THU0537 Clinical Response of Tophus and Flares To Extended Use of Lesinurad in Combination with A Xanthine Oxidase Inhibitor in Patients with Gout
Authors: T. Bardin, N. Dalbeth, R. Terkeltaub, C. Storgard, M. Fung, J. Hu, F. Perez-Ruiz
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Three randomized, double-blind, Phase III trials reported that greater proportions of patients treated with lesinurad 200 mg (LESU200) or 400 mg (LESU400), combined with the xanthine oxidase inhibitor (XOI) allopurinol (ALLO; CLEAR 1 and 2) or febuxostat (FBX; CRYSTAL), achieved serum uric acid (sUA) targets at 6 months versus xanthine oxidase inhibitor (XOI) + placebo (PBO). <h3>Objectives</h3> To evaluate the impact of long-term treatment with lesinurad + XOI on tophus and flares for at least 1 year and up to 2 years. <h3>Methods</h3> Patients completing 12 months in the core CLEAR and CRYSTAL studies could enroll in respective uncontrolled, open-label extension studies (NCT01808131; NCT01808144). Patients randomized to LESU200 + XOI or LESU400 + XOI in the core studies who continued on combination therapy in the extension studies were analyzed. Efficacy endpoints included: (1) proportions of patients with complete resolution (CR) of ≥1 target tophus (i.e. measurable tophus on hands/wrists and/or feet/ankles 5–20 mm in longest diameter), (2) percent reductions in the total area of all target tophi, and (3) proportions of patients experiencing gout flares requiring treatment (GFRT). <h3>Results</h3> A total of 239 (LESU200+ALLO) and 232 (LESU400+ALLO) patients continued in the CLEAR extension; 64 (LESU200+FBX) and 65 (LESU400+FBX) patients continued in the CRYSTAL extension. Proportions of patients with CR of ≥1 target tophus increased from end of core study (1 year) to 2 years: from 25.0% to 43.8% in LESU200+ALLO and 30.3% to 36.4% in LESU400+ALLO, and from 26.6% to 53.1% in LESU200+FBX and 35.4% to 58.5% in LESU400+FBX (LOCF). Percent reduction in the total area of all target tophi versus baseline changed from end of core study to 2 years: from 11.6% to 41.8% in LESU200+ALLO and 42.7% to 49.3% in LESU400+ALLO, and from 54.8% to 68.3% in LESU200+FBX and 58.6% to 72.4% in LESU400+FBX (LOCF). Proportions of subjects with a GFRT per month decreased during continued combination treatment in both extension studies (Figure). The proportions of patients with a GFRT during Months 1, 12, and 24 were, respectively, 16.3, 7.9, and 5.6 in LESU200+ALLO; 18.1, 6.9, and 3.0 in LESU400+ALLO; 26.6, 10.9, 6.3 in LESU200+FBX; and 36.9, 4.6, 1.9 in LESU400+FBX. Extended treatment with LESU + XOI did not result in increased exposure-adjusted incidence rates of adverse events (AEs), AEs leading to discontinuation of lesinurad, serious AEs, or clinical laboratory abnormalities. <h3>Conclusions</h3> The CLEAR and CRYSTAL extension studies showed that patients treated with lesinurad + XOI for up to 2 years exhibited continued increases in the rate of complete resolution of tophi and reduction in tophus area, as well as decreased rates of GFRT. <h3>Acknowledgement</h3> This study was funded by Ardea Biosciences/AstraZeneca. Editorial support was provided by PAREXEL and was funded by AstraZeneca. <h3>Disclosure of Interest</h3> T. Bardin Grant/research support from: Ipsen, Menarini., Consultant for: AstraZeneca, Ipsen, Menarini, Novartis, Savient, Sobi, Takeda, Cymabay., N. Dalbeth Grant/research support from: AstraZeneca, Fonterra, Novartis., Consultant for: AstraZeneca, Fonterra, Pfizer, Takeda, Crealta, Cymabay., Speakers bureau: AstraZeneca, Teijin., R. Terkeltaub Consultant for: Ardea Biosciences, AstraZeneca, Takeda, Relburn, REVIVE., C. Storgard Employee of: Ardea Biosciences, a member of the AstraZeneca Group., M. Fung Employee of: Ardea Biosciences, a member of the AstraZeneca Group., J. Hu Employee of: Ardea Biosciences, a member of the AstraZeneca Group., F. Perez-Ruiz Consultant for: AstraZeneca, Menarini, Pfizer., Speakers bureau: AstraZeneca, Menarini, Pfizer.