Treatment of acromegaly with the GH receptor antagonist pegvisomant in clinical practice: safety and efficacy evaluation from the German Pegvisomant Observational Study

Eur J Endocrinol. 2007 Jan;156(1):75-82. doi: 10.1530/eje.1.02312.

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.

Design: 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.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Acromegaly / complications
  • Acromegaly / drug therapy*
  • Adult
  • Aged
  • Female
  • Germany
  • Glucose / metabolism
  • Glycated Hemoglobin A / metabolism
  • Human Growth Hormone / adverse effects
  • Human Growth Hormone / analogs & derivatives*
  • Human Growth Hormone / therapeutic use
  • Humans
  • Insulin-Like Growth Factor I / metabolism
  • Male
  • Middle Aged
  • Receptors, Somatotropin / antagonists & inhibitors*
  • Surveys and Questionnaires

Substances

  • Glycated Hemoglobin A
  • Receptors, Somatotropin
  • Human Growth Hormone
  • Insulin-Like Growth Factor I
  • Glucose
  • pegvisomant