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- Title
Efficacy and safety of switching to pasireotide in acromegaly patients controlled with pegvisomant and somatostatin analogues: PAPE extension study.
- Authors
Muhammad, Ammar; Coopmans, Eva C.; Delhanty, Patric J. D.; Dallenga, Alof H. G.; Haitsma, Iain K.; Janssen, Joseph A. M. J. L.; van der Lely, Aart J.; Neggers, Sebastian J. C. M. M.
- Abstract
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: Fifty-nine out of 61 patients entered the extension study. Efficacy was defined as the percentage of patients achieving IGF-I normalization (=1.2× 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× 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 nine 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 50% 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.
- Subjects
ACROMEGALY; SOMATOSTATIN; DRUG efficacy
- Publication
European Journal of Endocrinology, 2018, Vol 179, Issue 5, p269
- ISSN
0804-4643
- Publication type
Article
- DOI
10.1530/EJE-18-0353