Pegvisomant and current approaches to the medical treatment of acromegaly (literature review and case report)
https://doi.org/10.14341/omet12207
Abstract
This review provides the main results of clinical trials and the literature on the experience of using pegvisomant, the first drug from the class of growth hormone receptor antagonists. The mechanism of action of the drug, its effectiveness with respect to disease control and its effect on complications, information on adverse events, and brief information on the experience of use during pregnancy are discussed in detail. In conclusion, a clinical observation of successful use of pegvisomant in resistant to standart treatment acromegaly is given. A discussion of the available literature data, the results of clinical studies and practical experience allows us to conclude that the drug is highly effective in terms of achieving biochemical remission of acromegaly, and also has a number of additional valuable properties: it is capable of improvement of patients’ glucose metabolism and quality of life and has a minimal amount of adverse events. Pegvisomant is currently registered in the Russian Federation only for use in monotherapy; the possibility of combination therapy with somatostatin analogues will additionally allow to reliably control the growth of the pituitary adenoma and significantly cut treatment costs by reducing the dose of pegvisomant. These features of the drug make it very relevant when discussing issues related to drug therapy of acromegaly, and suggest a good prospect for use in clinical practice.
About the Authors
Larisa K. DzeranovaRussian Federation
ScD
Alexandra A. Povaliaeva
Russian Federation
M.D.
Anastasia A. Romanova
Russian Federation
M.D.
Elena G. Przhiyalkovskaya
Russian Federation
PhD
Ekaterina A. Pigarova
Russian Federation
MD, PhD
Natalia S. Fedorova
Russian Federation
MD, PhD
References
1. Melmed S. Medical progress: Acromegaly. N Engl J Med. 2006;355(24):2558-2573. DOI:10.1056/NEJMra062453
2. Holdaway IM, Bolland MJ, Gamble GD. A meta-analysis of the effect of lowering serum levels of GH and IGF-I on mortality in acromegaly. Eur J Endocrinol. 2008;159(2):89-95. DOI:10.1530/EJE-08-0267
3. Melmed S, Bronstein MD, Chanson P, et al. A Consensus Statement on acromegaly therapeutic outcomes. Nat Rev Endocrinol. 2018;14(9):552-561. DOI:10.1038/s41574-018-0058-5
4. Stewart PM. Pegvisomant: an advance in clinical efficacy in acromegaly. Eur J Endocrinol. 2003;148 Suppl 2:S27-32. DOI:10.1530/eje.0.148s027
5. van der Lely AJ, Hutson RK, Trainer PJ, et al. Long-term treatment of acromegaly with pegvisomant, a growth hormone receptor antagonist. Lancet. 2001;358(9295):1754-1759. DOI:10.1016/s0140-6736(01)06844-1
6. Trainer PJ, Drake WM, Katznelson L, et al. Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant. N Engl J Med. 2000;342(16):1171-1177. DOI:10.1056/NEJM200004203421604
7. van der Lely AJ, Biller BMK, Brue T, et al. Long-Term Safety of Pegvisomant in Patients with Acromegaly: Comprehensive Review of 1288 Subjects in ACROSTUDY. J Clin Endocrinol Metab. 2012;97(5):1589-1597. DOI:10.1210/jc.2011-2508
8. Neggers SJ, van der Lely AJ. Combination treatment with somatostatin analogues and pegvisomant in acromegaly. Growth Horm IGF Res. 2011;21(3):129-133. DOI:10.1016/j.ghir.2011.03.004
9. Neggers SJ, de Herder WW, Janssen JA, et al. Combined treatment for acromegaly with long-acting somatostatin analogs and pegvisomant: long-term safety for up to 4.5 years (median 2.2 years) of follow-up in 86 patients. Eur J Endocrinol. 2009;160(4):529-533. DOI:10.1530/EJE-08-0843
10. Goffin V, Bernichtein S, Carriere O, et al. The human growth hormone antagonist B2036 does not interact with the prolactin receptor. Endocrinology. 1999;140(8):3853-3856. DOI:10.1210/endo.140.8.7047
11. Fuh G, Cunningham BC, Fukunaga R, et al. Rational design of potent antagonists to the human growth hormone receptor. Science. 1992;256(5064):1677-1680. DOI:10.1126/science.256.5064.1677
12. Olarescu NC, Ueland T, Godang K, et al. Inflammatory adipokines contribute to insulin resistance in active acromegaly and respond differently to different treatment modalities. Eur J Endocrinol. 2014;170(1):39-48. DOI:10.1530/EJE-13-0523
13. Agudo J, Ayuso E, Jimenez V, et al. Vascular endothelial growth factor-mediated islet hypervascularization and inflammation contribute to progressive reduction of beta-cell mass. Diabetes. 2012;61(11):2851-2861. DOI:10.2337/db12-0134
14. Rose DR, Clemmons DR. Growth hormone receptor antagonist improves insulin resistance in acromegaly. Growth Horm IGF Res. 2002;12(6):418-424. DOI:10.1016/s1096-6374(02)00083-7
15. Urbani C, Sardella C, Calevro A, et al. Effects of medical therapies for acromegaly on glucose metabolism. Eur J Endocrinol. 2013;169(1):99-108. DOI:10.1530/EJE-13-0032
16. Biagetti B, Obiols G, Valladares S, et al. Abnormalities of carbohydrate metabolism in acromegaly. Med Clin (Barc). 2013;141(10):442-446. DOI:10.1016/j.medcli.2013.05.035
17. Drake WM, Rowles SV, Roberts ME, et al. Insulin sensitivity and glucose tolerance improve in patients with acromegaly converted from depot octreotide to pegvisomant. Eur J Endocrinol. 2003;149(6):521-527. DOI:10.1530/eje.0.1490521
18. Droste M, Domberg J, Buchfelder M, et al. Therapy of acromegalic patients exacerbated by concomitant type 2 diabetes requires higher pegvisomant doses to normalise IGF1 levels. Eur J Endocrinol. 2014;171(1):59-68. DOI:10.1530/EJE-13-0438
19. van der Lely AJ, Bernabeu I, Cap J, et al. Coadministration of lanreotide Autogel and pegvisomant normalizes IGF1 levels and is well tolerated in patients with acromegaly partially controlled by somatostatin analogs alone. Eur J Endocrinol. 2011;164(3):325-333. DOI:10.1530/EJE-10-0867
20. Veldhuis JD. Lowering Total Plasma Insulin-Like Growth Factor I Concentrations by Way of a Novel, Potent, and Selective Growth Hormone (GH) Receptor Antagonist, Pegvisomant (B2036-Peg), Augments the Amplitude of GH Secretory Bursts and Elevates Basal/Nonpulsatile GH Release in Healthy Women and Men. J Clin Endocrinol Metab. 2001;86(7):3304-3310. DOI:10.1210/jc.86.7.3304
21. Buchfelder M, Weigel D, Droste M, et al. Pituitary tumor size in acromegaly during pegvisomant treatment: experience from MR re-evaluations of the German Pegvisomant Observational Study. Eur J Endocrinol. 2009;161(1):27-35. DOI:10.1530/EJE-08-0910
22. Marazuela M, Paniagua AE, Gahete MD, et al. Somatotroph tumor progression during pegvisomant therapy: a clinical and molecular study. J Clin Endocrinol Metab. 2011;96(2):E251-259. DOI:10.1210/jc.2010-1742
23. Parkinson C, Burman P, Messig M, Trainer PJ. Gender, body weight, disease activity, and previous radiotherapy influence the response to pegvisomant. J Clin Endocrinol Metab. 2007;92(1):190-195. DOI:10.1210/jc.2006-1412
24. Neggers SJ, Kopchick JJ, Jorgensen JO, van der Lely AJ. Hypothesis: Extra-hepatic acromegaly: a new paradigm? Eur J Endocrinol. 2011;164(1):11-16. DOI:10.1530/EJE-10-0969
25. Neggers SJ, van der Lely AJ. Pegvisomant and improvement of quality of life in acromegalic patients. Horm Res Paediatr. 2011;76 Suppl 1:102-105. DOI:10.1159/000329189
26. Auriemma RS, Pivonello R, De Martino MC, et al. Treatment with GH receptor antagonist in acromegaly: effect on cardiac arrhythmias. Eur J Endocrinol. 2013;168(1):15-22. DOI:10.1530/EJE-12-0596
27. Paisley AN, O’Callaghan CJ, Lewandowski KC, et al. Reductions of circulating matrix metalloproteinase 2 and vascular endothelial growth factor levels after treatment with pegvisomant in subjects with acromegaly. J Clin Endocrinol Metab. 2006;91(11):4635-4640. DOI:10.1210/jc.2005-2589
28. De Martino MC, Auriemma RS, Brevetti G, et al. The treatment with growth hormone receptor antagonist in acromegaly: effect on vascular structure and function in patients resistant to somatostatin analogues. J Endocrinol Invest. 2010;33(9):663-670. DOI:10.1007/BF03346667
29. Ghigo E, Biller BM, Colao A, et al. Comparison of pegvisomant and long-acting octreotide in patients with acromegaly naive to radiation and medical therapy. J Endocrinol Invest. 2009;32(11):924-933. DOI:10.3275/6723 10.1007/BF03345774
30. Neggers SJ, van Aken MO, Janssen JA, et al. Long-term efficacy and safety of combined treatment of somatostatin analogs and pegvisomant in acromegaly. J Clin Endocrinol Metab. 2007;92(12):4598-4601. DOI:10.1210/jc.2007-1234
31. Bernabeu I, Marazuela M, Lucas T, et al. Pegvisomant-induced liver injury is related to the UGT1A1*28 polymorphism of Gilbert’s syndrome. J Clin Endocrinol Metab. 2010;95(5):2147-2154. DOI:10.1210/jc.2009-2547
32. Kepicoglu H, Hatipoglu E, Bulut I, et al. Impact of treatment satisfaction on quality of life of patients with acromegaly. Pituitary. 2014;17(6):557-563. DOI:10.1007/s11102-013-0544-7
33. Brian SR, Bidlingmaier M, Wajnrajch MP, et al. Treatment of acromegaly with pegvisomant during pregnancy: maternal and fetal effects. J Clin Endocrinol Metab. 2007;92(9):3374-3377. DOI:10.1210/jc.2007-0997
34. van der Lely AJ, Gomez R, Heissler JF, et al. Pregnancy in acromegaly patients treated with pegvisomant. Endocrine. 2015;49(3):769-773. DOI:10.1007/s12020-014-0508-3
Supplementary files
![]() |
1. Picture 1 | |
Subject | ||
Type | Исследовательские инструменты | |
Download
(525KB)
|
Indexing metadata ▾ |
|
2. Fig. 1. Effects of somatostatin and pegvisomant analogues in patients with acromegaly (adapted from [24]) | |
Subject | ||
Type | Other | |
View
(375KB)
|
Indexing metadata ▾ |
|
3. Fig. 1. Effects of somatostatin and pegvisomant analogues in patients with acromegaly (adapted from [24]) | |
Subject | ||
Type | Other | |
View
(337KB)
|
Indexing metadata ▾ |
Review
For citations:
Dzeranova L.K., Povaliaeva A.A., Romanova A.A., Przhiyalkovskaya E.G., Pigarova E.A., Fedorova N.S. Pegvisomant and current approaches to the medical treatment of acromegaly (literature review and case report). Obesity and metabolism. 2019;16(4):73-79. (In Russ.) https://doi.org/10.14341/omet12207

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND 4.0).