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08-09-2016 | Gout | Article

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

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


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.

Sci Rep. 2016;6:33082. doi: 10.1038/srep33082.

Hyperuricemia (HUA), defined as a serum urate concentration exceeding the limit of solubility (approximately 6.8 mg/dl), is considered a common biochemical abnormality that reflects supersaturation of the extracellular fluid with urate1. The Global Burden of Disease (GBD) 2010 Study reported that the global prevalence of gout was 0.08%2. Recent epidemiological studies have shown evidence that hyperuricemia and gout cases have continued to grow for decades3. In view of the rapid economic development and the magnitude of populations, the prevalence rate has increased noticeably in developing countries, such as China4,5. There were 15.3 million who were diagnosed with chronic gout in major countries in 2013, and the number with gout is projected to be 17.7 million in 20216. Hyperuricemia results either from the overproduction of uric acid (10%) or the under-excretion of urate (90%)7, leading to the deposition of monosodium urate crystals in and around the joints8,9. Thus, elevated serum urate acid (sUA) levels increase the risk of gout and various comorbidities10,11,12,13,14,15.

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