Abstract: 【Abstract】 Objective To evaluate the efficacy and safety of recombinant human tumor necrosis factor-α receptorⅡ: IgG Fc fusion protein （rhTNFR:Fc） in the treatment of drug-induced toxic epidermal necrolysis （TEN）. Methods From 2009 to 2018, 22 patients with TEN were enrolled from 8 centers such as the Second Affiliated Hospital of Soochow University, including 10 males and 12 females, whose age ranged from 22 to 75 years. These patients were subcutaneously injected with rhTNFR:Fc at a dose of 25 mg once every 3 days for 6 - 8 consecutive sessions, and the initial dose was doubled. The drug eruption area and severity index （DASI） score and DASI improvement indices （DASI50, DASI75 and DASI90） were assessed before treatment and on days 4, 7, 10, 13, 16, 19, 22 and 25 after treatment; cytometric bead array （CBA） technology was used to detect the level of tumor necrosis factor （TNF）-α in peripheral blood and blister fluid samples. During the treatment, body temperature, rash changes, liver and kidney function of patients were monitored, and adverse reactions were recorded. Statistical analysis was carried out by using repeated measures analysis of variance, paired t test and Pearson correlation analysis. Results Of the 22 patients, the temperature stopped rising in 20 patients without infections 24 - 72 hours after the first treatment, and returned to normal after 48 - 120 hours. Among the 22 patients, new blisters stopped appearing 24 - 48 hours after the first treatment, the skin color changed from bright red to dark purple after 48 - 96 hours, and most skin lesions subsided after 2 weeks. After 2 - 4 weeks of treatment, levels of alanine aminotransferase and aspartate aminotransferase returned to normal in 19 patients with abnormal liver function. After 4 - 13 days of treatment, levels of creatinine and urea nitrogen stopped rising in 7 patients with abnormal renal function. During the treatment, the DASI score of the 22 patients gradually decreased （F = 532.81, P < 0.01）, from 53.64 ± 8.67 before treatment to 2.05 ± 1.21 on day 25 after treatment （t = 26.60, P < 0.001）. On day 10 after treatment, 22 patients （100%） achieved DASI50; on day 19, 22 （100%） achieved DASI75; on day 25, 20 （90.90%） achieved DASI90. The level of TNF-α in peripheral blood of the 22 patients gradually decreased along with the extension of treatment duration, from 33.95 ± 27.90 ng/L before treatment to 2.38 ± 0.79 ng/L on day 25. Before treatment, the level of TNF-α in blister fluid of 15 patients was 111.99 ± 99.41 ng/L, and the ratio of blister-fluid TNF-α level to peripheral blood TNF-α level was 1.83 - 28.21. Before treatment, no correlation was observed between the serum level of TNF-α and DASI score in the 22 patients （P = 0.10）, while the blister-fluid TNF-α level was positively correlated with DASI score in the 15 patients （r = 0.59, P = 0.02）. No acute adverse reactions were observed during the treatment. All the 22 patients completed the treatment and were discharged with complete recovery. During 6 months of follow-up after discharge, no recurrence or any complication was observed. Conclusion rhTNFR:Fc is effective and safe for the treatment of drug-induced TEN.

Key words: Epidermal necrolysis, toxic, Tumor necrosis factor-alpha, Treatment outcome, Biological agents, Tumor necrosis factor-alpha antagonists