Fleseriu, M., Newell-Price, J., Pivonello, R. et al. (12 more authors) (2022) Long-term outcomes of osilodrostat in Cushing’s disease: LINC 3 study extension. European Journal of Endocrinology, 187 (4). pp. 531-541. ISSN 0804-4643
Abstract
Objective
To investigate the long-term efficacy and tolerability of osilodrostat, a potent oral 11β-hydroxylase inhibitor, for treating Cushing’s disease (CD).
Design/methods
A total of 137 adults with CD and mean 24-h urinary free cortisol (mUFC) > 1.5 × upper limit of normal (ULN) received osilodrostat (starting dose 2 mg bid; maximum 30 mg bid) during the prospective, Phase III, 48-week LINC 3 (NCT02180217) core study. Patients benefiting from osilodrostat at week 48 could enter the optional extension (ending when all patients had received ≥ 72 weeks of treatment or discontinued). Efficacy and safety were assessed for all enrolled patients from the core study baseline.
Results
Median osilodrostat exposure from the core study baseline to study end was 130 weeks (range 1–245) and median average dose was 7.4 mg/day (range 0.8–46.6). The reduction in mean mUFC achieved during the core was maintained during the extension and remained ≤ ULN. Of 106 patients, 86 (81%) patients who entered the extension had mUFC ≤ ULN at week 72. Improvements in cardiovascular/metabolic-related parameters, physical manifestations of hypercortisolism (fat pads, central obesity, rubor, striae, and hirsutism in females), and quality of life in the core study were also maintained or improved further during the extension. No new safety signals were reported; 15/137 (10.9%) and 12/106 (11.3%) patients discontinued for adverse events during the core and extension, respectively. Mean testosterone in females decreased towards baseline levels during the extension.
Conclusions
Data from this large, multicentre trial show that long-term treatment with osilodrostat sustains cortisol normalisation alongside clinical benefits in most patients with CD and is well tolerated.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | © 2022 The Authors. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
Keywords: | Adult; Female; Humans; Hydrocortisone; Imidazoles; Mixed Function Oxygenases; Pituitary ACTH Hypersecretion; Prospective Studies; Pyridines; Quality of Life; Testosterone; Treatment Outcome |
Dates: |
|
Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Sheffield Teaching Hospitals |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 17 Oct 2022 14:30 |
Last Modified: | 17 Oct 2022 14:30 |
Status: | Published |
Publisher: | Bioscientifica |
Refereed: | Yes |
Identification Number: | 10.1530/eje-22-0317 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:191770 |
Download
Filename: Long-term outcomes of osilodrostat in Cushings disease LINC 3 study extension.pdf
Licence: CC-BY 4.0