Relacorilant or surgery improved hemostatic markers in Cushing syndrome.

Purpose: Glucocorticoid-mediated hypercoagulability can persist in patients with endogenous Cushing syndrome (CS) after curative surgery and may transiently worsen early postoperatively. These studies aimed to characterize coagulation markers at baseline in patients with CS and the impact of relacorilant or remission post-surgery in an open-label, phase 2 study (NCT02804750) and a retrospective, longitudinal, surgical cohort study.

Methods: In the relacorilant study, 34 patients received relacorilant (100-200 mg/day for up to 12 weeks or 250-400 mg/day for up to 16 weeks) and had postbaseline data. Coagulation markers were assessed before and during treatment. In the surgical study, conducted at "Federico II" University of Naples, Italy, coagulation markers were assessed in 30 patients before surgery and after biochemical remission.

Results: In the relacorilant study, significant mean changes from baseline to last observed visit were reported in factor VIII (- 18.9%, P = 0.022), activated partial thromboplastin time (aPTT) (+ 1.5 s, P = 0.046), and platelet count (- 68.8*10⁹/L, P < 0.0001), whereas von Willebrand factor was unchanged. In the surgical study, the mean time to hemostasis assessment was 6.2 months. Significant mean changes from baseline to hemostasis assessment were reported in factor VIII (- 24.2%, P = 0.044), von Willebrand factor (- 20.6%, P = 0.018), and aPTT (+ 2.0 s, P = 0.031), whereas platelet count was unchanged.

Conclusions: Several coagulation markers improved in patients with CS after 3-4 months of relacorilant treatment and within an average of 6 months after surgery. Relacorilant's positive effects on coagulation markers support further investigation of its use preoperatively in patients with CS or in patients who are not eligible for surgery.

Clinical trial registration number: NCT0280475 (registration date: 15 June 2016).