CONTEXT Few meta-analyses regarding the incidence of endocrine immune related adverse effects (eirAEs) have been published and many trials were published thereafter. OBJECTIVE To assess the risk and incidence of eirAEs of any grade and grade 3-5 by immune checkpoint inhibitor (ICI) mono or combination-therapy in solid tumors current literature was updated in this comprehensive meta-analysis. METHODS An electronic search using PubMed/Medline, Embase and the Cochrane Library was performed. Randomized controlled studies (RCT) assessing eirAEs under ICI-mono or ICI-combination therapy were selected. Stata software version 17 was used for statistical analyses and risk of bias was evaluated by using Review Manager version 5.3. RESULTS 69 RCTs with 80 independent reports, involving 42,886 patients were included in the study. Meta-analysis revealed the following pooled estimates for the risk ratio and the incidence, respectively: for any grade hypothyroidism 7.81 (95% CI, 5.68-10.74, p< 0.0001) and 7.64% (95% CI, 6.23-9.17, p< 0.0001); significantly increased also for hyperthyroidism, hypophysitis/hypopituitarism and adrenal insufficiency; and for insulin-dependent diabetes mellitus 1.52 (95% CI, 1.07-2.18, p= 0.02), and 0.087% (95% CI, 0.019-0.189, p= 0.0006), respectively. Meta-regression showed that combination of ICIs (nivolumab plus ipilimumab and durvalumab plus tremelimumab, respectively) is an independent risk factor for any grade hypophysitis/hypopituitarism, and that ICI agent is an independent factor of risk for adrenal insufficiency, but that cancer type is not an independent risk factor for eirAEs. CONCLUSION We showed that risk, independent from cancer type, and incidence of eAEs are substantially increased under ICI therapy. Combination of ICIs is increasing the risk for eirAEs, in particular for hypophysitis/hypopituitarism.

中文翻译：

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检查点抑制剂单药或联合治疗实体瘤中内分泌免疫相关不良反应的风险和发生率：随机对照试验的荟萃分析。

背景 关于内分泌免疫相关不良反应 (eirAE) 发生率的荟萃分析很少发表，许多试验随后发表。目的 为了评估免疫检查点抑制剂 (ICI) 单药或联合治疗实体瘤中任何级别和 3-5 级 eirAE 的风险和发生率，本综合荟萃分析更新了当前文献。方法 使用 PubMed/Medline、Embase 和 Cochrane 图书馆进行电子检索。选择评估 ICI 单药或 ICI 联合治疗下 eirAE 的随机对照研究 (RCT)。Stata 软件版本 17 用于统计分析，并使用 Review Manager 版本 5.3 评估偏倚风险。结果 研究纳入 69 项随机对照试验，80 份独立报告，涉及 42,886 名患者。荟萃分析显示，风险比和发病率的汇总估计值分别如下：对于任何级别的甲状腺功能减退症，7.81（95% CI，5.68-10.74，p<0.0001）和 7.64%（95% CI，6.23-9.17，p< 0.0001); 甲状腺功能亢进症、垂体炎/垂体功能减退症和肾上腺功能不全时也显着增加；对于胰岛素依赖型糖尿病，该值分别为 1.52（95% CI，1.07-2.18，p= 0.02）和 0.087%（95% CI，0.019-0.189，p= 0.0006）。荟萃回归显示，ICI 组合（分别为纳武单抗加伊匹单抗和杜瓦鲁单抗加曲美木单抗）是任何级别垂体炎/垂体功能减退症的独立危险因素，并且 ICI 药物是肾上腺功能不全的独立风险因素，但癌症类型是不是 eirAE 的独立危险因素。结论 我们发现，独立于癌症类型的 eAE 风险和发生率在 ICI 治疗下显着增加。ICI 的组合会增加 eirAE 的风险，特别是垂体炎/垂体功能减退症。