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评价依那西普联合全身皮质类固醇治疗史蒂文斯-约翰逊综合征和中毒性表皮坏死松解症的疗效:一项多中心观察性研究。

Evaluation of Combination Therapy With Etanercept and Systemic Corticosteroids for Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A Multicenter Observational Study.

机构信息

Department of Dermatology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China.

Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou, Taipei, and Keelung, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Dermatology, Xiamen Chang Gung Hospital, Xiamen, China; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Immune-Oncology Center of Excellence, Chang Gung Memorial Hospital, Linkou, Taiwan.

出版信息

J Allergy Clin Immunol Pract. 2022 May;10(5):1295-1304.e6. doi: 10.1016/j.jaip.2022.01.038. Epub 2022 Feb 4.

Abstract

BACKGROUND

Stevens-Johnson syndrome-toxic epidermal necrolysis (SJS-TEN) are fatal severe cutaneous adverse reactions, without consensus on the medical treatment. The use of systemic corticosteroids or intravenous immunoglobulin (IVIG) remains debatable. Tumor necrosis factor-alpha inhibitors are potentially effective.

OBJECTIVE

To evaluate the effectiveness and safety of combination therapy using etanercept combined with corticosteroids or IVIG combined with corticosteroids versus corticosteroid monotherapy for patients with SJS-TEN.

METHODS

We retrospectively enrolled SJS-TEN patients from Taiwan and the Chinese mainland, during 2014 to 2019. Patients enrolled were treated with corticosteroid monotherapy, or combinations with IVIG or etanercept. We analyzed the clinical characteristics, skin healing time, mortality, and adverse events among these treatment groups.

RESULTS

Among the 242 patients (187 with SJS or SJS-TEN overlapping and 55 with TEN), patients who received combination therapy with etanercept and corticosteroids had lower actual mortality than those with corticosteroid monotherapy and those with IVIG combined with corticosteroids, respectively (0% vs 6.63% and 4.76%). There was a tendency of reducing standardized (observed/predicted) mortality rate (SMR) based on the Score of Toxic Epidermal Necrolysis in etanercept combined with corticosteroids compared with corticosteroid monotherapy and IVIG combined with corticosteroids therapy (SMR [95% CI] 0 [1.80-3.59], 0.71 [0.83-2.64], 0.30 [0.68-6.22]; P = .006). Etanercept combined with corticosteroids showed a reduced skin healing time (12.0 [8.5-14.0], median days [interquartile range]), compared with corticosteroid monotherapy (13.0 [10.0-18.0]) and IVIG combined with corticosteroids therapy (13.5 [10.0-19.5]); P = .004 and P = .012, respectively). Etanercept combined with corticosteroids also showed a lower incidence of adverse event with gastrointestinal hemorrhage than corticosteroid monotherapy, especially in patients with TEN (P = .001).

CONCLUSIONS

The tumor necrosis factor-alpha inhibitors and corticosteroids combination therapy was effective and safer than corticosteroid monotherapy for SJS-TEN, and may be considered as an alternative therapy for SJS-TEN patients who responded poorly to conventional corticosteroid therapy.

摘要

背景

史蒂文斯-约翰逊综合征-中毒性表皮坏死松解症(SJS-TEN)是致命的严重皮肤不良反应,目前对于其医学治疗方法尚未达成共识。全身性皮质类固醇或静脉注射免疫球蛋白(IVIG)的使用仍存在争议。肿瘤坏死因子-α抑制剂可能具有疗效。

目的

评估依那西普联合皮质类固醇或 IVIG 联合皮质类固醇与皮质类固醇单药治疗 SJS-TEN 患者的疗效和安全性。

方法

我们回顾性纳入了 2014 年至 2019 年来自中国台湾和中国大陆的 SJS-TEN 患者。患者接受皮质类固醇单药治疗或 IVIG 或依那西普联合皮质类固醇治疗。我们分析了这些治疗组的临床特征、皮肤愈合时间、死亡率和不良事件。

结果

在 242 名患者(187 名 SJS 或 SJS-TEN 重叠患者和 55 名 TEN 患者)中,与皮质类固醇单药治疗和 IVIG 联合皮质类固醇治疗相比,接受依那西普联合皮质类固醇治疗的患者实际死亡率较低(0% vs 6.63%和 4.76%)。依那西普联合皮质类固醇治疗组的标准化死亡率(基于毒性表皮坏死松解评分)较皮质类固醇单药治疗组和 IVIG 联合皮质类固醇治疗组有降低死亡率的趋势(SMR [95%CI] 0 [1.80-3.59]、0.71 [0.83-2.64]、0.30 [0.68-6.22];P=.006)。与皮质类固醇单药治疗(13.0 [10.0-18.0])和 IVIG 联合皮质类固醇治疗(13.5 [10.0-19.5])相比,依那西普联合皮质类固醇治疗的皮肤愈合时间更短(12.0 [8.5-14.0],中位数[四分位间距]);P=.004 和 P=.012)。与皮质类固醇单药治疗相比,依那西普联合皮质类固醇治疗组胃肠道出血的不良事件发生率较低,尤其是 TEN 患者(P=.001)。

结论

肿瘤坏死因子-α抑制剂和皮质类固醇联合治疗对 SJS-TEN 有效且比皮质类固醇单药治疗更安全,对于对常规皮质类固醇治疗反应不佳的 SJS-TEN 患者,可考虑作为替代治疗。

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