SAT-092 Disease-Specific Mortality in Patients With Acromegaly Treated With Pegvisomant - An ACROSTUDY Analysis

Abstract Disclosure: N.A. Tritos: None. M.O. Carlsson: Pfizer, Inc. G. Vila: Takeda, Lundbeck, Recordati, Ascendis, Novo Nordisk, Pharmanovia, Pfizer, Inc., HRA Pharmaceuticals, Merck. C. Jimenez: None. D. La Torre: Pfizer srl. M.P. Wajnrajch: Pfizer, Inc. B.M. Biller: Crinetics, Amolyt, Camurus, Chiesi, Crinetics, Pfizer, Inc., Recordati. L. Céspedes: Pfizer, Inc. K.K. Miller: Amgen Inc, Bristol-Myers Squibb, General Electric, Boston Scientific, Becton Dickinson. The objective of the present study was to characterize disease-specific mortality rates in patients with acromegaly on pegvisomant therapy, and identify risk factors for mortality, including on-therapy serum insulin-like growth factor I (IGF-I) levels. A retrospective cohort analysis of ACROSTUDY (global surveillance study of patients with acromegaly on pegvisomant) was conducted, and cumulative incidence functions were used to estimate disease-specific mortality rates. Regression analyses were performed to characterize pertinent risk factors. Disease-specific standardized mortality rates (SMR) were calculated, and Poisson regression models were used to characterize the association between disease-specific SMR, serum IGF-I and other risk factors. 2077 participants were followed for a median interval of 4.1 years. Mortality secondary to cardiovascular/cerebrovascular causes increased with higher on-treatment serum IGF-I levels [1.97 (1.45,2.67), P<0.0001] and older age at entry [1.09 (1.07,1.13), P<0.0001]. Mortality secondary to malignant [1.57 (1.17,2.09), P=0.0024] or respiratory [1.64 (1.23,2.19), P=0.0008] causes also increased with higher on-treatment serum IGF-I levels. On-treatment serum IGF-I exceeding the upper limit of normal were associated with higher SMR ratios for cardiovascular/cerebrovascular causes (P=0.0127). On Poisson regression, younger attained age [SMR ratio (95% CI): 0.93 (0.91,0.96), P<0.0001], younger age at diagnosis [<35 yr vs. >50 yr, 3.64 (1.33,9.93), P=0.0117], higher on-treatment serum IGF-I [1.69 (1.12,2.55), P=0.0127], and history of pituitary radiotherapy [2.25 (1.09,4.63), P=0.0280] were associated with higher SMR ratios for cardiovascular/cerebrovascular causes. Younger attained age [0.93 (0.89,0.96), P<0.0001], higher serum IGF-I at ACROSTUDY entry [>2xULN vs. <1xULN, 4.89 (1.09,21.8), P=0.0378], and history of malignancy at entry [7.05 (2.36,21.03), P=0.0005], were associated with higher SMR ratios for malignant causes. Younger age at diagnosis [35-50 yr vs. >50 yr, 4.50 (1.08,18.83), P=0.0394] and history of sleep apnea [4.98 (1.34,18.53), P=0.0168] were associated with higher SMR ratios for respiratory causes. In patients with acromegaly treated with pegvisomant, higher on-therapy serum IGF-I levels are associated with higher disease-specific mortality and higher SMR ratios for cardiovascular/cerebrovascular causes, highlighting the importance of achieving IGF-I normalization towards optimizing patient outcomes. Presentation: Saturday, July 12, 2025