Comparative Efficacy And Safety Of Uricosuric Agents In The Treatment Of Gout Or Hyperuricemia: A Systematic Review And Network Meta-analysis

Objective:The prevalence of hyperuricemia and gout has been increasing,but the ranking of the comparative efficacy and safety of currently available uricosuric agents remain uncertain.We herein aimed to investigate the appropriate uricosuric agent for gout or hyperuricemia patients.Methods:In this study,frequentist network meta-analysis method was used to comprehensively evaluate the efficacy and safety of seven uricosuric drugs(probenecid,benzbromarone,arhalofenate,lesinurad,verinurad,dotinurad,and SHR4640)for gout or hyperuricemia.Outcomes for evaluation were the achievement of target serum uric acid(<360 μmol/L)and the adverse events.Pub Med,Embase,Cochrane Library databases,Clinical Trials.gov,Chinese National Knowledge Infrastructure(CNKI),Wan Fang Database,and VIP Database for Chinese Technical Periodicals(VIP)from inception to December 2022 were searched to retrieve eligible studies assessing efficacy and safety of uricosuric drugs in hyperuricemia or gout patients.The literature that met the inclusion criteria was statistically described and statistically analyzed after quality evaluation.Network meta-analysis was carried out using the Stata 16.0 software.Results:Twelve randomized controlled trials comprising 1851 patients were eventually included.The treatment duration ranged from 1 month to 8.5 months,and the sample size ranged from 14 to 319.For the achievement of target serum uric acid,compared with placebo group,the relative risks(RRs)and 95% confidence interval(CI)of dotinurad 4mg/d,verinurad,dotinurad 2mg/d,benzbromarone and dotinurad 1mg/d were 38.79(9.72-154.83),65.14(4.12-1029.52),33.84(8.49-134.90),32.72(8.21-130.45)and 29.97(6.93-112.89),respectively.Combining with the risk probability table,network meta-analysis showed that dotinurad 4mg once daily,verinurad,dotinurad 2mg once daily,benzbromarone,and dotinurad 1mg once daily were the top 5 effective treatments to achieve target serum uric acid.For adverse events,compared with arhalofenate 800mg/d group,dotinurad 2mg/d,probenecid and lesinurad had higher incidence of adverse events(RR of arhalofenate 800mg/d vs.dotinurad2mg/d: 0.60,95% CI: [0.36-0.99];RR of arhalofenate 800mg/d vs.probenecid: 0.34,95% CI: [0.13-0.95];RR of arhalofenate 800mg/d vs.lesinurad: 0.57,95% CI:[0.36-0.91]).Combining with the risk probability table,network meta-analysis showed that arhalofenate 800mg/d,arhalofenate 600mg/d,SHR4640,dotinurad 1mg/d,and verinurad were the top 5 treatments to have lower adverse events.Conclusions:This network meta-analysis demonstrated an important absolute benefit of dotinurad 4mg once daily to achieve target serum uric acid and low risk of adverse events for drug treatment of gout or hyperuricemia patients.Additionally,verinurad might be used as an alternative uricosuric therapeutic option to dotinurad.These findings provided further comprehensive insight into the treatment value of current uricosuric agents for gout or hyperuricemia.