Introduction: The multi-receptor targeted somatostatin analogue pasireotide has demonstrated efficacy in reducing cortisol in patients with Cushings disease in a large, randomized, double-blind, Phase III study. The effects of pasireotide on the signs and symptoms of Cushings disease were also investigated as secondary objectives in this trial.
Methods: Adult patients with persistent/recurrent or de novo Cushings disease were randomized to receive pasireotide 600 (n=82) or 900 (n=80) μg sc bid for 12 months. Dose increases of 300 μg bid were permitted after month 3 depending on 24-h urinary-free cortisol (UFC) levels. Clinical signs and symptoms of Cushings disease were evaluated at regular intervals. Health-related quality of life (HRQoL) was assessed using the CushingQoL questionnaire at baseline, month 3, 6 and 12.
Results: Reductions in mean UFC were accompanied by a rapid and substantial reduction in both mean (±S.D.) systolic and diastolic blood pressure (from 133.5±19.1 to 126.1±14.1 mmHg and 86.4±12.7 to 82.8±9.7 mmHg respectively) over the course of the 12-month study period. Mean weight decreased from 81.6±21.6 to 74.4±18.7 kg, accompanied by a reduction in BMI. Mean LDL-cholesterol and triglyceride levels were reduced from 3.52±1.02 to 3.04±1.16 mmol/l and 1.83±1.02 to 1.55±0.80 mmol/l respectively. Mean HRQoL scores increased from values of 41.1±20.4 at baseline to 50.4±20.1 at month 6 and 52.5±19.2 at month 12. Improvements in facial rubor, supraclavicular and dorsal fat pads were also observed. These clinical changes were achieved irrespective of patients achieving normalized UFC levels. Adverse effects were fairly typical of somatostatin analogues, except for hyperglycemia.
Conclusion: Rapid and substantial improvements in the signs and symptoms of Cushings disease were seen following pasireotide treatment, and were maintained during 12 months therapy. Improvements in these parameters were not dependent on UFC normalization, suggesting a reduction in UFC can be associated with long-term clinical benefit.