Endocrine Abstracts

Introduction: Subcutaneous (sc) pasireotide effectively reduces cortisol levels, improves signs/symptoms and is generally well tolerated in Cushing’s disease (CD) patients, as shown in previous clinical trials. We report interim results from a multicentre, real-world observational study evaluating the long-term safety and efficacy of pasireotide sc in clinical practice in CD patients.

Methods: Adults with CD, for whom surgery has failed or is not an option, are being enrolled. Primary objective: document the long-term (3-year follow-up) safety and tolerability of pasireotide. Secondary objective: document the short- and long-term efficacy of pasireotide as measured by the proportion of patients achieving mean urinary free cortisol (mUFC) below the upper limit of normal (ULN) at months 1, 3, 6, 12, 24 and 36. Patients are grouped by whether pasireotide was started before (prior-use) or at (new-use) study entry.

Results: As of 1 October 2016, 99 patients have been recruited and received ≥1 pasireotide dose after enrolment: 78 prior-use (mean time from diagnosis, 81.3 months; female, 80.8%) and 21 new-use (mean time from diagnosis, 40.7 months; female, 66.7%). Median (range) exposure to pasireotide: prior-use, 7.2 months (0.1–36.3) on study, 25.3 months (2.0–108.5) from drug initiation; new-use, 2.9 months (0.1–12.1) on study. Eighty-nine (prior-use, n=69; new-use, n=20) patients had ≥1 safety assessment after enrolment, of whom 65 (73.0%) experienced ≥1 adverse event (AE). Forty-three patients (48.3%) had ≥1 drug-related AE, most commonly nausea (prior-use, n=6 (8.7%); new-use, n=7 (35.0%)), diarrhoea (prior-use, n=5 (7.2%); new-use, n=3 (15.0%)) and hyperglycaemia (prior-use, n=3 (4.3%); new-use, n=5 (25.0%)). Drug-related serious AEs were documented in 8/69 prior-use (11.6%; hyperglycaemia, n=1 (1.4%)) and 4/20 new-use (20.0%; hyperglycaemia, n=3 (15.0%)) patients. Of patients with a normal/pre-diabetic HbA_1c level at baseline, 3/15 (20.0%) prior-use and 4/6 (66.7%) new-use patients had a highest-reported level in the diabetic range during the study. Of evaluable patients in the prior-use and new-use groups, respectively, mUFC was ≤ULN in 23/34 (67.6%) and 1/10 (10.0%) patients at baseline, 9/16 (56.3%) and 7/14 (50.0%) at month 1, 18/22 (81.8%) and 1/3 (33.3%) at month 6, and 16/18 (88.9%) and 0/0 at month 12.

Conclusions: Results from this study demonstrate the favourable risk/benefit profile of pasireotide sc in CD patients, confirming findings from previous clinical trials. The lower incidence of hyperglycaemia in prior-use versus new-use patients indicates that glycaemic control does not deteriorate over time, which is potentially attributable to appropriate management at its onset.