Emily Huneycutt1, Chase Board2, Jennifer N Clements3. 1. 1 Lebanon Veterans Affairs Medical Center, Lebanon, PA, USA. 2. 2 Presbyterian College School of Pharmacy, Clinton, SC, USA. 3. 3 Department of Pharmacy Practice, Presbyterian College School of Pharmacy, Clinton, SC, USA.
Abstract
OBJECTIVE: To review the pharmacokinetics, clinical efficacy, safety, and role of lesinurad for the management of hyperuricemia associated with gout. DATA SELECTION: A MEDLINE search (2000 to April 2017) was conducted using the terms hyperuricemia, gout, URAT-1, URAT-1 transporter, and lesinurad. Published articles and scientific posters relevant to the efficacy and safety of lesinurad were reviewed and summarized. DATA SYNTHESIS: Lesinurad was evaluated in 3 randomized, phase 3 clinical trials (CRYSTAL, CLEAR 1 and 2). The primary endpoint for CRYSTAL trial was the percentage of patients achieving serum uric acid (SUA) concentration ≤ 5 mg/dL. The CLEAR 1 and 2 trials had a primary endpoint of percentage of patients achieving SUA concentration ≤ 6 mg/dL. Lesinurad at either 200 or 400 mg/d was superior to xanthine oxidase inhibitor (XOI) monotherapy in reducing the SUA concentration to 5 or 6 mg/dL, when added to either allopurinol or febuxostat. CONCLUSION: Data from phase 3 clinical studies suggest the addition of lesinurad to allopurinol or febuxostat is superior to XOI monotherapy alone in reducing SUA concentrations while increasing the risk of renal-related adverse events. Lesinurad, 200 mg orally per day, would be a safe recommendation, in combination with an XOI, among patients with adequate renal function (i.e., above 45 mL/min) who need additional therapy for inadequately controlled hyperuricemia associated with gout.
OBJECTIVE: To review the pharmacokinetics, clinical efficacy, safety, and role of lesinurad for the management of hyperuricemia associated with gout. DATA SELECTION: A MEDLINE search (2000 to April 2017) was conducted using the terms hyperuricemia, gout, URAT-1, URAT-1 transporter, and lesinurad. Published articles and scientific posters relevant to the efficacy and safety of lesinurad were reviewed and summarized. DATA SYNTHESIS: Lesinurad was evaluated in 3 randomized, phase 3 clinical trials (CRYSTAL, CLEAR 1 and 2). The primary endpoint for CRYSTAL trial was the percentage of patients achieving serum uric acid (SUA) concentration ≤ 5 mg/dL. The CLEAR 1 and 2 trials had a primary endpoint of percentage of patients achieving SUA concentration ≤ 6 mg/dL. Lesinurad at either 200 or 400 mg/d was superior to xanthine oxidase inhibitor (XOI) monotherapy in reducing the SUA concentration to 5 or 6 mg/dL, when added to either allopurinol or febuxostat. CONCLUSION: Data from phase 3 clinical studies suggest the addition of lesinurad to allopurinol or febuxostat is superior to XOI monotherapy alone in reducing SUA concentrations while increasing the risk of renal-related adverse events. Lesinurad, 200 mg orally per day, would be a safe recommendation, in combination with an XOI, among patients with adequate renal function (i.e., above 45 mL/min) who need additional therapy for inadequately controlled hyperuricemia associated with gout.
Authors: Robert Terkeltaub; Kenneth G Saag; David S Goldfarb; Scott Baumgartner; Bruce M Schechter; Ritu Valiyil; Diana Jalal; Michael Pillinger; William B White Journal: Rheumatology (Oxford) Date: 2019-01-01 Impact factor: 7.580