Immune-related serious adverse events with immune checkpoint inhibitors: Systematic review and network meta-analysis.

IF 2.7 3区医学 Q3 PHARMACOLOGY & PHARMACY European Journal of Clinical Pharmacology Pub Date : 2024-05-01 Epub Date: 2024-02-19 DOI:10.1007/s00228-024-03647-z

Clara Oliveira, Beatrice Mainoli, Gonçalo S Duarte, Tiago Machado, Rita G Tinoco, Miguel Esperança-Martins, Joaquim J Ferreira, João Costa

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Abstract

Purpose: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, though uncertainty exists regarding their immune-related safety. The objective of this study was to assess the comparative safety profile (odds ratio) of ICIs and estimate the absolute rate of immune-related serious adverse events (irSAEs) in cancer patients undergoing treatment with ICIs.

Methods: We searched for randomized trials till February 2021, including all ICIs for all cancers. Primary outcome was overall irSAEs, and secondary outcomes were pneumonitis, colitis, hepatitis, hypophysitis, myocarditis, nephritis, and pancreatitis. We conducted Bayesian network meta-analyses, estimated absolute rates and ranked treatments according to the surface under the cumulative ranking curve (SUCRA).

Results: We included 96 trials (52,811 participants, median age 62 years). Risk of bias was high in most trials. Most cancers were non-small cell lung cancer (28 trials) and melanoma (15 trials). The worst-ranked ICI was ipilimumab (SUCRA 14%; event rate 848/10,000 patients) while the best-ranked ICI was atezolizumab (SUCRA 82%; event rate 119/10,000 patients).

Conclusion: Each ICI showed a unique safety profile, with certain events more frequently observed with specific ICIs, which should be considered when managing cancer patients.

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免疫检查点抑制剂的免疫相关严重不良事件：系统综述和网络荟萃分析。

目的：免疫检查点抑制剂（ICIs）给癌症治疗带来了革命性的变化，但其与免疫相关的安全性仍存在不确定性。本研究旨在评估ICIs的安全性比较（几率比），并估算接受ICIs治疗的癌症患者发生免疫相关严重不良事件（irSAEs）的绝对比率：我们搜索了截至 2021 年 2 月的随机试验，包括所有癌症的所有 ICIs。主要结果为总体irSAEs，次要结果为肺炎、结肠炎、肝炎、肾上腺皮质功能减退症、心肌炎、肾炎和胰腺炎。我们进行了贝叶斯网络荟萃分析，估算了绝对发生率，并根据累积排序曲线下表面（SUCRA）对治疗进行了排序：我们纳入了 96 项试验（52811 名参与者，中位年龄 62 岁）。大多数试验的偏倚风险较高。大多数癌症是非小细胞肺癌（28 项试验）和黑色素瘤（15 项试验）。排名最差的 ICI 是伊匹单抗（SUCRA 14%；事件发生率为 848/10,000），而排名最好的 ICI 是阿特珠单抗（SUCRA 82%；事件发生率为 119/10,000）：结论：每种 ICI 都显示出独特的安全性，某些事件在特定 ICI 上发生的频率更高，在管理癌症患者时应考虑到这一点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

European Journal of Clinical Pharmacology 医学-药学

CiteScore

5.40

自引率

3.40%

发文量

170

审稿时长

3-8 weeks

期刊介绍： The European Journal of Clinical Pharmacology publishes original papers on all aspects of clinical pharmacology and drug therapy in humans. Manuscripts are welcomed on the following topics: therapeutic trials, pharmacokinetics/pharmacodynamics, pharmacogenetics, drug metabolism, adverse drug reactions, drug interactions, all aspects of drug development, development relating to teaching in clinical pharmacology, pharmacoepidemiology, and matters relating to the rational prescribing and safe use of drugs. Methodological contributions relevant to these topics are also welcomed. Data from animal experiments are accepted only in the context of original data in man reported in the same paper. EJCP will only consider manuscripts describing the frequency of allelic variants in different populations if this information is linked to functional data or new interesting variants. Highly relevant differences in frequency with a major impact in drug therapy for the respective population may be submitted as a letter to the editor. Straightforward phase I pharmacokinetic or pharmacodynamic studies as parts of new drug development will only be considered for publication if the paper involves -a compound that is interesting and new in some basic or fundamental way, or -methods that are original in some basic sense, or -a highly unexpected outcome, or -conclusions that are scientifically novel in some basic or fundamental sense.