Comparative efficacy and safety of urate-lowering therapy for the treatment of hyperuricemia: a systematic review and network meta-analysis.

Shu Li,Xilin Yang,Weili Xu,Yanan Guo,Fengjiang Wei,Weidong Li,Li Sun,Yaogang Wang,Daiqing Li,Mingzhen Li,Ying Gao,Hongxi Yang

doi:10.1038/srep33082

Abstract

The prevalence of hyperuricemia and gout has been increasing, but the comparative effectiveness and safety of different treatments remain uncertain. We aimed to compare the effectiveness and safety of different treatments for hyperuricemia using network meta-analysis methodology. We systematically reviewed fifteen randomized controlled trials (involving 7,246 patients through January 2016) that compared the effects of different urate-lowering drugs (allopurinol, benzbromarone, febuxostat, pegloticase and probenecid) on hyperuricemia. Drug efficacy and safety, as outcomes, were measured by whether the target level of serum urate acid was achieved and whether any adverse events occurred, respectively. We derived pooled effect sizes expressed as odds ratios (ORs) and 95% confidence intervals (CIs). The efficacy and safety of the drugs were ranked by cumulative ranking probabilities. Our findings show that febuxostat, benzbromarone, probenecid, pegloticase, and allopurinol were all highly effective at reducing the risk of hyperuricemia compared to placebo. Febuxostat had the best efficacy and safety compared to the other drugs. Furthermore, febuxostat 120 mg QD was more effective at achieving urate-lowering targets (OR: 0.17, 95% CI: 0.12–0.24) and safer (OR: 0.72, 95% CI: 0.56–0.91) than allopurinol.

Highlights

Urate-lowering therapy (ULT) has been widely used to control hyperuricemia and prevent gout
This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) extension statement for network meta-analyses of health care intervention studies[32]
Studies meeting the following criteria were included: (a) Patients: adults with hyperuricemia with or without chronic gout; (b) Intervention: established ULT with at least one of five agents; (c) Comparator: placebo or another agent of the five mentioned above; (d) the outcome of efficacy was defined as a failure to achieve the serum urate acid (sUA) treatment target level, i.e., ≤6 mg/dl with ULT, and the outcome of safety was defined as any adverse events during the period of the trial, including abnormal liver function, renal impairment, hyperlipidaemia, diarrhoea, gastrointestinal disorders, joint-related signs and symptoms; and (e) Study design: randomized controlled trial (RCT)

Summary

Introduction

Urate-lowering therapy (ULT) has been widely used to control hyperuricemia and prevent gout. Humans lack urate oxidase, an enzyme that catalyses the oxidation of uric acid to allantoin, resulting in hyperuricemia if accumulated in the blood[20]. In 2014, a panel of 78 international rheumatologists raised ten key clinical questions pertinent to the diagnosis and management of gout, and one of these questions was how to determine the efficacy, cost-efficacy and safety of ULT (allopurinol, benzbromarone, febuxostat, peg-uricase and probenecid) in the treatment of gout[22]. Two previous pairwise meta-analyses analysed available individual studies and suggested that febuxostat may be associated with better urate lowering efficacy than allopurinol[23,24]. We performed a network meta-analysis to evaluate the comparative efficacy and safety of five urate-lowering drugs, focusing on their ability to achieve target serum urate acid levels and the risk of adverse events

Objectives

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Discussion

Conclusion