ECE2018 Oral Communications Novel aspects of puberty development and Cushing's disease (5 abstracts)
Late-night salivary cortisol (LNSC) levels in a Phase III study of long–acting pasireotide in patients with Cushing’s disease (CD)
John Newell-Price 1 , Rosario Pivonello 2 , Antoine Tabarin 3 , Maria Fleseriu 4 , Przemysław Witek 5 , Mônica Gadelha 6 , Stephan Petersenn 7 , Libuse Tauchmanova 8 , Shoba Ravichandran 9 , Michael Roughton 8 , André Lacroix 10 & Beverly MK Biller 11
1The Medical School, University of Sheffield, Sheffield, UK; 2Università Federico II di Napoli, Naples, Italy; 3Department of Endocrinology, CHU of Bordeaux, Bordeaux, France; 4Northwest Pituitary Center, Oregon Health & Science University, Portland, Oregon, USA; 5Department of Gastroenterology, Endocrinology and Internal Diseases, Military Institute of Medicine, Warsaw, Poland; 6Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; 7ENDOC Center for Endocrine Tumors, Hamburg, Germany; 8Novartis Pharma AG, Basel, Switzerland; 9Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA; 10Centre hospitalier de l’Université de Montréal, Montreal, Canada; 11Neuroendocrine Clinical Center, Massachussetts General Hospital, Boston, Massachussetts, USA.
Introduction: LNSC has shown high sensitivity and specificity for the initial diagnosis of CD and detection of disease recurrence; however, the use of LNSC to monitor medical treatment of CD is not well established. The results of an exploratory analysis evaluating changes in LNSC in CD patients receiving long-acting pasireotide during a Phase III study (CSOM230G2304; Lacroix et al. Lancet Diabetes Endocrinol 2018) are reported here.
Methods: Patients (N=150) with persistent, recurrent or de novo (non-surgical candidates) CD and mean urinary free cortisol (mUFC) 1.5–5x the upper limit of normal (ULN) were randomized to monthly pasireotide 10 mg (n=74) or 30 mg (n=76). mUFC≤ULN at month (M) 7 was the primary endpoint, with change in LNSC an exploratory objective. At each time point, mean LNSC (mLNSC) was calculated as the mean of two measurements from single samples collected at 23:00 (±1 h) on the same days as the first two of three 24-hour UFC measurements. UFC and LNSC samples were analysed at central laboratories by LC-MS/MS.
Results: Mean (S.D.) mLNSC at baseline was 10.4 (8.2) nmol/l, with mLNSC>ULN (3.2 nmol/l) in 125/137 (91.2%) evaluable patients. Mean (95%CI) changes in mLNSC from baseline to M7 and M12 were −1.6 (−3.7,0.5) and −3.3 (−5.6,−1.0) nmol/l, respectively. Mean (95%CI) change from baseline to M7 in mLNSC was greatest in patients with mUFC≤ULN at M7 (−5.1 (−8.3,−2.0) nmol/l). Changes in blood pressure (BP) and weight by mUFC and/or mLNSC response among 113 evaluable patients at M7 are shown in the Table.
| Both mUFC and mLNSC≤ULN N=20 | mUFC≤ULN only N=36 | mLNSC≤ULN only N=5 | Both mUFC and mLNSC>ULN N=52 | |
| Systolic BP | −10.8 (−15.7,−5.9) | −3.9 (−7.7,0.0) | −7.4 (−16.6,1.9) | −1.2 (−3.9,1.5) |
| Diastolic BP | −10.5 (−16.1,−5.0) | −4.7 (−10.2,0.9) | −4.5 (−18.7,9.7) | −0.8 (−4.6,2.9) |
| Weight | −5.7 (−9.1,−2.3) | −3.7 (−5.8,−1.6) | −2.0 (−10.9,7.0) | −4.3 (−5.8,−2.7) |
Conclusion: Long-acting pasireotide decreased mLNSC levels, with greatest reductions seen in patients with controlled mUFC at M7. More patients achieved normal mUFC than normal mLNSC at M7, with few patients having normal mLNSC but elevated mUFC. Greatest reductions in BP were seen for patients with normal mUFC and mLNSC. Further studies designed to assess the effect of medical therapies on LNSC in CD patients are warranted.
Article tools
My recent searches
My recently viewed abstracts
Authors
Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
© Bioscientifica 2024 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more