贝利尤单抗治疗狼疮肾炎的临床疗效与安全性研究

目的： 探讨贝利尤单抗（belimumab， BLM）在狼疮肾炎（lupus nephritis， LN）患者中的临床疗效与安全性，为临床治疗提供参考依据。方法： 纳入在郑州大学第一附属医院风湿免疫科使用BLM治疗6个月以上的LN患者17例，回顾性分析患者临床资料，收集基线时及4、12、24周患者系统性红斑狼疮疾病活动度指数（systemic lupus erythematosus disease activity index， SLEDAI）评分，糖皮质激素和其他背景治疗药物用量，抗ANA抗体，抗ds-DNA抗体，C3和C4补体，血常规，血清白蛋白，尿常规，血清肌酐和24 h尿蛋白定量。同时记录药物使用过程中发生的不良事件，采用IBM SPSS 28软件进行统计学分析。结果： 17例患者（2名男性及15名女性）均完成超过6个月的BLM药物治疗。其中15例（88.2%）有肾脏活检病理支持，合并血液系统损伤10例（58.8%）、合并神经系统损伤2例（12%）。治疗期间SLEDAI评分下降有统计学意义（P<0.001）；血白蛋白量（P<0.001）、补体C3（P=0.002）、补体C4（P<0.001）水平明显升高；24 h尿蛋白定量由基线时的（4.89±3.68） g·L^-1，经6个月的治疗后下降到（0.44±0.62） g·L^-1（P=0.002）；6个月后糖皮质激素用量由基线时的（45.47±14.06） mg·d^-1减少到（9.59±4.52） mg·d^-1（P<0.001）。患者总体对贝利尤单抗反应性良好，5名患者发生不良反应，1例为带状疱疹病毒感染，2例为尿路细菌感染，2例为上呼吸道病毒感染。结论： 在LN患者中，BLM联合标准治疗可显著降低疾病活动度；延缓肾脏炎症性病变进展，减少肾脏的不可逆损伤，改善长期预后；明显减少糖皮质激素用量；具有良好的安全性。其中应用标准治疗后多次复发或病情急进性发展的狼疮肾炎患者获益更多。

Clinical efficacy and safety of belimumab in the treatment of lupus nephritis

OBJECTIVE To investigate the clinical efficacy and safety of belimumab(BLM) in patients with lupus nephritis(LN), and provide reference for clinical treatment.METHODS Seventeen patients with LN were enrolled, who were treated with BLM over 6 months in Department of Rheumatology and Immunology, Fist Affiliated Hospital of zhengzhou university. The clinical data of patients were analyzed retrospectively, and systemic lupus erythematosus disease activity index(SLEDAI), glucocorticoids dose and other therapy drugs, anti-ANA antibody, anti-ds-ANA antibody, C3 and C4, routine blood, serum albumin, routine urine, serum creatinine and 24-hour proteinuria were collected at baseline and at 4, 12 and 24 weeks. And adverse events during drug use were also recorded. IBM SPSS 28 software was used for statistical analysis.RESULTS The seventeen patients(2 males and 15 females) received BLM for more than 6 months. Among them, 15 cases(88.2%) were supported by renal biopsy, and combined with blood system damage in 10 cases(58.8%), and combined with nervous system damage in 2 cases(12%). During the treatment, SLEDAI score decreased with statistical significance(P<0.001); the levels of blood albumin(P<0.001), C3(P=0.002) and C4(P<0.001) were significantly increased. The 24-hour proteinuria decreased from(4.89±3.68) g·L^-1 at baseline to(0.44±0.62) g·L^-1 after 6-month treatment(P=0.002). Glucocorticoids dose decreased from(45.47±14.06) mg·d^-1 at baseline to(9.59±4.52) mg·d^-1 6 months later(P<0.001). Patients generally responded well to BLM, and 5 patients had adverse reactions, including 1 case with herpes zoster, 2 cases with urinary tract bacterial infection, and 2 cases with upper respiratory tract viral infection.CONCLUSION In patients with LN, BLM plus standard therapy can significantly reduce disease activity, delay the progression of renal inflammation, reduce irreversible renal damage, and improve the long-term prognosis. Furthermore, glucocorticoids dose can be significantly reduced with good security. Especially, patients with recurrent or progressive LN following standard treatment may obtain more benefits.