Pharmacovigilance study on the reporting frequency of atrial fibrillation with immune checkpoint inhibitors: insights from FDA Adverse Event Reporting System

Background: Immune checkpoint inhibitors (ICIs) have transformed cancer therapy but are linked with immune-related adverse events (irAEs), including cardiac events. Objective: This study aims to assess the reporting frequency of atrial fibrillation with ICIs using data from the Food and Drug Adminis...

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Main Authors: Nunzia Balzano, Annamaria Mascolo, Donatella Ruggiero, Concetta Rafaniello, Giuseppe Paolisso, Francesco Rossi, Annalisa Capuano
Format: Article
Language:English
Published: SAGE Publishing 2025-04-01
Series:Therapeutic Advances in Drug Safety
Online Access:https://doi.org/10.1177/20420986241312497
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author Nunzia Balzano
Annamaria Mascolo
Donatella Ruggiero
Concetta Rafaniello
Giuseppe Paolisso
Francesco Rossi
Annalisa Capuano
author_facet Nunzia Balzano
Annamaria Mascolo
Donatella Ruggiero
Concetta Rafaniello
Giuseppe Paolisso
Francesco Rossi
Annalisa Capuano
author_sort Nunzia Balzano
collection DOAJ
description Background: Immune checkpoint inhibitors (ICIs) have transformed cancer therapy but are linked with immune-related adverse events (irAEs), including cardiac events. Objective: This study aims to assess the reporting frequency of atrial fibrillation with ICIs using data from the Food and Drug Administration Adverse Event Reporting System (FAERS). Design: It is an observational, retrospective, pharmacovigilance study. Methods: Individual Case Safety Reports (ICSRs) were retrieved from FAERS up to September 24, 2024. Cases reporting one or more ICIs (atezolizumab, avelumab, cemiplimab, dostarlimab, durvalumab, ipilimumab, nivolumab, pembrolizumab, and tremelimumab) and atrial fibrillation were selected. Disproportionality analyses were performed by applying the reporting odds ratio (ROR) and the Informational Component (IC) with a 95% confidence interval (95% CI). Results: A total of 1228 ICSRs were retrieved, of which 218 (17.75%) were related to combinations of ICIs. Most ICSRs ( N  = 812; 66.1%) referred to male patients and the age group most represented was ⩾65 years ( N  = 772; 62.9%). Atrial fibrillation was serious in 99.3% ( N  = 1220) of cases and had a fatal outcome ( N  = 248; 20.3%). Atezolizumab, avelumab, durvalumab, nivolumab, and pembrolizumab were associated with a statistically significant higher reporting frequency of atrial fibrillation compared to all other drugs (ROR: 1.90, IC: 0.91; ROR: 1.94, IC: 0.92; ROR: 1.52, IC: 0.60; ROR: 1.30, IC: 0.38; ROR: 1.66, IC: 0.72, respectively). The anti-CTLA-4 ipilimumab showed a statistically significant lower reporting frequency of atrial fibrillation compared to all other drugs (ROR: 0.69, IC: −0.53) and to all other ICIs (ROR: 0.45, IC: −1.02). Moreover, anti-PD-L1 (ROR: 2.60, IC: 0.47) and anti-PD-1 (ROR: 2.12, IC: 0.16) were associated with a higher reporting of atrial fibrillation compared to anti-CTLA-4. Conclusion: ICI-induced atrial fibrillation was serious and had severe outcomes. The anti-CTLA-4 showed a lower likelihood of reporting atrial fibrillation, while higher reporting was found with anti-PD-1 and anti-PD-L1. Further studies are needed to confirm this safety aspect.
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spelling doaj-art-0a46f99af0574b76b5d66d3c875d75bf2025-08-20T03:53:32ZengSAGE PublishingTherapeutic Advances in Drug Safety2042-09942025-04-011610.1177/20420986241312497Pharmacovigilance study on the reporting frequency of atrial fibrillation with immune checkpoint inhibitors: insights from FDA Adverse Event Reporting SystemNunzia BalzanoAnnamaria MascoloDonatella RuggieroConcetta RafanielloGiuseppe PaolissoFrancesco RossiAnnalisa CapuanoBackground: Immune checkpoint inhibitors (ICIs) have transformed cancer therapy but are linked with immune-related adverse events (irAEs), including cardiac events. Objective: This study aims to assess the reporting frequency of atrial fibrillation with ICIs using data from the Food and Drug Administration Adverse Event Reporting System (FAERS). Design: It is an observational, retrospective, pharmacovigilance study. Methods: Individual Case Safety Reports (ICSRs) were retrieved from FAERS up to September 24, 2024. Cases reporting one or more ICIs (atezolizumab, avelumab, cemiplimab, dostarlimab, durvalumab, ipilimumab, nivolumab, pembrolizumab, and tremelimumab) and atrial fibrillation were selected. Disproportionality analyses were performed by applying the reporting odds ratio (ROR) and the Informational Component (IC) with a 95% confidence interval (95% CI). Results: A total of 1228 ICSRs were retrieved, of which 218 (17.75%) were related to combinations of ICIs. Most ICSRs ( N  = 812; 66.1%) referred to male patients and the age group most represented was ⩾65 years ( N  = 772; 62.9%). Atrial fibrillation was serious in 99.3% ( N  = 1220) of cases and had a fatal outcome ( N  = 248; 20.3%). Atezolizumab, avelumab, durvalumab, nivolumab, and pembrolizumab were associated with a statistically significant higher reporting frequency of atrial fibrillation compared to all other drugs (ROR: 1.90, IC: 0.91; ROR: 1.94, IC: 0.92; ROR: 1.52, IC: 0.60; ROR: 1.30, IC: 0.38; ROR: 1.66, IC: 0.72, respectively). The anti-CTLA-4 ipilimumab showed a statistically significant lower reporting frequency of atrial fibrillation compared to all other drugs (ROR: 0.69, IC: −0.53) and to all other ICIs (ROR: 0.45, IC: −1.02). Moreover, anti-PD-L1 (ROR: 2.60, IC: 0.47) and anti-PD-1 (ROR: 2.12, IC: 0.16) were associated with a higher reporting of atrial fibrillation compared to anti-CTLA-4. Conclusion: ICI-induced atrial fibrillation was serious and had severe outcomes. The anti-CTLA-4 showed a lower likelihood of reporting atrial fibrillation, while higher reporting was found with anti-PD-1 and anti-PD-L1. Further studies are needed to confirm this safety aspect.https://doi.org/10.1177/20420986241312497
spellingShingle Nunzia Balzano
Annamaria Mascolo
Donatella Ruggiero
Concetta Rafaniello
Giuseppe Paolisso
Francesco Rossi
Annalisa Capuano
Pharmacovigilance study on the reporting frequency of atrial fibrillation with immune checkpoint inhibitors: insights from FDA Adverse Event Reporting System
Therapeutic Advances in Drug Safety
title Pharmacovigilance study on the reporting frequency of atrial fibrillation with immune checkpoint inhibitors: insights from FDA Adverse Event Reporting System
title_full Pharmacovigilance study on the reporting frequency of atrial fibrillation with immune checkpoint inhibitors: insights from FDA Adverse Event Reporting System
title_fullStr Pharmacovigilance study on the reporting frequency of atrial fibrillation with immune checkpoint inhibitors: insights from FDA Adverse Event Reporting System
title_full_unstemmed Pharmacovigilance study on the reporting frequency of atrial fibrillation with immune checkpoint inhibitors: insights from FDA Adverse Event Reporting System
title_short Pharmacovigilance study on the reporting frequency of atrial fibrillation with immune checkpoint inhibitors: insights from FDA Adverse Event Reporting System
title_sort pharmacovigilance study on the reporting frequency of atrial fibrillation with immune checkpoint inhibitors insights from fda adverse event reporting system
url https://doi.org/10.1177/20420986241312497
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