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Pegvisomant in the treatment of acromegaly


Authors: Ivana Ságová 1,2;  Marián Mokáň 2;  Juraj Payer 3;  Peter Vaňuga 1
Authors place of work: Endokrinologické oddelenie, Národný endokrinologický a diabetologický ústav Ľubochňa 1;  1. interná klinika UN a JLFUK Martin 2;  V. interná klinika LFUK a UN Bratislava 3
Published in the journal: Vnitř Lék 2022; 68(E-7): 17-22
Category: Review Articles
doi: https://doi.org/10.36290/vnl.2022.101

Summary

Despite improvements in surgical techniques, current radiotherapy options and development of long-acting somatostatin analogues, biochemical control of acromegaly is not achieved in some patients. The failure to achieve optimal serum growth hormone (RH) and insulin-like growth factor-1 (IGF-1) levels means increased morbidity and mortality of acromegaly patients. The RH receptor antagonist pegvisomant (PEG) is a genetically engineered RH analog that prevents of RH receptor dimerization, i.e. a process that is crucial for the action of RH at the cellular level. The effect of the treatment is suppression of IGF-1 production. In pilot studies, normalization of IGF-1 levels was achieved in up to 90 % of patients receiving PEG. However, PEG efficacy in clinical settings is slightly lower (65 to 97 %) than reported in the key studies. A rare side effect of treatment is elevations of liver transaminases. In addition, pituitary tumor growth progression has been reported in several cases. In this review article, we present long-term data on pegvisomant treatment and discuss its associated risks and benefits.

Keywords:

Growth hormone – acromegaly – insulin‑like growth factor 1 – pegvisomant


Zdroje

1. John A Jane Jr., Edward R Laws. Surgical Treatment of Pituitary Adenomas. Dostupné z https://www.ncbi.nlm.nih.gov/books/NBK278983/.

2. Hána V, Švancara J, Bandúrová L, Brabec P et al. Acromegaly With Cardiomyopathy, Cardiac Thrombus and Hemorrhagic Cerebral Infarct: A Case Report of Therapeutic Dilemma With Review of Literature. Int J Endocrinol Metab. 2015; 13(2): 1-4.RESET: Diagnostic and therapy of acromegaly in Czech and Slovak republics in the 21st century. Diabetes, metabolizmus, endokrinologie a výživa. 2013;16:219-224.

3. Zahr R, Fleseriu M. Updates in Diagnosis and Treatment of Acromegaly. European Endocrinology. 2018;10:57-61.

4. Carmichael JD et al. Acromegaly clinical trial methodology impact on reported biochemical efficacy rates of somatostatin receptor ligand treatments: a meta‑analysis. J Clin Endocrinol Metab. 2014;99:1825-1833.

5. Gadelha MR, Bronstein MD, Brue T et al. Pasireotide versus continued treatment with octreotide or lanreotide in patients with inadequately controlled acromegaly (PAOLA): a randomised, phase 3 trial. Lancet: Diabetes and Endocrinology. 2014;2:875-884.

6. Kumar N, Shah NL. Pasireotide‑ induced hyperglycemia. MOJ Clin Med Case Rep. 2017;6(2):45-46.

7. Kopchick JJ, List EO, Kelder B, Gosney ES, Berryman DE. Evaluation of growth hormone (GH) action in mice: discovery of GH receptor antagonists and clinical indications. Mol Cell Endocrinol. 2014;386:34-45.

8. Ross RJM, Leung KC, Maamra M, Bennett W, et al. Binding and functional studies with the growth hormone receptor antagonist B2036-PEG (Pegvisomant), reveal effects of pegylation and evidence that it binds to a receptor dimer. J Clin Endocrinol Metab 2001;86:1716-1723.

9. Somavert. Summary of product characteristics. Pfizer 1

10. Somavert (Pegvisomant) for Injection, for Subcutaneous Use Prescribing Information. New York, NY: Pfizer, 2013.

11. Brue T. ACROSTUDY: status update on 469 patients. Hormone Research 2009;71: (Supplement 1) 34-38.

12. Neggers SJ, van der Lely AJ. Combination treatment with somatostatin analogues and pegvisomant in acromegaly. Growth Horm IGF Res. 2011;21:129-133.

13. Trainer PJ. ACROSTUDY: the first 5 years. European Journal of Endocrinology 2009;161: (Supplement 1) S19-S24.

14. van der Lely AJ, Biller BM, Brue T, Buchfelder M et al. Long‑term safety of pegvisomant in patients with acromegaly: comprehensive review of 1288 subjects in ACROSTUDY. Journal of Clinical Endocrinology and Metabolism. 2012;97:1589-1597.

15. Buchfelder M, van der Lely AJ, Biller BMK, Webb SM et al. Long‑term treatment with pegvisomant: observations from 2090 acromegaly patients in ACROSTUDY. European Journal of Endocrinology. 2018;179:419-427.

16. Brue T. ACROSTUDY: status update on 469 patients. Hormone Research 2009;71: (Supplement 1) 34-38.

17. Sesmilo G, Resmini E, Bernabeu I et al. Escape and lipodystrophy in acromegaly during pegvisomant therapy, a retrospective multicentre Spanish study. Clin Endocrinol (Oxf). 2014;81:883-890.

18. Gutierrez LP, Koltowska‑Haggstrom M, Jonsson PJ et al. Registries as a tool in evidence based medicine: example of KIMS (Pfizer International Metabolic Database). Pharmaco epidemiol Drug Saf. 2008;17:90-102.

19. Freda PU, Gordon MB, Kelepouris N et al. Long‑term treatment with pegvisomant as monotherapy in patients with acromegaly: experience from ACROSTUDY. Endocrine Practice. 2015;21:264-274.

20. Strasburger CJ, Mattsson A, Wilton P et al. Increasing frequency of combination medical therapy in the treatment of acromegaly with the GH receptor antagonist pegvisomant. European Journal of Endocrinology. 2018;178:321-329.

21. Chanson P, Brue T, Delemer B, Caron P et al. Médecins de l’Étude ACROSTUDY. Pegvisomant treatment in patients with acromegaly in clinical practice: the French ACROSTUDY. Annales d’Endocrinologie. 2015;76:664-670.

22. Fleseriu M, Führer‑Sakel D, van der Lely AJ, De Marinis L et al. More than a decade of real‑world experience of pegvisomant for acromegaly: ACROSTUDY. Eur J Endocrinol. 2021;185(4):525-538.

23.Drake WM, Rowles SV, Roberts ME, Fode FK et al. Insulin sensitivity and glucose tolerance improve in patients with acromegaly converted from depot octreotide to Pegvisomant. Eur J Endocrinol. 2003;149:521-527

24. Urbani C, Sardella C, Calevro A, Rossi G et al. Effects of medical therapies for acromegaly on glucose metabolism. Eur J Endocrinol 2013;169:99-108.

25. Ghigo E, Biller BM, Colao A, Kourides IA, Rajicic N et al. Comparison of Pegvisomant and long‑acting octreotide in patients with acromegaly naıve to radiation and medical therapy. J Endocrinol Invest. 2009;32:924-933.

26. Lindberg‑Larsen R, Møller N, Schmitz O, Nielsen S et al. The impact of Pegvisomant treatment on substrate metabolism and insulin sensitivity in patients with acromegaly. J Clin Endocrinol Metab. 2007;92:1724-1728.

27. Higham CE, Rowles S, Russell‑Jones D et al. Pegvisomant improves insulin sensitivity and reduces overnight free fatty acid concentrations in patients with acromegaly. J Clin Endocrinol Metab. 2009;94:2459-2463.

28. Rose DR, Clemmons Dr. Growth hormone receptor antagonist improves insulin resistance in acromegaly. Growth Horm IGF Res.2002;12:418-424.

29. Parkinson C, Drake WM, Wieringa G, Yates AP et al. Serum lipoprotein changes following IGF‑ I normalization using a growth hormone receptor antagonist in acromegaly. Clin Endocrinol. 2002;56:303-311.

30. Sesmilo G, Fairfield WP, Katznelson L et al. Cardiovascular risk factors in acromegaly before and after normalization of serum IGF‑ I levels with the GH antagonist Pegvisomant. J Clin Endocrinol Metab. 2002; 87:1692-1699.

31. Berg C, Petersenn S, Lahner H, Herrmann BL et al. Investigative Group of the Heinz Nixdorf Recall Study and the German Pegvisomant Observational Study Board and Investigators. Cardiovascular risk factors in patients with uncontrolled and long‑term acromegaly: comparison with matched data from the general population and the effect of disease control. J Clin Endocrinol Metab.2010;95:3648-3656.

32. Colao A, Pivonello R, Grasso LF, Auriemma RS et al. Determinants of cardiac disease in newly diagnosed patients with acromegaly: results of a 10 year survey study. Eur J Endocrinol. 2011;165:713-721.

33. Colao A, Pivonello R, Auriemma RS, De Martino MC et al. Efficacy of 12-monthtreatment with the GH receptor antagonist pegvisomant inpatients with acromegaly resistant to long‑term, high‑dosesomatostatin analog treatment: effect on IGF‑ I levels, tumor mass, hypertension and glucose tolerance. Eur J Endocrinol. 2006;154(3):467-477.

34. Auriemma RS, Pivonello R, De Martino MC et al. Treatmentwith GH receptor antagonist in acromegaly: effect on cardiacarrhythmias. Eur J Endocrinol. 2012;168(1):15-22.

35. De Martino MC, Auriemma RS, Brevetti G et al. The treatment with growth hormone receptor antagonistin acromegaly: effect on vascular structure and function in patients resistant to somatostatin analogues. J Endocrinol Invest. 2010;33(9):663-670.

36. Pivonello R, Galderisi M, Auriemma RS, De Martino MC et al. Treatment with growth hormonereceptor antagonist in acromegaly: effect on cardiac structure and performance. J Clin Encocrinol Metab. 2007;92(2):476-482.

37. Kuhn E, Maione L, Bouchachi A et al. Long‑term effects ofpegvisomant on comorbidities in patients with acromegaly: retrospective single‑ center study. Eur J Endocrinol. 2015;173(5):693-702.

38. Auriemma RS, Grasso LF, Galdiero M, Galderisi M et al. Effects of long‑term combined treatment with somatostatin analogues and pegvisomant on cardiac structure and performance in acromegaly. Endocrine. 2016;55:872-884.

39. 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;164:325-333.

40. Schreiber I, Buchfelder M, Droste M et al. Treatment of acromegaly with the GH receptor antagonist pegvisomant in clinical practice: safety and efficacy evaluation from the German Pegvisomant Observational Study. Eur J Endocrinol 2007;156:75-82.

41. 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;92:4598-4601.

42. Neggers SJ, Franck SE, de Rooij FW et al. Long term efficacy and safety of pegvisomant in combination with long‑acting somatostatin analogues in acromegaly. J Clin Endocrinol Metab. 2014;99:3644-3652.

43. 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: 2147-2154.

44. Madsen M, Krusenstjerna‑Hafstrom T, Moller L et al. Fat content in liver and skeletal muscle changes in a reciprocal manner in patients with acromegaly during combination therapy with a somatostatin analog and a GH receptor antagonist: a randomized clinical trial. J Clin Endocrinol Metab. 2012;97:1227-1235.

45. 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: E251-E259.

46. De Marinis L, Bonadonna S, Bianchi A et al. Primary empty sella. J Clin Endocrinol Metab. 2005;90:5471-5477.

47. Sandret L, Maison P, Chanson P. Place of cabergoline in acromegaly: a meta‑analysis. J Clin Endocrinol Metab. 2011; 96:1325-1335.

48. Melmed S, Colao A, Barkan A et al. Acromegaly Consensus Group. Guidelines for acromegaly management: an update. J Clin Endocrinol Metab. 2009;94:1509-1517.

49. Giustina A, Ambrosio MR, Beck Peccoz P et al. Use of Pegvisomant in acromegaly. An Italian Society of Endocrinology guideline. J Endocrinol Invest. 2014;37(10):1017-30.

Štítky
Diabetology Endocrinology Internal medicine
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