Myocarditis in Patients Treated With Immune Checkpoint Inhibitors.
Myocarditis in Patients Treated With Immune Checkpoint Inhibitors.
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DOI：
10.1016/j.jacc.2018.02.037
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发表时间：
2018-04-24
影响因子：
24
通讯作者：
Neilan TG
中科院分区：
文献类型：
--
作者：
Mahmood SS;Fradley MG;Cohen JV;Nohria A;Reynolds KL;Heinzerling LM;Sullivan RJ;Damrongwatanasuk R;Chen CL;Gupta D;Kirchberger MC;Awadalla M;Hassan MZO;Moslehi JJ;Shah SP;Ganatra S;Thavendiranathan P;Lawrence DP;Groarke JD;Neilan TG
心肌炎是免疫检查点抑制剂(ICI)的一种罕见但具有潜在致命性的毒性。ICI后心肌炎的特征尚不清楚。作者试图了解ICI相关性心肌炎的表现和临床病程。在观察了散发性ICI相关性心肌炎病例后，作者创建了一个有8个位点的多中心注册中心。从2013年11月到2017年7月，有35名ICI相关性心肌炎患者，他们与随机抽样的105名接受ICI治疗的非心肌炎患者进行了比较。从医疗记录中提取感兴趣的协变量，包括主要不良心脏事件(MACE)的发生，MACE被定义为心血管死亡、心源性休克、心脏骤停和血流动力学显著的完全性心脏传导阻滞的组合。心肌炎的患病率为1.14%，中位发病时间为开始ICI后34天(四分位数范围：21至75天)。6例患者年龄为65±13岁，女性占29%，无其他免疫相关副作用占54%。与对照组相比，合并脑梗塞(34%比2%；p<；0.001)和糖尿病(34%比13%；p=0.001)更常见。中位随访期超过102天(四分位数范围：62至214天)，16例(46%)发生MACE；38%的MACE发生时射血分数正常。肌钙蛋白T为≥1.5 ng/ml时发生MACE的风险增加4倍(危险比：4.0；95%可信区间：1.5-10.9；p=0.003)。89%的患者使用了类固醇，较低的类固醇剂量与较高的肌钙蛋白残留量和较高的MACE发生率相关。ICI治疗后的心肌炎可能比人们认识到的更常见，发生在开始治疗后的早期，有恶性病程，对较高剂量的类固醇有反应。
Myocarditis is an uncommon, but potentially fatal, toxicity of immune checkpoint inhibitors (ICI). Myocarditis after ICI has not been well characterized. The authors sought to understand the presentation and clinical course of ICI-associated myocarditis. After observation of sporadic ICI-associated myocarditis cases, the authors created a multicenter registry with 8 sites. From November 2013 to July 2017, there were 35 patients with ICI-associated myocarditis, who were compared to a random sample of 105 ICI-treated patients without myocarditis. Covariates of interest were extracted from medical records including the occurrence of major adverse cardiac events (MACE), defined as the composite of cardiovascular death, cardiogenic shock, cardiac arrest, and hemodynamically significant complete heart block. The prevalence of myocarditis was 1.14% with a median time of onset of 34 days after starting ICI (inter-quartile range: 21 to 75 days). Cases were 65 ± 13 years of age, 29% were female, and 54% had no other immune-related side effects. Relative to controls, combination ICI (34% vs. 2%; p < 0.001) and diabetes (34% vs. 13%; p = 0.01) were more common in cases. Over 102 days (interquartile range: 62 to 214 days) of median follow-up, 16 (46%) developed MACE; 38% of MACE occurred with normal ejection fraction. There was a 4-fold increased risk of MACE with troponin T of ≥1.5 ng/ml (hazard ratio: 4.0; 95% confidence interval: 1.5 to 10.9; p = 0.003). Steroids were administered in 89%, and lower steroids doses were associated with higher residual troponin and higher MACE rates. Myocarditis after ICI therapy may be more common than appreciated, occurs early after starting treatment, has a malignant course, and responds to higher steroid doses.
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DOI：
10.1056/nejmoa1003466
发表时间：
2010-08-19
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hodi FS;O'Day SJ;McDermott DF;Weber RW;Sosman JA;Haanen JB;Gonzalez R;Robert C;Schadendorf D;Hassel JC;Akerley W;van den Eertwegh AJ;Lutzky J;Lorigan P;Vaubel JM;Linette GP;Hogg D;Ottensmeier CH;Lebbé C;Peschel C;Quirt I;Clark JI;Wolchok JD;Weber JS;Tian J;Yellin MJ;Nichol GM;Hoos A;Urba WJ
通讯作者：
Urba WJ
影响因子：
24
作者：
Neilan, Tomas G.;Shah, Ravi V.;Abbasi, Siddique A.;Farhad, Hoshang;Groarke, John D.;Dodson, John A.;Coelho-Filho, Otavio;McMullan, Ciaran J.;Heydari, Bobak;Michaud, Gregory F.;John, Roy M.;van der Geest, Rob;Steigner, Michael L.;Blankstein, Ron;Jerosch-Herold, Michael;Kwong, Raymond Y.
通讯作者：
Kwong, Raymond Y.
影响因子：
45.3
作者：
Sznol, Mario;Ferrucci, Pier Francesco;Wolchok, Jedd D.
通讯作者：
Wolchok, Jedd D.
影响因子：
37.8
作者：
Ammirati, Enrico;Cipriani, Manlio;Frigerio, Maria
通讯作者：
Frigerio, Maria
影响因子：
24
作者：
Hicks, Karen A.;Tcheng, James E.;Wang, Tracy Y.
通讯作者：
Wang, Tracy Y.