Long-Term Efficacy and Safety of Combined Treatment of Somatostatin Analogs and Pegvisomant in Acromegaly

• Published in: The journal of clinical endocrinology and metabolism Vol. 92; no. 12; pp. 4598 - 4601
• Main Authors: Neggers, Sebastian J. C. M. M., van Aken, Maarten O., Janssen, Joop A. M. J. L., Feelders, Richard A., de Herder, Wouter W., van der Lely, Aart-Jan
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Oxford University Press 01.12.2007; Endocrine Society
• Subjects: Acromegaly; Acromegaly - drug therapy; Acromegaly - psychology; Adult; Aged; Aged, 80 and over; Biological and medical sciences; Diabetes; Diabetes Complications - complications; Diabetes Complications - drug therapy; Diabetes mellitus; Diabetes Mellitus - metabolism; Dosage; Endocrinopathies; Enzymes; Feeding. Feeding behavior; Female; Follow-Up Studies; Fundamental and applied biological sciences. Psychology; Hormone Antagonists - adverse effects; Hormone Antagonists - therapeutic use; Human Growth Hormone - adverse effects; Human Growth Hormone - analogs & derivatives; Human Growth Hormone - blood; Human Growth Hormone - therapeutic use; Humans; Hypothalamus. Hypophysis. Epiphysis (diseases); Insulin-like growth factor I; Insulin-Like Growth Factor I - metabolism; Liver; Liver Function Tests; Male; Medical sciences; Middle Aged; Non tumoral diseases. Target tissue resistance. Benign neoplasms; Pituitary; Quality of Life; Somatostatin; Somatostatin - adverse effects; Somatostatin - analogs & derivatives; Somatostatin - therapeutic use; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology; Endocrinopathy; Obesity; Nutrition; Pegvisomant; Toxicity; Treatment efficiency; Peptide hormone; Diseases of the osteoarticular system; Nutrition disorder; Acromegaly; Metabolic diseases; Neuropeptide; Long term; Somatotropin; Adenohypophyseal hormone; Analog; Pituitary diseases; Combined treatment; Antagonist; Somatostatin; Safety; Endocrinology; Nutritional status
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2007-1234

Background: We previously reported the efficacy of a combined treatment of active acromegaly with both long-acting somatostatin analogs (SSA) and pegvisomant (PEG-V). Objective: Our objective was to assess long-term efficacy and safety in a larger group of acromegalic patients after a period of 138 (35–149) wk [median (range)]. Design: PEG-V was added to high-dose SSA treatment in 32 subjects (13 females) who had not shown a normalization in serum IGF-I concentrations during SSA monotherapy. PEG-V dosage was increased until IGF-I concentration normalized. The maximal dose was 80 mg twice weekly. Results: After dose finding, IGF-I remained within the normal range in all subjects with PEG-V administered once (n = 24) or twice (n = 8) weekly, on a total weekly dose of 60 (40–160) mg. Baseline IGF-I levels were positively correlated with the required dosage of PEG-V (r = 0.48; P = 0.006). PEG-V-dependent liver enzyme disturbances were observed in 11 (6 diabetic) subjects, of which symptomatic gallstones explained two cases. These liver enzyme disturbances were transient in all subjects without discontinuation or dose adaptation of PEG-V. In our series, diabetic patients had a 5.1 times (odds ratio) (confidence interval, 1.02–25.54; P < 0.05) higher risk for developing liver enzyme disturbances. These liver enzyme disturbances seemed to occur earlier. Pituitary adenoma size decreased in four patients. No increase in tumor size was observed in any of the patients. Conclusion: Long-term combined treatment with long-acting SSA and (twice) weekly PEG-V for active acromegaly seems to be effective and safe. Patients with acromegaly and diabetes seem to have a higher risk of developing transient liver enzyme disturbances.