Background: Treating hypercortisolism in patients with Cushing’s disease after failed surgery often requires chronic medication, underlining the need for therapies with favourable long-term efficacy and safety profiles. Methods: In a randomised, double-blind study, 162 adult patients with persistent/recurrent or de novo Cushing’s disease received pasireotide. Patients with mean urinary free cortisol at/below the upper limit of normal or clinical benefit at month 12 could continue receiving pasireotide during an open-ended, open-label phase, the outcomes of which are described herein. Results: Sixteen patients received 5 years of pasireotide treatment. Among these, median (95% confidence interval) percentage change from baseline in mean urinary free cortisol was −82.6% (−89.0, −41.9) and −81.8% (−89.8, −67.4) at months 12 and 60. Eleven patients had mean urinary free cortisol ≤ upper limit of normal at month 60. Improvements in clinical signs were sustained during long-term treatment. The safety profile of pasireotide at 5 years was similar to that reported after 12 months. Fifteen of 16 patients experienced a hyperglycaemia-related adverse event; glycated haemoglobin levels were stable between months 6 and 60. Adverse events related to hyperglycaemia, bradycardia, gallbladder/biliary tract, and liver safety were most likely to first occur by month 6; adverse event severity did not tend to worsen over time. Conclusions: This represents the longest prospective trial of a medical therapy for Cushing’s disease to date. A subset of patients treated with pasireotide maintained biochemical and clinical improvements for 5 years, with no new safety signals emerging. These data support the use of pasireotide as an effective long-term therapy for some patients with Cushing’s disease.

Long-term treatment of Cushing’s disease with pasireotide: 5-year results from an open-label extension study of a Phase III trial / Petersenn, S.; Salgado, L. R.; Schopohl, J.; Portocarrero-Ortiz, L.; Arnaldi, G.; Lacroix, A.; Scaroni, C.; Ravichandran, S.; Kandra, A.; Biller, B. M. K.. - In: ENDOCRINE. - ISSN 1355-008X. - 57:1(2017), pp. 156-165. [10.1007/s12020-017-1316-3]

Long-term treatment of Cushing’s disease with pasireotide: 5-year results from an open-label extension study of a Phase III trial

Arnaldi G.;
2017-01-01

Abstract

Background: Treating hypercortisolism in patients with Cushing’s disease after failed surgery often requires chronic medication, underlining the need for therapies with favourable long-term efficacy and safety profiles. Methods: In a randomised, double-blind study, 162 adult patients with persistent/recurrent or de novo Cushing’s disease received pasireotide. Patients with mean urinary free cortisol at/below the upper limit of normal or clinical benefit at month 12 could continue receiving pasireotide during an open-ended, open-label phase, the outcomes of which are described herein. Results: Sixteen patients received 5 years of pasireotide treatment. Among these, median (95% confidence interval) percentage change from baseline in mean urinary free cortisol was −82.6% (−89.0, −41.9) and −81.8% (−89.8, −67.4) at months 12 and 60. Eleven patients had mean urinary free cortisol ≤ upper limit of normal at month 60. Improvements in clinical signs were sustained during long-term treatment. The safety profile of pasireotide at 5 years was similar to that reported after 12 months. Fifteen of 16 patients experienced a hyperglycaemia-related adverse event; glycated haemoglobin levels were stable between months 6 and 60. Adverse events related to hyperglycaemia, bradycardia, gallbladder/biliary tract, and liver safety were most likely to first occur by month 6; adverse event severity did not tend to worsen over time. Conclusions: This represents the longest prospective trial of a medical therapy for Cushing’s disease to date. A subset of patients treated with pasireotide maintained biochemical and clinical improvements for 5 years, with no new safety signals emerging. These data support the use of pasireotide as an effective long-term therapy for some patients with Cushing’s disease.
2017
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11566/287190
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