ECE2023 Poster Presentations Late-Breaking (40 abstracts)
Comparison of Metyrapone, OSilodrostat and KEToconazolE in the short-term thERapy of endogenous Cushing’s syndrome: preliminary results of the MOSKETEER study
Mario Detomas 1 , Chiara Simeoli 2 , Filippo Ceccato 3 , Ana Aulinas Maso 4 , Pasquale Dolce 5 , German Rubinstein 6 , Simone Antonini 7 , Maria Stelmachowska-Banaś 8 , Marianna Minnetti 9 , Andrea Corsello 10 , Ulrich Dischinger 1 , Nicola Di Paola 2 , Giacomo Voltan 3 , Alicia Santos Vives 4 , Leah Braun 6 , Alessandro Mazzarella 2 , Timo DEUTSCHBEIN 1,11 , Andrea Lania 7 , Andrea Isidori 9 , Martin Reincke 6 , Scaroni Carla 3 , Susan M Webb 4 , Rosario Pivonello 2 , Martin Fassnacht 1 & Barbara Altieri 1
1Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital Würzburg, University of Würzburg, Würzburg, Germany; 2Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Università Federico II di Napoli, Naples, Italy.; 3Endocrine Disease Unit, University-Hospital of Padova, Padova, Italy.; 4Department of Endocrinology, Hospital S Pau, Barcelona; IIB-Sant Pau, Research Center for Pituitary Diseases, Barcelona; CIBERER Unit 747, ISCIII and Department of Medicine, Univ Autonoma Barcelona, Spain.; 5Department of Public Health, University of Naples Federico II, Naples, Italy.; 6Medizinische Klinik und Poliklinik IV, Klinikum der Universität, Ludwig-Maximilians-Universität München, Munich 80336, Germany.; 7Endocrinology, Diabetology and Medical Andrology Unit, IRCCS Humanitas Research Hospital, via Manzoni 56, 20089 Rozzano, Milan, Italy.; 8Department of Endocrinology, Centre of Postgraduate Medical Education, Warsaw, Poland.; 9Department of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena, 324, 00161, Rome, Italy.; 10Department of Translational Medicine and Surgery, Unit of Endocrinology, Università Cattolica del Sacro Cuore-Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo Gemelli 8, I-00168 Rome, Italy.; 11Medicover Oldenburg MVZ, Oldenburg, Germany
Background: Steroid synthesis inhibitors, like metyrapone, osilodrostat, and ketoconazole are used as second-line treatment in all types of endogenous Cushing’s syndrome (CS). However, a direct comparison of these three drugs is missing. This study aimed to compare these drugs in the short-term therapy of CS.
Design: Retrospective multicenter study involving 15 European centers.
Methods: Patients with CS treated with metyrapone, osilodrostat or ketoconazole as monotherapy for at least 2 weeks were considered eligible. Main outcomes were changes in serum cortisol and 24h urinary free cortisol (24h-UFC) after 2 (T1), 4 (T2), and 12 weeks (T3) of therapy compared to baseline (T0), evaluated as delta (change) percentage from T0 to the different time points. A mixed model was used to explore the data.
Results: Data of 210 patients from 9/15 centers were available. Of the 210 patients (78% females), 158 (75 %) suffered from ACTH-dependent and 52 (25%) from ACTH-independent CS. 83 (40%) patients were treated with metyrapone, 78 (37%) with osilodrostat and 49 (23%) with ketoconazole. No difference in terms of CS subtypes (P=0.19) and baseline 24h-UFC (median 295.5µg/24h, 286.0µg/24h and 360.0µg/24h for metyrapone, osilodrostat and ketoconazole, respectively, P=0.32) was identified. Median daily starting doses were 750 (range 250-2000)mg, 2 (1-10)mg and 400 (200-800)mg for metyrapone, osilodrostat and ketoconazole, which increased during the treatment for all drugs up to 1000 (250-3000)mg, 5 (1-40)mg and 400 (200-1200)mg, respectively (all P<0.05). 24h-UFC significantly decreased in all time points only in the osilodrostat group (-34% in T1, -46% in T2, and -68% in T3, P<0.001), being more pronounced at T3 than metyrapone (-37%, P=0.02). Under ketoconazole 24h-UFC decreased of -48% at T3. A decrease in serum cortisol was observed at T3 in all groups (metyrapone -7.8%; osilodrostat -39%; ketoconazole -36%). At T3 no significant changes in potassium levels were identified (metyrapone 0%; osilodrostat +2%; ketoconazole -0.6%); and 7 (15%) patients under metyrapone, 6 (10%) under osilodrostat and 0 under ketoconazole were supplemented (P=0.03 per trend). At T1, a decrease in number of antihypertensives was identified in 10% of patients under metyrapone, 22% under osilodrostat and 6% under ketoconazole (P=0.006), whereas at T2 and T3 no significant differences were identified. No significant change was observed in Hb1Ac(%).
Conclusion: These preliminary results confirmed the efficacy of all the three drugs in decreasing hypercortisolism. Osilodrostat might act faster in decreasing blood pressure. However, these preliminary results need to be validated in the final cohort.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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