Endocrine Abstracts (2013) 32 P841 | DOI: 10.1530/endoabs.32.P841

The benefits of pasireotide in patients with Cushing's disease are not restricted to patients with normalisation of UFC; results from a large, 12-month study

Rosario Pivonello1, Stephan Petersenn2, Feng Gu3, Andrew Trovato4, Gareth Hughes5, Monica Ligueros-Saylan5, Luiz Roberto Salgado6, André Lacroix7, Jochen Schopohl8 & Beverly Biller9


1Federico II University, Naples, Italy; 2ENDOC Center for Endocrine Tumors, Hamburg, Germany; 3Peking Union Medical College Hospital, Beijing, China; 4Novartis Pharma AG, Basel, Switzerland; 5Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA; 6University of São Paulo Medical School, São Paulo, Brazil; 7Centre hospitalier de l’Université de Montréal, Montréal, Canada; 8University of Munich, Munich, Germany; 9Massachusetts General Hospital, Boston, Massachusetts, USA.


Introduction: Pasireotide normalized or reduced UFC in patients with Cushing’s disease in a large, 12-month study. This analysis evaluates the effects of pasireotide on the signs/symptoms of Cushing’s disease according to the degree of UFC control.

Methods: Adult patients (n=162) with persistent/recurrent or de novo Cushing’s disease were randomized to pasireotide 600/900 μg s.c. bid. Dose titration (max: 1200 μg bid) was allowed after month 3 and initiation/change in antihypertensive, antidiabetic and lipid-lowering medications was permitted throughout the study. Changes in the symptoms of Cushing’s disease during pasireotide treatment were evaluated at 6 and 12 months. UFC measurements were conducted at central laboratories. UFC control was defined as UFC≤ULN, partial control as UFC>ULN but with at least 50% reduction from baseline, and uncontrolled UFC as UFC>ULN without a ≥50% reduction from baseline.

Results: In general, improvements in blood pressure, weight and BMI were observed in patients with and without UFC control, although the greatest changes were observed in those with UFC control (see Table). Similar results were seen for facial rubor and striae. Fasting plasma glucose and HbA1c levels increased from baseline in all patients receiving pasireotide, irrespective of UFC control. The relative impact of concomitant medications on signs and symptoms could not be evaluated.

Table 1
Change from baseline to month 6 (mean (95% CI))Change from baseline to month 12 (mean (95% CI))
C (n=32)PC (n=22)U (n=62)C (n=28)PC (n=17)U (n=33)
SBP (mmHg)−13.4 (−20.1, −6.8)−7.5 (−15.5, 0.4)−7.3 (−11.4, −3.2)−11.8 (−18.0, −5.6)−3.8 (−11.6, 4.1)−2.5 (−8.0, 3.1)
DBP (mmHg)−7.7 (−12.3, −3.2)−3.9 (−9.8, 2.0)−3.2 (−6.1, −0.3)−7.3 (−11.4, −3.2)−3.2 (−8.7, 2.3)−0.9 (−4.6, 2.8)
BMI (kg/m2)−2.1 (−2.7, −1.5)−1.2 (−2.1, −0.4)−1.5 (−1.9, −1.1)−2.9 (−3.8, −2.1)−1.6 (2.6, −0.6)−2.5 (−3.3, −1.8)
Weight (kg)−5.6 (−7.2, −4.0)−3.2 (−5.3, −1.1)−4.1 (−5.2, −3.1)−8.0 (−10.3. −5.6)−4.2 (−6.8, −1.6)−6.9 (−8.9, −4.9)
C, controlled; PC, partially controlled; U, uncontrolled; DBP, diastolic blood pressure; SBP, systolic blood pressure.

Conclusions: Reduction in UFC levels observed during treatment with pasireotide was accompanied by corresponding improvements in the signs and symptoms of Cushing’s disease, which were maintained for 12 months. Importantly, improvements were observed even without complete UFC normalization, suggesting that partial improvements in UFC produced by pasireotide may be beneficial in improving signs and symptoms in patients with Cushing’s disease.