New Urate-Lowing Therapies

Abhishek Abhishek


Curr Opin Rheumatol. 2018;30(2):177-182. 

In This Article

Abstract and Introduction


Purpose of review: To discuss recent studies of lesinurad and arhalofenate.

Recent findings: Lesinurad acts by blocking urate reabsorption channels URAT-1 and OAT-4. It has urate-lowering effect when used alone and in combination with xanthine oxidase inhibitors (XOIs). Its uricosuric activity depends on glomerular filtration, and its' efficacy is impaired at eGFR less than 30 ml/min. Lesinurad monotherapy (400 mg/day) associates with serum creatinine elevations. However, this risk is substantially attenuated with coprescription of a XOI and when prescribed at a dose of 200 mg/day. Given its' modest urate-lowering effect, and the risk of serum creatinine elevation when used alone, it is licenced for use in combination with XOI for people unable to achieve target serum uric acid with XOI alone. Lesinurad does not have the drug interactions associated with probenecid, however, it is metabolized by CYP2C9, and should be used with caution if CYP2C9 inhibitors are coprescribed. Arhalofenate also acts by blocking URAT-1; however, it also blocks the NALP-3 inflammasome providing gout-specific anti-inflammatory effect. Arhalofenate has a weaker urate-lowering effect than lesinurad and further phase III evaluation is planned.

Summary: Lesinurad provides an additional option for people with gout unable to achieve target serum uric acid with XOI alone.


Gout is the commonest inflammatory arthritis and affects 2.5–3.9% adults in the United Kingdom and the United States of America.[1,2] It occurs as a consequence of hyperuricaemia and is the only form of arthritis that has the potential of being cured with urate-lowering treatment (ULT) in the long term. Although most people with gout have reduced urinary urate excretion, historically, the greater efficacy and safety of xanthine oxidase inhibitors (XOIs) allopurinol and febuxostat compared with the uricosuric drugs such as probenecid, sulfinpyrazone, and benzbromarone have resulted in the XOIs being the first choice pharmacologic ULT.[3–6] The purpose of this review is to discuss lesinurad, a recently licenced uricosuric ULT, and arhalofenate, an emerging uricosuric anti-inflammatory ULT.[7*,8,9*,10–12,13*,14] Of these, lesinurad has been approved by the US Food and Drug Administration (FDA) in December 2015 and by the European Medicines Agency in February 2016 for the management of hyperuricaemia in gout. It is indicated in combination with another XOI in people who have not achieved the target serum uric acid (SUA) level with an XOI alone.