: B
authors.initials: B
authors.lastname: Saller
authors.forename: C J
authors.initials: CJ
authors.lastname: Strasburger
mesh_terms: D000172:Acromegaly / Q000150:complications / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D005260:Female; D005858:Germany; D005947:Glucose / Q000378:metabolism; D006442:Glycated Hemoglobin / Q000378:metabolism; D019382:Human Growth Hormone / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011986:Receptors, Somatotropin / Q000037:antagonists & inhibitors*; D011795:Surveys and Questionnaires
chemical_list: D005947:Glucose; D006442:Glycated Hemoglobin; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D011986:Receptors, Somatotropin; C406545:pegvisomant