nach oben

Journal of Endocrinological Investigation

Erschienen in:

11.09.2023 | Original Article

Pasireotide effects on biochemical control and glycometabolic profile in acromegaly patients switched from combination therapies or unconventional dosages of somatostatin analogs

verfasst von: G. Corica, R. Pirchio, A. Milioto, F. Nista, A. Arecco, L. Mattioli, R. S. Auriemma, F. Cocchiara, R. Pivonello, A. Colao, D. Ferone, F. Gatto

Erschienen in: Journal of Endocrinological Investigation | Ausgabe 3/2024

Einloggen, um Zugang zu erhalten

Abstract

Purpose

To evaluate the impact of pasireotide (PAS) therapy on hormonal and glycometabolic outcome in patients with acromegaly previously treated with combination medical therapies or unconventional dosages of first-generation somatostatin receptor ligands (fg-SRLs).

Methods

Retrospective study carried out in two referral centers for pituitary diseases. Twenty-one acromegalic patients were switched to PAS (12 had biochemical control, 9 were uncontrolled). Data were collected after 3- and 6-months PAS treatment, and at the last available visit (median 35 months).

Results

After switching to PAS therapy, a significant reduction in IGF-1 values was observed [median 39%; 0.79 xULN (IQR 0.5–1.01) vs 1.29 xULN (IQR 1.06–1.83); p = 0.009]. IGF-1 reduction was statistically significant in the 9 patients previously uncontrolled (61%, p = 0.016), and in the 12 controlled subjects (33%, p = 0.037). At last follow-up, the number of patients reaching an acceptable biochemical control (IGF-1 < 1.3 xULN) raised from 57 to 90% (p = 0.032). Mean HbA1c levels increased from 5.7% (5.5–5.9) to 6.0% (5.9–7) (p = 0.002), and the percentage of diabetic patients raised from 14% (3/21) to 67% (14/21) (p = 0.004). At the last evaluation HbA1c was ≥ 7.0% in 5 patients (24%). Antidiabetic drugs were initiated in 9 new patients, and in 7 out of 9 metformin alone was effective. Younger age and male sex were predictors for the maintenance of glucose homeostasis.

Conclusion

PAS monotherapy can be effective in acromegalic patients previously treated with combination medical therapies or unconventional dosages of fg-SRLs. Glucose imbalance can be managed in the vast majority of cases by use of lifestyle interventions and metformin.

Nur mit Berechtigung zugänglich

Melmed S (2009) Acromegaly pathogenesis and treatment. J Clin Invest 119(11):3189–3202. https://doi.org/10.1172/JCI39375CrossRefPubMedPubMedCentral

Crisafulli S, Luxi N, Sultana J et al (2021) Global epidemiology of acromegaly: a systematic review and meta-analysis. Eur J Endocrinol 185(2):251–263. https://doi.org/10.1530/EJE-21-0216CrossRefPubMed

Melmed S (2006) Medical progress: Acromegaly. N Engl J Med 355(24):2558–2573. https://doi.org/10.1056/NEJMra062453CrossRefPubMed

Holdaway IM, Bolland MJ, Gamble GD (2008) A meta-analysis of the effect of lowering serum levels of GH and IGF-I on mortality in acromegaly. Eur J Endocrinol 159(2):89–95. https://doi.org/10.1530/EJE-08-0267CrossRefPubMed

Corica G, Ceraudo M, Campana C et al (2020) Octreotide-resistant acromegaly: challenges and solutions. Ther Clin Risk Manag 16:379–391. https://doi.org/10.2147/TCRM.S183360CrossRefPubMedPubMedCentral

Gatto F, Trifiro G, Lapi F et al (2018) Epidemiology of acromegaly in Italy: analysis from a large longitudinal primary care database. Endocrine 61(3):533–541. https://doi.org/10.1007/s12020-018-1630-4CrossRefPubMed

Melmed S, Bronstein MD, Chanson P et al (2018) A consensus statement on acromegaly therapeutic outcomes. Nat Rev Endocrinol 14(9):552–561. https://doi.org/10.1038/s41574-018-0058-5CrossRefPubMedPubMedCentral

Giustina A, Chanson P, Kleinberg D et al (2014) Expert consensus document: a consensus on the medical treatment of acromegaly. Nat Rev Endocrinol 10(4):243–248. https://doi.org/10.1038/nrendo.2014.21CrossRefPubMed

Gatto F, Campana C, Cocchiara F et al (2019) Current perspectives on the impact of clinical disease and biochemical control on comorbidities and quality of life in acromegaly. Rev Endocr Metab Disord 20(3):365–381. https://doi.org/10.1007/s11154-019-09506-yCrossRefPubMed

10.

Mazziotti G, Battista C, Maffezzoni F et al (2020) Treatment of acromegalic osteopathy in real-life clinical practice: the BAAC (Bone Active Drugs in Acromegaly) study. J Clin Endocrinol Metab. https://doi.org/10.1210/clinem/dgaa363CrossRefPubMedPubMedCentral

11.

Babu H, Ortega A, Nuno M et al (2017) Long-term endocrine outcomes following endoscopic endonasal transsphenoidal surgery for acromegaly and associated prognostic factors. Neurosurgery 81(2):357–366. https://doi.org/10.1093/neuros/nyx020CrossRefPubMed

12.

Colao A, Auriemma RS, Pivonello R et al (2016) Interpreting biochemical control response rates with first-generation somatostatin analogues in acromegaly. Pituitary 19(3):235–247. https://doi.org/10.1007/s11102-015-0684-zCrossRefPubMed

13.

Colao A, Auriemma RS, Lombardi G et al (2011) Resistance to somatostatin analogs in acromegaly. Endocr Rev 32(2):247–271. https://doi.org/10.1210/er.2010-0002CrossRefPubMed

14.

Gadelha MR, Wildemberg LE, Kasuki L (2022) The future of somatostatin receptor ligands in acromegaly. J Clin Endocrinol Metab 107(2):297–308. https://doi.org/10.1210/clinem/dgab726CrossRefPubMed

15.

Gadelha MR, Wildemberg LE, Bronstein MD et al (2017) Somatostatin receptor ligands in the treatment of acromegaly. Pituitary 20(1):100–108. https://doi.org/10.1007/s11102-017-0791-0CrossRefPubMed

16.

Fleseriu M, Biller BMK, Freda PU et al (2021) A pituitary society update to acromegaly management guidelines. Pituitary 24(1):1–13. https://doi.org/10.1007/s11102-020-01091-7CrossRefPubMed

17.

Cocchiara F, Campana C, Nista F et al (2022) Evaluation of acromegaly treatment direct costs with respect to biochemical control and follow-up length. Pituitary 25(2):246–257. https://doi.org/10.1007/s11102-021-01193-wCrossRefPubMed

18.

Giustina A, Bonadonna S, Bugari G et al (2009) High-dose intramuscular octreotide in patients with acromegaly inadequately controlled on conventional somatostatin analogue therapy: a randomised controlled trial. Eur J Endocrinol 161(2):331–338. https://doi.org/10.1530/EJE-09-0372CrossRefPubMed

19.

Giustina A, Mazziotti G, Cannavo S et al (2017) High-dose and high-frequency Lanreotide Autogel in acromegaly: a randomized Multicenter Study. J Clin Endocrinol Metab 102(7):2454–2464. https://doi.org/10.1210/jc.2017-00142CrossRefPubMed

20.

Colao A, Pivonello R, Auriemma RS et al (2007) Beneficial effect of dose escalation of octreotide-LAR as first-line therapy in patients with acromegaly. Eur J Endocrinol 157(5):579–587. https://doi.org/10.1530/EJE-07-0383CrossRefPubMed

21.

Auriemma RS, Pivonello R, Ferreri L et al (2015) Cabergoline use for pituitary tumors and valvular disorders. Endocrinol Metab Clin North Am 44(1):89–97. https://doi.org/10.1016/j.ecl.2014.10.007CrossRefPubMed

22.

Sandret L, Maison P, Chanson P (2011) Place of cabergoline in acromegaly: a meta-analysis. J Clin Endocrinol Metab 96(5):1327–1335. https://doi.org/10.1210/jc.2010-2443CrossRefPubMed

23.

Coopmans EC, van Meyel SWF, van der Lely AJ et al (2019) The position of combined medical treatment in acromegaly. Arch Endocrinol Metab 63(6):646–652. https://doi.org/10.20945/2359-3997000000195CrossRefPubMedPubMedCentral

24.

Fleseriu M, Fuhrer-Sakel D, van der Lely AJ et al (2021) More than a decade of real-world experience of pegvisomant for acromegaly: ACROSTUDY. Eur J Endocrinol 185(4):525–538. https://doi.org/10.1530/EJE-21-0239CrossRefPubMedPubMedCentral

25.

Colao A, Bronstein MD, Freda P et al (2014) Pasireotide versus octreotide in acromegaly: a head-to-head superiority study. J Clin Endocrinol Metab 99(3):791–799. https://doi.org/10.1210/jc.2013-2480CrossRefPubMedPubMedCentral

26.

Gadelha MR, Bronstein MD, Brue T et al (2014) Pasireotide versus continued treatment with octreotide or lanreotide in patients with inadequately controlled acromegaly (PAOLA): a randomised, phase 3 trial. Lancet Diabetes Endocrinol 2(11):875–884. https://doi.org/10.1016/S2213-8587(14)70169-XCrossRefPubMed

27.

Samson SL, Gu F, Feldt-Rasmussen U et al (2021) Managing pasireotide-associated hyperglycemia: a randomized, open-label Phase IV study. Pituitary 24(6):887–903. https://doi.org/10.1007/s11102-021-01161-4CrossRefPubMedPubMedCentral

28.

Bolanowski M, Kaluzny M, Witek P et al (2022) Pasireotide-a novel somatostatin receptor ligand after 20 years of use. Rev Endocr Metab Disord 23(3):601–620. https://doi.org/10.1007/s11154-022-09710-3CrossRefPubMedPubMedCentral

29.

Coopmans EC, Muhammad A, van der Lely AJ et al (2019) How to position pasireotide LAR treatment in acromegaly. J Clin Endocrinol Metab 104(6):1978–1988. https://doi.org/10.1210/jc.2018-01979CrossRefPubMed

30.

Bruns C, Lewis I, Briner U et al (2002) SOM230: a novel somatostatin peptidomimetic with broad somatotropin release inhibiting factor (SRIF) receptor binding and a unique antisecretory profile. Eur J Endocrinol 146(5):707–716. https://doi.org/10.1530/eje.0.1460707CrossRefPubMed

31.

Gatto F, Biermasz NR, Feelders RA et al (2016) Low beta-arrestin expression correlates with the responsiveness to long-term somatostatin analog treatment in acromegaly. Eur J Endocrinol 174(5):651–662. https://doi.org/10.1530/EJE-15-0391CrossRefPubMed

32.

Gatto F, Arvigo M, Amaru J et al (2019) Cell specific interaction of pasireotide: review of preclinical studies in somatotroph and corticotroph pituitary cells. Pituitary 22(1):89–99. https://doi.org/10.1007/s11102-018-0926-yCrossRefPubMed

33.

Poll F, Lehmann D, Illing S et al (2010) Pasireotide and octreotide stimulate distinct patterns of sst2A somatostatin receptor phosphorylation. Mol Endocrinol 24(2):436–446. https://doi.org/10.1210/me.2009-0315CrossRefPubMedPubMedCentral

34.

Gatto F, Barbieri F, Arvigo M et al (2019) Biological and biochemical basis of the differential efficacy of first and second generation somatostatin receptor ligands in neuroendocrine neoplasms. Int J Mol Sci. https://doi.org/10.3390/ijms20163940CrossRefPubMedPubMedCentral

35.

Schmid HA (2008) Pasireotide (SOM230): development, mechanism of action and potential applications. Mol Cell Endocrinol 286(1–2):69–74. https://doi.org/10.1016/j.mce.2007.09.006CrossRefPubMed

36.

Gadelha M, Bex M, Colao A et al (2019) Evaluation of the efficacy and safety of switching to pasireotide in patients with acromegaly inadequately controlled with first-generation somatostatin analogs. Front Endocrinol (Lausanne) 10:931. https://doi.org/10.3389/fendo.2019.00931CrossRefPubMed

37.

Colao A, Bronstein MD, Brue T et al (2020) Pasireotide for acromegaly: long-term outcomes from an extension to the Phase III PAOLA study. Eur J Endocrinol 182(6):583. https://doi.org/10.1530/EJE-19-0762CrossRefPubMedPubMedCentral

38.

Gatto F, Feelders RA, Franck SE et al (2017) In vitro head-to-head comparison between octreotide and pasireotide in GH-secreting pituitary adenomas. J Clin Endocrinol Metab 102(6):2009–2018. https://doi.org/10.1210/jc.2017-00135CrossRefPubMed

39.

Lasolle H, Ferriere A, Vasiljevic A et al (2019) Pasireotide-LAR in acromegaly patients treated with a combination therapy: a real-life study. Endocr Connect 8(10):1383–1394. https://doi.org/10.1530/EC-19-0332CrossRefPubMedPubMedCentral

40.

Witek P, Bolanowski M, Szamotulska K et al (2021) The effect of 6 months’ treatment with pasireotide LAR on glucose metabolism in patients with resistant acromegaly in real-world clinical settings. Front Endocrinol (Lausanne) 12:633944. https://doi.org/10.3389/fendo.2021.633944CrossRefPubMed

41.

Shimon I, Adnan Z, Gorshtein A et al (2018) Efficacy and safety of long-acting pasireotide in patients with somatostatin-resistant acromegaly: a multicenter study. Endocrine 62(2):448–455. https://doi.org/10.1007/s12020-018-1690-5CrossRefPubMed

42.

Stelmachowska-Banas M, Czajka-Oraniec I, Tomasik A et al (2022) Real-world experience with pasireotide-LAR in resistant acromegaly: a single center 1-year observation. Pituitary 25(1):180–190. https://doi.org/10.1007/s11102-021-01185-wCrossRefPubMed

43.

Muhammad A, van der Lely AJ, Delhanty PJD et al (2018) Efficacy and safety of switching to pasireotide in patients with acromegaly controlled with pegvisomant and first-generation somatostatin analogues (PAPE Study). J Clin Endocrinol Metab 103(2):586–595. https://doi.org/10.1210/jc.2017-02017CrossRefPubMed

44.

American Diabetes Association Professional Practice C, American Diabetes Association Professional Practice C, Practice C, Draznin B et al (2022) Classification and diagnosis of diabetes: standards of medical care in diabetes-2022. Diabetes Care 45(Suppl 1):S17–S38. https://doi.org/10.2337/dc22-S002CrossRef

45.

Giustina A, Barkhoudarian G, Beckers A et al (2020) Multidisciplinary management of acromegaly: a consensus. Rev Endocr Metab Disord 21(4):667–678. https://doi.org/10.1007/s11154-020-09588-zCrossRefPubMedPubMedCentral

46.

van Esdonk MJ, van Zutphen EJM, Roelfsema F et al (2018) How are growth hormone and insulin-like growth factor-1 reported as markers for drug effectiveness in clinical acromegaly research? A comprehensive methodologic review. Pituitary 21(3):310–322. https://doi.org/10.1007/s11102-018-0884-4CrossRefPubMedPubMedCentral

47.

Fleseriu M, Dreval A, Bondar I et al (2022) Maintenance of response to oral octreotide compared with injectable somatostatin receptor ligands in patients with acromegaly: a phase 3, multicentre, randomised controlled trial. Lancet Diabetes Endocrinol 10(2):102–111. https://doi.org/10.1016/S2213-8587(21)00296-5CrossRefPubMed

48.

Fleseriu M, Molitch M, Dreval A et al (2021) Disease and treatment-related burden in patients with acromegaly who are biochemically controlled on injectable somatostatin receptor ligands. Front Endocrinol (Lausanne) 12:627711. https://doi.org/10.3389/fendo.2021.627711CrossRefPubMed

49.

Giustina A, Barkan A, Beckers A et al (2020) A consensus on the diagnosis and treatment of acromegaly comorbidities: an update. J Clin Endocrinol Metab. https://doi.org/10.1210/clinem/dgz096CrossRefPubMedPubMedCentral

50.

Kasuki L, Wildemberg LE, Gadelha MR (2018) Management of endocrine disease: Personalized medicine in the treatment of acromegaly. Eur J Endocrinol 178(3):R89–R100. https://doi.org/10.1530/EJE-17-1006CrossRefPubMed

51.

Gadelha M, Marques NV, Fialho C et al (2023) Long-term efficacy and safety of pasireotide in patients with acromegaly: 14 years’ single-center real-world experience. J Clin Endocrinol Metab. https://doi.org/10.1210/clinem/dgad378CrossRefPubMedPubMedCentral

52.

Mondin A, Manara R, Voltan G et al (2022) Pasireotide-induced shrinkage in GH and ACTH secreting pituitary adenoma: a systematic review and meta-analysis. Front Endocrinol (Lausanne) 13:935759. https://doi.org/10.3389/fendo.2022.935759CrossRefPubMed

53.

Henry RR, Ciaraldi TP, Armstrong D et al (2013) Hyperglycemia associated with pasireotide: results from a mechanistic study in healthy volunteers. J Clin Endocrinol Metab 98(8):3446–3453. https://doi.org/10.1210/jc.2013-1771CrossRefPubMed

54.

Gadelha MR, Gu F, Bronstein MD et al (2020) Risk factors and management of pasireotide-associated hyperglycemia in acromegaly. Endocr Connect 9(12):1178–1190. https://doi.org/10.1530/EC-20-0361CrossRefPubMedPubMedCentral

55.

Dal J, Rosendal C, Karmisholt J et al (2023) Sex difference in patients with controlled acromegaly-A multicentre survey. Clin Endocrinol (Oxf) 98(1):74–81. https://doi.org/10.1111/cen.14750CrossRefPubMed

56.

Pivonello R, Auriemma RS, Grasso LF et al (2017) Complications of acromegaly: cardiovascular, respiratory and metabolic comorbidities. Pituitary 20(1):46–62. https://doi.org/10.1007/s11102-017-0797-7CrossRefPubMed

57.

Giordano C, Ciresi A, Amato MC et al (2012) Clinical and metabolic effects of first-line treatment with somatostatin analogues or surgery in acromegaly: a retrospective and comparative study. Pituitary 15(4):539–551. https://doi.org/10.1007/s11102-011-0365-5CrossRefPubMed

58.

Reyes-Vidal C, Fernandez JC, Bruce JN et al (2014) Prospective study of surgical treatment of acromegaly: effects on ghrelin, weight, adiposity, and markers of CV risk. J Clin Endocrinol Metab 99(11):4124–4132. https://doi.org/10.1210/jc.2014-2259CrossRefPubMedPubMedCentral

59.

Caron PJ, Petersenn S, Houchard A et al (2017) Glucose and lipid levels with lanreotide autogel 120 mg in treatment-naive patients with acromegaly: data from the PRIMARYS study. Clin Endocrinol (Oxf) 86(4):541–551. https://doi.org/10.1111/cen.13285CrossRefPubMed

60.

Chen X, Shen G, Jiang J et al (2014) Pharmacokinetics and safety of subcutaneous pasireotide and intramuscular pasireotide long-acting release in Chinese male healthy volunteers: a phase I, single-center, open-label, randomized study. Clin Ther 36(8):1196–1210. https://doi.org/10.1016/j.clinthera.2014.06.006CrossRefPubMed

61.

Albani A, Ferrau F, Ciresi A et al (2018) Pasireotide treatment reduces cardiometabolic risk in Cushing’s disease patients: an Italian, multicenter study. Endocrine 61(1):118–124. https://doi.org/10.1007/s12020-018-1524-5CrossRefPubMed

62.

Simeoli C, Ferrigno R, De Martino MC et al (2020) The treatment with pasireotide in Cushing’s disease: effect of long-term treatment on clinical picture and metabolic profile and management of adverse events in the experience of a single center. J Endocrinol Invest 43(1):57–73. https://doi.org/10.1007/s40618-019-01077-8CrossRefPubMed

Titel: Pasireotide effects on biochemical control and glycometabolic profile in acromegaly patients switched from combination therapies or unconventional dosages of somatostatin analogs
verfasst von: G. Corica
R. Pirchio
A. Milioto
F. Nista
A. Arecco
L. Mattioli
R. S. Auriemma
F. Cocchiara
R. Pivonello
A. Colao
D. Ferone
F. Gatto
Publikationsdatum: 11.09.2023
Verlag: Springer International Publishing
Erschienen in: Journal of Endocrinological Investigation / Ausgabe 3/2024
Elektronische ISSN: 1720-8386
DOI: https://doi.org/10.1007/s40618-023-02186-1

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Pasireotide effects on biochemical control and glycometabolic profile in acromegaly patients switched from combination therapies or unconventional dosages of somatostatin analogs