Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, Napoli, Italy; Department of Experimental Medicine - Section of Pharmacology "L. Donatelli", University of Campania "Luigi Vanvitelli", Napoli, Italy.
Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, Napoli, Italy; Department of Experimental Medicine - Section of Pharmacology "L. Donatelli", University of Campania "Luigi Vanvitelli", Napoli, Italy.
Biomed Pharmacother. 2023 Aug;164:114912. doi: 10.1016/j.biopha.2023.114912. Epub 2023 May 19.
Despite the available evidence showing an association between cardiac arrhythmia and Immune Checkpoint Inhibitors (ICIs), few studies have compared this risk between ICIs.
We aim to evaluate Individual Case Safety Reports (ICSRs) of ICIs-induced cardiac arrhythmias and compare the reporting frequency of cardiac arrhythmias among ICIs.
ICSRs were retrieved from the European Pharmacovigilance database (Eudravigilance). ICSRs were classified based on the ICI reported (pembrolizumab, nivolumab, atezolizumab, ipilimumab, durvalumab, avelumab, cemiplimab, and dostarlimab). If more than one ICI was reported, the ICSR was classified as a combination of ICIs. ICSRs of ICI-related arrhythmias were described and the reporting frequency of cardiac arrhythmias was assessed by applying the reporting odds ratio (ROR) and its 95 % confidence interval (95 %CI).
A total of 1262 ICSRs were retrieved, of which 147 (11.65 %) were related to combinations of ICIs. A total of 1426 events of cardiac arrhythmias were identified. The three most reported events were atrial fibrillation, tachycardia, and cardiac arrest. Ipilimumab was associated with a reduced reporting frequency of cardiac arrhythmias compared to all other ICIs (ROR 0.71, 95 %CI 0.55-0.92; p = 0.009). Anti-PD1 was associated with a higher reporting frequency of cardiac arrhythmias than anti-CTLA4 (ROR 1.47, 95 %CI 1.14-1.90; p = 0.003).
This study is the first comparing ICIs for the risk of cardiac arrhythmias. We found that ipilimumab was the only ICI associated with a reduced reporting frequency. Further high-quality studies are needed to confirm our results.
尽管已有证据表明心律失常与免疫检查点抑制剂（ICIs）之间存在关联，但很少有研究比较过这些 ICI 之间的风险。
我们旨在评估免疫检查点抑制剂引起的心律失常的个体病例安全报告（ICSRs），并比较这些 ICI 中心律失常的报告频率。
从欧洲药物警戒数据库（Eudravigilance）中检索 ICSRs。根据报告的 ICI（pembrolizumab、nivolumab、atezolizumab、ipilimumab、durvalumab、avelumab、cemiplimab 和 dostarlimab）对 ICSRs 进行分类。如果报告了多种 ICI，则将 ICSR 归类为 ICI 的组合。描述 ICI 相关心律失常的 ICSRs，并应用报告比值比（ROR）及其 95%置信区间（95%CI）评估心律失常的报告频率。
共检索到 1262 份 ICSRs，其中 147 份（11.65%）与 ICI 组合有关。共确定了 1426 例心律失常事件。报告最多的三个事件是心房颤动、心动过速和心脏骤停。与所有其他 ICI 相比，ipilimumab 与心律失常报告频率降低相关（ROR 0.71，95%CI 0.55-0.92；p=0.009）。抗 PD1 与心律失常的报告频率高于抗 CTLA4（ROR 1.47，95%CI 1.14-1.90；p=0.003）。
本研究是首次比较不同 ICI 治疗心律失常风险的研究。我们发现，ipilimumab 是唯一与降低报告频率相关的 ICI。需要进一步开展高质量的研究来证实我们的结果。
