Long-term treatment of acromegaly with pegvisomant, a growth hormone receptor antagonist

Background Pegvisomant is a new growth hormone receptor antagonist that imp roves symptoms and normalises insulinlike growth factor-1 (IGF-1) in a high proportion of patients with acromegaly treated for up to 12 weeks. We asse ssed the effects of pegvisomant in 160 patients with acromegaly treated for an average of 425 days. Methods Treatment efficacy was assessed by measuring changes in tumour volu me by magnetic resonance imaging, and serum growth hormone and IGF-1 concen trations in 152 patients who received pegvisomant by daily subcutaneous inj ection for up to 18 months. The safety analysis included 160 patients some of whom received weekly injections and are excluded from the efficacy analy sis. Findings Mean serum IGF-1 concentrations fell by at least 50%: 467 mug/L (S E 24), 526 mug/L (29), and 523 mug/L (40) in patients treated for 6, 12 and 18 months, respectively (p<0.001), whereas growth hormone increased by 12. 5 <mu>g/L (2.1), 12.5 mug/L (3.0), and 14.2 mug/L (5.7) (p<0.001). Of the p atients treated for 12 months or more, 87 of 90 (97%) achieved a normal ser um IGF-1 concentration. In patients withdrawn from pegvisomant (n=45), seru m growth hormone concentrations were 8.0 <mu>g/L (2.5) at baseline, rose to 15.2 mug/L (2.4) on drug, and fell back within 30 days of withdrawal to 8. 3 mug/L (2.7). Antibodies to growth hormone were detected in 27 (16.9%) of patients, but no tachyphylaxis was seen. Serum insulin and glucose concentr ations were significantly decreased (p<0.05). Two patients experienced prog ressive growth of their pituitary tumours, and two other patients had incre ased alanine and asparate aminotransferase concentrations requiring withdra wal from treatment. Mean pituitary tumour volume in 131 patients followed f or a mean of 11.46 months (0.70) decreased by 0.033 cm(3) (0.057; p=0.353). Interpretation Pegvisomant is an effective medical treatment for acromegaly .