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Randomized, controlled trial of TNF-α antagonist in CTL-mediated severe cutaneous adverse reactions.
- Source :
-
Journal of Clinical Investigation . Mar2018, Vol. 128 Issue 3, p985-996. 12p. 1 Diagram, 8 Charts, 3 Graphs. - Publication Year :
- 2018
-
Abstract
- <bold>Background: </bold>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.<bold>Methods: </bold>We enrolled 96 patients with SJS-TEN in a randomized trial to compare the effects of the TNF-α antagonist etanercept versus traditional corticosteroids.<bold>Results: </bold>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.<bold>Conclusions: </bold>The anti-TNF-α biologic agent etanercept serves as an effective alternative for the treatment of CTL-mediated SCARs.<bold>Trial Registration: </bold>ClinicalTrials.gov NCT01276314.<bold>Funding: </bold>Ministry of Science and Technology of Taiwan. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00219738
- Volume :
- 128
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- Journal of Clinical Investigation
- Publication Type :
- Academic Journal
- Accession number :
- 128665849
- Full Text :
- https://doi.org/10.1172/JCI93349