Combo therapy kicks urate target goals

The use of combined xanthine oxidase inhibitors (febuxostat) with a uricosuric agent (lesinurad) has shown long term safety and efficacy in patients with tophaceous gout in a trial involving Australian centres.

In a two year follow up study, febuxostat and lesinurad were effective in lowering serum urate levels, reducing gout flares and decreasing the size and number of tophi, without comprising renal safety.

A 12-month extension of the CRYSTAL study, which first compared combination therapy with febuxostat alone, has also confirmed there were no new adverse events in a second year of combination therapy.

The extension study included patients who had been on combination treatment and continued on the same therapy as well as patients who crossed over to combination therapy from febuxostat alone.

“For those who crossed over from receiving febuxostat alone to receiving combination therapy, the proportions of patients achieving target sUA increased, reaching proportions similar to the groups that continued lesinurad therapy at the end of month 12,” the study authors reported in Arthritis Research and Therapy.

They found the proportion of serum urate levels <5.0mg/dl (<0.3 mmol/L) increased in all patient groups regardless of their previous treatment regimen or lesinurad dose (200 v 400 mg).

As well, tophi resolution and a reduction in the size of tophi was demonstrated in all groups with the biggest effect in patients continuing on 400 mg lesinurad from the first study.

“The proportion of patients with complete resolution of at least one target tophus increased in all groups with exposure to combination therapy in the extension study.”

The proportion of patients requiring treatment for a gout flare also generally decreased over time in all groups.

The study, conducted across six countries including Australia and New Zealand, supports the combination of a uricosuric agent with a xanthine oxidase inhibitor in the treatment of patients with tophaceous gout.

“Although not addressed in the present study, an improvement in quality of life would be consistent with the observed reduction in gout flares and increased tophus resolution as a result of lower sUA levels with lesinurad plus febuxostat treatment,” the researchers said.

“The present results are also consistent with the conclusion that more than 1 year of urate-lowering therapy is required to reduce gout flares and increase tophus resolution, presumably because it takes time to reduce the body urate load.”

The study found the combination therapy was generally well tolerated although ongoing monitoring of kidney function was important.

Co-author Professor Graeme Jones, from the University of Tasmania, told the limbic that while lesinurad was not yet approved in Australia, feboxustat was a good option for achieving target urate levels when allopurinol had failed.

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