Comparative efficacy and safety of lesinurad 200 mg and 400 mg combined with a xanthine oxidase inhibitor in hyperuricemic patients with gout: A Bayesian network meta-analysis of randomized controlled trials

Objectives: We aimed to assess the relative efficacy and safety of once-daily administration of lesinurad in combination with xanthine oxidase inhibitor (XOI) in hyperuricemic patients with gout. Materials and methods: A Bayesian random-effects network meta-analysis was performed to combine the direct and indirect evidence from randomized controlled trials (RCTs) for evaluating the efficacy and safety of lesinurad 200 mg + XOI, lesinurad 400 mg + XOI, and XOI monotherapy in hyperuricemic patients with gout. Results: Three RCTs including a total of 1,537 patients fulfilled the inclusion criteria. The number of patients who had achieved a target serum uric acid (sUA) level was significantly higher in the lesinurad 40 mg + XOI and lesinurad 200 mg + XOI groups than in the XOI monotherapy group (R 4.55, 95% credible interval (CrI) 2.13 – 9.81 and OR 2.78, 95% CrI 1.28 – 5.71, respectively). The ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that lesinurad 400 mg + XOI was more likely to achieve the best target sUA level (SUCRA = 0.968), followed by lesinurad 200 mg + XOI (SUCRA = 0.526), and XOI (SUCRA = 0.006). The frequency of treatment-emergent adverse events (TEAEs) in the XOI group was significantly lower than that in the lesinurad 400 mg + XOI group (OR 0.59, 95% CrI 0.39 – 0.90). Conclusion: Lesinurad 200 mg + XOI and lesinurad 400 mg + XOI were more effective than XOI for hyperuricemic patients with gout, but lesinurad 400 mg + XOI had a significant risk of TEAE development.