All-cause mortality in patients with acromegaly treated with pegvisomant: An ACROSTUDY analysis

Nicholas A. Tritos, Anders F. Mattsson, Greisa Vila, Beverly M.K. Biller, Anne Klibanski, Srinivas Valluri, Judith Hey Hadavi, Nicky Kelepouris, Camilo Jimenez

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Objective: To examine all-cause mortality rates in patients with acromega ly on pegvisomant and identify pertinent risk factors, including insulin-like growth factor I (IGF-I). Design: Retrospective cohort analysis of data from ACROSTUDY (global s urveillance study of patients with acromegaly treated with pegvisomant). Methods: Kaplan-Meier analyses and Cox regression techniques were used to examine survival rates. Standardized mortality ratios (SMR) with reference to general population (WH O GBD 2016) were estimated. Multiplicative multiple Poisson regression models were used to characterize the associa tion between SMR, IGF-I, and other risk factors associated with mortality risk. Results: The study consisted of 2077 subjects who were followed for a m edian interval of 4.1 years, contributing to 8957 patient-years. Higher on-treatment IGF-I (P = 0.0035), older attained age (P < 0.0001), and longer duration of acromegaly (>10 years) before starting pegvisomant (P = 0.05) were associated with higher mortality rates. In reference to general population rates, higher SMR (1.10, 1.42, and 2.62, at attained age 55 years) were observed with higher serum IGF-I category (SMR trend: 1.44 (44%)/per fold level of I GF-I/ULN (95% CI: 1.10, 1.87), P = 0.0075). SMR increased per year of younger attained age (1.04 (1.02-1.04), P < 0.0001) and were higher for longer disease duration (>10 years) before starting pegvisomant (1.57 (1.02, 2.43), P = 0.042). Serum IGF-I levels within the normal range during pegvisomant therapy were associated with all-cause mortality ra tes that were indistinguishable from the general population. Conclusions: Higher on-treatment IGF-I, older attained age, and longer dura tion of acromegaly before starting pegvisomant are associated with higher all-cause mortality rate s. Younger patients with uncontrolled acromegaly have higher excess all-cause mortality rates in comparison with olde r patients.

Original languageEnglish (US)
Pages (from-to)285-292
Number of pages8
JournalEuropean journal of endocrinology
Issue number3
StatePublished - Jan 1 2020


ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Tritos, N. A., Mattsson, A. F., Vila, G., Biller, B. M. K., Klibanski, A., Valluri, S., Hadavi, J. H., Kelepouris, N., & Jimenez, C. (2020). All-cause mortality in patients with acromegaly treated with pegvisomant: An ACROSTUDY analysis. European journal of endocrinology, 182(3), 285-292.