Network Meta Analysis Of The Therapeutic Effect Of Pifenidone And Nintedanib On Idiopathic Pulmonary Fibrosis

Objective:In 2016 edition of the Chinese expert consensus on the diagnosis and treatment of idiopathic pulmonary fibrosis(IPF),the anti fibrosis drugs pirfenidone and nintedanib were recommended to be used in the treatment of IPF.However,there is no head-to-head test to directly compare the efficacy of pirfenidone and nintedanib in IPF.To further systematically evaluate the efficacy of Pirfenidone and Nintedanib in the treatment of idiopathic pulmonary interstitial fibrosis(IPF),Phase Ⅱ and ⅢRandomized controlled trial of Pirfenidone and Nintedanib were searched,the curative effect was analyzed by Reticular META-analysis to provide evidence-based for clinical treatment.Methods:Searched MEDLINE,EMBASE,the Cochrane Library,CNKI,Wanfang database,find phase Ⅱ and phase Ⅲ randomized controlled trials(RCTs)research of pirfenidone and nintedanib in the treatment of IPF.The retrieval time limit is from the establishment of the database to October 2019.Two researchers independently conducted literature screening,data extraction and research bias risk assessment.The extracted data were evaluated according to the "Cochrane risk bias assessment tool",and the network meta analysis was conducted by using Revman 5.3 direct meta analysis Addis 1.16.8 statistical software.Results:A total of 3464 patients were enrolled in 10 RCT studies.Compared with Placebo in improving FVC,direct Meta analysis showed that there was no significant difference between pirfenidone[MD=0.08,95%CI(-0.00,0.17),P=0.05].Nintedanib could significantly improve the FVC decline,the difference was statistically significant[MD=0.12,95%CI(0.08,0.15),P<0.00001].The results of network meta-analysis were not statistically significant in efficacy between Pirfenidone and Nintedanib[MD:0.07,95%CI(-0.05,0.19)].Direct Meta-analysis results showed that pirfenidone decreased the proportion of patients with FVC decline≥10%compared with placebo[OR=0.45,95%CI(0.33,0.61),P<0.00001].The incidence of FVC decline ≥10%in nintedanib was significantly lower than that in control group.The results of network Meta analysis showed that there was no significant difference between Pirfenidone and Nintedanib[OR:1.26,95%CI(0.66,2.33)].In terms of reducing all cause mortality,direct Meta analysis showed that there was no significant difference between Pirfenidone[OR=0.69,95%CI(0.45,1.06),P=0.09]or Nintedanib[OR=0.62,95%CI(0.39,0.99),P=0.05]compared with placebo.The results of network Meta analysis showed no statistical significance between Pirfenidone and Nintedanib[OR:0.68,95%CI(0.28,2.10)].Rank Probability result:Efficacy of IPF patients with decreased FVC,FVC decline≥10%compared tobaseline,and all cause mortality:nintedanib>pirfenidone>placebo.Conclusion(s):Based on RCTs of patients with IPF,a positive effect on lung function was noted for both treatments,but no significant differences were noted between treatments.Based on Rank Probability result,nintedanib is more likely to be more effective than Pirfenidone in patients with IPF.