重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白治疗中毒性表皮坏死松解症的疗效及安全性

Efficacy and safety of recombinant human typeⅡtumor necrosis factor receptor-antibody fusion protein in the treatment of toxic epidermal necrolysis

目的探讨重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白(rhTNFR:Fc)治疗中毒性表皮坏死松解症(TEN)患者的临床疗效及安全性。方法回顾性选取2020年1月至2022年1月海南医学院第一附属医院TEN患者20例,均给予rhTNFR:Fc治疗。治疗21 d后,记录TEN患者临床疗效,比较治疗前与治疗后不同时段(治疗后7、14、21 d)的药疹面积和严重程度指数(DASI)评分[DASI评分平均值,50%DASI(DASI50)、75%DASI(DASI75)、90%DASI(DASI90)所占比例]、血清肿瘤坏死因子α(TNF-α)水平、体温下降时间、皮疹控制时间、住院时间及药物治疗的安全性。结果治疗21 d后,TEN患者中,显效18例(90.00%),有效2例(10.00%)。TEN患者治疗后7、14、21 d的DASI评分分别为(30.44±5.68)、(5.28±2.31)、(2.04±1.12)分,均明显低于治疗前[(52.34±7.45)分],差异均有统计学意义(P<0.05)。相较治疗前、治疗7 d、治疗14 d,治疗21 d后的DASI50(100.00%)、DASI75(100.00%)、DASI90(90.00%)的改善比率最高,差异均有统计学意义(P<0.05)。TEN患者治疗后7、14、21 d的血清TNF-α水平分别为(22.73±5.58)、(15.99±4.60)、(4.44±1.10)pg/mL,均低于治疗前[(33.63±17.36)pg/mL],差异均有统计学意义(P<0.05)。TEN患者体温下降时间为(2.49±0.81)d,皮疹控制时间为(5.19±1.90)d,住院时间为(11.92±4.20)d。治疗期间患者未出现终止治疗或失访,均未出现急性不良反应,随访期间病情未见复发,定期复查结果显示并无合并症、活动性肝炎与结核疾病等。结论rhTNFR:Fc作为治疗TEN疾病的药物其疗效随治疗时间延长而提高,可降低血清TNF-α水平与DASI评分,且安全性较高。

Objective To explore the clinical efficacy and safety of recombinant human typeⅡtumor necrosis factor receptor-antibody fusion protein(rhTNFR:Fc)in the treatment of toxic epidermal necrolysis(TEN)patients.Methods Twenty patients with TEN admitted to the First Affiliated Hospital of Hainan Medical College from January 2020 to January 2022 were retrospectively selected,and all of them were treated with rhTNFR:Fc.After 21 days of treatment,the clinical efficacy of TEN patients was recorded.The drug eruption area and severity index(DASI)[DASI scores,50%DASI(DASI50)ratio,75%DASI(DASI90)ratio,90%DASI(DASI90)ratio]and TNF-αlevels before and after treatment(7,14,21 days after treatment),temperature reduction time,rash control time,and hospitalization time,as well as the safety of drug treatment were compared.Results After 21 days of treatment,18 patients(90.00%)showed marked improvement and 2 patients(10.00%)showed effective results.The DASI scores of TEN patients at 7,14,21 days after treatment were(30.44±5.68),(5.28±2.31),and(2.04±1.12)points,respectively,which were significantly lower than those before treatment[(52.34±7.45)points],the differences were statistically significant(P<0.05).Compared with before treatment,7 days after treatment,and 14 days after treatment,the improvement rates of DASI50(100.00%),DASI75(100.00%),and DASI90(90.00%)after treatment for 21 days were the highest,the differences were statistically significant(P<0.05).The levels of serum TNF-αin TEN patients at 7,14,21 days after treatment were(22.73±5.58),(15.99±4.60),(4.44±1.10)pg/mL,respectively,which were lower than those before treatment[(33.63±17.36)pg/mL],the differences were statistically significant(P<0.05).The time for temperature reduction,rash control and hospitalization of TEN patients was(2.49±0.81)days,(5.19±1.90)days and(11.92±4.20)days,respectively.During the treatment,no patient discontinued treatment or was lost to follow-up,and no acute adverse reactions occurred.There was no recurrence of the disease during the follow-up period,and regular examinations showed that there were no complications,active hepatitis,or tuberculosis.Conclusion rhTNFR:Fc can be used as an effective drug in the treatment of TEN diseases,and can reduce TNF-αvalue and DASI score,with high safety.