Systematic review and model-based analysis to identify whether renal safety risks of URAT1 inhibitors are fully determined by uric acid-lowering efficacies
Authors' conclusion
Uric acid-lowering efficacy is not an independent factor for the renal safety risk of different URAT1 inhibitors, and structural differences could be responsible for the difference.
Study context
- Population
- Patients with hyperuricemia in published RCTs of URAT1 inhibitors
- Participants
- 1,264 / 284 / 421 / 213 / 393
- Comparison
- Lesinurad, verinurad, dotinurad, SHR4640 and benzbromarone
- Lesinuradn = 1,264
- Verinuradn = 284
- Dotinuradn = 421
- SHR4640n = 213
- Benzbromaronen = 393
- Outcome
- Incidence of renal safety events
Methodological detailssemi-mechanistic pharmacokinetic/pharmacodynamic model
- Semi-mechanistic pharmacokinetic/pharmacodynamic model
Pooled result
As reported in the abstract
Overall renal safety event incidence
Further pooled results
Modelled uric acid-lowering efficacy, intermediate once-daily dose (ranking)
- Efficacy ranking: 2 mg dotinurad > 10 mg verinurad > 5 mg SHR4640 > 400 mg lesinurad
Reduction in 24-h cumulative renal uric acid excretion with XOI combination
%
- 80 mg febuxostat combination
- 48.4
- 600 mg allopurinol combination
- 48.3
Original publication
Systematic review and model-based analysis to identify whether renal safety risks of URAT1 inhibitors are fully determined by uric acid-lowering efficacies. Semin Arthritis Rheum. Published 13 October 2023. doi:10.
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