Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant

N Engl J Med. 2000 Apr 20;342(16):1171-7. doi: 10.1056/NEJM200004203421604.

Abstract

Background: Patients with acromegaly are currently treated with surgery, radiation therapy, and drugs to reduce hypersecretion of growth hormone, but the treatments may be ineffective and have adverse effects. Pegvisomant is a genetically engineered growth hormone-receptor antagonist that blocks the action of growth hormone.

Methods: We conducted a 12-week, randomized, double-blind study of three daily doses of pegvisomant (10 mg, 15 mg, and 20 mg) and placebo, given subcutaneously, in 112 patients with acromegaly.

Results: The mean (+/-SD) serum concentration of insulin-like growth factor I (IGF-I) decreased from base line by 4.0+/-16.8 percent in the placebo group, 26.7+/-27.9 percent in the group that received 10 mg of pegvisomant per day, 50.1+/-26.7 percent in the group that received 15 mg of pegvisomant per day, and 62.5+/-21.3 percent in the group that received 20 mg of pegvisomant per day (P<0.001 for the comparison of each pegvisomant group with placebo), and the concentrations became normal in 10 percent, 54 percent, 81 percent, and 89 percent of patients, respectively (P<0.001 for each comparison with placebo). Among patients treated with 15 mg or 20 mg of pegvisomant per day, there were significant decreases in ring size, soft-tissue swelling, the degree of excessive perspiration, and fatigue. The score fortotal symptoms and signs of acromegaly decreased significantly in all groups receiving pegvisomant (P< or =0.05). The incidence of adverse effects was similar in all groups.

Conclusions: On the basis of these preliminary results, treatment of patients who have acromegaly with a growth hormone-receptor antagonist results in a reduction in serum IGF-I concentrations and in clinical improvement.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acromegaly / blood
  • Acromegaly / drug therapy*
  • Adenoma / drug therapy
  • Adenoma / pathology
  • Adult
  • Autoantibodies / blood
  • Double-Blind Method
  • Female
  • Human Growth Hormone / adverse effects
  • Human Growth Hormone / analogs & derivatives*
  • Human Growth Hormone / blood
  • Human Growth Hormone / immunology
  • Human Growth Hormone / therapeutic use
  • Humans
  • Insulin-Like Growth Factor I / metabolism
  • Male
  • Middle Aged
  • Pituitary Neoplasms / drug therapy
  • Pituitary Neoplasms / pathology
  • Receptors, Somatotropin / antagonists & inhibitors*

Substances

  • Autoantibodies
  • Receptors, Somatotropin
  • Human Growth Hormone
  • Insulin-Like Growth Factor I
  • pegvisomant