For patients with gout, new evidence suggests arhalofenate can be used to safely prevent flare-ups, as well as reduce serum levels.
A Phase IIb study published in the April 7 issue of Nature Reviews Rheumatology demonstrated the dual mode of action of arhalofenate has a significant advantage over other urate-lowering therapies that can prompt an initial increase in flare-up risk. That spike occurs due to mobilization of stored urate and shrinkage of intra-articular urate crystals, causing phagocytosis and an inflammatory response.
Overall, researchers said, gout is an overlooked and poorly-managed disease, and these new findings could alter treatment.
In a 12-week, double-blind study, 239 participants were randomly assigned to four different treatment protocols: once-daily arhalofenate 600 mg or 800 mg, allopurinol 300 mg, allopurinol 600 mg plus colchicine 0.6 mg, or a placebo. Participants must have experienced more than three gout flare-ups during the previous year, could not have taken colchicine or urate-lowering therapy, and had baseline serum uric acid levels between 7.5 mg/dl and 12.0 mg/dl.
“All of a sudden, we were killing two birds with one stone,” said corresponding study author Pol Boudes, M.D. “IL-1ß is the cytokine that is key to triggering gout flare. The demonstration (in mice) that arholafenate was acting as a brake on local release of IL-1ß following an inflammatory challenge with urate crystals was very relevant to making this drug an ideal candidate for gout.”
According to study results, flare incidence was significantly lower in the high-dose arhalofenate group (0.66) than in the allopurinol-only group (1.24, P=0.0056) or the placebo group (1.13, P=0.0049). It was similar to the allopurinol plus colchicine group (0.40, P=0.091). The arhalofenate 600 mg group experienced a non-significant 16 percent reduction in flare incidence versus allopurinol.
The next step, researchers said, is a Phase III study to determine if the combination treatment could significantly improvement gout management.