Evaluation of urate-lowering therapy in hyperuricemia patients: a systematic review and Bayesian network meta-analysis of randomized controlled trials

Objective: Hyperuricemia is a strong precursor of gout, which deteriorates patients’ health and quality of life. Sustained adherence to urate-lowering therapies (ULTs) is crucial for efficacy and therapeutic cost-effectiveness. Recently, several new ULTs have been proposed. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to reassess the efficacy and safety of the current ULTs, focusing on adherence attrition-related adverse event reporting. Method: The Bayesian network meta-analysis was applied to compare ULTs. Drug efficacy and safety were measured by whether the target level of serum urate acid was achieved and whether any adverse events occurred. The results were summarized using the pooled estimates of effect sizes (odds ratios), their precisions (95% credible interval), and the ranking probabilities. Results and Conclusions: Thirty-nine RCTs were identified, accumulating 19,401 patients. Consistent with previous studies, febuxostat (≥ 40 mg/day) was superior to other monoagent ULTs. The new findings were as follows: (i) dual-agent ULTs were superior to febuxostat alone, and further surveillance on the adverse effects when lesinurad is uptitrated is needed, and (ii) terminalia bellerica 500 mg/day, a novel xanthine oxidase inhibitor (XOI) made of natural fruit extracts, and topiroxostat ≥ 80 mg/day, an XOI used mostly in Japan, could be new effective options for lowering the occurrence of adherence attrition events. Evidence from RCTs regarding second-line agents, such as probenecid and pegloticase, remains insufficient for clinical decision-making.Key Points• Dual-agent ULTs were superior to febuxostat alone, and further surveillance on the adverse-effects when lesinurad is uptitrated is needed.• Terminalia bellerica 500 mg/day, a novel xanthine oxidase inhibitor (XOI) made of natural fruit extracts, and topiroxostat 80 mg/day, an XOI used mostly in Japan, could be new effective options for lowering the occurrence of adherence attrition events.