Abstract：
Immune checkpoint inhibitors (ICIs) cause immune-related adverse events (irAEs) across various organ systems including oral health complications such as dry mouth and stomatitis. In this study, we aimed to determine the risk of periodontitis among patients on immune checkpoint inhibitors (ICIs) and to test the associations between ICI-associated periodontitis and other immune-related adverse events (irAEs). We performed a retrospective cohort study involving adult cancer patients between January 2010 and November 2021. Patients on an ICI were propensity score-matched to patients not on an ICI. The primary outcome was the occurrence of periodontitis. ICIs included programmed cell death 1 (PD-1) inhibitors programmed cell death ligand 1 (PD-L1) inhibitors, and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors. The risk of periodontitis following ICI use was derived through a Cox proportional hazard model and Kaplan-Meier survival analysis. Overall, 868 patients on an ICI were matched to patients not on an ICI. Among the ICI cohort, 41 (4.7%) patients developed periodontitis. The incidence rate of periodontitis was significantly higher in patients on an ICI than in patients not on an ICI (55.3 vs 25.8 per 100 patient-years, incidence rate ratio=2.14, 95% CI=1.38-3.33). Both the use of PD-L1 inhibitors (multivariate HR=2.5, 95%CI=1.3-4.7) and PD-1 inhibitors (multivariate HR=2.0, 95%CI=1.2-3.2) were associated with the risk of periodontitis. The presence of immune-related periodontitis was associated with better overall survival (not reached vs 17 months, log-rank p-value<0.001), progression-free survival (14.9 vs 5.6 months, log-rank p-value=0.01), and other concomitant immune-related cutaneous adverse events. In conclusion, ICI was associated with an increased risk of periodontitis. Immune-related periodontitis as an irAE was associated with better cancer survival and concomitant cutaneous irAEs.
摘要：
免疫检查点抑制剂（ICIs）会导致各种器官系统的免疫相关不良事件（irAE），包括口腔健康并发症，如口干和口腔炎。在这项研究中,我们旨在确定使用免疫检查点抑制剂(ICIs)的患者患牙周炎的风险,并检验ICI相关牙周炎与其他免疫相关不良事件(irAEs)之间的关联.我们在2010年1月至2021年11月之间进行了一项涉及成年癌症患者的回顾性队列研究。ICI患者与非ICI患者的倾向评分匹配。主要结果是牙周炎的发生。ICIs包括程序性细胞死亡1（PD-1）抑制剂程序性细胞死亡配体1（PD-L1）抑制剂，和细胞毒性T淋巴细胞相关蛋白4（CTLA-4）抑制剂。使用ICI后牙周炎的风险是通过Cox比例风险模型和Kaplan-Meier生存分析得出的。总的来说,ICI上的868名患者与非ICI上的患者匹配。在ICI队列中，41例（4.7％）患者发生牙周炎。ICI患者牙周炎的发病率明显高于非ICI患者(55.3vs25.8/100患者年,发病率比=2.14，95%CI=1.38-3.33)。PD-L1抑制剂（多变量HR=2.5，95CI=1.3-4.7）和PD-1抑制剂（多变量HR=2.0，95CI=1.2-3.2）的使用均与牙周炎的风险相关。免疫相关性牙周炎的存在与更好的总生存期相关（未达到vs17个月，对数秩p值<0.001)，无进展生存期（14.9vs5.6个月，对数秩p值=0.01)，和其他伴随的免疫相关皮肤不良事件。总之,ICI与牙周炎风险增加有关。免疫相关性牙周炎作为irAE与更好的癌症生存率和伴随的皮肤irAE相关。
