Endocrine Abstracts

Introduction: Pasireotide sc has a proven favourable efficacy and safety profile in CD patients, as shown in clinical trials. Here, we report safety and efficacy results from an expanded-access study designed to allow CD patients to receive pasireotide until regulatory approval for commercial use and reimbursement was obtained in their country.

Methods: Pasireotide-naïve adults with CD (mean 24-hour urinary free cortisol [mUFC; of three samples] exceeding the upper limit of normal [ULN]) were enrolled and initiated pasireotide sc at 600 μg bid (EU countries) or 900 μg bid (non-EU countries; 600 μg bid in patients with impaired glucose metabolism). Pasireotide dose could be increased/decreased in 300 μg increments/decrements to a maximum of 900 μg or a minimum of 300 μg for sustained UFC normalization/tolerability issues. The primary objective was to document the safety of pasireotide (primary endpoint: proportion of patients with a grade 3/4 or serious drug-related adverse event [AE]). Key secondary objectives included assessment of mUFC normalization and changes from baseline in clinical signs and quality of life (QoL) to weeks 12, 24 and 48.

Results: 104 patients received pasireotide: female, n=84 (80.8%); median duration of pasireotide exposure, 25.1 weeks; median (range) baseline UFC, 321.2 nmol/24h (142–10,920). Sixty-four (61.5%) patients discontinued treatment, most commonly for unsatisfactory therapeutic effect (25.0%), AEs (19.2%) and consent withdrawal (13.5%). Drug-related AEs occurred in 102 (98.1%) patients. Most AEs were mild/moderate severity; grade 3/4 drug-related AEs or serious AEs were documented in 42 (40.4%) patients, primarily metabolism/nutrition (n=20; 19.2%) and gastrointestinal (n=13; 12.5%) disorders. Most common grade 3/4 drug-related AEs were diabetes mellitus (10.6%) and hyperglycaemia (7.7%). At weeks 12, 24 and 48, respectively, 36/66 (54.5%), 22/46 (47.8%) and 9/21 (42.9%) evaluable patients had mUFC≤ULN. Improvements were observed in clinical signs; mean percentage change from baseline to week 48 in weight and sitting systolic and diastolic blood pressure was –7.0% (95%CI –9.1, –5.0), –4.9% (95%CI –7.9, –1.9) and –3.8% (95%CI –7.3, –0.4), respectively. Patients experienced a favourable shift in clinical signs and QoL improvement; mean CushingQoL scores increased by 34.4% (95%CI 19.5, 49.4) from baseline to week 48.

Conclusions: This study demonstrates that pasireotide is generally well tolerated, effectively reduces UFC (normalization in ~50% of evaluable patients) and improves clinical signs and QoL of CD patients in a setting similar to ‘real-world’ clinical practice. AEs were frequent but manageable for most patients, with <20% discontinuing because of AEs.