Biologic TNF-α Inhibitors for Stevens–Johnson Syndrome, Toxic Epidermal Necrolysis, and TEN-SJS Overlap: A Study-Level and Patient-Level Meta-Analysis

Abstract

Abstract Introduction Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse reactions with high morbidity and mortality and not clearly established treatment protocol. This meta-analysis aimed to evaluate the efficacy and safety of three biologic TNF-α inhibitors (infliximab, etanercept, adalimumab) in the treatment of SJS, SJS-TEN overlap, and TEN. Methods Electronic databases were searched for original studies containing human participants diagnosed with SJS/TEN and treated with biologic TNF-α inhibitors. Individual patient data were collected and summarized to provide a comprehensive overview on therapeutic efficacy of different biologic TNF-α inhibitors for SJS, SJS-TEN overlap, and TEN, respectively. Meta-analyses on aggregated study data were conducted using random-effects model. Results Overall, 55 studies with 125 sets of individual patient data were included. Infliximab was used to treat 3 patients with SJS-TEN overlap and 28 patients with TEN, and the actual mortality rate was 33.3% and 17%, respectively. Etanercept was administered to 17 patients with SJS, 9 patients with SJS-TEN overlap, and 64 patients with TEN, and mortality rate was reported to be 0%, 0%, and 12.5%, respectively. For participants with TEN, no significant difference was found in time of reepithelialization, hospitalization time, and mortality rate comparing etanercept with infliximab. More sequelae were reported in patients receiving infliximab than in patients treated with etanercept (39.3% versus 6.4%). Adalimumab was administered to four patients with TEN, and mortality rate was 25%. Meta-analyses on aggregated study data revealed significantly shortened hospitalization time in etanercept compared with non-etanercept groups [weighted mean differences (WMD) −5.30; 95% confidence interval (CI) −8.65 to −1.96]. Etanercept was associated with a survival benefit for patients when compared with non-etanercept treatment, however, the analysis was not statistically significant (odds ratio 0.55; 95% CI 0.23–1.33). Conclusions On the basis of the current findings, etanercept is currently the most promising biologic therapy for SJS/TEN. Further evaluation in prospective studies is required to confirm its efficacy and safety.

Keywords

• Stevens–Johnson syndrome
• Toxic epidermal necrolysis
• Biologic
• TNF-α inhibitors
• Etanercept