Jing Zhang1, Chun-Wei Lu2, Chun-Bing Chen3, Chuang-Wei Wang4, Wei-Ti Chen5, Bo Cheng1, Chao Ji6, Wen-Hung Chung7. 1. Department of Dermatology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China. 2. 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. 3. 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; Chang Gung Immunology Consortium, Chang Gung Memorial Hospital, and Chang Gung University, Taoyuan, Taiwan; Cancer Vaccine and Immune Cell Therapy Core Laboratory, Chang Gung Memorial Hospital, Linkou, Taiwan; Whole-Genome Research Core Laboratory of Human Diseases, Chang Gung Memorial Hospital, Keelung, Taiwan. 4. Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou, Taipei, and Keelung, Taiwan; Department of Dermatology, Xiamen Chang Gung Hospital, Xiamen, China; Chang Gung Immunology Consortium, Chang Gung Memorial Hospital, and Chang Gung University, Taoyuan, Taiwan; Cancer Vaccine and Immune Cell Therapy Core Laboratory, Chang Gung Memorial Hospital, Linkou, Taiwan. 5. 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. 6. Department of Dermatology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China. Electronic address: jichaofy@fjmu.edu.cn. 7. 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; Immune-Oncology Center of Excellence, Chang Gung Memorial Hospital, Linkou, Taiwan; Chang Gung Immunology Consortium, Chang Gung Memorial Hospital, and Chang Gung University, Taoyuan, Taiwan; Cancer Vaccine and Immune Cell Therapy Core Laboratory, Chang Gung Memorial Hospital, Linkou, Taiwan; Whole-Genome Research Core Laboratory of Human Diseases, Chang Gung Memorial Hospital, Keelung, Taiwan; Department of Dermatology, Beijing Tsinghua Chang Gung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China; School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Genomic Medicine Core Laboratory, Chang Gung Memorial Hospital, Linkou, Taiwan. Electronic address: wenhungchung@yahoo.com.
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.
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.
Authors: Teresa Bellón; Olga González-Valle; Elena Sendagorta; Victoria Lerma; Javier Martínez Del Río; Celia Martínez; Guillermo Servera; Carlos González-Herrada; Lucía Cachafeiro; José A Lorente; Rosario Cabañas; Pedro Herranz; Francisco de Abajo Journal: Biomedicines Date: 2022-08-02