Introduction: A monthly, long-acting formulation of pasireotide normalized or reduced mean urinary free cortisol (mUFC) in most patients with Cushings disease (CD) in a multicentre, double-blind, Phase III study. The effects of long-acting pasireotide on signs and symptoms of CD are reported here.
Methods: Patients with persistent/recurrent (n=123) or de novo (non-surgical candidates; n=27) CD and mUFC≥1.55xULN were randomized to monthly pasireotide 10 mg (n=74) or 30 mg (n=76). Dose could be up-titrated (1030 mg/3040 mg) at month (M) 4 if mUFC>1.5xULN and/or at M7, M9, or M12 if mUFC>1.0xULN. Primary endpoint was mUFC≤ULN at M7, regardless of dose titration. Signs/symptoms of CD were evaluated at regular intervals. All data shown are mean (95%CI).
Results: mUFC reduction was accompanied by substantial clinical improvements. Mean changes (95%CI) in clinical signs to M12 in the 10mg and 30mg groups included: weight, −3.4 kg (−4.8,−2.0) and −6.5 kg (−8.3,−4.7); BMI, −1.3 kg/m2 (−1.8,−0.8) and −2.6 kg/m2 (−3.3,−1.9); waist circumference, −4.5 cm (−7.2,−1.8) and −6.2 cm (−8.7,−3.6); health-related QoL score, 6.4 (1.3,11.6) and 7.0 (3.0,10.9). Clinically relevant decreases in systolic (−5.0 mmHg (−8.8,−1.3)) and diastolic (−3.1 mmHg (−5.7,−0.5)) BP were reported in the 30 mg group; downward trends were also seen with pasireotide 10 mg (systolic BP: −4.6 mmHg (−9.9,0.7); diastolic BP: −3.4 mmHg (−7.3,0.4)). A significant (P<0.0001) relationship was found between change in mUFC and systolic/diastolic BP, after adjusting for antihypertensive medication. Changes in other clinical parameters occurred irrespective of whether patients achieved mUFC≤ULN at M7. The safety profile of long-acting pasireotide was similar to that of twice-daily pasireotide.
Conclusion: Reductions in mUFC levels during 12 months long-acting pasireotide treatment were accompanied by improvements in clinical signs of CD. Long-acting pasireotide is an effective treatment option for patients with CD, with a convenient monthly administration schedule.
20 May 2017 - 23 May 2017