Mesh Meta-analysis Of The Efficacy And Safety Of Uric Acid-lowering Drugs In The Treatment Of Gout And Primary Hyperuricemia

Objective: To evaluate and understand the ranking of the clinical efficacy and safety of three common uric-acid-lowering drugs for gout or primary hyperuricemia by Bayesian mesh meta-analysis.Methods:In this study,Bayesian mesh meta-analysis method was used to comprehensively evaluate the efficacy and safety of three uric-acid-lowering drugs,i.e.allopurinol,febuxostat,benzbromarone for gout or primary hyperuricemia.Outcomes for evaluation were the achievement of target serum uric acid(<360 ?mol/L),the level of the final serum uric acid and the adverse events.The relevant randomized controlled trials(RCTs)were obtained by searching the databases as Pub Med,Embase,Cochrane Library,CNKI,Wan Fang Data,and Weipu database.The literature that met the inclusion criteria was statistically described and statistically analyzed after quality evaluation.The R3.5.3 software was used for data analysis.Results:A total of 42 RCTs were included.None of these RCTs was of low risk bias.The treatment duration ranged from 8 weeks to 52 weeks.The sample size ranged from 40 to 2269 with a total number of 8011.Forty-one RCTs took allopurinol treatment as control group.For the achievement of target serum uric acid,the proportion in allopurinol 100 mg/d group was 42.1%.Compared with allopurinol 100 mg/d group,the relative risks(RRs)and 95% confidence interval(CI)of benzbromarone 25 mg/d,benzbromarone 50 mg/d and febuxostat 40 mg/d group were 1.1(0.84,1.4),1.1(0.97,1.2)and 1.4(1.2,1.8),respectively.Comparing with 80 mg/d group,the RR(95% CI)of febuxostat 40 mg/d was 0.99(0.82,1.2).Combining with the risk probability table,the ranking from high to low was febuxostat 80 mg/d,febuxostat 40 mg/d,allopurinol 300 mg/d,benzbromarone 50 mg/d,benzbromarone 25 mg/d,allopurinol 100 mg/d.For the level of final serum uric acid,the average of the final serum uric acid in allopurinol 100 mg/d group was 427.0 ?mol.Compared with it,the mean difference(MD)(95% CI)of allopurinol 300mg/d group was-8.8?mol/L(-43?mol/L,26?mol/L),showing no significant difference.The MDs(95% CI)of benzbromarone 25 mg/d and 50 mg/d groups were-25?mol/L(-47?mol/L,-3?mol/L)and-44?mol/L(-70?mol/L,-18?mol/L),respectively.The MDs(95% CI)of febuxostat 40 mg/d and 80 mg/d group were-60?mol/L(-92?mol/L,-27?mol/L)and-68?mol/L(-100?mol/L,-36?mol/L),respectively.These results showed that mean serum uric acid in these groups were significantly lower than that of allopurinol 100 mg/d group.Combining with the risk probability table,the ranking from high to low final serum uric acid was allopurinol 100 mg/d,allopurinol 300 mg/d,benzbromarone 25 mg/d,benzbromarone 50 mg/d,febuxostat 40 mg/d and febuxostat 80 mg/d.For adverse events,the incidence of adverse events in allopurinol 100mg/d group was 15.5%.With allopurinol 100 mg/d group as control,RRs(95% CI)of febuxostat 40 mg/d and 80 mg/d group were 0.67(0.33,1.2)and 0.72(0.36,1.3),respectively,showing no significant difference.The RRs(95% CI)of benzbromarone 25 mg/d and 50 mg/d group were 0.25(0.099,0.59)and 0.39(0.21,0.66),respectively,meaning significantly lower adverse events than allopurinol 100mg/d group.The adverse events in allopurinol 300 mg/d group was significantly higher than allopurinol 100 mg/d group,with RR(95% CI)1.6(1.2,2,4).Combining with the risk probability table,the ranking from high to low was allopurinol 300 mg/d,allopurinol 100 mg/d,febuxostat 80 mg/d,febuxostat 40 mg/d,benzbromarone 50 mg/d and benzbromarone 25 mg/d.Conclusion:For the patients with gout and primary hyperuricemia,the febuxostat is recommanded when taking the clinical efficacy into consideration;while the benzbromarone or febuxostat is recommanded when considerating both the clinical efficacy and safety.