A Randomized, Double‐Blind, Active‐ and Placebo‐Controlled Efficacy and Safety Study of Arhalofenate for Reducing Flare in Patients With Gout

Abstract

ObjectiveArhalofenate is a novel antiinflammatory uricosuric agent. The objective of this study was to evaluate its antiflare activity in patients with gout.MethodsThis was a 12‐week, randomized, double‐blind, controlled phase IIb study. Eligible patients had had ≥3 flares of gout during the previous year, had discontinued urate‐lowering therapy and colchicine, and had a serum uric acid (UA) level of 7.5–12 mg/dl. Patients were randomly assigned at a 2:2:2:2:1 ratio to receive 600 mg arhalofenate, 800 mg arhalofenate, 300 mg allopurinol, 300 mg allopurinol plus 0.6 mg colchicine, or placebo once a day. The primary outcome measure was the flare incidence (number of flares divided by time of exposure). The serum UA level was a secondary outcome measure.ResultsA total of 239 gout patients were randomized and took at least 1 dose of study medication. The primary outcome measure comparing flare incidence between 800 mg arhalofenate and 300 mg allopurinol was achieved, with a 46% decrease in the 800 mg arhalofenate group (0.66 versus 1.24; P = 0.0056). Treatment with 800 mg arhalofenate was also significantly better than placebo (P = 0.049) and not significantly different from treatment with 300 mg allopurinol plus 0.6 mg colchicine (P = 0.091). Mean changes in serum UA level were −12.5% with 600 mg arhalofenate and −16.5% with 800 mg arhalofenate (P = 0.001 and P = 0.0001, respectively, versus −0.9% with placebo). There were no meaningful differences in adverse events (AEs) between groups, and there were no serious AEs related to arhalofenate. Urinary calculus occurred in 1 patient receiving 300 mg allopurinol. No abnormal serum creatinine values >1.5‐fold the baseline value were observed in the arhalofenate‐treated groups.ConclusionArhalofenate at a dosage of 800 mg decreased gout flares significantly compared to allopurinol at a dosage of 300 mg. Arhalofenate was well tolerated and appeared safe. Arhalofenate is the first urate‐lowering antiflare therapy.

The Pharmacodynamics, Pharmacokinetics, and Safety of Arhalofenate in Combination with Febuxostat When Treating Hyperuricemia Associated with Gout

“…Therefore, ARH promotes a gradual excretion of UA in the kidney without inducing dangerously high values that might lead to intratubular UA precipitation 23 . This gradual excretion is consistent with the favorable renal safety profile observed to date in clinical studies with ARH 14 .…”

“…In isolated murine macrophages, ARH acid suppressed urate crystal-stimulated release of IL-1β by 83% and this was associated with a 73% reduction in the mRNA encoding pro-IL-1β 13 . In a recent phase II study, ARH at a daily dose of 800 mg was shown to significantly reduce the incidence of gout flares by 46% compared with allopurinol 300 mg 14 .…”

“…It lowers SUA by blocking the tubular reabsorption of uric acid (UA) by URAT-1 and reduces gout flares by blocking the urate crystal-stimulated release of interleukin 1β (IL-1β) 13,14 . IL-1β is the key cytokine that triggers gout flares 15 and specifically blocking it reduces gout flares 16 .…”

Uric acid transporter inhibitors for gout

“…This URAT1 inhibitor is currently in clinical trials for gout [71]. Arhalofenate when dosed at 800 mg per day reduced serum uric acid similarly to 300 mg of allopurinol.…”

Gout: will the “King of Diseases” be the first rheumatic disease to be cured?

“…In a RCT, 239 gout patients were randomized, respectively assigned at a 2:2:2:2:1 ratio to receive 600 mg arhalofenate, 800 mg arhalofenate, 300 mg allopurinol, 300 mg allopurinol plus 0.6 mg colchicine, or placebo once a day [37]. Gout flares were significantly reduced with 800 mg arhalofenate versus 300 mg allopurinol, with a 46 % decrease in the 800 mg arhalofenate group (0.66 vs. 1.24 ( P  = 0.006) and vs. placebo ( P  = 0.049)) [37]. Several other treatments with great potential as ULTs or for acute flares are currently under development [32].…”