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Lesinurad, a Selective Uric Acid Reabsorption Inhibitor, in Combination With Febuxostat in Patients With Tophaceous Gout: Findings of a Phase III Clinical Trial.

ABSTRACT: To investigate the efficacy and safety of lesinurad in combination with febuxostat in a 12-month phase III trial in patients with tophaceous gout.Patients with serum urate (UA) ?8.0 mg/dl (?6.0 mg/dl with urate-lowering therapy) and ?1 measurable target tophus were given febuxostat 80 mg/day for 3 weeks before randomization to receive lesinurad (200 or 400 mg daily) or placebo in addition to the febuxostat. The primary end point was the proportion of patients achieving a serum UA level of <5.0 mg/dl (month 6). The key secondary end point was the proportion of patients with complete resolution of ?1 target tophus (month 12). Other end points included the percentage change in total target tophi area. Safety assessments included adverse events and laboratory data.Patients (n?=?324) were predominantly male, with a mean age of 54.1 years. Significantly more patients achieved the serum UA target by month 6 with the addition of lesinurad 400 mg (76.1%; P?

SUBMITTER: Dalbeth N

PROVIDER: S-EPMC5601200 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Lesinurad, a Selective Uric Acid Reabsorption Inhibitor, in Combination With Febuxostat in Patients With Tophaceous Gout: Findings of a Phase III Clinical Trial.

Dalbeth Nicola N Jones Graeme G Terkeltaub Robert R Khanna Dinesh D Kopicko Jeff J Bhakta Nihar N Adler Scott S Fung Maple M Storgard Chris C Baumgartner Scott S Perez-Ruiz Fernando F

Arthritis & rheumatology (Hoboken, N.J.) 20170804 9

<h4>Objective</h4>To investigate the efficacy and safety of lesinurad in combination with febuxostat in a 12-month phase III trial in patients with tophaceous gout.<h4>Methods</h4>Patients with serum urate (UA) ≥8.0 mg/dl (≥6.0 mg/dl with urate-lowering therapy) and ≥1 measurable target tophus were given febuxostat 80 mg/day for 3 weeks before randomization to receive lesinurad (200 or 400 mg daily) or placebo in addition to the febuxostat. The primary end point was the proportion of patients ac ...[more]

PMID: 28597604

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Project description:BACKGROUND:In gout, long-term urate-lowering therapy (ULT) promotes dissolution of tissue urate crystal deposits. However, no studies using combined xanthine oxidase inhibition and uricosuric ULT have focused on clinical outcomes or adverse events (AEs) beyond 12?months of therapy. Our objective in the present study was to examine efficacy and long-term safety in patients with tophaceous gout receiving febuxostat plus lesinurad as combination therapy. METHODS:Patients receiving combined lesinurad and febuxostat in the 12-month core CRYSTAL study continued at the same doses in the extension study ("200CONT", "400CONT"), whereas those receiving only febuxostat 80?mg were randomized to lesinurad 200 or 400?mg with febuxostat ("200CROSS", "400CROSS"). The primary endpoint was the proportion of patients experiencing complete resolution (CR) of at least one target tophus by extension month (EM) 12. The key secondary endpoint was mean rate of gout flares requiring treatment from the end of EM 2 to the end of EM 12. Secondary endpoints included reduction in the sum of areas for all target tophi. Safety assessments included AEs and laboratory data for the entire extension study (median length of lesinurad exposure, 800?days). RESULTS:Of 235 patients completing the core study, 196 (83.4%) enrolled in the extension: 200CONT (n?=?64), 200CROSS (n?=?33), 400CONT (n?=?65), and 400CROSS (n?=?34). At EM 12, 59.6%, 43.5%, 66.7%, and 50.0% of patients, respectively, had CR of at least one target tophus. The sum of areas for all target tophi was reduced by 76.4%, 58.1%, 77.5%, and 62.8%, respectively. The adjusted mean (SE) rates of gout flares requiring treatment from the end of EM 2 to the end of EM 12 were 0.6 (0.19), 1.3 (0.48), 0.2 (0.08), and 1.9 (0.93), respectively. Target sUA <?5.0?mg/dl was achieved by 77.1%, 79.2%, 88.5%, and 71.4% of patients, respectively. Exposure-adjusted incidence rates of treatment-emergent adverse events (TEAEs) and renal-related TEAEs in the core study were not increased with prolonged lesinurad exposure in the extension study. CONCLUSIONS:Patients receiving lesinurad plus febuxostat therapy for 2?years continued to be at sUA target. Patients exhibited a progressive increase in CR of at least one target tophus, progressive reduction in tophus size, and reduction of gout flares requiring treatment over the second year, with AEs consistent with those observed in the core study. TRIAL REGISTRATION:ClinicalTrials.gov , NCT01510769 . Registered on 13 January 2012.

Dataset Information

Lesinurad, a Selective Uric Acid Reabsorption Inhibitor, in Combination With Febuxostat in Patients With Tophaceous Gout: Findings of a Phase III Clinical Trial.

Publications

Lesinurad, a Selective Uric Acid Reabsorption Inhibitor, in Combination With Febuxostat in Patients With Tophaceous Gout: Findings of a Phase III Clinical Trial.

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