Lesinurad combination therapy with allopurinol in gout: do CLEAR studies make the treatment of gout clearer?

Gout is an often forgotten disease, despite being the most common inflammatory arthritis in adults in the Western world. Lesinurad, a new urate-lowering therapy (ULT), is now approved for the treatment of gout in the USA and the European Union, 6 and is in phase III programmes as a combination therapy in many other countries. Lesinurad is a selective inhibitor of urate/anion exchanger 1 and organic acid transporter 4, two urate transporters responsible for the reabsorption of urate from the proximal renal tubule. Probenecid and benzbromarone are the other uricosurics available for use in gout as monotherapy or combination with allopurinol in case of an inadequate response to allopurinol. In the current issue of the journal, Bardin et al present the results of a 12-month, randomised, phase III trial efficacy and safety of oral lesinurad (200 or 400 mg) in combination with allopurinol. Combining Lesinurad with Allopurinol in Inadequate Responders (CLEAR) were two replicate studies, one in the USA (CLEAR-1) and one in Europe (CLEAR-2), published in the current issue of this journal. CLEAR-2 compared daily lesinurad (200 or 400 mg orally) with placebo when added to allopurinol in 610 patients with gout with serum uric acid (sUA) above target (<6 mg/dL or <0.36 mmol/L) and frequent gout flares (≥2 gout flares in the prior year).