Disproportionality analysis of adverse events associated with ipilimumab and nivolumab combination therapy based on FAERS database

Abstract The combination of immune checkpoint inhibitors (ICIs), such as ipilimumab and nivolumab, has revolutionized cancer treatment, particularly for advanced melanoma and other solid tumors. However, rare adverse events (AEs) associated with this combination are often underreported in clinical t...

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Main Authors: Xianyu Dai, Hongliang Cao, Jiajun Li, Tao Zhang, Yuchuan Hou
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-07287-w
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author Xianyu Dai
Hongliang Cao
Jiajun Li
Tao Zhang
Yuchuan Hou
author_facet Xianyu Dai
Hongliang Cao
Jiajun Li
Tao Zhang
Yuchuan Hou
author_sort Xianyu Dai
collection DOAJ
description Abstract The combination of immune checkpoint inhibitors (ICIs), such as ipilimumab and nivolumab, has revolutionized cancer treatment, particularly for advanced melanoma and other solid tumors. However, rare adverse events (AEs) associated with this combination are often underreported in clinical trials. This study aimed to investigate the safety profile of these drugs using the FDA Adverse Event Reporting System (FAERS) database. A retrospective analysis of data from 2015 to the first quarter of 2024 was conducted, focusing on AEs submitted by healthcare professionals. Disproportionality analysis, using algorithms like Reporting Odds Ratio (ROR) and Bayesian Confidence Propagation Neural Network (BCPNN), identified AE signals. A total of 19,462 reports related to the combination therapy were retrieved, spanning 20 System Organ Classes (SOCs), with endocrine and hepatobiliary disorders being most affected. Additionally, 125 unexpected significant AEs were identified, including thyrotoxic crisis, diabetes insipidus, immune-mediated optic neuritis, cystitis, eyelid ptosis, complete atrioventricular block, etc. The highest frequency of AEs occurred within the first 30 days of treatment (38.1%), with a decrease in incidence over time, as indicated by the Weibull Shape Parameter (WSP) test. These findings highlight the importance of continuous monitoring of ICIs in clinical practice.
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spelling doaj-art-6289a9ec076d40a8b6c3dfecf2834bbd2025-08-20T03:03:42ZengNature PortfolioScientific Reports2045-23222025-07-0115111210.1038/s41598-025-07287-wDisproportionality analysis of adverse events associated with ipilimumab and nivolumab combination therapy based on FAERS databaseXianyu Dai0Hongliang Cao1Jiajun Li2Tao Zhang3Yuchuan Hou4Department of Urology, The First Hospital of Jilin UniversityDepartment of Urology, The First Hospital of Jilin UniversityDepartment of Hepatic Surgery, The First Affiliated Hospital of Harbin Medical UniversityDepartment of Gastric and Colorectal Surgery, General Surgery Center, The First Hospital of Jilin UniversityDepartment of Urology, The First Hospital of Jilin UniversityAbstract The combination of immune checkpoint inhibitors (ICIs), such as ipilimumab and nivolumab, has revolutionized cancer treatment, particularly for advanced melanoma and other solid tumors. However, rare adverse events (AEs) associated with this combination are often underreported in clinical trials. This study aimed to investigate the safety profile of these drugs using the FDA Adverse Event Reporting System (FAERS) database. A retrospective analysis of data from 2015 to the first quarter of 2024 was conducted, focusing on AEs submitted by healthcare professionals. Disproportionality analysis, using algorithms like Reporting Odds Ratio (ROR) and Bayesian Confidence Propagation Neural Network (BCPNN), identified AE signals. A total of 19,462 reports related to the combination therapy were retrieved, spanning 20 System Organ Classes (SOCs), with endocrine and hepatobiliary disorders being most affected. Additionally, 125 unexpected significant AEs were identified, including thyrotoxic crisis, diabetes insipidus, immune-mediated optic neuritis, cystitis, eyelid ptosis, complete atrioventricular block, etc. The highest frequency of AEs occurred within the first 30 days of treatment (38.1%), with a decrease in incidence over time, as indicated by the Weibull Shape Parameter (WSP) test. These findings highlight the importance of continuous monitoring of ICIs in clinical practice.https://doi.org/10.1038/s41598-025-07287-wIpilimumabNivolumabAdverse eventsPharmacovigilanceFAERS
spellingShingle Xianyu Dai
Hongliang Cao
Jiajun Li
Tao Zhang
Yuchuan Hou
Disproportionality analysis of adverse events associated with ipilimumab and nivolumab combination therapy based on FAERS database
Scientific Reports
Ipilimumab
Nivolumab
Adverse events
Pharmacovigilance
FAERS
title Disproportionality analysis of adverse events associated with ipilimumab and nivolumab combination therapy based on FAERS database
title_full Disproportionality analysis of adverse events associated with ipilimumab and nivolumab combination therapy based on FAERS database
title_fullStr Disproportionality analysis of adverse events associated with ipilimumab and nivolumab combination therapy based on FAERS database
title_full_unstemmed Disproportionality analysis of adverse events associated with ipilimumab and nivolumab combination therapy based on FAERS database
title_short Disproportionality analysis of adverse events associated with ipilimumab and nivolumab combination therapy based on FAERS database
title_sort disproportionality analysis of adverse events associated with ipilimumab and nivolumab combination therapy based on faers database
topic Ipilimumab
Nivolumab
Adverse events
Pharmacovigilance
FAERS
url https://doi.org/10.1038/s41598-025-07287-w
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