Endocrine Abstracts

Background: Improving physical manifestations of hypercortisolism is an important treatment goal for patients with Cushing’s disease (CD). In the Phase III LINC 3 study (NCT02180217), osilodrostat therapy, a potent oral 11β-hydroxylase inhibitor, rapidly normalised mean urinary free cortisol (mUFC) in most patients with CD and sustained control of mUFC over a median treatment period of 130 weeks (W). Here we describe concomitant improvements in physical manifestations of hypercortisolism.

Methods: 137 adults with CD and mUFC >1.5 times the upper limit of normal were enrolled in the published 48W core phase. 106 patients opted to enter the extension phase, which ended when all patients had received ≥72W of treatment. Photographs from the shoulders up (frontal and lateral) and of the trunk with the patient standing (frontal and dorsal) were taken by investigators at baseline, every 12W during the core phase, and at W72; manifestations were rated subjectively on a semi-quantitative scale: 0=absent; 1=mild; 2=moderate; 3=severe. Body weight and waist circumference were also measured. Data are presented descriptively for all patients with an assessment at baseline and the given visit.

Results: At baseline, most patients had mild, moderate or severe physical features of hypercortisolism: dorsal fat pad (73.7%), supraclavicular fat pad (68.6%), central obesity (71.5%), facial rubor (63.5%), hirsutism (58.5% [females only; n=62/106]), proximal muscle atrophy (51.8%), striae (48.9%) and ecchymosis (38.7%). At W48 (n=97) and W72 (n=86), respectively, improvements in physical features scores from baseline were noted in 52.6% and 57.0% of patients for dorsal fat pad, 51.5% and 53.5% for supraclavicular fat pad, 42.3% and 39.5% for central obesity, 46.4% and 52.3% for facial rubor, 34.2% (n=26/76) and 34.4% (n=22/64) for hirsutism, 38.1% and 34.9% for proximal muscle atrophy, 32.0% and 30.2% for striae, and 35.1% and 31.4% for ecchymosis. Mean weight improved from 80.8 kg at baseline to 75.5 kg (–4.6%) at W48 and 74.1 kg (–5.8%) at W72. Mean waist circumference decreased from 103.5 cm at baseline to 97.4 cm (–4.2%) at W48 and 95.6 cm (–5.8%) at W72. Mean body mass index improved from 30.3 kg/m² at baseline to 28.4 kg/m² (–4.6%) at W48 and 27.9 kg/m2 (–5.8%) at W72.

Conclusions: Most patients in LINC 3 had physical manifestations of hypercortisolism at baseline. Osilodrostat therapy provided long-term mUFC control and clinical improvements, with reductions in patient weight and the severity of physical manifestations, including hirsutism, that were sustained through to W72.