OBJECTIVE: To review the pharmacology, efficacy, and safety of lesinurad and determine its role relative to other agents in the management of chronic gout. DATA SOURCES: A PubMed search (1946 to February 2018) using the terms lesinurad and RDEA594 was conducted to identify relevant articles. STUDY SELECTION AND DATA EXTRACTION: In vitro or in vivo evaluations of lesinurad published in the English language were eligible for inclusion. Phase II and III trials were selected for review of efficacy and safety. DATA SYNTHESIS: Five clinical trials were evaluated. In 4 trials in which lesinurad was used in combination with a xanthine oxidase inhibitor (XOI), a greater percentage of patients receiving lesinurad 200 mg (54.0%-63.0%) compared with placebo (23.3%-46.8%) achieved a serum uric acid (sUA) level of <6 mg/dL at 1 to 6 months. In one trial involving lesinurad used as monotherapy, a sUA level of <6 mg/dL was achieved by a significantly greater percentage of patients receiving lesinurad 400 mg (29.9%) compared with placebo (1.9%) at 6 months. When used as combination therapy, the drug had an acceptable safety profile, with upper-respiratory-tract infection, nasopharyngitis, and hypertension occurring most commonly and transient renal-related events detected less frequently. CONCLUSIONS: Lesinurad has a novel mechanism of action and is safe and effective for the treatment of chronic gout. At this time, lesinurad may be considered as an add-on therapy for patients who have an inadequate response to maximum tolerated doses of a XOI.
OBJECTIVE: To review the pharmacology, efficacy, and safety of lesinurad and determine its role relative to other agents in the management of chronic gout. DATA SOURCES: A PubMed search (1946 to February 2018) using the terms lesinurad and RDEA594 was conducted to identify relevant articles. STUDY SELECTION AND DATA EXTRACTION: In vitro or in vivo evaluations of lesinurad published in the English language were eligible for inclusion. Phase II and III trials were selected for review of efficacy and safety. DATA SYNTHESIS: Five clinical trials were evaluated. In 4 trials in which lesinurad was used in combination with a xanthine oxidase inhibitor (XOI), a greater percentage of patients receiving lesinurad 200 mg (54.0%-63.0%) compared with placebo (23.3%-46.8%) achieved a serum uric acid (sUA) level of <6 mg/dL at 1 to 6 months. In one trial involving lesinurad used as monotherapy, a sUA level of <6 mg/dL was achieved by a significantly greater percentage of patients receiving lesinurad 400 mg (29.9%) compared with placebo (1.9%) at 6 months. When used as combination therapy, the drug had an acceptable safety profile, with upper-respiratory-tract infection, nasopharyngitis, and hypertension occurring most commonly and transient renal-related events detected less frequently. CONCLUSIONS:Lesinurad has a novel mechanism of action and is safe and effective for the treatment of chronic gout. At this time, lesinurad may be considered as an add-on therapy for patients who have an inadequate response to maximum tolerated doses of a XOI.
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Keywords:
arthritis; clinical pharmacology; drug development and approval; gout; literature evaluation