Lipoatrophy in GH deficient patients treated with a long-acting pegylated GH

• Published in: European journal of endocrinology Vol. 161; no. 4; pp. 533 - 540
• Main Authors: Touraine, Philippe, D'Souza, Gwyn A, Kourides, Ione, Abs, Roger, Barclay, Paul, Xie, Rujia, Pico, Antonio, Torres-Vela, Elena, Ekman, Bertil
• Format: Journal Article
• Language: English
• Published: Bristol BioScientifica 01.10.2009
• Subjects: Adipose Tissue - pathology; Adult; Atrophy; Biological and medical sciences; Clinical Study; Delayed-Action Preparations; Dermatology; Double-Blind Method; Endocrinopathies; Female; Fundamental and applied biological sciences. Psychology; Headache - chemically induced; Headache - epidemiology; Human Growth Hormone - adverse effects; Human Growth Hormone - deficiency; Human Growth Hormone - therapeutic use; Humans; Injections, Subcutaneous; Insulin-Like Growth Factor Binding Protein 3 - metabolism; Insulin-Like Growth Factor I - metabolism; Male; Medical sciences; MEDICIN; MEDICINE; Middle Aged; Pharmaceutic Aids; Pharmaceutical Solutions; Polyethylene Glycols; Recombinant Proteins; Skin involvement in other diseases. Miscellaneous. General aspects; Vertebrates: endocrinology; Human; Somatotropin; Skin disease; Adenohypophyseal hormone; Hormone therapy; Controlled release form; Lipoatrophy; Deficiency; Patient; Adipose tissue disorders; Pegylated form; Endocrinology
• ISSN: 0804-4643; 1479-683X; 1479-683X
• DOI: 10.1530/EJE-09-0422

ObjectiveChanges observed during adult GH deficiency (GHD) are most often reversed with the administration of recombinant human GH (rhGH). To avoid daily injections, a long-acting GH molecule has been obtained by covalent binding of polyethylene glycol (PEG) with rhGH (PEG–GH), allowing weekly s.c. injections. This study was designed to assess its efficacy and safety, in adult GHD subjects.Design and methodsThis was a randomized, double-blind, placebo-controlled, multiple-dose, parallel group study. Subjects were recruited from 34 centers. A total of 105 subjects with GHD were assigned a treatment. They received 6 weekly injections of either PEG–GH or placebo. Subjects were randomized into one out of four treatment groups (Groups A–D) or placebo (Group E). Groups A, B, and C received 1, 3, and 4 mg PEG–GH respectively, for the first 3 weeks followed by 2, 6, and 8 mg PEG–GH respectively, for the remaining 3 weeks. Group D received 4 mg PEG–GH for 6 weeks. Group E received placebo. The study was suspended because of the development of lipoatrophy in certain subjects and restarted with an injection rotation plan, before being terminated due to further subjects developing lipoatrophy.ResultsA total of 13 cases of injection-site lipoatrophy were reported, of which ten were in females and three occurred after the first injection; all cases were independent of PEG–GH dose or IGF1 levels, either basal or under treatment.ConclusionThe unpredictable occurrence of injection-site lipoatrophy with weekly long-acting pegylated GH molecules may be a limiting factor for their development.