培维索孟治疗肢端肥大症患者的疾病特异性死亡率：一项ACROSTUDY分析

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

作者信息

Tritos Nicholas A, Carlsson Martin O, Vila Greisa, Jimenez Camilo, La Torre Daria, Wajnrajch Michael P, Biller Beverly Mk, Cespedes Lissette, Miller Karen K

机构信息

Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.

Pfizer Endocrine Care, Inc, New York, NY, USA.

出版信息

Endocr Connect. 2025 Sep 9;14(9). doi: 10.1530/EC-25-0247.

DOI:10.1530/EC-25-0247

PMID:40923548

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12464337/

Abstract

OBJECTIVE

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.

DESIGN

Retrospective cohort analysis of ACROSTUDY, a global surveillance study of patients with acromegaly receiving pegvisomant.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

摘要

目的

描述接受培维索孟治疗的肢端肥大症患者的疾病特异性死亡率，并确定相关风险因素，包括治疗期间的胰岛素样生长因子I（IGF-I）水平。

设计

对ACROSTUDY进行回顾性队列分析，这是一项对接受培维索孟治疗的肢端肥大症患者的全球监测研究。

方法

采用累积发病率函数估计疾病特异性死亡率，并进行回归分析以确定风险因素。计算疾病特异性标准化死亡率（SMR）；泊松回归模型描述了疾病特异性SMR、IGF-I和其他风险因素之间的关联。

结果

对2077例患者进行了随访（中位时间：4.1年）。心血管/脑血管原因导致的死亡率（HR，95%CI）随着治疗期间IGF-I水平升高（1.97[1.45-2.67]，P<0.0001）和入组时年龄较大（1.10[1.07-1.13]，P<0.0001）而增加。恶性肿瘤（1.57[1.17-2.09]，P=0.0024）或呼吸系统（1.64[1.23-2.19]，P=0.0008）原因导致的死亡率随着治疗期间IGF-I水平升高而增加。达到的年龄较小（0.93[0.91-0.96]，P<0.0001）、诊断时年龄较小（<35岁 vs >50岁：3.64[1.33-9.93]，P=0.0117）、治疗期间IGF-I水平较高（1.69[1.12-2.55]，P=0.0127）以及垂体放疗（2.25[1.09-4.63]，P=0.0280）与心血管/脑血管原因导致的较高SMR（95%CI）相关。达到的年龄较小（0.93[0.89-0.96]，P<0.0001）、入组时IGF-I水平较高（>2倍 vs <1倍正常上限：4.89[1.09-21.8]，P=0.0378）以及入组时患有恶性肿瘤（7.05[2.36-21.03]，P=0.0005）与恶性原因导致的较高SMR（95%CI）相关。诊断时年龄较小（35-50岁 vs >50岁：4.50[1.08-18.83]，P=0.0394）和睡眠呼吸暂停（4.98[1.34-18.53]，P=0.0168）与呼吸系统原因导致的较高SMR比值相关。