Department of Internal Medicine, Dankook University College of Medicine, Cheonan, Korea.
Department of Internal Medicine, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Korea.
Endocrinol Metab (Seoul). 2023 Dec;38(6):750-759. doi: 10.3803/EnM.2023.1785. Epub 2023 Nov 13.
This study investigated the incidence of endocrine immune-related adverse events (irAEs) for recently developed immune checkpoint inhibitor (ICI) drugs.
We collected studies on newly developed ICI drugs using PubMed/Medline, Embase, and Cochrane Library from inception through January 31, 2023. Among ICI drugs, nivolumab, pembrolizumab, and ipilimumab were excluded from the new ICI drugs because many papers on endocrine-related side effects have already been published.
A total of 44,595 patients from 177 studies were included in this analysis. The incidence of hypothyroidism was 10.1% (95% confidence interval [CI], 8.9% to 11.4%), thyrotoxicosis was 4.6% (95% CI, 3.8% to 5.7%), hypophysitis was 0.8% (95% CI, 0.5% to 1.1%), adrenal insufficiency was 0.9% (95% CI, 0.7% to 1.1%), and hyperglycemia was 2.3% (95% CI, 1.6% to 3.4%). Hypothyroidism and thyrotoxicosis occurred most frequently with programmed cell death protein-1 (PD-1) inhibitors (13.7% and 7.5%, respectively). The rate of endocrine side effects for the combination of a programmed death-ligand 1 inhibitor (durvalumab) and cytotoxic T lymphocyte-associated antigen 4 inhibitor (tremelimumab) was higher than that of monotherapy. In a meta-analysis, the combination of tremelimumab and durvalumab had a 9- to 10-fold higher risk of pituitary and adrenal-related side effects than durvalumab alone.
Newly developed PD-1 inhibitors had a high incidence of thyroid-related irAEs, and combined treatment with durvalumab and tremelimumab increased the risk of pituitary- and adrenal-related irAEs. Based on these facts, it is necessary to predict the endocrine side effects corresponding to each ICI drug, diagnose and treat them appropriately, and try to reduce the morbidity and mortality of patients.
本研究调查了最近开发的免疫检查点抑制剂（ICI）药物内分泌免疫相关不良事件（irAE）的发生率。
我们使用 PubMed/Medline、Embase 和 Cochrane Library 从成立到 2023 年 1 月 31 日收集了关于新开发的 ICI 药物的研究。在 ICI 药物中，纳武利尤单抗、帕博利珠单抗和伊匹单抗被排除在新的 ICI 药物之外，因为已经发表了许多关于内分泌相关副作用的论文。
共有 177 项研究的 44595 名患者纳入本分析。甲状腺功能减退症的发生率为 10.1%（95%置信区间[CI]，8.9%至 11.4%），甲状腺功能亢进症为 4.6%（95%CI，3.8%至 5.7%），垂体炎为 0.8%（95%CI，0.5%至 1.1%），肾上腺功能不全为 0.9%（95%CI，0.7%至 1.1%），高血糖为 2.3%（95%CI，1.6%至 3.4%）。程序性细胞死亡蛋白-1（PD-1）抑制剂最常引起甲状腺功能减退症和甲状腺功能亢进症（分别为 13.7%和 7.5%）。程序性死亡配体 1 抑制剂（度伐鲁单抗）与细胞毒性 T 淋巴细胞相关抗原 4 抑制剂（替西木单抗）联合治疗的内分泌副作用发生率高于单药治疗。荟萃分析显示，替西木单抗联合度伐鲁单抗治疗发生垂体和肾上腺相关副作用的风险是单独使用度伐鲁单抗的 9-10 倍。
新开发的 PD-1 抑制剂甲状腺相关 irAE 发生率较高，度伐鲁单抗与替西木单抗联合治疗增加了垂体-肾上腺相关 irAE 的风险。基于这些事实，有必要预测每种 ICI 药物对应的内分泌副作用，进行适当的诊断和治疗，并尽量降低患者的发病率和死亡率。
