Lessons from 6 years of GH receptor antagonist therapy for acromegaly.

Pegvisomant is a GH receptor antagonist and a new agent for the medical management of acromegaly. The clinical efficacy and safety of pegvisomant in the treatment of active acromegaly were demonstrated in a 12-week, placebo-controlled trial of 112 patients. After a washout period, patients were randomized to a fixed dose of pegvisomant (10, 15 or 20 mg/day) or placebo given by sc injection. Serum IGF-I levels were within the normal age-adjusted reference range in 54, 81 and 89% of patients in the 10-, 15- and 20-mg/day groups, respectively. The decrease in serum IGF-I levels was accompanied by considerable improvement in the signs and symptoms of active acromegaly. This efficacy profile was maintained in a long-term continuation trial, with normalization of serum IGF-I at 12 months occurring in 97% of patients. Pegvisomant has been well tolerated with an adverse event profile similar to placebo. Two patients had elevations in liver function tests that resolved after discontinuing treatment with pegvisomant. During treatment with pegvisomant, liver function tests should be monitored on a regular basis. Two patients had an increase in pituitary tumor volume during pegvisomant therapy; however, the relationship to pegvisomant therapy was not clear. In 131 patients treated for at least 6 months, there was no increase in mean tumor volume, regardless of whether they underwent previous radiotherapy. Pegvisomant is an effective new treatment for the management of patients with acromegaly. Longer-term data are needed to confirm the safety profile that has been demonstrated in studies up to 18 months.