Published by Bioscientifica Ltd. Printed in Great Britain © 2020 European Society of Endocrinology https://eje.bioscientifca.com https://doi.org/10.1530/EJE-19-0794 European Journal of Endocrinology 182:3 285–292 N A Tritos and others Mortality in acromegaly on pegvisomant All-cause mortality in patients with acromegaly treated with pegvisomant: an ACROSTUDY analysis Nicholas A Tritos 1 , Anders F Mattsson 2 , Greisa Vila 3 , Beverly M K Biller 1 , Anne Klibanski 1 , Srinivas Valluri 4 , Judith Hey-Hadavi 5 , Nicky Kelepouris 5 and Camilo Jimenez 6 1 Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA, 2 Pfzer Endocrine Care, Pfzer Health AB, Sollentuna, Sweden, 3 Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria, 4 Global Biometrics and Data Management, Pfzer Inc, New York, New York, USA, 5 Pfzer Endocrine Care, Inc, New York, New York, USA, and 6 Department of Endocrine Neoplasia and Hormonal Disorders, University of Texas MD Anderson Cancer Center, Houston, Texas, USA Abstract Objective: To examine all-cause mortality rates in patients with acromegaly on pegvisomant and identify pertinent risk factors, including insulin-like growth factor I (IGF-I). Design: Retrospective cohort analysis of data from ACROSTUDY (global surveillance 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 (WHO GBD 2016) were estimated. Multiplicative multiple Poisson regression models were used to characterize the association between SMR, IGF-I, and other risk factors associated with mortality risk. Results: The study consisted of 2077 subjects who were followed for a median 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 IGF-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 rates that were indistinguishable from the general population. Conclusions: Higher on-treatment IGF-I, older attained age, and longer duration of acromegaly before starting pegvisomant are associated with higher all-cause mortality rates. Younger patients with uncontrolled acromegaly have higher excess all-cause mortality rates in comparison with older patients. Introduction Acromegaly has been associated with increased all- cause mortality, attributed to higher cardiovascular and cerebrovascular mortality (1, 2, 3, 4, 5). Whether malignancy-related morbidity and mortality is increased in patients with acromegaly is less certain (6, 7). Achieving biochemical control of excess growth hormone (GH) Correspondence should be addressed to N A Tritos Email ntritos@mgh.harvard.edu Clinical Study European Journal of Endocrinology (2020) 182, 285–292 Downloaded from Bioscientifica.com at 02/08/2022 04:18:11PM via free access