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Do antibody–drug conjugates increase the risk of sepsis in cancer patients? A pharmacovigilance study

Introduction: Antibody–drug conjugates (ADCs) produce unparalleled efficacy in refractory neoplasms but can also lead to serious toxicities. Although ADC-related sepsis has been reported, the clinical features are not well characterized in real-world studies. Objective: The aim of this study was to...

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Autores principales: Xia, Shuang, Zhao, Yi-Chang, Guo, Lin, Gong, Hui, Wang, Yi-Kun, Ma, Rui, Zhang, Bi-Kui, Sheng, Yue, Sarangdhar, Mayur, Noguchi, Yoshihiro, Yan, Miao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9710632/
https://www.ncbi.nlm.nih.gov/pubmed/36467034
http://dx.doi.org/10.3389/fphar.2022.967017
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author Xia, Shuang
Zhao, Yi-Chang
Guo, Lin
Gong, Hui
Wang, Yi-Kun
Ma, Rui
Zhang, Bi-Kui
Sheng, Yue
Sarangdhar, Mayur
Noguchi, Yoshihiro
Yan, Miao
author_facet Xia, Shuang
Zhao, Yi-Chang
Guo, Lin
Gong, Hui
Wang, Yi-Kun
Ma, Rui
Zhang, Bi-Kui
Sheng, Yue
Sarangdhar, Mayur
Noguchi, Yoshihiro
Yan, Miao
author_sort Xia, Shuang
collection PubMed
description Introduction: Antibody–drug conjugates (ADCs) produce unparalleled efficacy in refractory neoplasms but can also lead to serious toxicities. Although ADC-related sepsis has been reported, the clinical features are not well characterized in real-world studies. Objective: The aim of this study was to identify the association between ADCs and sepsis using FAERS data and uncover the clinical characteristics of ADC-related sepsis. Methods: We performed disproportionality analysis using FAERS data and compared rates of sepsis in cancer patients receiving ADCs vs. other regimens. Associations between ADCs and sepsis were assessed using reporting odds ratios (RORs) and information component (IC). For each treatment group, we detected drug interaction signals, and conducted subgroup analyses (age, gender, and regimens) and sensitivity analyses. Results: A total of 24,618 cases were reported with ADCs between Q1, 2004 and Q3, 2021. Sepsis, septic shock, multiple organ dysfunction syndrome, and other sepsis-related toxicities were significantly associated with ADCs than other drugs in this database. Sepsis and multiple organ dysfunction syndrome have the highest safety concerns with ADCs compared with other anticancer monotherapies. Gemtuzumab ozogamicin and inotuzumab ozogamicin showed increased safety risks than other ADCs. For the top nine ADC-related sepsis, males showed higher sepsis safety concern than females (p <0.001); however, age did not exert influence on the risk of sepsis. We identified that 973 of 2,441 (39.9%) cases had acute myeloid leukemia (AML), and 766 of 2613 (29.3%) cases on ADCs died during therapy. Time-to-onset analysis indicated ADC-related sepsis is prone to occur within a month after administration. Co-administration of ADCs with colony-stimulating factors, proton pump inhibitors, H2-receptor antagonists, or CYP3A4/5 inhibitors showed to synergistically increase the risk of sepsis-related toxicities. Conclusion: Antibody–drug conjugates may increase the risk of sepsis in cancer patients, leading to high mortality. Further studies are warranted to characterize the underlying mechanisms and design preventive measures for ADC-related sepsis.
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spelling pubmed-97106322022-12-01 Do antibody–drug conjugates increase the risk of sepsis in cancer patients? A pharmacovigilance study Xia, Shuang Zhao, Yi-Chang Guo, Lin Gong, Hui Wang, Yi-Kun Ma, Rui Zhang, Bi-Kui Sheng, Yue Sarangdhar, Mayur Noguchi, Yoshihiro Yan, Miao Front Pharmacol Pharmacology Introduction: Antibody–drug conjugates (ADCs) produce unparalleled efficacy in refractory neoplasms but can also lead to serious toxicities. Although ADC-related sepsis has been reported, the clinical features are not well characterized in real-world studies. Objective: The aim of this study was to identify the association between ADCs and sepsis using FAERS data and uncover the clinical characteristics of ADC-related sepsis. Methods: We performed disproportionality analysis using FAERS data and compared rates of sepsis in cancer patients receiving ADCs vs. other regimens. Associations between ADCs and sepsis were assessed using reporting odds ratios (RORs) and information component (IC). For each treatment group, we detected drug interaction signals, and conducted subgroup analyses (age, gender, and regimens) and sensitivity analyses. Results: A total of 24,618 cases were reported with ADCs between Q1, 2004 and Q3, 2021. Sepsis, septic shock, multiple organ dysfunction syndrome, and other sepsis-related toxicities were significantly associated with ADCs than other drugs in this database. Sepsis and multiple organ dysfunction syndrome have the highest safety concerns with ADCs compared with other anticancer monotherapies. Gemtuzumab ozogamicin and inotuzumab ozogamicin showed increased safety risks than other ADCs. For the top nine ADC-related sepsis, males showed higher sepsis safety concern than females (p <0.001); however, age did not exert influence on the risk of sepsis. We identified that 973 of 2,441 (39.9%) cases had acute myeloid leukemia (AML), and 766 of 2613 (29.3%) cases on ADCs died during therapy. Time-to-onset analysis indicated ADC-related sepsis is prone to occur within a month after administration. Co-administration of ADCs with colony-stimulating factors, proton pump inhibitors, H2-receptor antagonists, or CYP3A4/5 inhibitors showed to synergistically increase the risk of sepsis-related toxicities. Conclusion: Antibody–drug conjugates may increase the risk of sepsis in cancer patients, leading to high mortality. Further studies are warranted to characterize the underlying mechanisms and design preventive measures for ADC-related sepsis. Frontiers Media S.A. 2022-11-09 /pmc/articles/PMC9710632/ /pubmed/36467034 http://dx.doi.org/10.3389/fphar.2022.967017 Text en Copyright © 2022 Xia, Zhao, Guo, Gong, Wang, Ma, Zhang, Sheng, Sarangdhar, Noguchi and Yan. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Xia, Shuang
Zhao, Yi-Chang
Guo, Lin
Gong, Hui
Wang, Yi-Kun
Ma, Rui
Zhang, Bi-Kui
Sheng, Yue
Sarangdhar, Mayur
Noguchi, Yoshihiro
Yan, Miao
Do antibody–drug conjugates increase the risk of sepsis in cancer patients? A pharmacovigilance study
title Do antibody–drug conjugates increase the risk of sepsis in cancer patients? A pharmacovigilance study
title_full Do antibody–drug conjugates increase the risk of sepsis in cancer patients? A pharmacovigilance study
title_fullStr Do antibody–drug conjugates increase the risk of sepsis in cancer patients? A pharmacovigilance study
title_full_unstemmed Do antibody–drug conjugates increase the risk of sepsis in cancer patients? A pharmacovigilance study
title_short Do antibody–drug conjugates increase the risk of sepsis in cancer patients? A pharmacovigilance study
title_sort do antibody–drug conjugates increase the risk of sepsis in cancer patients? a pharmacovigilance study
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9710632/
https://www.ncbi.nlm.nih.gov/pubmed/36467034
http://dx.doi.org/10.3389/fphar.2022.967017
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