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 IGF-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 (> or = 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 properly. After 6 months, IGF-I levels decreased by 63 +/- 19% (767.8 +/- 152.9 vs 299.8 +/- 162.9 microg/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.