Optimizing gout treatment: A comprehensive review of current and emerging uricosurics

Gout is the most common inflammatory arthritis, affecting approximately 5.1% of adults in the United States (US) population. Gout is a metabolic and autoinflammatory disease. Elevated uric acid pools lead to the precipitation of monosodium urate (MSU) crystals in and around joints, as well as other tissues, and the subsequent autoinflammatory response. Since elevated serum urate (SU) levels (hyperuricemia) correspond with gout severity, urate-lowering therapies (ULTs) are the cornerstone of gout treatment. ULTs include xanthine oxidoreductase inhibitors, uricosurics, less commonly used in the US but widely used in Europe and Asia, including benzbromarone, dotinurad, and probenecid (the only US Food and Drug Administration (FDA) approved uricosuric in the US), and uricases, including rasburicase and pegloticase (available only in the US). Over 90% of the daily load of uric acid filtered by the kidneys is reabsorbed through renal transporters. These urate transporters include uric acid transporter 1 (URAT1), glucose transporter 9, and organic anion transporters 1, 3, and 4 (OAT1, OAT3, OAT4). They are the target of approved and in-the-pipeline uricosurics. Any drug that increases renal excretion of uric acid, independently of the mechanism through which it exerts its effect, may be considered a uricosuric drug. This review discusses drugs that increase renal excretion of uric acid, either approved or in development, as well as off-label drugs with uricosuric properties.