Abstract
BackgroundTreating 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.MethodsIn 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.ResultsSixteen 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.ConclusionsThis 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.
Highlights
Cushing’s disease is a rare and often severe disorder of chronic hypercortisolism caused by hypersecretion of adrenocorticotropic hormone (ACTH) from a corticotrophEndocrine (2017) 57:156–165 adenoma [1]
The safety profile of pasireotide at 5 years was similar to that reported after 12 months
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
Summary
Cushing’s disease is a rare and often severe disorder of chronic hypercortisolism caused by hypersecretion of adrenocorticotropic hormone (ACTH) from a corticotrophEndocrine (2017) 57:156–165 adenoma [1]. Cushing’s disease is a rare and often severe disorder of chronic hypercortisolism caused by hypersecretion of adrenocorticotropic hormone (ACTH) from a corticotroph. Transsphenoidal resection of the causative pituitary adenoma is first-line therapy for most patients with Cushing’s disease [5]. Tailoring treatment to meet the individual patient’s characteristics along with a consideration of the benefit:risk profiles of the various medical therapies is recommended [5]. Given that Cushing’s disease often requires chronic medical treatment, medications with favourable long-term efficacy and safety profiles are required to meet the needs of patients and their clinicians. Cushing’s disease after failed surgery often requires chronic medication, underlining the need for therapies with favourable long-term efficacy and safety profiles. 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 Electronic supplementary material The online version of this article (doi:10.1007/s12020-017-1316-3) contains supplementary material, which is available to authorized users.
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