生物制剂治疗类风湿关节炎相关间质性肺病疗效与安全性的meta分析

Efficacy and safety of biological agents for rheumatoid arthritis-associated interstitial lung disease:a meta-analysis

目的系统评价生物制剂治疗类风湿关节炎相关间质性肺病(RA-ILD)的有效性和安全性,为临床治疗提供循证依据。方法在PubMed、Cochrane Library、Embase、Web of Science、中国知网、万方、维普、中国生物医学文献数据库中检索关于生物制剂治疗RA-ILD的研究,采用R软件进行meta分析。结果共纳入10项研究,其中关于利妥昔单抗(RTX)及阿巴西普(ABA)的研究各4项,肿瘤坏死因子α(TNF-α)抑制剂的研究2项。Meta分析结果显示:接受RTX治疗的患者,治疗后用力肺活量占预计值百分比(FVC%pred)较治疗前显著增加[WMD=9.58,95%CI(3.91,15.25),P<0.05];而治疗前后一氧化碳弥散量占预计值百分比(DLCO%pred)的差异无统计学意义[WMD=8.90,95%CI(-1.06,18.86),P>0.05]。接受ABA治疗的患者,治疗前后FVC%pred[WMD=-1.10,95%CI(-3.83,1.63),P>0.05]和DLCO%pred[WMD=0.65,95%CI(-2.24,3.53),P>0.05]的差异均无统计学意义;治疗后患者肺高分辨率CT的好转、稳定、恶化合并率分别为16%[95%CI(12%,22%)]、69%[95%CI(57%,79%)]、19%[95%CI(14%,24%)]。接受TNF-α抑制剂治疗的患者,治疗后的FVC%pred与治疗前相比未出现明显下降。RTX的总体不良事件合并发生率为33%[95%CI(21%,45%)],与不良事件相关的死亡的合并发生率为7%[95%CI(2%,16%)]。结论生物制剂(RTX、ABA、TNF-α抑制剂)具有稳定或改善RA-ILD患者肺功能和影像学表现的作用,是治疗RA-ILD有效且安全的方法。

Objective To systematically evaluate the efficacy and safety of biological agents in patients with rheumatoid arthritis-associated interstitial lung disease(RA-ILD),and to provide evidence for clinical treatment.Methods Databases including PubMed,Cochrane Library,Embase,Web of Science,CNKI,Wanfang,VIP,and CBM were searched for studies on biological agents for RA-ILD.Meta-analysis was performed by R software.Results Totally 10 studies were included:4 on rituximab(RTX),4 on abatacept(ABA)and 2 on tumor necrosis factor-alpha(TNF-α)inhibitors.In patients treated with RTX,the percentage of forced vital capacity in predicted value(FVC%pred)after the treatment was significantly improved as compared with before[WMD=9.58,95%CI(3.91,15.25),P<0.05],while there was no significant difference in percentage of diffusion capacity of the lung for the carbon monoxide in predicted value(DLCO%pred)before and after the treatment[WMD=8.90,95%CI(-1.06,18.86),P>0.05].In patients treated with ABA,no significant difference was found in either FVC%pred[WMD=8.90,95%CI(-3.85,1.63),P>0.05]or DLCO%pred[WMD=0.65,95%CI(-2.24,3.53),P>0.05]before and after the treatment,and pooled proportions of improvement,stability,worsening in lung high resolution computed tomography(HRCT)after the treatment were 16%[95%CI(12%,22%)],69%[95%CI(57%,79%)],and 19%[95%CI(14%,24%)]respectively.In patients treated with TNF-αinhibitor,no significant decline was found in FVC%pred from before to after the treatment.The pooled proportion of overall adverse events for RTX was 33%[95%CI(21%,45%)],and the pooled proportion of death related with adverse events was 7%[95%CI(2%,16%)].Conclusion Biological agents(RTX,ABA and TNF-αinhibitors)are safe and effective for patients with RA-ILD,contributing to the stability and improvement in pulmonary functions and HRCT results.