Long-acting pasireotide improves clinical signs and quality of life in Cushing's disease: results from a phase III study

J Endocrinol Invest. 2020 Nov;43(11):1613-1622. doi: 10.1007/s40618-020-01246-0. Epub 2020 May 8.

Abstract

Purpose: Cushing's disease (CD) is associated with significant clinical burden, increased mortality risk, and impaired health-related quality of life (HRQoL). This analysis explored the effect of long-acting pasireotide on clinical signs of hypercortisolism and HRQoL in a large subset of patients with CD.

Methods: In this phase III study (clinicaltrials.gov: NCT01374906), 150 adults with CD and a mean urinary free cortisol (mUFC) level between 1.5 and 5.0 times the upper limit of normal (ULN) started long-acting pasireotide 10 or 30 mg every 28 days with dose increases/decreases permitted based on mUFC levels/tolerability (minimum/maximum dose: 5/40 mg). Changes in clinical signs of hypercortisolism and HRQoL were assessed over 12 months of treatment and were stratified by degree of mUFC control for each patient.

Results: Patients with controlled mUFC at month 12 (n = 45) had the greatest improvements from baseline in mean systolic (- 8.4 mmHg [95% CI - 13.9, - 2.9]) and diastolic blood pressure (- 6.0 mmHg [- 10.0, - 2.0]). Mean BMI, weight, and waist circumference improved irrespective of mUFC control. Significant improvements in CushingQoL total score of 5.9-8.3 points were found at month 12 compared with baseline, irrespective of mUFC control; changes were driven by improvements in physical problem score, with smaller improvements in psychosocial score.

Conclusions: Long-acting pasireotide provided significant improvements in clinical signs and HRQoL over 12 months of treatment, which, in some cases, occurred regardless of mUFC control. Long-acting pasireotide represents an effective treatment option and provides clinical benefit in patients with CD.

Clinical trial registration number: NCT01374906.

Keywords: Cushing’s disease; Health-related quality of life; Hypercortisolism; Pasireotide.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Blood Pressure / drug effects
  • Cushing Syndrome / drug therapy
  • Cushing Syndrome / etiology
  • Cushing Syndrome / metabolism
  • Cushing Syndrome / physiopathology
  • Delayed-Action Preparations / therapeutic use
  • Female
  • Humans
  • Hydrocortisone / urine
  • Male
  • Middle Aged
  • Pituitary ACTH Hypersecretion / complications
  • Pituitary ACTH Hypersecretion / drug therapy*
  • Pituitary ACTH Hypersecretion / metabolism
  • Pituitary ACTH Hypersecretion / physiopathology
  • Quality of Life*
  • Somatostatin / analogs & derivatives*
  • Somatostatin / therapeutic use
  • Treatment Outcome

Substances

  • Delayed-Action Preparations
  • Somatostatin
  • pasireotide
  • Hydrocortisone

Associated data

  • ClinicalTrials.gov/NCT01374906

Grants and funding