吡非尼酮治疗特发性肺纤维化的有效性与安全性系统评价

Effectiveness and Safety of Pirfenidone in the Treatment of Idiopathic Pulmonary Fibrosis: A Systematic Review and Meta-Analysis

目的系统评价吡非尼酮治疗特发性肺纤维化(IPF)的有效性与安全性。方法计算机检索Medline,EMBase,The Cochrane Library,中国期刊全文数据库、万方数据库和中文科技期刊全文数据库,检索吡非尼酮治疗IPF的随机对照试验(RCT),检索时限为自建库至2019年1月,由2位研究人员独立进行文献筛选、数据提取和研究偏倚风险评价,使用RevMan 5. 3软件进行Meta分析。结果共纳入6个RCT研究。Meta分析结果显示,随访24周时,吡非尼酮组患者用力肺活量(FVC)提高程度优于对照组[MD=0. 10,95%CI(0. 04,0. 15),P=0. 000 7],随访48周时与对照组比较无显著差异[MD=0. 08,95%CI(0. 00,0. 17),P=0. 05];第1秒用力呼气容积(FVC1)改善程度在24周时纳入文献仅有1篇,故作描述性分析,在48周时两组比较无显著差异[MD=0. 05,95%CI(-0. 08,0. 18,P=0. 43];吡非尼酮组在24周[MD=0. 56,95%CI(-0. 02,1. 14),P=0. 06]或48周[MD=0. 71,95%CI(0. 01,1. 42),P=0. 76]时的一氧化碳弥散量(DLCO)与对照组相比均无显著差异;吡非尼酮组FVC较基线下降≥10%例数[MD=0. 63,95%CI(0. 47,0. 85),P=0. 002]、6 min步行距离(6MWD)较基线缩短≥50 m例数[MD=0. 73,95%CI(0. 63,0. 85),P <0. 000 1]均优于对照组;两组全因死亡率相比无显著差异[MD=0. 71,95%CI(0. 47,1. 05),P=0. 09];两组不良反应发生率相比无显著差异[MD=0. 06,95%CI(-0. 02,0. 14),P=0. 13]。结论吡非尼酮治疗IPF疗效较好,且安全性较高。

Objective To systematically review the effectiveness and safety of pirfenidone in the treatment of idiopathic pulmonary fibrosis( IPF). Methods The random clinical trials( RCTs) of pirfenidone in the treatment of IPF were searched in databases of Medline,EMbase,Cochrane Library,CNKI,WanFang Data and VIP from the inception to January 2019. Two reviewers independently screened the literatures,extracted the data and assessed the risk of bias of the included studies. Meta-analysis was conducted by RevMan 5. 3 software. Results A total of 6 studies were included. The results of meta-analysis showed that at 24 weeks of the follow-up,the reduction of forced vital capacity( FVC) in the pirfenidone group was superior to the control group [ MD = 0. 10,95% CI( 0. 04,0. 15),P =0. 000 7 ];at 48 weeks of follow-up,no statistically significant difference was found between the pirfenidone group and the control group [ MD = 0. 08,95% CI( 0. 00,0. 17),P = 0. 05 ];there was only one article included which described the improvement degree of FVC in the first second( FVC1) at 24 weeks,so descriptive analysis was performed;at 48 weeks of follow-up,no statistically significant difference was found between the two group on the degree of improvement of FVC1 [ MD = 0. 05,95% CI(-0. 08,0. 18,P =0. 43) ];the diffusion capacity for carbon monoxide of the Lung( DLCO) in the pirfenidone group was not statistically significant at either 24 [ MD = 0. 56,95% CI(-0. 02,1. 14),P = 0. 06 ] or 48 weeks [ MD = 0. 71,95% CI( 0. 01,1. 42),P = 0. 76 ] compared with the control group;the number of cases with FVC decreased by 10% compared with the baseline [ MD = 0. 63,95% CI( 0. 47,0. 85),P = 0. 002 ],and the number of cases with 6-minute walking distance shortened by 50 meters [ MD = 0. 73,95% CI( 0. 63,0. 85),P <0. 000 1 ] compared with the baseline,and the pirfenidone group was superior to the control group;there was no significant difference in all-cause mortality between the two groups [ MD = 0. 71,95% CI( 0. 47,1. 05),P = 0. 09 ];the incidence of adverse reactions was not statistically significant between the two groups [ MD = 0. 06,95% CI(-0. 02,0. 14),P = 0. 13 ]. Conclusion Pirfenidone is effective and safe in the treatment of IPF.