接受免疫检查点抑制剂治疗的患者发生史蒂文斯-约翰逊综合征/中毒性表皮坏死松解症：一项对临床试验和美国食品药品监督管理局药物警戒数据库的安全性分析
Stevens-Johnson syndrome/toxic epidermal necrolysis in patients treated with immune checkpoint inhibitors: A safety analysis of clinical trials and FDA pharmacovigilance database.
作者信息
Zhu Jianhong, Chen Guanghui, He Zhichao, Zheng Yayuan, Gao Siyuan, Li Jianfang, Ling Yin, Yu Xiaoxia, Qiu Kaifeng, Wu Junyan
机构信息
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, PR China.
Department of pharmacy, Sun-Yat-Sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang West Road, Guangzhou 510120, PR China.
出版信息
EClinicalMedicine. 2021 Jun 10;37:100951. doi: 10.1016/j.eclinm.2021.100951. eCollection 2021 Jul.
BACKGROUND
The association between immune checkpoint inhibitors (ICIs) and Stevens-Johnsons syndrome (SJS) /toxic epidermal necrolysis (TEN) is unclear. We assessed the risk of SJS and TEN related to ICIs, via a systematic analysis of SJS/TEN cases reported in clinical trials and the FDA Adverse Event Reporting System (FAERS).
METHODS
We explored ICIs related SJS/TEN events in randomized control trials available in ClinicalTrials.gov and electronic databases (Pubmed, Embase, the Cochrane Central Register of Controlled Trials) up to 12 January 2021. Meta-analysis was performed by using Peto odds ratios (ORs) with 95% CIs. In a separate retrospective pharmacovigilance study of FAERs, cases of ICIs related SJS/TEN were extracted between the first quarter (Q1) of 2004 and Q4 of 2020. Disproportionality was analyzed using the proportional reports reporting odds ratio (ROR) and information components (IC). PROSPERO registration number: CRD42021232399.
FINDINGS
A total of 20 RCTs (11597 patients) were included. ICIs were associated with an increased risk of SJS/TEN (OR= 4.33, 95%CI:1.90-9.87). FAERS pharmacovigilance data identified 411 cases of SJS ( = 253) or TEN ( 184) related to ICIs therapy. ICIs were significantly associated with SJS/TEN ( 411; ROR=2.88, 95%CI:2.61-3.17; IC=1.49, 95%CI:1.35-1.65). The median onset time of SJS/TEN was 25.5 days (SJS:21.5 days; TEN:32 days) ( 190), 97.5% of patients discontinued use of ICIs when suffering from SJS/TEN ( 201). Of 305 cases that reported outcomes, 113 (37%) resulted in death (SJS:19.9%, TEN:61.6%).
INTERPRETATION
These data suggest that ICIs were significantly associated with increased risk of SJS/TEN.
背景
免疫检查点抑制剂（ICIs）与史蒂文斯-约翰逊综合征（SJS）/中毒性表皮坏死松解症（TEN）之间的关联尚不清楚。我们通过对临床试验和美国食品药品监督管理局不良事件报告系统（FAERS）中报告的SJS/TEN病例进行系统分析，评估了与ICIs相关的SJS和TEN风险。
方法
我们在ClinicalTrials.gov和电子数据库（PubMed、Embase、Cochrane对照试验中央注册库）中检索截至2021年1月12日的随机对照试验中与ICIs相关的SJS/TEN事件。采用Peto比值比（OR）及95%置信区间（CI）进行荟萃分析。在另一项对FAERS的回顾性药物警戒研究中，提取2004年第一季度（Q1）至2020年第四季度与ICIs相关的SJS/TEN病例。使用成比例报告比值比（ROR）和信息成分（IC）分析不成比例性。国际前瞻性系统评价注册编号：CRD42021232399。
结果
共纳入20项随机对照试验（11597例患者）。ICIs与SJS/TEN风险增加相关（OR = 4.33，95%CI：1.90 - 9.87）。FAERS药物警戒数据确定了411例与ICIs治疗相关的SJS（n = 253）或TEN（n = 184）病例。ICIs与SJS/TEN显著相关（n = 411；ROR = 2.88，95%CI：2.61 - 3.17；IC = 1.49，95%CI：1.35 - 1.65）。SJS/TEN的中位发病时间为25.5天（SJS：21.5天；TEN：32天）（n = 190），97.5%的患者在患SJS/TEN时停用了ICIs（n = 201）。在报告结局的305例病例中，113例（37%）导致死亡（SJS：19.9%，TEN：61.6%）。
解读
这些数据表明ICIs与SJS/TEN风险增加显著相关。
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