THU0444 Integrated safety of lesinurad, a novel uric acid reabsorption inhibitor for the treatment of gout
Authors: MA Becker, RT Keenan, PP Khanna, R Malamet, K Bos, J Li, J Hu, WB White
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Lesinurad is a selective uric acid reabsorption inhibitor recently approved at 200 mg daily in combination with a xanthine oxidase inhibitor (XOI) for treatment of hyperuricemia associated with gout in patients who have not achieved target serum uric acid on an XOI (allopurinol or febuxostat) alone. <h3>Objectives</h3> To investigate the safety profile of lesinurad (LESU), we integrated safety data based on: (1) 3 large, pivotal, placebo-controlled, 12-month phase III (core) trials evaluating LESU 200 mg and LESU 400 mg in combination with an XOI; and (2) 2 extension studies, in which LESU-treated patients continued to receive LESU + XOI at the same dose and initially placebo-treated patients were randomized to receive LESU 200 mg or LESU 400 mg in addition to the XOI provided in the preceding core trial. <h3>Methods</h3> Safety data were pooled from the 3 core studies and 2 12-month extension studies using descriptive statistics for patients receiving ≥1 dose of study medication. To adjust for varying treatment durations, treatment-emergent adverse events (TEAEs) are expressed as exposure-adjusted incidence rates (number of subjects with events per 100 person-years [PY]). <h3>Results</h3> In the core studies, adverse event rates were comparable for XOI alone and LESU 200 mg + XOI groups for any TEAEs, serious TEAEs, and TEAEs leading to discontinuation (Table 1). Adverse event rates were higher with LESU 400 mg + XOI. Major adverse cardiovascular event (MACE) rates, which included cardiovascular death, myocardial infarction, or stroke, in the core studies were 0.71 (95% CI 0.15, 2.08), 0.96 (0.26, 2.47), and 1.94 (0.84, 3.82) per 100 PY for XOI alone, LESU 200 mg + XOI, and LESU 400 mg + XOI, respectively. Renal-related TEAE rates in the core studies were 5.6, 7.3, and 15.4 per 100 PY, respectively. Longer exposure in the core + extension studies did not result in increases in any TEAEs, serious TEAEs, or TEAEs leading to discontinuation (Table 2). MACE rates were low in the core + extension studies, at 1.05 (95% CI 0.50, 1.93) and 1.48 (0.81, 2.48) in the LESU 200 mg + XOI and LESU 400 mg + XOI groups, respectively. Renal events in the core + extension studies were lower in the LESU 200 mg + XOI than LESU 400 mg + XOI group at 8.6 and 14.6, respectively. <h3>Conclusions</h3> Lesinurad at the approved dose of 200 mg once daily demonstrated a consistent, acceptable safety profile. There were no new safety concerns in the extension studies. <h3>Acknowledgements</h3> This study was funded by Ardea Biosciences/AstraZeneca. <h3>Disclosure of Interest</h3> M. Becker Grant/research support from: Takeda, Savient, Ardea/AstraZeneca, Consultant for: Takeda, Savient, Horizon, Ardea/AstraZeneca, CymaBay, Pfizer, R. Keenan Consultant for: AstraZeneca, Ironwood, Horizon, P. Khanna Grant/research support from: AstraZeneca, R. Malamet Employee of: AstraZeneca, K. Bos Employee of: AstraZeneca, J. Li Employee of: AstraZeneca, J. Hu Employee of: Ardea Biosciences, W. White Consultant for: AstraZeneca