Endocrine Abstracts

Background: Pasireotide is a multi-ligand somatostatin analogue licensed in a long-acting release formulation (PAS-LAR) for the treatment of acromegaly. The real-life reports with PAS-LAR are still scanty.

Objectives: To assess the efficacy and safety of PAS-LAR in patients with acromegaly.

Patients and methods: Prospective observational multi-centre study enrolling acromegalics evaluated before (baseline) and 1, 6, 12, 24, and 36 months after PAS-LAR start. Biochemical and radiological studies have been collected. Acromegaly symptoms and drug-related adverse events (AEs) have also been recorded. Patients achieving an IGF1-index (IGF1 normalised to the upper limit of normal) ≤1.3 were considered as controlled.

Results: forty-eight acromegalics were enrolled (22 females; mean age 43 years). All patients have been previously treated with first-generation somatostatin analogues. 77% of them had received multimodal treatments for acromegaly. The PAS-LAR starting dose was 40 mg/28 days in all and was escalated to 60 mg/28 days in 16 patients and decreased to 20 mg/28 days in 3. PAS-LAR significantly decreased IGF1-index levels (baseline vs the last visit: 1.9 ± 0.6 vs 1.2 ± 0.6, P < 0.0001) and controlled the disease in 62% of cases at last visit. Interestingly, the effects of PAS-LAR on IGF1 have been already observed during the 1-month visit (IGF1-index 1.4 ± 0.7, P = 0.0002 vs baseline; disease control rate 60%, P < 0.0001). Only minor changes were observed by carrying on the treatment and escalating the dose, not achieving a statistical significance. PAS-LAR was associated with a rapid improvement or disappearance of headache in 50% of the symptomatic patients even after the first drug dose. MRI showed a decrease in tumour volume in 44% of subjects and no changes in 56%. Hyperglycaemia was the most common adverse event of PAS-LAR. The prevalence of diabetes increased from 33% at baseline to 54% at the last visit. Three patients developed DKA. The second most frequent AEs was mild gastrointestinal discomfort. Most glycaemic and gastrointestinal AEs was recognised in the 1st-month visit or after dose escalation. Eleven patients had discontinued PAS-LAR mainly forlack of disease control or worsening of hyperglycaemia, both occurring in eight cases.

Conclusions: PAS-LAR significantly decreases IGF1 and the size of adenoma and may quickly improve headache in a significant percentage of acromegalic patients. The beneficial effects of PAS-LAR on IGF1 levels and headache as well as its glycaemic AEs may occur even after the first administration of the drug. The 1st-month evaluation should be considered part of the standard care of PAS-LAR treated acromegalics.