Hepatobiliary Adverse Events Associated with Pembrolizumab: A Pharmacovigilance Study from the FDA Adverse Event Reporting System (FAERS) Database

Background: Immuno-oncology has transformed cancer treatment, with immune checkpoint inhibitors (ICIs) like pembrolizumab playing a key role. While highly effective, these therapies can also cause immune-related adverse events. This study examines the incidence and characteristics of hepatobiliary a...

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Main Author: Connor Frey
Format: Article
Language:English
Published: MDPI AG 2024-12-01
Series:Pharmacoepidemiology
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Online Access:https://www.mdpi.com/2813-0618/4/1/1
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author Connor Frey
author_facet Connor Frey
author_sort Connor Frey
collection DOAJ
description Background: Immuno-oncology has transformed cancer treatment, with immune checkpoint inhibitors (ICIs) like pembrolizumab playing a key role. While highly effective, these therapies can also cause immune-related adverse events. This study examines the incidence and characteristics of hepatobiliary adverse events (AEs) linked to pembrolizumab, using data from the FDA Adverse Event Reporting System (FAERS). Objective: To investigate the rates of hepatobiliary AEs linked to pembrolizumab, providing insights into the risks of liver and biliary system damage in patients prescribed pembrolizumab. Methods: This study utilized the FAERS database via OpenVigil 2.1. Adverse events (AEs) related to pembrolizumab were identified and compared to those associated with other drugs. Reporting odds ratios (RORs) were calculated to assess the likelihood of hepatobiliary AEs in pembrolizumab-treated patients. Results: In total, 594 hepatic AEs and 181 biliary AEs were identified. Significant hepatic AEs included elevated ALT (ROR 3.00, 95% CI: 2.685–3.351), hepatotoxicity (ROR 6.436, 95% CI: 5.72–7.242), and hepatic cytolysis (ROR 15.721, 95% CI: 13.854–17.84). Immune-mediated hepatitis exhibited the highest ROR of 346.716 (95% CI: 303.568–395.997). For biliary AEs, cholangitis (ROR 19.597, 95% CI: 16.852–22.791) and sclerosing cholangitis (ROR 24.735, 95% CI: 19.888–30.763) were the most prominent. Conclusions: Pembrolizumab is associated with a significant risk of hepatobiliary adverse events, particularly immune-mediated hepatitis and cholangitis. The elevated RORs for these conditions highlight the importance of close monitoring and managing liver and biliary functions in patients undergoing pembrolizumab checkpoint blockade. These findings emphasize the need for personalized treatment strategies to mitigate risks and optimize outcomes in cancer immunotherapy, especially for those with preexisting hepatobiliary conditions.
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spelling doaj-art-87c3df0954a748048ec5f27dbf44e4d62025-08-20T02:42:24ZengMDPI AGPharmacoepidemiology2813-06182024-12-0141110.3390/pharma4010001Hepatobiliary Adverse Events Associated with Pembrolizumab: A Pharmacovigilance Study from the FDA Adverse Event Reporting System (FAERS) DatabaseConnor Frey0Department of Medicine, University of British Columbia, 317-2194 Health Sciences Mall, Vancouver, BC V6T 1Z3, CanadaBackground: Immuno-oncology has transformed cancer treatment, with immune checkpoint inhibitors (ICIs) like pembrolizumab playing a key role. While highly effective, these therapies can also cause immune-related adverse events. This study examines the incidence and characteristics of hepatobiliary adverse events (AEs) linked to pembrolizumab, using data from the FDA Adverse Event Reporting System (FAERS). Objective: To investigate the rates of hepatobiliary AEs linked to pembrolizumab, providing insights into the risks of liver and biliary system damage in patients prescribed pembrolizumab. Methods: This study utilized the FAERS database via OpenVigil 2.1. Adverse events (AEs) related to pembrolizumab were identified and compared to those associated with other drugs. Reporting odds ratios (RORs) were calculated to assess the likelihood of hepatobiliary AEs in pembrolizumab-treated patients. Results: In total, 594 hepatic AEs and 181 biliary AEs were identified. Significant hepatic AEs included elevated ALT (ROR 3.00, 95% CI: 2.685–3.351), hepatotoxicity (ROR 6.436, 95% CI: 5.72–7.242), and hepatic cytolysis (ROR 15.721, 95% CI: 13.854–17.84). Immune-mediated hepatitis exhibited the highest ROR of 346.716 (95% CI: 303.568–395.997). For biliary AEs, cholangitis (ROR 19.597, 95% CI: 16.852–22.791) and sclerosing cholangitis (ROR 24.735, 95% CI: 19.888–30.763) were the most prominent. Conclusions: Pembrolizumab is associated with a significant risk of hepatobiliary adverse events, particularly immune-mediated hepatitis and cholangitis. The elevated RORs for these conditions highlight the importance of close monitoring and managing liver and biliary functions in patients undergoing pembrolizumab checkpoint blockade. These findings emphasize the need for personalized treatment strategies to mitigate risks and optimize outcomes in cancer immunotherapy, especially for those with preexisting hepatobiliary conditions.https://www.mdpi.com/2813-0618/4/1/1pembrolizumabimmune checkpoint inhibitorPD-1hepaticbiliaryFAERS
spellingShingle Connor Frey
Hepatobiliary Adverse Events Associated with Pembrolizumab: A Pharmacovigilance Study from the FDA Adverse Event Reporting System (FAERS) Database
Pharmacoepidemiology
pembrolizumab
immune checkpoint inhibitor
PD-1
hepatic
biliary
FAERS
title Hepatobiliary Adverse Events Associated with Pembrolizumab: A Pharmacovigilance Study from the FDA Adverse Event Reporting System (FAERS) Database
title_full Hepatobiliary Adverse Events Associated with Pembrolizumab: A Pharmacovigilance Study from the FDA Adverse Event Reporting System (FAERS) Database
title_fullStr Hepatobiliary Adverse Events Associated with Pembrolizumab: A Pharmacovigilance Study from the FDA Adverse Event Reporting System (FAERS) Database
title_full_unstemmed Hepatobiliary Adverse Events Associated with Pembrolizumab: A Pharmacovigilance Study from the FDA Adverse Event Reporting System (FAERS) Database
title_short Hepatobiliary Adverse Events Associated with Pembrolizumab: A Pharmacovigilance Study from the FDA Adverse Event Reporting System (FAERS) Database
title_sort hepatobiliary adverse events associated with pembrolizumab a pharmacovigilance study from the fda adverse event reporting system faers database
topic pembrolizumab
immune checkpoint inhibitor
PD-1
hepatic
biliary
FAERS
url https://www.mdpi.com/2813-0618/4/1/1
work_keys_str_mv AT connorfrey hepatobiliaryadverseeventsassociatedwithpembrolizumabapharmacovigilancestudyfromthefdaadverseeventreportingsystemfaersdatabase