Journal Article

Randomized, controlled trial of TNF-α antagonist in CTL-mediated severe cutaneous adverse reactions

Ho, Hsin-Chun, Yang, Chih-Hsun, Chang, Wei-Yang, Chang, Ya-Ching, Fan, Wen-Lang, Ho, Ji-Chen, Yang, Lan-Yan, Chung, Wen-Hung, Huang, Li-Fang, Su, Shih-Chi, Hung, Shuen-Iu, Hui, Rosaline Chung-Yee, Lin, Yang Yu-Wei, Chang, Chee-Jen, Yang, Chin-Yi, Wang, Chuang-Wei, Chin, See-Wen, Chen, Chun-Bing, Lu, Chun-Wei

2018

Overview

Cytotoxic T lymphocyte-mediated (CTL-mediated) severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), are rare but life-threatening adverse reactions commonly induced by drugs. Although high levels of CTL-associated cytokines, chemokines, or cytotoxic proteins, including TNF-α and granulysin, were observed in SJS-TEN patients in recent studies, the optimal treatment for these diseases remains controversial. We aimed to evaluate the efficacy, safety, and therapeutic mechanism of a TNF-α antagonist in CTL-mediated SCARs. We enrolled 96 patients with SJS-TEN in a randomized trial to compare the effects of the TNF-α antagonist etanercept versus traditional corticosteroids. Etanercept improved clinical outcomes in patients with SJS-TEN. Etanercept decreased the SCORTEN-based predicted mortality rate (predicted and observed rates, 17.7% and 8.3%, respectively). Compared with corticosteroids, etanercept further reduced the skin-healing time in moderate-to-severe SJS-TEN patients (median time for skin healing was 14 and 19 days for etanercept and corticosteroids, respectively; P = 0.010), with a lower incidence of gastrointestinal hemorrhage in all SJS-TEN patients (2.6% for etanercept and 18.2% for corticosteroids; P = 0.03). In the therapeutic mechanism study, etanercept decreased the TNF-α and granulysin secretions in blister fluids and plasma (45.7%-62.5% decrease after treatment; all P < 0.05) and increased the Treg population (2-fold percentage increase after treatment; P = 0.002), which was related to mortality in severe SJS-TEN. The anti-TNF-α biologic agent etanercept serves as an effective alternative for the treatment of CTL-mediated SCARs. ClinicalTrials.gov NCT01276314. Ministry of Science and Technology of Taiwan.

• Publisher: American Society for Clinical Investigation
• Subject: Administration, Cutaneous / Adrenal Cortex Hormones - pharmacology / Adult / Aged / Antigens, Differentiation, T-Lymphocyte - metabolism / Apoptosis / Biomedical research / Chemokines / Chemokines - metabolism / Clinical Medicine / Clinical outcomes / Corticosteroids / Cytokines - metabolism / Cytotoxicity / Etanercept / Etanercept - therapeutic use / FDA approval / Female / Gastrointestinal Hemorrhage - prevention & control / Gene expression / Hemorrhage / Humans / Immunophenotyping / Lymphocytes / Lymphocytes T / Male / Middle Aged / Mortality / Patients / Rheumatoid arthritis / Secretions / Side effects / Skin / Skin - drug effects / Skin - immunology / Stevens-Johnson syndrome / Stevens-Johnson Syndrome - drug therapy / Studies / Systematic review / T-Lymphocytes, Cytotoxic - cytology / Toxic epidermal necrolysis / Tumor Necrosis Factor-alpha - antagonists & inhibitors / Tumor necrosis factor-α