Gout is a painful form of arthritis caused by the buildup of too much uric acid in the body, and usually appears first as redness, soreness, and swelling in the big toe. Uric acid in the blood is produced by the breakdown of substances called purines, which are found in all the body’s tissues. Uric acid usually
dissolves in the blood then passes through the kidneys and out of the body in urine. Uric acid can build up in the blood, a condition called hyperuricemia. This occurs when the body increases the amount of uric acid it makes, the kidneys do not get rid of enough uric acid, or a person eats too many foods high in purines. Most people with hyperuricemia do not develop gout, but if uric acid forms crystals in the body, gout can develop.
Gout may also have a genetic background, contributing to about 60% of variability in uric acid levels. Three genes called SLC2A9, SLC22A12, and ABCG2 have been found commonly associated with gout, and variations in them can approximately double the risk. Loss-of-function mutations in SLC2A9 and SLC22A12 cause hereditary hypouricaemia by reducing urate absorption and unopposed rate secretion (read a phantastic free overview study in Nature Reviews Rheumatology from 2012). A few rare genetic disorders, including familial juvenile hyperuricemic nephropathy, medullary cystic kidney disease, phosphoribosylpyrophosphate synthetase superactivity, and hypoxanthine-guanine phosphoribosyltransferase deficiency as seen in Lesch-Nyhan syndrome, are complicated by gout.
Lesinurad (Zurampic) works by helping the kidney excrete uric acid. It does this by inhibiting the function of transporter proteins involved in uric acid reabsorption in the kidney. The efficacy for Lesinurad (Zurampic) was evaluated in three randomized, placebo-controlled studies in combination with a XOI involving 1,537 participants for up to 12 months. Participants treated with Lesinurad (Zurampic) in combination with a XOI experienced reduced serum uric acid levels compared to placebo.
The most common adverse reactions in clinical trials were headache, influenza, increased blood creatinine, and gastroesophageal reflux disease. Lesinurad (Zurampic) has a boxed warning that provides important safety information for health care professionals, including the risk for acute kidney (renal) failure, which is more common when used without an XOI and with higher than approved doses of Lesinurad (Zurampic). The FDA is also requiring a postmarketing study to further evaluate the renal and cardiovascular safety of Lesinurad (Zurampic).
Very recently, the European Medicine Agency (EMA) also issued a positive opinion on Lesinurad (Zurampic);