生物制剂治疗系统性红斑狼疮的有效性和安全性网状meta分析

    Efficacy and Safety of Biologics for the Treatment of Systemic Lupus Erythematosus: A Network Meta-analysis 

    • 摘要:
      目的 评价生物制剂治疗系统性红斑狼疮(systemic lupus erythematosus,SLE)的有效性和安全性。
      方法 检索中国知网、万方、PubMed、EMB和Cochrane Library等数据库,检索时限为各数据库自建库至2024年4月1日,获取生物制剂治疗SLE的随机对照试验(randomized controlled trials,RCTs)。由2名研究者独立筛选文献、提取数据、评价纳入文献质量之后,采用R 4.2.3软件进行贝叶斯网状meta分析。
      结果 最终纳入27项研究,共涉及14种药物干预措施,共计12955例患者。网状meta分析结果显示:在提高SRI-4应答率方面,贝利尤单抗、阿尼鲁单抗、他贝芦单抗、泰它西普的效果优于安慰剂组,且泰它西普效果优于其他药物(P<0.05);根据SUCRA值排序,排名第一的药物为泰它西普(0.99)。在提高SRI-6应答率方面,泰它西普的效果优于安慰剂组(P<0.05),其余药物两两比较,差异无明显统计学意义(P>0.05);根据SUCRA值排序,排名第一的药物为泰它西普(0.95)。在改善BICLA应答率方面,阿尼鲁单抗的效果优于安慰剂(P<0.05);根据SUCRA值排序,排名第一的药物为阿尼鲁单抗(0.87)。在提高完全肾脏缓解率方面,各药物两两比较差异无统计学差异( P>0.05);根据SUCRA值排序,排名第一的药物为奥妥珠单抗(0.81)。在改善糖皮质激素减量率方面,阿尼鲁单抗、贝利尤单抗的效果优于安慰剂组(P<0.05)。根据SUCRA值排序,排名第一的药物为阿尼鲁单抗(0.80)。在不良反应发生率方面,阿尼鲁单抗的发生风险高于安慰剂、贝利尤单抗、PF-04236921、Blisibimod、依帕珠单抗、他贝芦单抗及奥瑞利珠单抗 (P<0.05),泰它西普高于安慰剂、贝利尤单抗、PF-04236921及奥瑞利珠单抗(P<0.05),阿塞西普高于PF-04236921。由于不良反应发生风险越低,其安全性越好,故SUCRA值越低,代表该药物安全性越好。根据SUCRA值排序,不良反应发生率方面排名第一的药物为奥瑞利珠单抗(0.17)。
      结论 基于研究结果,泰它西普在提高SRI-4和SRI-6应答率方面具备优势,但尚需更多高质量研究验证其安全性;阿尼鲁单抗在改善BICLA应答率和糖皮质激素减量方面均具有优势;奥妥珠单抗在改善完全肾脏缓解率上更具备优势。然而,受研究的限制,上述结论仍需要更多高质量、多中心的RCTs进一步验证。

       

      Abstract:
      OBJECTIVE To evaluate the efficacy and safety of biologics in the treatment of systemic lupus erythematosus(SLE).
      METHODS The databases of CNKI, Wanfang, PubMed, EMB and Cochrane Library were searched, and the search time limit was from the construction of each database to April 1, 2024, to obtain randomized controlled trials(RCTs) using biologics for the treatment of SLE. After 2 investigators independently screened the literature, extracted the data, and evaluated the included literature, Bayesian network meta-analysis was performed using R 4.2.3.
      RESULTS A total of 27 studies including 12955 patients were selected, 14 pharmacologic interventions were included. Network meta-analysis showed that in improving the SRI-4 response rate, Belimumab, Anifrolumab, Tabalumab and Telitacicept were more effective than the placebo group, and the effect of Telitacicept was better than the other drugs(P<0.05); according to the SUCRA values, the top-ranked drug was Telitacicept(0.99). In terms of improving SRI-6 response rate, the effect of Telitacicept was better than that of the placebo group(P<0.05), and the difference between the two comparisons of the rest of the drugs was not statistically significant(P>0.05); according to the SUCRA values, the top-ranked drug was Telitacicept(0.95). In terms of improving the BICLA response rate, Anifrolumab was superior to placebo(P<0.05); according to the SUCRA values, the top-ranked drug was Anifrolumab(0.87). There was no significant difference between the two comparisons of each drug in terms of improving the complete renal response rate(P>0.05); according to the SUCRA values, the top-ranked drug was Obinutuzumab(0.81). The effect of Belimumab and Anifrolumab was better than that of the placebo control group in improving the steroid reduction rate (P<0.05); according to the SUCRA values, the top-ranked drug was Anifrolumab(0.80). In terms of the incidence of adverse reactions, Anifrolumab had a higher risk of occurrence than placebo, Belimumab, PF-04236921, Blisibimod, Epratuzumab, Tabalumab, and Ocrelizumab(P<0.05), and Telitacicept had a higher risk than placebo, Belimumab, PF-04236921, and Ocrelizumab(P<0.05), and Atacicept over PF-04236921. Because the lower the risk of adverse reactions, the better the safety, so the lower the SUCRA value, the better the safety of the drug. According to the SUCRA values, the top-ranked drug of the incidence of adverse reaction was Ocrelizumab(0.17).
      CONCLUSIONS Based on the results of the study, Telitacicept has advantages in improving SRI-4 and SRI-6 response rate, but more high-quality studies are needed to validate its safety; Anifrolumab has advantages in improving BICLA response rate and steroid reduction rate; and Ocrelizumab is more advantageous in improving the rate of complete renal response rate. However, due to study limitations, the above conclusions need to be further validated by more high-quality, multicenter RCTs.

       

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