贝利尤单抗治疗重型Ⅳ、Ⅳ+Ⅴ及Ⅴ型狼疮性肾炎的有效性及安全性分析

Efficacy and safety of belimumab in the treatment of severe lupus nephritis types Ⅳ,Ⅳ+Ⅴ and Ⅴ

目的 探讨贝利尤单抗治疗重型Ⅳ、Ⅳ+Ⅴ及Ⅴ型狼疮性肾炎(Lupus nephritis, LN)的有效性及安全性。方法 回顾性选取2019年1月至2022年4月在郑州大学第一附属医院接受贝利尤单抗联合常规治疗(常规治疗分为3种:(1)糖皮质激素联合他克莫司;(2)糖皮质激素联合他克莫司及霉酚酸酯;(3)糖皮质激素联合霉酚酸酯)的重型Ⅳ、Ⅳ+Ⅴ及Ⅴ型LN患者为治疗组,接受常规治疗患者为对照组,按照1∶2分层匹配。根据治疗组和对照组的常规治疗中有无他克莫司再分为2个亚组(他克莫司亚组和霉酚酸酯亚组)。主要终点是24周完全缓解(Complete remission, CR)。结果 共81例患者入选,治疗组27例,对照组54例。在24周时,治疗组的CR率显著高于对照组(48.1%vs.25.9%,χ^(2)=4.000,P=0.046)。亚组分析显示,治疗组的贝利尤单抗联合他克莫司亚组的CR率显著高于对照组(χ^(2)=5.511,P=0.019),贝利尤单抗联合霉酚酸酯亚组的CR率与对照组差异无统计学意义(P>0.05)。在24周时,治疗组的24小时尿蛋白和糖皮质激素累积剂量显著低于对照组(P=0.023;P=0.041)。治疗组与对照组间的补体C3、C4、系统性红斑狼疮疾病活动性评分、抗dsDNA抗体阳性率等差异无统计学意义(P>0.05)。治疗组与对照组的不良事件发生率差异无统计学意义(P>0.05)。结论 贝利尤单抗联合常规治疗的疗效优于常规治疗,其中贝利尤单抗联合他克莫司治疗重型Ⅳ、Ⅳ+Ⅴ及Ⅴ型LN的疗效更佳。

Objective To evaluate the efficacy and safety of belimumab in the treatment of severe Ⅳ,Ⅳ+Ⅴ and Ⅴ lupus nephritis(LN).Methods The patients with severe type Ⅳ,Ⅳ+Ⅴ and Ⅴ LN who received belimumab combined with conventional treatment(including glucocorticoid+tacrolimus,glucocorticoid+tacrolimus+mycophenolate mofetil,glucocorticoid+mycophenolate mofetil)in the First Affiliated Hospital of Zhengzhou University from January 2019 to April 2022 were retrospectively selected as the treatment group,and the patients receiving conventional treatment were selected as the control group,matching according to 1∶2 stratification.The treatment and control groups were subdivided into two subgroups based on the presence or absence of tacrolimus in the conventional treatment(including tacrolimus subgroup and mycophenolate mofetil subgroup).The clinical endpoint was complete remission(CR)at 24 weeks.Results A total of 81 patients were enrolled,27 in the treatment group and 54 in the control group.At week 24,the CR rate in the treatment group was significantly higher than that in the control group(48.1%vs.25.9%)(χ^(2)=4.000,P=0.046).Subgroup analysis showed that the CR rate of belimumab combined with tacrolimus subgroup in the treatment group was significantly higher than that in the control group(χ^(2)=5.511,P=0.019),the CR rate of belimumab combined with mycophenolate mofetil subgroup was not significantly different from the control group(P>0.05).The 24-hour total urinary protein and cumulative glucocorticoid dose were significantly lower in the treatment group than in the control group(P=0.023;P=0.041).There was no statistically significant difference between the two groups in complement C3,C4,SLE disease activity index score or anti-dsDNA antibody positivity rate(P>0.05).The difference in the incidence of adverse events between the two groups was not statistically significant(P>0.05).Conclusion Belimumab in combination with conventional therapy is superior to conventional therapy alone,with the better efficacy being belimumab in combination with tacrolimus in the treatment of severe LN types Ⅳ,Ⅳ+Ⅴ and Ⅴ.