Real-life data on pasireotide in monotherapy or combined in active Cushing's Disease.

Alessandro Mondin^1,2*Filippo Ceccato^1,2Carla Scaroni^1,2Luca Denaro³Renzo Manara^4,5Umberto Maria Robertazzo^4,5Mattia Barbot^1,2

• ¹Endocrinology Unit, University Hospital of Padova, Padova, Italy
• ²Department of Medicine - DIMED, University of Padova, Padova, Italy
• ³Academic Neurosurgery, Department of Neurosciences, University of Padova, Padova, Italy
• ⁴Department of Neuroscience (DNS), University of Padova, Padova, Italy
• ⁵Neuroradiology Unit, University-Hospital of Padova, Padova, Italy

Context: In the last few years, the use of medical treatment in Cushing's Disease (CD) has increased thanks to the availability of new molecules. Nevertheless, real-life data on combination treatments are still lacking. Methods: Retrospective monocentric study evaluating real-life efficacy and safety of pasireotide alone or combined with cabergoline or metyrapone. Results: 18 patients (female 94%, median age 45 years) with active CD received pasireotide (median 8 months) followed in half by a combination treatment (median 22 months) with either cabergoline (2/9) or metyrapone (7/9). Pasireotide alone significantly reduced urinary free cortisol (UFC) and late-night salivary cortisol (LNSC) (p<0.01), achieving normal values in 59% and 38% of cases respectively. The second cortisol lowering agent tended to further reduce UFC (overall normalization 67%) but had little effect on LNSC. Pasireotide led to significant hyperglycaemia in 61% of cases, while the add-on drug was well-tolerated. Comorbidities were analysed accounting for the individual cardiovascular risk and for changes in concomitant treatments. Half patients showed improved pressure profile. Cholesterol levels tended to decrease, and a significant weight loss was observed (>5% in 47% of cases). Add-on treatment with dose reduction of pasireotide allowed better glycaemic control in one of 2 cases. Discussion: Our experience confirms the efficacy of pasireotide on the UFC, especially in combined regimens, but also the difficulty of restoring circadian rhythm in CD. This is the first study reporting metyrapone add-on to pasireotide, but larger studies are needed to further investigate this association. Pasireotide surely worsens the glucose homeostasis, but its positive effects, alone or combined, on blood pressure, lipid profile and body weight justify its use under careful hyperglycaemia management.