Efficacy and safety of urate-lowering therapies in asymptomatic hyperuricaemia: a systematic review and network meta-analysis of key clinical outcomes

Abstract

Objective: Asymptomatic hyperuricaemia (AH) is an independent risk factor for chronic kidney disease, cardiovascular events, and metabolic disorders. However, controversies persist regarding the clinical use of urate-lowering therapies (ULTs). This study employs a network meta-analysis (NMA) to systematically evaluate the efficacy and safety of ULTs in AH across seven key endpoints: serum uric acid (SUA), estimated glomerular filtration rate (eGFR), high-sensitivity C-reactive protein (hs-CRP), systolic blood pressure (SBP), major adverse cardiovascular events (MACE), composite renal events (CREs) and drug-induced liver injury (DILI). The findings aim to inform clinical decision-making. Method: Four databases were systematically searched from their inception to March 2025 for all relevant literature, screening and evaluating randomized controlled trials (RCTs) assessing ULTs in AH. A frequentist NMA was conducted using R software. The Risk of Bias 2.0 tool was employed for bias assessment, and therapies were ranked via P-scores. In addition, transitivity assessment, network meta-regression, and sensitivity analysis were also performed. Results: A total of 51 studies involving 8 ULTs and 10,281 subjects were included in this NMA. Random-effects modelling showed that, compared to controls, Verinurad_Febuxostat (P-score = 0.82; pooled mean difference [95% CI]: −3.20 [−4.76 to −1.64]) was the most effective in reducing SUA, Febuxostat (P-score = 0.78; 1.91 [0.47 to 3.35]) was the most effective in improving eGFR, Topiroxostat (P-score = 0.96; −6.10 [−11.75 to −0.45]) was most effective in improving SBP, and Febuxostat (P-score = 0.78; 0.77 [0.61 to 0.98]) reduced the risk of CREs most effectively. A None of the interventions showed significant differences in hs-CRP, MACE, or DILI. The Confidence in Network Meta-Analysis (CINeMA) assessment indicated that the overall quality of evidence was low to moderate. Conclusion: Available evidence suggests that febuxostat not only plays a significant role in lowering SUA levels but also significantly delays the decline in eGFR and reduces the risk of CREs.