Efficacy and Safety of switching to Pasireotide in Acromegaly Patients controlled with Pegvisomant and Somatostatin Analogues: PAPE extension study.

OBJECTIVE

to assess the efficacy and safety after 48 weeks of treatment with pasireotide long-acting-release (PAS-LAR) alone or in combination with pegvisomant in patients with acromegaly. In addition, we assessed the relation between insulin secretion and pasireotide-induced hyperglycemia.

DESIGN

The PAPE extension study is a prospective follow-up study until 48 weeks after the core study of 24 weeks.

METHODS

59 out of 61 patients entered the extension study. Efficacy was defined as the percentage of patients achieving IGF-I normalization (≤ 1.2 x the Upper Limit of Normal (ULN)) at 48-weeks through protocol-based adjustment of pegvisomant and PAS-LAR doses. At baseline, insulin secretion was assessed by an oral glucose tolerance test (OGTT).

RESULTS

At the end of the study median IGF-I was 0.98 x ULN, and 77% of patients achieved normal IGF-I levels with a mean pegvisomant dose of 64 mg/week, and an overall cumulative pegvisomant dose reduction of 52%. Frequency of diabetes mellitus increased from 68% at 24 weeks to 77% at 48 weeks, and 9 patients discontinued PAS-LAR treatment, mainly because of severe hyperglycemia. Pasireotide-induced hyperglycemia was inversely correlated with baseline insulin secretion (r = -0.37, P < 0.005).

CONCLUSIONS

PAS-LAR normalizes IGF-I levels in most acromegaly patients, with a fifty percent pegvisomant-sparing effect. However, PAS-LAR treatment coincided with a high incidence of diabetes mellitus. The risk for developing diabetes during PAS-LAR treatment seems inversely related to insulin secretion at baseline.