Safety Of Lesinurad Research Articles

Efficacy and Safety of Lesinurad in Patients with Hyperuricemia Associated with Gout: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

To evaluate the efficacy and safety of lesinurad for the treatment of hyperuricemia in patients with gout. Systematic review and meta-analysis of randomized controlled trials (RCTs). Five RCTs, which included 1959 patients, compared the efficacy and safety of lesinurad in patients with hyperuricemia associated with gout. Relevant studies were identified from PubMed, EMBASE, Cochrane Library databases, and the ClinicalTrials.gov registry. Two reviewers independently assessed the studies. Individual effect sizes were standardized, and a meta-analysis was conducted to calculate the pooled effect size by using a random-effect model. The primary outcomes were the proportion of patients achieving target serum uric acid (sUA) levels by month 6 and the mean sUA levels at month 6 and month 12. Gout-related outcomes were also assessed. The secondary outcome was the number of treatment-emergent adverse events (TEAEs). Compared with xanthine oxidase inhibitor (XOI) monotherapy, lesinurad 200mg or 400mg in combination with allopurinol or febuxostat exhibited a higher proportion of patients achieving target sUA levels of < 6.0mg/dl or < 5.0mg/dl, respectively, by month 6. Lesinurad-plus-XOI groups also significantly sustained lower mean sUA levels at month 6 and month 12 compared to XOI alone group. In gout-related outcomes, no significant treatment group differences favored lesinurad. The number of TEAEs was comparable between the lesinurad 200mg-plus-XOI group and the XOI-monotherapy group. Although lesinurad 400mg monotherapy demonstrated superior efficacy compared with placebo, significantly more TEAEs occurred. Although the combination of lesinurad 200mg and XOI is effective and well tolerated for treating patients with gout who have not achieved an adequate response to XOI monotherapy, clinical gout-related outcomes were not improved. Therefore, additional studies investigating the long-term clinical implication of lesinurad are warranted.

Lesinurad: A Novel Agent for Management of Chronic Gout.

To review the pharmacology, efficacy, and safety of lesinurad and determine its role relative to other agents in the management of chronic gout. A PubMed search (1946 to February 2018) using the terms lesinurad and RDEA594 was conducted to identify relevant articles. 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. 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. 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.

Lesinurad monotherapy in gout patients intolerant to a xanthine oxidase inhibitor: a 6 month phase 3 clinical trial and extension study

To investigate the efficacy and safety of lesinurad, a selective uric acid reabsorption inhibitor, in a 6 month, phase 3 clinical trial and extension study. Patients with gout who cannot take a xanthine oxidase inhibitor (XOI) and have serum uric acid (sUA) ⩾6.5 mg/dl were randomized to receive oral lesinurad (400 mg daily) or placebo. The primary endpoint was the proportion of patients with sUA <6.0 mg/dl at month 6. Safety assessments included treatment-emergent adverse events (TEAEs) and laboratory data. Patients who completed the study were eligible for an open-label, uncontrolled extension study of lesinurad 400 mg monotherapy. Patients (n = 214) were primarily white males (mean age 54.4 years; gout duration 11.2 years). Significantly more patients achieved the primary endpoint with lesinurad than placebo (29.9 vs 1.9%; P < 0.0001). Overall TEAE rates were higher with lesinurad (77.6 vs 65.4%); renal-related TEAEs (17.8%), renal-related serious TEAEs (4.7%) and serum creatinine elevations (1.5 times baseline, 24.3%) occurred only with lesinurad. A total of 143 patients (65 lesinurad, 78 placebo) enrolled in the extension study. Treatment with lesinurad 400 mg resulted in rapid and sustained sUA lowering that persisted for up to 18 months before the study was terminated prematurely. No new safety findings were observed in the extension. In patients with gout and intolerance/contraindication to XOIs, lesinurad 400 mg monotherapy demonstrated superior sUA lowering compared with placebo, with sustained effects for up to 18 months. Due to a high incidence of serum creatinine elevations and renal-related adverse events, including serious adverse events with lesinurad 400 mg, lesinurad should not be used as monotherapy. ClinicalTrials.gov (http://clinincaltrials.gov), NCT01508702.

Pharmacodynamic, pharmacokinetic and tolerability evaluation of concomitant administration of lesinurad and febuxostat in gout patients with hyperuricaemia

The aim of this study was to evaluate the pharmacodynamics (PDs), pharmacokinetics (PKs) and safety of lesinurad (selective uric acid reabsorption inhibitor) in combination with febuxostat (xanthine oxidase inhibitor) in patients with gout. This study was a phase IB, multicentre, open-label, multiple-dose study of gout patients with serum uric acid (sUA) >8 mg/dl following washout of urate-lowering therapy with colchicine flare prophylaxis. Febuxostat 40 or 80 mg/day was administered on days 1-21, lesinurad 400 mg/day was added on days 8-14 and then lesinurad was increased to 600 mg/day on days 15-21. sUA, urine uric acid and PK profiles were evaluated at the end of each week. Safety was assessed by adverse events, laboratory tests and physical examinations. Initial treatment with febuxostat 40 or 80 mg/day monotherapy resulted in 67% and 56% of subjects, respectively, achieving a sUA level <6 mg/dl. Febuxostat 40 or 80 mg/day plus lesinurad 400 or 600 mg/day resulted in 100% of subjects achieving sUA <6 mg/dl and up to 100% achieving sUA <5 mg/dl. No clinically relevant changes in the PKs of either drug were noted. The combination was well tolerated. The clinically important targets of sUA <6 mg/dl and <5 mg/dl are achievable in 100% of patients when combining lesinurad and febuxostat.

FRI0370 Efficacy and safety of lesinurad (RDEA594), a novel URAT1 inhibitor, in combination with allopurinol in allopurinol-refractory gout patients: Results from a randomized, blinded, placebo-controlled, phase 2b extension study

BackgroundLesinurad (LESUR) is an oral investigational URAT1 inhibitor for the treatment of gout. A Phase 2B study in 208 gout patients with an inadequate response to allopurinol (ALLO) (200-600 mg/day...