Long-term efficacy and safety of subcutaneous pasireotide alone or in combination with cabergoline in Cushing's disease.

Autor:	Feelders RA; Department of Internal Medicine, Division of Endocrinology, Erasmus Medical Center, Rotterdam, Netherlands., Fleseriu M; Pituitary Center, Departments of Medicine and Neurological Surgery, Oregon Health & Science University, Portland, OR, United States., Kadioglu P; Division of Endocrinology, Metabolism and Diabetes, Cerrahpasa Medical Faculty, Istanbul University - Cerrahpasa, Istanbul, Türkiye., Bex M; Department of Endocrinology, University Hospitals Leuven, Leuven, Belgium., González-Devia D; Departamento de Medicina Interna, Sección de Endocrinologia, Hospital Universitario Fundación Santa Fé de Bogotá, Bogota, Colombia., Boguszewski CL; Department of Internal Medicine, Endocrine Division (SEMPR), Federal University of Paraná, Curitiba, Parana, Brazil., Yavuz DG; Section of Endocrinology and Metabolism, Marmara University School of Medicine, Department of Internal Medicine, Division of Endocrinology and Metabolism, Istanbul, Türkiye., Patino H; Global Medical Affairs, Novartis Pharmaceuticals Corporation, East Hanover, NJ, United States., Pedroncelli AM; Recordati AG, Basel, Switzerland.; Global Medical Affairs, Novartis Pharma AG, Basel, Switzerland., Maamari R; Global Medical Affairs, Novartis Pharmaceuticals Corporation, East Hanover, NJ, United States., Chattopadhyay A; Global Medical Affairs, Novartis Healthcare Private Limited, Hyderabad, Telangana, India., Biller BMK; Neuroendocrine & Pituitary Tumor Clinical Center, Massachusetts General Hospital, Boston, MA, United States., Pivonello R; Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Università Federico II di Napoli, Naples, Italy.
Jazyk:	angličtina
Zdroj:	Frontiers in endocrinology [Front Endocrinol (Lausanne)] 2023 Oct 09; Vol. 14, pp. 1165681. Date of Electronic Publication: 2023 Oct 09 (Print Publication: 2023).
DOI:	10.3389/fendo.2023.1165681
Abstrakt:	Objective: This study evaluated short- and long-term efficacy and safety of the second-generation somatostatin receptor ligand pasireotide alone or in combination with dopamine agonist cabergoline in patients with Cushing's disease (CD). Study Design: This is an open-label, multicenter, non-comparative, Phase II study comprising 35-week core phase and an optional extension phase. All patients started with pasireotide, and cabergoline was added if cortisol remained elevated. Eligible patients had active CD, with or without prior surgery, were pasireotide naïve at screening or had discontinued pasireotide for reasons other than safety. Primary endpoint was proportion of patients with a mean urinary free cortisol (mUFC) level not exceeding the upper limit of normal (ULN) at week 35 with missing data imputed using last available post-baseline assessments. Results: Of 68 patients enrolled, 26 (38.2%) received pasireotide monotherapy and 42 (61.8%) received pasireotide plus cabergoline during the core phase. Thirty-four patients (50.0%; 95% CI 37.6-62.4) achieved the primary endpoint, of whom 17 (50.0%) received pasireotide monotherapy and 17 (50.0%) received combination therapy. Proportion of patients with mUFC control remained stable during the extension phase up to week 99. Treatment with either mono or combination therapy provided sustained improvements in clinical symptoms of hypercortisolism up to week 99. Hyperglycemia and nausea (51.5% each), diarrhea (44.1%) and cholelithiasis (33.8%) were the most frequent adverse events. Conclusion: Addition of cabergoline in patients with persistently elevated mUFC on maximum tolerated doses of pasireotide is an effective and well-tolerated long-term strategy for enhancing control of hypercortisolism in some CD patients. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT01915303, identifier NCT01915303. Competing Interests: HP and RM were Novartis employees and owned Novartis stocks. AMP was employed by Novartis and Recordati. AC is a Novartis employee and owns Novartis stocks. RF received research grants from Strongbridge and Corcept, consulting fee from Recordati, honoraria and financial support for meetings and/or travel from HRA Pharma and Recordati, and attended advisory boards for Recordati. MF has received research support to Oregon Health & Science University as a principal investigator from Recordati and Xeris Strongbridge and has performed occasional scientific consultancy for Recordati, HRA Pharma, Sparrow, and Xeris Strongbridge. PK attended advisory boards for Recordati. MB’s institution received consulting fee and attended advisory boards from Recordati. DG-D received research grants from Recordati Rare Disease and Bayer, consulting fee from Abbott-Lafrancol, Biotoscana, PTC lab, Glaxo/Helou, Recordati Rare Disease, and Bayer, honoraria from Valentech Pharma, Sanofi, and Bayer, travel grants from Recordati Rare Disease, advocacy groups and other leadership roles from Asociación Colombiana de Endocrinologia and Asociación Colombiana de Osteoporosis y Metabolismo, and other financial and non-financial interests include Asociacion Colombiana de Endocrinologia y Metabolismo, Hospital Universitario Fundación Santa Fé de Bogota, and Asociación Colombiana de Osteoporosis y Metabolismo. CB received research grants from Novartis and Recordati, and consulting and speaker fee from Novartis. BB served as the principal investigator for grants to Massachusetts General Hospital from Cortendo/Strongbridge Xeris, Millendo, and Novartis and has occasionally consulted for Cortendo/Strongbridge Xeris, HRA Pharma, Novartis Recordati, and Sparrow. RP and his institution received research grants and honoraria from Pfizer, Ipsen, Novartis, Merck Serono, IBSA Farmaceutici, Corcept, Shire, HRA Pharma, ICON, Covance, Neuroendocrine CAH, Camurus, Recordati, Janssen Cilag, and CMED Clinical Services, received consulting fee from Recordati Rare Disease, Organon Italia, Siunergos Pharma, Corcept, S&R Farmaceutici S.p.A., DAMOR Farmaceutici, and Pfizer, attended advisory boards from Crinetics Pharmaceuticals, Recordati Rare Disease, Pfizer, and HRA Pharma. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare that this study received funding from Novartis Pharma AG. Novartis was involved in the study design, analysis, interpretation of data, and providing financial support for medical editorial assistance of this article. (Copyright © 2023 Feelders, Fleseriu, Kadioglu, Bex, González-Devia, Boguszewski, Yavuz, Patino, Pedroncelli, Maamari, Chattopadhyay, Biller and Pivonello.)
Databáze:	MEDLINE
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