scholarly journals Immune checkpoint inhibitors-related myocarditis in patients with cancer: an analysis of international spontaneous reporting systems

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Rulan Ma ◽  
Quanziang Wang ◽  
Deyu Meng ◽  
Kang Li ◽  
Yong Zhang
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Adverse Drug Events ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Adverse Event Reporting System ◽  
Adverse Event Reporting ◽  
Reporting Odds Ratio ◽  
Real World Data ◽  
Safety Issues

Abstract Background Immune checkpoint inhibitors-induced myocarditis presents unique clinical challenges. Here, we assessed post-marketing safety of cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), programmed cell death-1 (PD-1), and programmed death-ligand 1 (PD-L1) inhibitors by mining the real-world data reported in two international pharmacovigilance databases. Methods We analyzed immune checkpoint inhibitors (ICIs)-associated fatal adverse drug events (ADEs) reports from the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) collected from July 1, 2014 to December 31, 2019 and data from EudraVigilance (EV) database accessed on February 29, 2020. Three different data mining approaches were used to detect the signal of fatal myocarditis caused by ICIs. Results Based on 7613 ICIs-related ADEs reported to the EV database and 5786 ICIs-associated ADEs submitted to the FAERS database, the most frequently reported ADE was ipilimumab-related colitis. For myocarditis, nivolumab-associated myocarditis was the most common. Among the five fatal toxic effects associated with ICIs, the lethality rate of myocarditis was the highest. Therefore, we further analyzed ICI-associated myocarditis and found that elderly patients and male patients were more likely to develop ICIs-related myocarditis. The results of signal detection showed that the risk signal of avelumab-related myocarditis detected by reporting odds ratio (ROR) method and proportional reporting ratios (PRR) method was the highest, whereas the signal strength of ipilimumab-related myocarditis detected by Bayesian confidence propagation neural networks (BCPNN) method was the strongest. Conclusion The findings of this study indicated the potential safety issues of developing myocarditis when using ICIs, which were consistent with the results of previous clinical trials and could provide a reference for clinical workers when using ICIs.

scholarly journals Immune checkpoint inhibitors-related myocarditis in patients with cancer: an analysis of international spontaneous reporting systems

2020 ◽  
Author(s):  
Rulan Ma ◽  
Quanziang Wang ◽  
Deyu Meng ◽  
Kang Li ◽  
yong zhang
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Adverse Drug Events ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Adverse Event Reporting System ◽  
Adverse Event Reporting ◽  
Reporting Odds Ratio ◽  
Real World Data ◽  
Safety Issues

Abstract Background: Immune checkpoint inhibitors induced myocarditis presents unique clinical challenges. Here, we assessed post-marketing safety of cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), programmed cell death-1 (PD-1), and programmed death-ligand 1 (PD-L1) inhibitors by mining the real-world data reported in two international pharmacovigilance databases. Methods: We analyzed immune checkpoint inhibitors (ICIs)-associated fatal adverse drug events (ADRs) reports from the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) collected from July 1, 2014 to December 31, 2019 and data from EudraVigilance (EV) database accessed on February 29, 2020. Three different data mining approaches were used to detect the signal of fatal myocarditis caused by ICIs. Results: Based on 7613 ICIs-related ADEs reported to the EV database and 5786 ICIs-associated ADEs submitted to the FAERS database, the most frequently reported ADE was ipilimumab-related colitis. For myocarditis, nivolumab-associated myocarditis was the most common. Among the five fatal toxic effects associated with ICIs, the lethality rate of myocarditis was the highest. Therefore, we further analyzed ICI-associated myocarditis and found that elderly patients and male patients were more likely to develop ICIs-related myocarditis. The results of signal detection showed that the risk signal of avelumab-related myocarditis detected by reporting odds ratio (ROR) method and proportional reporting ratios (PRR) method was the highest, whereas the signal strength of ipilimumab-related myocarditis detected by Bayesian confidence propagation neural networks (BCNPP) method was the strongest. Conclusion: The findings of this study indicated the potential safety issues of developing myocarditis when using ICIs, which are consistent with the results of previous clinical trials and can provide a reference for clinical workers when using ICIs.

scholarly journals Immune Checkpoint Inhibitors-related Myocarditis in Patients With Cancer: an Analysis of International Spontaneous Reporting Systems

2020 ◽  
Author(s):  
Rulan Ma ◽  
Quanziang Wang ◽  
Deyu Meng ◽  
Kang Li ◽  
yong zhang
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Adverse Drug Events ◽  
Checkpoint Inhibitors ◽  
Adverse Event Reporting System ◽  
Adverse Event Reporting ◽  
Toxic Effects ◽  
Reporting Odds Ratio ◽  
Real World Data ◽  
Post Marketing

Abstract Background:Immune checkpoint inhibitors induced myocarditis presents unique clinical challenges. Here, we assessed post-marketing safety of PD-1, PD-L1 and CTLA-4 inhibitors by mining the real-world data reported in two international pharmacovigilance databases.Methods: We analyzed immune checkpoint inhibitors (ICIs)-associated fatal adverse drug events (ADRs) reports from the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) collected from July 1, 2014, to December 31, 2019, and data from EudraVigilance (EV) database accessed on February 29, 2020. Three different data mining methods were used to detect the signal of five fatal toxic effects caused by ICIs.Results: Based on 7613 ICIs-related ADEs reported to the EV database and 5786 ICIs-associated ADEs submitted to the FAERS database, the most frequently reported ADEwasipilimumab-related colitis. For myocarditis, nivolumab-associated myocarditis was the most common. Among the five fatal toxic effects associated with ICIs, the lethality rate of myocarditis was the highest. Elderly patients and male patients were more likely to develop ICIs-related myocarditis.The results of signal detection showed that the risk of avelumab-related myocarditis detected by reporting odds ratio (ROR) method and proportional reporting ratios (PRR) method was the highest, whereas the signal strength of ipilimumab-related myocarditis detected by Bayesian confidence propagation neural networks (BCNPP)method was the strongest.Conclusion:The findings of this study showed the risk of developing myocarditis and other fatal ADRs when using ICIs, which are consistent with the results of previous clinical trials and can provide a reference for clinical workers when using ICIs.

scholarly journals Cardiotoxicity Induced by Immune Checkpoint Inhibitors: A Pharmacovigilance Study From 2014 to 2019 Based on FAERS

2021 ◽  
Vol 12 ◽  
Author(s):  
Chenxin Chen ◽  
Ting Chen ◽  
Jizhou Liang ◽  
Xiaojing Guo ◽  
Jinfang Xu ◽  
...  
Keyword(s):  
Adverse Event ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Adverse Event Reporting System ◽  
Adverse Event Reporting ◽  
Cardiac Complications ◽  
Cardiac Adverse Events

This study was to scientifically and systematically explore the association between cardiotoxicity and immune checkpoint inhibitors (ICIs) and also to characterize the spectrum of ICI-related cardiac complications. From the first quarter of 2014 to the fourth quarter of 2019, data from the FDA Adverse Event Reporting System database were selected to conduct the disproportionality analysis. Reporting odds ratios and information components were used to evaluate the signal after statistical shrinkage transformation. In total, 7,443,137 cases and 36,326,611 drug-adverse event pairs were collected, among which 9,271 cases were identified to be related to ICI-induced cardiotoxicities. The number of male patients was much higher than that of females (5,579 vs. 3,031) and males presented a slightly higher reporting frequency than females in general, which was statistically significant (ROR = 1.04, 95%CI: 0.99–1.09, p < 0.001). Simultaneously, the proportion of serious or life-threatening outcomes in males was significantly higher than in females (ROR = 1.05, 95%CI: 0.96–1.15, p < 0.001). Importantly, ICIs were associated with over-reporting frequencies of cardiotoxicities in general (ROR025 = 1.06, IC025 = 0.08). PD-1 and PD-L1 were found to be related to cardiac adverse events, corresponding to ROR025 = 1.06, IC025 = 0.08, and ROR025 = 1.06, IC025 = 0.08, respectively, while anti-CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) was significantly associated with some specific adverse events rather than common adverse events. The spectrum of cardiotoxicities induced by ICIs mostly differed among individual agents, but also demonstrated some common features. Dyspnea (N = 2,527, 21.25%), myocarditis (N = 614, 5.16%), atrial fibrillation (N = 576, 4.84%), cardiac failure (N = 476, 4.00%), and pericardial effusion (N = 423, 3.56%) were the top five cardiac adverse events reported in the database. Among them, myocarditis was the only one caused by all ICIs with strong signal value and high risk, warranting further attention. Overall, this investigation mainly showed the profile of cardiotoxicities caused by ICIs, which varied between different ICI therapies, but also shared some similarities in specific symptoms such as myocarditis. Therefore, it is vital and urgent to recognize and manage ICI-related cardiotoxicities, known to frequently occur in clinical practice, at the earliest point.

scholarly journals Pericardial Toxicities Associated With Immune Checkpoint Inhibitors: A Pharmacovigilance Analysis of the FDA Adverse Event Reporting System (FAERS) Database

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhuo Ma ◽  
Jie Pei ◽  
Ximu Sun ◽  
Lihong Liu ◽  
Wenchao Lu ◽  
...  
Keyword(s):  
Adverse Event ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Reporting System ◽  
Checkpoint Inhibitors ◽  
Adverse Event Reporting System ◽  
Adverse Event Reporting ◽  
Interquartile Range ◽  
Event Reporting

Introdution: Immune checkpoint inhibitors (ICIs) have significantly improved clinical outcomes for a wide range of cancers but can also lead to serious or fatal immune-related adverse events (irAEs). Although ICI-related pericardial toxicities have been reported, the clinical features are not well characterized in real-world studies.Objective: To characterize the main features of ICI-related pericardial toxicities and identify factors associated with death.Methods: Data from January 1, 2011 to March 31, 2020 in the FDA Adverse Event Reporting System database were retrieved for disproportionality analysis. We used the reporting odds ratio and the information component (IC) to evaluate the association between ICIs and pericardial adverse events. Clinical characteristics of patients with ICI-associated pericardial toxicities were collected and compared between fatal and non-fatal groups. The time to onset following different ICI regimens was further investigated.Results: We identified a total of 705 ICI-associated pericardial toxicities which appeared to influence more men (53.90%) than women (36.03%), with a median age of 63 (interquartile range [IQR] 54–69) years. Patients with lung cancer accounted for the largest proportion (55.6%). ICI therapies were detected with pharmacovigilance signals of pericardial toxicities, corresponding to IC025 = 2.11 and ROR 4.87 [4.51–5.25]. Nevertheless, there was a lack of association between anti-CTLA-4 and pericardial toxicities. There was no difference in onset time among all ICI regimens. However, TTO of fatal cases (25 days (interquartile range [IQR] 6–70)) occurred statistically earlier than non-fatal cases (42 days (IQR 12–114), p = 0.003).Conclusion: ICI monotherapy (PD-1/PD-L1 therapy) and combination therapy can lead to pericardial toxicities that can result in serious outcomes and tend to occur early. Early recognition and management of ICI-related pericardial disorders should attract clinical attention. The findings require further clinical surveillance for the quantification.

Ear and labyrinth toxicities induced by immune checkpoint inhibitors: a disproportionality analysis from 2014 to 2019

Immunotherapy ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 531-540
Author(s):  
Fangyuan Hu ◽  
Xiaofei Ye ◽  
Yinghong Zhai ◽  
Jinfang Xu ◽  
Xiaojing Guo ◽  
...  
Keyword(s):  
Adverse Event ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Reporting System ◽  
Checkpoint Inhibitors ◽  
Adverse Event Reporting System ◽  
Adverse Event Reporting ◽  
Disproportionality Analysis ◽  
Event Reporting ◽  
System Database

Aim: We aimed to systematically characterize ear and labyrinth toxicities after immune checkpoint inhibitors (ICIs) initiation. Materials & methods: Data were extracted from the US FDA Adverse Event Reporting System database. Disproportionality analysis including information component and reporting odds ratio (ROR) was performed to access potential signals. Results: In FDA Adverse Event Reporting System database, 284 records for ICIs-associated ear/labyrinth adverse events (AEs) were involved. In general, there was no significant association between total ICIs use and total ear and labyrinth AEs (ROR025: 0.576). However, in ICIs monotherapy and polytherapy groups, signals were detected in several specific ear and labyrinth AEs. Conclusion: Total ear and labyrinth toxicities were not significantly reported with ICI immunotherapy, while class-specific ear toxicities were detected in some strategies.

scholarly journals A retrospective analysis of cardiovascular adverse events associated with immune checkpoint inhibitors

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Jessica Castrillon Lal ◽  
Sherry-Ann Brown ◽  
Patrick Collier ◽  
Feixiong Cheng
Keyword(s):  
Adverse Event ◽  
Adverse Events ◽  
Retrospective Analysis ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Adverse Event Reporting System ◽  
Adverse Event Reporting ◽  
Health Concern ◽  
Combination Immunotherapy

Abstract Background Modern therapies in oncology have increased cancer survivorship, as well as the incidence of cardiovascular adverse events. While immune checkpoint inhibitors have shown significant clinical impact in several cancer types, the incidence of immune-related cardiovascular (CV) adverse events poses an additional health concern and has been reported. Methods We performed a retrospective analysis of the FDA Adverse Event Reporting System data of suspect product reports for immunotherapy and classical chemotherapy from January 2010–March 2020. We identified 90,740 total adverse event reports related to immune checkpoint inhibitors and classical chemotherapy. Results We found that myocarditis was significantly associated with patients receiving anti-program cell death protein 1 (PD-1) or anti-program death ligand 1 (PD-L1), odds ratio (OR) = 23.86 (95% confidence interval [CI] 11.76–48.42, (adjusted p-value) q <  0.001), and combination immunotherapy, OR = 7.29 (95% CI 1.03–51.89, q = 0.047). Heart failure was significantly associated in chemotherapy compared to PD-(L)1, OR = 0.50 (95% CI 0.37–0.69, q <  0.001), CTLA4, OR = 0.08 (95% CI 0.03–0.20, q <  0.001), and combination immunotherapy, OR = 0.25 (95% CI 0.13–0.48, q <  0.001). Additionally, we observe a sex-specificity towards males in cardiac adverse reports for arrhythmias, OR = 0.81 (95% CI 0.75–0.87, q <  0.001), coronary artery disease, 0.63 (95% CI 0.53–0.76, q <  0.001), myocardial infarction, OR = 0.60 (95% CI 0.53–0.67, q <  0.001), myocarditis, OR = 0.59 (95% CI 0.47–0.75, q <  0.001) and pericarditis, OR = 0.5 (95% CI 0.35–0.73, q <  0.001). Conclusion Our study provides the current risk estimates of cardiac adverse events in patients treated with immunotherapy compared to conventional chemotherapy. Understanding the clinical risk factors that predispose immunotherapy-treated cancer patients to often fatal CV adverse events will be crucial in Cardio-Oncology management.

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