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Erschienen in: Endocrine 2/2021

03.06.2021 | Original Article

Long-term safety and efficacy of long-acting pasireotide in acromegaly

verfasst von: Amit Akirov, Alexander Gorshtein, Idit Dotan, Nariman Saba Khazen, Yulia Pauker, Michal Gershinsky, Ilan Shimon

Erschienen in: Endocrine | Ausgabe 2/2021

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Abstract

Background

Pasireotide long acting (LAR) can be effective in normalizing insulin-like growth factor (IGF)-1 level in acromegaly patients inadequately controlled by octreotide or lanreotide.

Objective

Determine the long-term efficacy and safety of pasireotide, including time to biochemical control and time to best response, and risk for diabetes mellitus.

Methods

A retrospective multicenter study investigating the efficacy and safety of pasireotide LAR treatment in patients with active acromegaly treated for >12 months.

Results

The study included 19 patients (10 men; mean age ± SD, 48.0 ± 12.9 years) treated with pasireotide for a mean of 50 ± 36 months. During the follow-up, 4 patients discontinued pasireotide treatment. Pasireotide LAR produced a tolerable and long-term significant biochemical response in 15 of 19 patients (79.0%). Mean time to IGF-1 normalization from pasireotide LAR initiation was 13.6 ± 16.9 months with early biochemical normalization (<12 months) evident in 11 (64.7%) patients and delayed IGF-1 normalization in 6 (35.2%) patients. Nadir IGF-1 values were recorded within the first 12 months in 6 patients (35.3%), while in 11 patients (64.7%) lowest values were reported after >12 months of treatment, including 4 of 11 patients with early IGF-1 normalization. New-onset diabetes was documented in 5 of 7 patients with pre-diabetes and in 1 of 5 patients with normal glucose homeostasis at baseline. Among patients with pre-diabetes or diabetes mellitus prior to initiating pasireotide, mean HbA1c increase was 0.56 ± 1.0%.

Conclusions

The results support the long-term efficacy and safety of pasireotide LAR for acromegaly and support the potential delayed effect of treatment on IGF-1 normalization.
Literatur
1.
Zurück zum Zitat R. Dineen, P.M. Stewart, M. Sherlock, Acromegaly. QJM 110(7), 411–420 (2017)PubMed R. Dineen, P.M. Stewart, M. Sherlock, Acromegaly. QJM 110(7), 411–420 (2017)PubMed
2.
Zurück zum Zitat A. Giustina, G. Barkhoudarian, A. Beckers, A. Ben-shlomo, N. Biermasz, B. Biller, Multidisciplinary management of acromegaly: a consensus. Rev. Endocr. Metab. Disord. 4(Dec), 667–678 (2020)CrossRef A. Giustina, G. Barkhoudarian, A. Beckers, A. Ben-shlomo, N. Biermasz, B. Biller, Multidisciplinary management of acromegaly: a consensus. Rev. Endocr. Metab. Disord. 4(Dec), 667–678 (2020)CrossRef
3.
Zurück zum Zitat M.R. Gadelha, M.D. Bronstein, T. Brue, M. Coculescu, M. Fleseriu, M. Guitelman, V. Pronin, G. Raverot, I. Shimon, K.K. Lievre, J. Fleck, M. Aout, A.M. Pedroncelli, A. Colao, 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 (2014)CrossRef M.R. Gadelha, M.D. Bronstein, T. Brue, M. Coculescu, M. Fleseriu, M. Guitelman, V. Pronin, G. Raverot, I. Shimon, K.K. Lievre, J. Fleck, M. Aout, A.M. Pedroncelli, A. Colao, 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 (2014)CrossRef
4.
Zurück zum Zitat A. Colao, M.D. Bronstein, P. Freda, F. Gu, C.C. Shen, M. Gadelha, M. Fleseriu, A.J. Van Der Lely, A.J. Farrall, K. Hermosillo Reséndiz, M. Ruffin, Y. Chen, M. Sheppard, Pasireotide versus octreotide in acromegaly: A head-to-head superiority study. J. Clin. Endocrinol. Metab. 99(3), 791–799 (2014)CrossRef A. Colao, M.D. Bronstein, P. Freda, F. Gu, C.C. Shen, M. Gadelha, M. Fleseriu, A.J. Van Der Lely, A.J. Farrall, K. Hermosillo Reséndiz, M. Ruffin, Y. Chen, M. Sheppard, Pasireotide versus octreotide in acromegaly: A head-to-head superiority study. J. Clin. Endocrinol. Metab. 99(3), 791–799 (2014)CrossRef
5.
Zurück zum Zitat A. Colao, M.D. Bronstein, T. Brue, L. De Marinis, M. Fleseriu, M. Guitelman, G. Raverot, I. Shimon, J. Fleck, P. Gupta, A.M. Pedroncelli, M.R. Gadelha, Pasireotide for acromegaly: Long-term outcomes from an extension to the phase III PAOLA study. Eur. J. Endocrinol. 182(6), 583–594 (2020)CrossRef A. Colao, M.D. Bronstein, T. Brue, L. De Marinis, M. Fleseriu, M. Guitelman, G. Raverot, I. Shimon, J. Fleck, P. Gupta, A.M. Pedroncelli, M.R. Gadelha, Pasireotide for acromegaly: Long-term outcomes from an extension to the phase III PAOLA study. Eur. J. Endocrinol. 182(6), 583–594 (2020)CrossRef
6.
Zurück zum Zitat M. Gadelha, M. Bex, A. Colao, E.M. Pedroza García, C. Poiana, M. Jimenez-Sanchez, S. Yener, R. Mukherjee, A. Bartalotta, R. Maamari, G. Raverot, Evaluation of the efficacy and safety of switching to pasireotide in patients with acromegaly inadequately controlled with first-generation somatostatin analogs. Front. Endocrinol. 10(Feb), 1–10 (2020) M. Gadelha, M. Bex, A. Colao, E.M. Pedroza García, C. Poiana, M. Jimenez-Sanchez, S. Yener, R. Mukherjee, A. Bartalotta, R. Maamari, G. Raverot, Evaluation of the efficacy and safety of switching to pasireotide in patients with acromegaly inadequately controlled with first-generation somatostatin analogs. Front. Endocrinol. 10(Feb), 1–10 (2020)
7.
Zurück zum Zitat J. Bollerslev, A. Heck, N.C. Olarescu, Individualised management of acromegaly. Eur. J. Endocrinol. 181(2), R57–R71. (2019)CrossRef J. Bollerslev, A. Heck, N.C. Olarescu, Individualised management of acromegaly. Eur. J. Endocrinol. 181(2), R57–R71. (2019)CrossRef
8.
Zurück zum Zitat M. Fleseriu, B.M.K. Biller, P.U. Freda, M.R. Gadelha, A. Giustina, L. Katznelson, M.E. Molitch, S.L. Samson, C.J. Strasburger, A.J. van der Lely, S. Melmed, A Pituitary Society update to acromegaly management guidelines. Pituitary 24(1), 1–13 (2021)CrossRef M. Fleseriu, B.M.K. Biller, P.U. Freda, M.R. Gadelha, A. Giustina, L. Katznelson, M.E. Molitch, S.L. Samson, C.J. Strasburger, A.J. van der Lely, S. Melmed, A Pituitary Society update to acromegaly management guidelines. Pituitary 24(1), 1–13 (2021)CrossRef
9.
Zurück zum Zitat E.C. Coopmans, A. Muhammad, A.J. Van Der Lely, J.A.M.J.L. Janssen, S.J.C.M.M. Neggers, How to position pasireotide LAR treatment in acromegaly. J. Clin. Endocrinol. Metab. 104(6), 1978–1988 (2019)CrossRef E.C. Coopmans, A. Muhammad, A.J. Van Der Lely, J.A.M.J.L. Janssen, S.J.C.M.M. Neggers, How to position pasireotide LAR treatment in acromegaly. J. Clin. Endocrinol. Metab. 104(6), 1978–1988 (2019)CrossRef
10.
Zurück zum Zitat A. Muhammad, A.J. Van Der Lely, P.J.D. Delhanty, A.H.G. Dallenga, I.K. Haitsma, J.A.M.J.L. Janssen, S.J.C.M.M. Neggers, 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 (2018)CrossRef A. Muhammad, A.J. Van Der Lely, P.J.D. Delhanty, A.H.G. Dallenga, I.K. Haitsma, J.A.M.J.L. Janssen, S.J.C.M.M. Neggers, 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 (2018)CrossRef
11.
Zurück zum Zitat I. Shimon, Z. Adnan, A. Gorshtein, L. Baraf, N. Saba Khazen, M. Gershinsky, Y. Pauker, A. Abid, M.J. Niven, C. Shechner, Y. Greenman, Efficacy and safety of long-acting pasireotide in patients with somatostatin-resistant acromegaly: a multicenter study. Endocrine 62(2), 448–455 (2018)CrossRef I. Shimon, Z. Adnan, A. Gorshtein, L. Baraf, N. Saba Khazen, M. Gershinsky, Y. Pauker, A. Abid, M.J. Niven, C. Shechner, Y. Greenman, Efficacy and safety of long-acting pasireotide in patients with somatostatin-resistant acromegaly: a multicenter study. Endocrine 62(2), 448–455 (2018)CrossRef
12.
Zurück zum Zitat Y.J. Kao, M. Ghosh, A. Schonbrunn, Ligand-dependent mechanisms of sst2A receptor trafficking: role of site-specific phosphorylation and receptor activation in the actions of biased somatostatin agonists. Mol. Endocrinol. 25(6), 1040–1054 (2011)CrossRef Y.J. Kao, M. Ghosh, A. Schonbrunn, Ligand-dependent mechanisms of sst2A receptor trafficking: role of site-specific phosphorylation and receptor activation in the actions of biased somatostatin agonists. Mol. Endocrinol. 25(6), 1040–1054 (2011)CrossRef
13.
Zurück zum Zitat G. Tulipano, R. Stumm, M. Pfeiffer, V. Ho, S. Schulz, Differential beta-arrestin trafficking and endosomal sorting of somatostatin receptor subtypes. J. Biol. Chem. 279(20), 21374–21382 (2004)CrossRef G. Tulipano, R. Stumm, M. Pfeiffer, V. Ho, S. Schulz, Differential beta-arrestin trafficking and endosomal sorting of somatostatin receptor subtypes. J. Biol. Chem. 279(20), 21374–21382 (2004)CrossRef
14.
Zurück zum Zitat I. Shimon, W. Saeger, L.E. Wildemberg, M.R. Gadelha, Somatotropinomas inadequately controlled with octreotide may over-respond to pasireotide: the importance of dose adjustment to achieve long-term biochemical control. Hormones 16(1), 84–91 (2017)PubMed I. Shimon, W. Saeger, L.E. Wildemberg, M.R. Gadelha, Somatotropinomas inadequately controlled with octreotide may over-respond to pasireotide: the importance of dose adjustment to achieve long-term biochemical control. Hormones 16(1), 84–91 (2017)PubMed
15.
Zurück zum Zitat M.R. Gadelha, F. Gu, M.D. Bronstein, T.C. Brue, M. Fleseriu, I. Shimon, A.J. van der Lely, S. Ravichandran, A. Kandra, A.M. Pedroncelli, A.A.L. Colao, Risk factors and management of pasireotide-associated hyperglycemia in acromegaly. Endocr. Connect 9(12), 1178–1190 (2020)CrossRef M.R. Gadelha, F. Gu, M.D. Bronstein, T.C. Brue, M. Fleseriu, I. Shimon, A.J. van der Lely, S. Ravichandran, A. Kandra, A.M. Pedroncelli, A.A.L. Colao, Risk factors and management of pasireotide-associated hyperglycemia in acromegaly. Endocr. Connect 9(12), 1178–1190 (2020)CrossRef
16.
Zurück zum Zitat H.A. Schmid, T. Brue, A. Colao, M.R. Gadelha, I. Shimon, K. Kapur, A.M. Pedroncelli, M. Fleseriu, Effect of pasireotide on glucose- and growth hormone-related biomarkers in patients with inadequately controlled acromegaly. Endocrine 53(1), 210–219 (2016)CrossRef H.A. Schmid, T. Brue, A. Colao, M.R. Gadelha, I. Shimon, K. Kapur, A.M. Pedroncelli, M. Fleseriu, Effect of pasireotide on glucose- and growth hormone-related biomarkers in patients with inadequately controlled acromegaly. Endocrine 53(1), 210–219 (2016)CrossRef
17.
Zurück zum Zitat M. Barbot, D. Regazzo, A. Mondin, M. Zilio, L. Lizzul, M. Zaninotto, M. Plebani, G. Arnaldi, F. Ceccato, C. Scaroni, Is pasireotide-induced diabetes mellitus predictable? A pilot study on the effect of a single dose of pasireotide on glucose homeostasis. Pituitary 23(5), 534–542 (2020)CrossRef M. Barbot, D. Regazzo, A. Mondin, M. Zilio, L. Lizzul, M. Zaninotto, M. Plebani, G. Arnaldi, F. Ceccato, C. Scaroni, Is pasireotide-induced diabetes mellitus predictable? A pilot study on the effect of a single dose of pasireotide on glucose homeostasis. Pituitary 23(5), 534–542 (2020)CrossRef
Metadaten
Titel
Long-term safety and efficacy of long-acting pasireotide in acromegaly
verfasst von
Amit Akirov
Alexander Gorshtein
Idit Dotan
Nariman Saba Khazen
Yulia Pauker
Michal Gershinsky
Ilan Shimon
Publikationsdatum
03.06.2021
Verlag
Springer US
Erschienen in
Endocrine / Ausgabe 2/2021
Print ISSN: 1355-008X
Elektronische ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-021-02782-2

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