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- Title
Efficacy and Safety of Osilodrostat in Paraneoplastic Cushing Syndrome: A Real-World Multicenter Study in France.
- Authors
Dormoy, Alexandre; Haissaguerre, Magalie; Vitellius, Géraldine; Do Cao, Christine; Geslot, Aurore; Drui, Delphine; Lasolle, Hélène; Vieira-Pinto, Oceana; Salenave, Sylvie; François, Maud; Puerto, Marie; Du Boullay, Hélène; Mayer, Anne; Rod, Anne; Laurent, Claire; Chanson, Philippe; Reznik, Yves; Castinetti, Frédéric; Chabre, Olivier; Baudin, Eric
- 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 x upper limit of normal [ULN; 2.9-659] to 0.11 x 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 x ULN [1.1-144] to 0.22 x ULN [0.12-0.66]; P<.01). Nine additional patients received osilodrostat in combination with another anticortisolic drug, decreasing 24h- UFC from 11.8 x ULN (0.3-247) to 0.43 x 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 with severe/intense hypercortisolism. Osilodrostat was generally well tolerated; adrenal insufficiency was the main side effect.
- Publication
Journal of Clinical Endocrinology & Metabolism, 2023, Vol 108, Issue 6, p1475
- ISSN
0021-972X
- Publication type
Article
- DOI
10.1210/clinem/dgac691