Nicholas A Tritos, Martin O Carlsson, Greisa Vila, Camilo Jimenez, Daria La Torre, Michael P Wajnrajch, Beverly Mk Biller, Lissette Cespedes, Karen K Miller
{"title":"用Pegvisomant治疗肢端肥大症患者的疾病特异性死亡率：一项ACROSTUDY分析。","authors":"Nicholas A Tritos, Martin O Carlsson, Greisa Vila, Camilo Jimenez, Daria La Torre, Michael P Wajnrajch, Beverly Mk Biller, Lissette Cespedes, Karen K Miller","doi":"10.1530/EC-25-0247","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>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.</p><p><strong>Design: </strong>Retrospective cohort analysis of ACROSTUDY, a global surveillance study of patients with acromegaly receiving pegvisomant.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":2.8000,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12464337/pdf/","citationCount":"0","resultStr":"{\"title\":\"Disease-Specific Mortality in Patients With Acromegaly Treated With Pegvisomant: An ACROSTUDY Analysis.\",\"authors\":\"Nicholas A Tritos, Martin O Carlsson, Greisa Vila, Camilo Jimenez, Daria La Torre, Michael P Wajnrajch, Beverly Mk Biller, Lissette Cespedes, Karen K Miller\",\"doi\":\"10.1530/EC-25-0247\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>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.</p><p><strong>Design: </strong>Retrospective cohort analysis of ACROSTUDY, a global surveillance study of patients with acromegaly receiving pegvisomant.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>\",\"PeriodicalId\":11634,\"journal\":{\"name\":\"Endocrine Connections\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2025-09-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12464337/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Endocrine Connections\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1530/EC-25-0247\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Endocrine Connections","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1530/EC-25-0247","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
Disease-Specific Mortality in Patients With Acromegaly Treated With Pegvisomant: An ACROSTUDY Analysis.
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.
期刊介绍：
Endocrine Connections publishes original quality research and reviews in all areas of endocrinology, including papers that deal with non-classical tissues as source or targets of hormones and endocrine papers that have relevance to endocrine-related and intersecting disciplines and the wider biomedical community.
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