Disease-Specific Mortality in Patients With Acromegaly Treated With Pegvisomant: An ACROSTUDY Analysis.

Characterize disease-specific mortality rates in patients with acromegaly on pegvisomant and identify pertinent risk factors, including on-therapy insulin-like growth factor I (IGF-I) levels. Retrospective cohort analysis of ACROSTUDY, a global surveillance study of patients with acromegaly receiving pegvisomant. Cumulative incidence function to estimate disease-specific mortality and regression analyses to characterize risk factors. Disease-specific standardized mortality rates (SMR) were calculated; Poisson regression models characterized the association between disease-specific SMR, IGF-I, and other risk factors. 2077 patients were followed (median: 4.1 years). Mortality (HR,95% CI) secondary to cardiovascular/cerebrovascular causes increased with higher on-treatment IGF-I (1.97 [1.45-2.67], P<.0001) and older age at enrollment (1.10 [1.07-1.13], P<.0001). Mortality secondary to malignant (1.57 [1.17-2.09), P=.0024) or respiratory (1.64 [1.23-2.19], P=.0008) causes increased with higher on-treatment IGF-I. Younger attained age (0.93 [0.91-0.96], P<.0001), younger age (<35 vs >50 years) at diagnosis (3.64 [1.33-9.93], P=.0117), higher on-treatment IGF-I (1.69 [1.12-2.55], P=.0127), and pituitary radiotherapy (2.25 [1.09-4.63], P=.0280) were associated with higher SMR (95% CI) for cardiovascular/cerebrovascular causes. Younger attained age (0.93 [0.89-0.96], P<.0001], higher IGF-I at enrollment (>2x vs <1x upper limit of normal: 4.89 [1.09-21.8], P=.0378), and malignancy at enrollment (7.05 [2.36-21.03], P=.0005) were associated with higher SMR (95% CI) for malignant causes. Younger age (35-50 vs >50 years) at diagnosis (4.50 [1.08-18.83], P=.0394) and sleep apnea (4.98 [1.34-18.53], P=.0168) were associated with higher SMR ratios for respiratory causes. Younger age, higher on-therapy IGF-I and radiotherapy were associated with higher SMR for cardiovascular/cerebrovascular causes, highlighting the importance of achieving IGF-I normalization.