Global clinical response in Cushing's syndrome patients treated with mifepristone

Objective Mifepristone, a glucocorticoid receptor antagonist, improves clinical status in patients with Cushing's syndrome (CS). We examined the pattern, reliability and correlates of global clinical response (GCR) assessments during a 6-month clinical trial of mifepristone in CS. Design Post hoc analysis of secondary end-point data from a 24-week multicentre, open-label trial of mifepristone (300-1200mg daily) in CS. Intraclass correlation coefficient (ICC) was used to examine rater concordance, and drivers of clinical improvement were determined by multivariate regression analysis. Patients Forty-six adult patients with refractory CS along with diabetes mellitus type 2 or impaired glucose tolerance, and/or a diagnosis of hypertension. Measurements Global clinical assessment made by three independent reviewers using a three-point ordinal scale (+1 = improvement; 0=no change; -1=worsening) based on eight broad clinical categories including glucose control, lipids, blood pressure, body composition, clinical appearance, strength, psychiatric/cognitive symptoms and quality of life at Weeks 6, 10, 16, and 24. Results Positive GCR increased progressively over time with 88% of patients having improved at Week 24 (P<0 center dot 001). The full concordance among reviewers occurred in 76 center dot 6% of evaluations resulting in an ICC of 0 center dot 652 (P<0 center dot 001). Changes in body weight (P<0 center dot 0001), diastolic blood pressure (P<0 center dot 0001), two-hour postoral glucose challenge glucose concentration (P = 0 center dot 0003), and Cushingoid appearance (P=0 center dot 022) were strong correlates of GCR. Conclusions Mifepristone treatment for CS results in progressive clinical improvement. Overall agreement among clinical reviewers was substantial and determinants of positive GCR included change in weight, blood pressure, glucose levels and appearance.