Arhalofenate combination therapy can be used to treat the gout

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Arhalofenate combination therapy can be used to treat the gout

Gout is a common disease resulting from deposition of uric acid crystals (monosodium urate) in tissues and fluids within the body. This condition is caused due to an overproduction or under excretion of uric acid. There is a need for new treatments for gout that provides better serum uric acid (sUA) and flare controls. Arhalofenate in combination with febuxostat appears to be well-tolerated and significantly decreased the number of gout flares.

Arhalofenate is a novel uricosuric drug that blocks URAT1, a tubular uric acid transporter. This study evaluated the serum uric acid lowering effect of arhalofenate when combined with febuxostat and the potential for a drug-drug interaction. The effect of arhalofenate on the fractional excretion of uric acid (FEUA) and its safety was assessed.

Researchers conducted a randomized open label phase II study with two cohorts of gout patients (n=16 each). The main objective of the study was to evaluate the SUA-lowering of arhalofenate when combined with febuxostat, to evaluate the potential for a drug interaction, and to assess the tolerability and safety of both drugs when used alone and in combination. Dosing was once daily oral. One cohort received arhalofenate 600 mg for 2 weeks followed by sequential one week periods of co-administration of febuxostat 80 mg and 40 mg. During the final two weeks, febuxostat 40 mg alone was continued. The second cohort received arhalofenate 800 mg for 2 weeks, followed by sequential one week periods of co-administration of febuxostat 40 mg and 80 mg. During the last two weeks of the study, febuxostat 80 mg alone was continued. The assessment of sUA was performed at multiple points. All patients received colchicine throughout for flare prophylaxis. The aassessment of FEUA was performed over three intervals (morning, afternoon, and night). Eight subjects on arhalofenate 800 mg alone had FEUA measured at baseline and 3rd, 7th and 14th  day.

Treatment with arhalofenate 800 mg monotherapy gradually decreased sUA with approximately half of the decrease on day 7. The values of FEUA increased from 3.5% to 4.6% on day 3, 7 and 14 (P<0.001), respectively and treatment with febuxostat monotherapy decreased FEUA (3.1%) relative to baseline. There were no serious adverse events and only one severe event of uncontrolled hypertension and one case of elevated liver transaminases were reported.

The study results demonstrated that the combination of arhalofenate with febuxostat was well tolerated, appeared safe and was more efficacious in decreasing sUA, thereby achieving the recommended goal of <6 mg/dL, and providing a potential treatment alternative for the gout.


The journal of rheumatology

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Original title of article:

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


Alexandra S. Steinberg, Bradley D. Vince, Yun-Jung Choi, Robert L. Martin, Charles A, McWherter and Pol F. Boudes

The journal of rheumatology
Therapeutic, Arhalofenate, Febuxostat, Gout, Joints, Xanthine Oxidase Inhibitor, URAT1 Inhibitor, Open Phase II Trial, Efficacy, Safety, Tolerability
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