دورية أكاديمية
Efficacy and Safety of Osilodrostat in Paraneoplastic Cushing Syndrome: A Real-World Multicenter Study in France
| العنوان: | Efficacy and Safety of Osilodrostat in Paraneoplastic Cushing Syndrome: A Real-World Multicenter Study in France |
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| المؤلفون: | Dormoy, Alexandre, Haissaguerre, Magalie, Vitellius, Géraldine, Do Cao, Christine, Geslot, Aurore, Drui, Delphine, Lasolle, Hélène, Vieira-Pinto, Oceana, Salenave, Sylvie, François, Maud, Puerto, Marie, Boullay, Hélène Du, Mayer, Anne, Rod, Anne, Laurent, Claire, Chanson, Philippe, Reznik, Yves, Castinetti, Frédéric, Chabre, Olivier, Baudin, Eric, Raverot, Gérald, Tabarin, Antoine, Young, Jacques |
| المساهمون: | Hôpital Bicêtre AP-HP, Le Kremlin-Bicêtre, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris-Saclay, Hôpital Haut-Lévêque CHU Bordeaux, CHU Bordeaux, Hôpital Robert Debré, Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes), ITX-lab unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Hospices Civils de Lyon (HCL), Hôpital Robert Debré-Hôpital universitaire Robert Debré Reims (CHU Reims), Centre Hospitalier Métropole Savoie Chambéry, Centre Hospitalier Georges Renon Niort (CH Georges Renon Niort), AP-HP. Université Paris Saclay, Physiologie et physiopathologie endocriniennes (PHYSENDO), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Hôpital Côte de Nacre CHU Caen, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital de la Conception CHU - APHM (LA CONCEPTION), Aix Marseille Université (AMU), Centre Hospitalier Universitaire CHU Grenoble (CHUGA), BioSanté (UMR BioSanté), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Département de médecine oncologique Gustave Roussy, Institut Gustave Roussy (IGR) |
| المصدر: | ISSN: 0021-972X. |
| بيانات النشر: | HAL CCSD Endocrine Society |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Cushing syndrome, adrenal insufficiency, corticotropin, ectopic adrenocorticotropic hormone syndrome, hypokalemia, neuroendocrine tumors, osilodrostat, paraneoplastic Cushing syndrome, steroidogenesis inhibitors, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism |
| الوصف: | International audience ; Abstract Context Prospective studies have demonstrated the efficacy of osilodrostat in Cushing disease. No study has evaluated osilodrostat in a series of patients with paraneoplastic Cushing syndrome/ectopic adrenocorticotropin syndrome (PNCS/EAS). Objective This work aimed to evaluate in France the real-world efficacy and safety of osilodrostat in patients with PNCS/EAS. Methods A total of 33 patients with PNCS/EAS with intense/severe hypercortisolism were involved in this retrospective, multicenter, real-world study. Patients received osilodrostat between May 2019 and March 2022 at a median initial dose (range) of 4 mg/day (1-60) and maximum dose, 20 mg/day (4-100), first under patient then cohort temporary authorizations and after marketing authorization. Regimens used titration (n = 6), block and replace (n = 16), or titration followed by block and replace (n = 11). Results In 11 patients receiving osilodrostat as first-line monotherapy, median 24-hour urinary free cortisol (24h-UFC) decreased dramatically (from 26 × upper limit of normal [ULN; 2.9-659] to 0.11 × ULN [0.08-14.9]; P < .001). In 9 of them, 24h-UFC normalization was achieved in 2 weeks (median). Thirteen additional patients were previously treated with classic steroidogenesis inhibitors but 10 of these 13 were not controlled. In these patients, osilodrostat monotherapy, used as second line, induced a significantly decreased of 24h-UFC (from 2.6 × ULN [1.1-144] to 0.22 × ULN [0.12-0.66]; P < .01). Nine additional patients received osilodrostat in combination with another anticortisolic drug, decreasing 24h-UFC from 11.8 × ULN (0.3-247) to 0.43 × ULN (0.33-2.4) (P < .01). In parallel, major clinical symptoms/comorbidities improved dramatically with improvement in blood pressure, hyperglycemia, and hypokalemia, allowing the discontinuation or dose reduction of patient treatments. Adrenal insufficiency (grade 3-4) was reported in 8 of 33 patients. Conclusion Osilodrostat is a rapidly efficient therapy for PNCS/EAS ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/36470583; hal-04332295; https://universite-paris-saclay.hal.science/hal-04332295Test; https://universite-paris-saclay.hal.science/hal-04332295/documentTest; https://universite-paris-saclay.hal.science/hal-04332295/file/dgac691.pdfTest; PUBMED: 36470583; PUBMEDCENTRAL: PMC10188310 |
| DOI: | 10.1210/clinem/dgac691 |
| الإتاحة: | https://doi.org/10.1210/clinem/dgac691Test https://universite-paris-saclay.hal.science/hal-04332295Test https://universite-paris-saclay.hal.science/hal-04332295/documentTest https://universite-paris-saclay.hal.science/hal-04332295/file/dgac691.pdfTest |
| حقوق: | http://creativecommons.org/licenses/by-nc-ndTest/ ; info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.1DD365D7 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1210/clinem/dgac691 |
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