Management of Osilodrostat Therapy in Patients With Cushing's Syndrome: A Modified Delphi Consensus Panel

Abstract

Introduction: Endogenous Cushing's syndrome (CS) is a rare endocrine disorder that chronically exposes patients to supraphysiological cortisol levels. Primary therapy for CS consists of surgery. Medical therapies are also considered for many patients with CS, including those who are not surgical candidates or have persistent or recurrent hypercortisolism after surgery. Osilodrostat, an adrenal steroidogenesis inhibitor, demonstrated sustained efficacy and safety in phase 3 clinical trials and is currently approved to treat endogenous CS in Europe and the United States. Because of limited clinical experience, questions remain about how to individualize osilodrostat treatment for different clinical scenarios and special populations. Additional guidance from experts based on clinical study and real-world experiences with osilodrostat is needed.

Methods: A modified Delphi consensus panel study was conducted consisting of 13 specialists from high-volume endocrinology centers with experience prescribing osilodrostat. Advisors participated in 3 consensus rounds (2 anonymous surveys, 1 virtual workshop) over approximately 10 months to provide guidance and recommendations on optimal osilodrostat use.

Results: Over 2 surveys and a 2-hour virtual workshop, 26 statements related to osilodrostat achieved consensus among Delphi panelists and 5 were excluded. Topics included patient preparation before osilodrostat initiation, baseline testing, dosing at onset and during treatment, managing dose adjustments, monitoring during dose titration, and treatment alterations for planned and unexpected clinical events.

Conclusion: Treatment guidance and recommendations for osilodrostat use were obtained using the Delphi method. These statements are intended to provide physicians with education and guidance on using osilodrostat to optimally treat patients with CS.

Keywords: Cushing's disease; adrenal crisis; adrenal insufficiency; endogenous Cushing's syndrome; glucocorticoid withdrawal syndrome; osilodrostat.

Figure 1.

Delphi panel consensus on best practices for preparing patients to initiate osilodrostat and choose osilodrostat dosage at initiation and reinitiation. ^aFor each statement, n values within each bar indicate the number of respondents per score (11-13 total responders each). ^bConsensus was achieved verbally during the workshop (n = 12) and endorsed in writing after the workshop (n = 1).Abbreviations: AI, adrenal insufficiency; BID, twice daily; GC, glucocorticoid; GWS, glucocorticoid withdrawal syndrome; QD, once daily.

Figure 2.

Delphi panel consensus on laboratory testing and imaging to acquire at baseline and throughout titration with osilodrostat. ^aFor each statement, n values within each bar indicate the number of respondents per score (11-13 total responders each). ^bNonmorning and nonfasted conditions are acceptable, with the caveat that food may increase cortisol levels. ^cConsensus was achieved verbally during the workshop (n = 12) and endorsed in writing after the workshop by the final panel member.Abbreviations: BID, twice daily; CD, Cushing's disease; CS, Cushing's syndrome; DHEAS, dehydroepiandrosterone sulfate; ECG, electrocardiogram; HbA1c, glycated hemoglobin; LC-MS, liquid chromatography–mass spectrometry; LNSC, late-night salivary cortisol; MRI, magnetic resonance imaging; UFC, urinary free cortisol.

Figure 3.

Delphi panel consensus on how to modify treatment with osilodrostat and concurrent medications in the event of intercurrent illness, planned surgeries, and unplanned surgeries. ^aFor each statement, n values within each bar indicate the number of respondents per score (11-13 total responders each). ^bConsensus was achieved verbally during the workshop (n = 12) and endorsed in writing after the workshop by the final panel member. Abbreviations: AI, adrenal insufficiency; CD, Cushing's disease; CS, Cushing's syndrome; GC, glucocorticoid.

Figure 4.

Delphi panel consensus on treatment modifications for adverse events and in special populations. ^aFor each statement, n values within each bar indicate the number of respondents per score (11-13 total responders each). Abbreviation: CS, Cushing's syndrome.

Figure 5.

Delphi panel statements and substatements that did not achieve consensus during the virtual workshop. Survey 2 scores are shown with representative feedback comments. ^aFor each statement, n values within each bar indicate the number of respondents per score (11-13 total responders each). Abbreviations: AI, adrenal insufficiency; DHEAS, dehydroepiandrosterone sulfate; GC, glucocorticoid; GWS, glucocorticoid withdrawal syndrome; UFC, urinary free cortisol.