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 i...
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.967017/full |
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| author | Shuang Xia Shuang Xia Shuang Xia Yi-Chang Zhao Yi-Chang Zhao Yi-Chang Zhao Lin Guo Lin Guo Lin Guo Hui Gong Hui Gong Hui Gong Yi-Kun Wang Yi-Kun Wang Yi-Kun Wang Rui Ma Rui Ma Rui Ma Bi-Kui Zhang Bi-Kui Zhang Bi-Kui Zhang Yue Sheng Mayur Sarangdhar Mayur Sarangdhar Mayur Sarangdhar Yoshihiro Noguchi Miao Yan Miao Yan Miao Yan |
| author_facet | Shuang Xia Shuang Xia Shuang Xia Yi-Chang Zhao Yi-Chang Zhao Yi-Chang Zhao Lin Guo Lin Guo Lin Guo Hui Gong Hui Gong Hui Gong Yi-Kun Wang Yi-Kun Wang Yi-Kun Wang Rui Ma Rui Ma Rui Ma Bi-Kui Zhang Bi-Kui Zhang Bi-Kui Zhang Yue Sheng Mayur Sarangdhar Mayur Sarangdhar Mayur Sarangdhar Yoshihiro Noguchi Miao Yan Miao Yan Miao Yan |
| author_sort | Shuang Xia |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-11T16:05:22Z |
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| last_indexed | 2024-04-11T16:05:22Z |
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| spelling | doaj.art-9b7ffb60bb1e46d18313c983be0547212022-12-22T04:14:51ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-11-011310.3389/fphar.2022.967017967017Do antibody–drug conjugates increase the risk of sepsis in cancer patients? A pharmacovigilance studyShuang Xia0Shuang Xia1Shuang Xia2Yi-Chang Zhao3Yi-Chang Zhao4Yi-Chang Zhao5Lin Guo6Lin Guo7Lin Guo8Hui Gong9Hui Gong10Hui Gong11Yi-Kun Wang12Yi-Kun Wang13Yi-Kun Wang14Rui Ma15Rui Ma16Rui Ma17Bi-Kui Zhang18Bi-Kui Zhang19Bi-Kui Zhang20Yue Sheng21Mayur Sarangdhar22Mayur Sarangdhar23Mayur Sarangdhar24Yoshihiro Noguchi25Miao Yan26Miao Yan27Miao Yan28Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, ChinaInternational Research Center for Precision Medicine, Transformative Technology and Software Services, Hunan, ChinaToxicology Counseling Center of Hunan Province (TCCH), Changsha, ChinaDepartment of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, ChinaInternational Research Center for Precision Medicine, Transformative Technology and Software Services, Hunan, ChinaToxicology Counseling Center of Hunan Province (TCCH), Changsha, ChinaDepartment of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, ChinaInternational Research Center for Precision Medicine, Transformative Technology and Software Services, Hunan, ChinaToxicology Counseling Center of Hunan Province (TCCH), Changsha, ChinaDepartment of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, ChinaInternational Research Center for Precision Medicine, Transformative Technology and Software Services, Hunan, ChinaToxicology Counseling Center of Hunan Province (TCCH), Changsha, ChinaDepartment of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, ChinaInternational Research Center for Precision Medicine, Transformative Technology and Software Services, Hunan, ChinaToxicology Counseling Center of Hunan Province (TCCH), Changsha, ChinaDepartment of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, ChinaInternational Research Center for Precision Medicine, Transformative Technology and Software Services, Hunan, ChinaToxicology Counseling Center of Hunan Province (TCCH), Changsha, ChinaDepartment of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, ChinaInternational Research Center for Precision Medicine, Transformative Technology and Software Services, Hunan, ChinaToxicology Counseling Center of Hunan Province (TCCH), Changsha, ChinaDepartment of Hematology, The Second Xiangya Hospital, Central South University, Changsha, ChinaDivision of Biomedical Informatics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United StatesDivision of Oncology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United StatesDepartment of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, United StatesLaboratory of Clinical Pharmacy, Gifu Pharmaceutical University, Gifu, JapanDepartment of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, ChinaInternational Research Center for Precision Medicine, Transformative Technology and Software Services, Hunan, ChinaToxicology Counseling Center of Hunan Province (TCCH), Changsha, ChinaIntroduction: 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.https://www.frontiersin.org/articles/10.3389/fphar.2022.967017/fullantibody–drug conjugatessepsispharmacovigilanceFAERSdata mining |
| spellingShingle | Shuang Xia Shuang Xia Shuang Xia Yi-Chang Zhao Yi-Chang Zhao Yi-Chang Zhao Lin Guo Lin Guo Lin Guo Hui Gong Hui Gong Hui Gong Yi-Kun Wang Yi-Kun Wang Yi-Kun Wang Rui Ma Rui Ma Rui Ma Bi-Kui Zhang Bi-Kui Zhang Bi-Kui Zhang Yue Sheng Mayur Sarangdhar Mayur Sarangdhar Mayur Sarangdhar Yoshihiro Noguchi Miao Yan Miao Yan Miao Yan Do antibody–drug conjugates increase the risk of sepsis in cancer patients? A pharmacovigilance study Frontiers in Pharmacology antibody–drug conjugates sepsis pharmacovigilance FAERS data mining |
| 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 | antibody–drug conjugates sepsis pharmacovigilance FAERS data mining |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.967017/full |
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