Network Meta-analysis Of The Efficacy And Safety Of Four Uric Acid-lowering Drugs

Objective:To compare the acid-lowering effects of allopurinol,febuxostat,benzbromarone and pegloticase in patients with gout using the method network meta-analysis.Methods:We searched for science papers using combination of keywords and freewords in databases of Pub Med,Cochrane Library,Embase;China National Knowledge Infrastructure(CNKI),Wanfang Database(WANFANG),Weipu Database(VIP),China Biomedical Literature Database(CBM).The search time is set from the establishment of the each library to December 20,2018.According to the pre-established incorporate and exclude criteria.High-quality randomized controlled trials(RCT)studies related to uric acid-lowering drugs(allopurinol,febuxostat,benzbromarone,and pegloticase)were included.The Revman software was used to evaluate the quality of the literatures,extract basic information and data from the literatures,then the stata13.0 software network,mvmeta and metan package Meta-analysis were used for network mata analysis.Odds ratio(OR)and 95% confidence interval(95% CI)were used to assess the effectiveness of four urate-lowering drugs,the incidence of adverse events,and the incidence of acute gout attacks.Results: A total of 16 articles were included,and 6,746 gout patients were enrolled.The results of the network meta-analysis came from a randomized controlled model in which direct comparisons are combined with indirect comparison effects.The results of the network meta-analysis are as following: Compared with placebo,there were significant differences in the effectiveness of the four drugs,which indicated that the four drugs had a good effect of reducing uric acid(P<0.05).In terms of safety,there was no significant difference in the incidence of adverse reactions between the four urate-lowering drugs compared with placebo(P>0.05),indicating that all four urate-lowering drugs had adverse reactions.Compared with placebo,4mg/2week,8mg/2week,8mg/4week pegloticase and 40mg/d febuxostat,there weresignificant differences in the incidence of acute gout attacks(P<0.05),indicating that4mg/2week,8mg/2week,8mg/4week pegloticase and 40mg/d febuxostat increased the incidence of acute gout attacks.Conclusion:Based on this analysis,febuxostat for uric acid therapy in patients with gout with hyperuricemia has a slight advantage in effectiveness.And the 120 mg and once daily dose of febuxostat showed the best uric acid-lowering effect.Although the incidence of adverse reactions was the highest,no serious adverse reactions occurred.However,due to the limitations and heterogeneity of this network meta-analysis.Therefore,more high-quality studies are needed to demonstrate the research conclusions.