Efficacy of 12-month treatment with the GH receptor antagonist pegvisomant in patients with acromegaly resistant to long-term, high-dose somatostatin analog treatment: effect on lGF-I levels, tumor mass, hypertension and glucose tolerance

Objective: We aimed to investigate the efficacy of pegvisomant in patients with acromegaly resistant to long-term (>= 24-month). high-dose treatment with octreotide-LAR (40 mg/month) or lanreotide (120 mg/month). Design: This was an open, prospective Study Subjects and Methods: We studied 16 patients with acromegaly (nine women: aged 28-61 years), The main outcome measures were IGF-I levels, blood pressure, glucose tolerance and safety (liver function and tumor size). Pegvisomant was given at doses of 10-40 mg S.C. daily. Dose titration was performed every month by IGF-I assay. Results: Three patients spontaneously stopped pegvisomant treatment after 6-9 months because of poor compliance: from the Measurement of serum pegvisomant. another patient was found not to inject herself property. After 6 months. IGF-I levels decreased by 63 +/- 19%, (767.8 +/- 152.9 vs 299.8 +/- 162.9 mu g/l. P < 0.0001. t-test): serum IGF-I levels normalized in 57%. After 12 months. IGF-I levels normalized in nine (75%,) patients and were reduced by over 50%, in another three (25%). The mean tumor Volume remained stable during the study (1198 +/- 1234 vs 1196 +/- 1351 mm(3) P = 0.37): it did not change (+/- 25% vs basal) in nine patients. increased by 39.4%, and 40.8% in two and decreased by 30.8-46.5%, in four. The total/high-density lipoprotein (HDL):cholesterol ratio (from 4.4 +/- 1.0 to 3.7 +/- 0.6. P=0.0012). glucose levels (from 5.6 +/- 1.2 to 4.4 +/- 1.4 mmol/l, P = 0.026), insulin levels (from 12.4 +/- 6.7 to 8.1 +/- 3.0 mUl/l, P = 0.0023) and homeostasis model assessment (HOMA) index (from 3.4 +/- 2.1 to 1.9 +/- 1.0, P = 0.0017) decreased. Conclusions: Treatment for 12 months with pegvisomant normalized IGF-I levels, and improved cardiovascular risk parameters and insulin sensitivity in patients with acromegaly resistant to long-term. high-dose treatment with somatostatin analogs. The tolerance of treatment was good.