New Option for Gout Patients
Managing the painful symptoms of gout can be challenging because many patients struggle to achieve the American College of Rheumatology's (ACR) recommended target serum uric acid (sUA) level of less than 6.0 mg/dL.
Current front-line medications for the condition are xanthine oxidase inhibitors (XOI), specifically allopurinol and febuxostat (Uloric), which work to increase urinary uric acid excretion, as well as enzymatically break down the uric acid, itself.
Lesinurad (Zurampic), a novel therapeutic option for gout, is the first selective uric acid reabsorption inhibitor of its kind to be approved by the FDA, which occurred in a somewhat mixed 10 to 4 advisory committee vote on October 23, 2015.
The reservations about lesinurad were related to concern about its long-term safety. It appears lesinurad’s safety is dose-dependent, such that oral 400-mg doses result in more AEs than 200 mg once daily doses for patients taking it in combination with an XOI.
The drug shows therapeutic efficacy, according to abstracts presented at this year’s ACR meeting. One abstract reported the results of 2 Phase III trials showing a noticeably higher proportion of patients given lesinurad achieving sUA levels <6.0 mg/dL at 6 and 12 months into therapy compared with placebo-treated patients.1
- At 6 months, 44 of 74 patients (59.5%) taking lesinurad 200 mg with an XOI and 46 of 69 patients (66.7%) taking lesinurad 400 mg with an XOI achieved sUA levels <6.0 mg/dL, compared to 26 of 77 patients (33.8%) taking a placebo with an XOI (with a <60 mL/min estimated creatinine clearance [eCrCl]).
- The results were comparable at 12 months, with 39 of 74 patients (52.7%) taking lesinurad 200 mg and 37 of 69 patients (53.6%) taking lesinurad 400 mg achieving sUA levels <6.0 mg/dL compared to 33.8% of patients on placebo same as 6 and 12 months (same eCrCl).
Patients may be at higher risk of dangerous elevations in serum creatinine levels, something that appeared evident with 400-mg regimens of the drug. These elevations do appear to be predominantly reversible.2
The drug appears to remain effective over time. An interim analysis of a lesinurad and febuxostat combination extension study showed consistent sUA targets over 2 plus years of therapy with a consistency with the core AE profile of the previous studies.3 However, there still is a question as to whether the drug should be widely prescribed, given the scant evidence supporting its safety in treatment of gout with various other comorbid conditions.