Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant

Background: Patients with acromegaly are treated with surgery, radiation th erapy, and drugs to reduce hypersecretion of growth hormone, but the treatm ents may be ineffective and have adverse effects. Pegvisomant is a genetica lly engineered growth hormone-receptor antagonist that blocks the action of growth hormone. Methods: We conducted a 12-week, randomized, double-blind study of three di fferent daily doses of pegvisomant (10 mg, 15 mg, and 20 mg) and placebo, g iven 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 gr oup, 26.7+/-27.9 percent in the group that received 10 mg of pegvisomant pe r 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 pegvis omant per day (P<0.001 for the comparison of each pegvisomant group with pl acebo), and the concentrations became normal in 10 percent, 54 percent, 81 percent, and 89 percent of patients, respectively (P<0.001 for each compari son with placebo). Among patients treated with 15 mg or 20 mg of pegvisoman t per day, there were significant decreases in ring size, soft-tissue swell ing, the degree of excessive perspiration, and fatigue. The score for total symptoms and signs of acromegaly decreased significantly in all groups rec eiving pegvisomant (P less/equal 0.05). The incidence of adverse effects wa s similar in all groups. Conclusions: On the basis of these preliminary results, treatment of patien ts who have acromegaly with a growth hormone-receptor antagonist results in a reduction in serum IGF-I concentrations and in clinical improvement. (N Engl J Med 2000;342:1171-7.) (C) 2000, Massachusetts Medical Society.