Combination urate-lowering therapy in the treatment of gout: What is the evidence?

Combination therapy that includes a uricosuric and xanthine oxidase inhibitor (XOI) is recommended in guidelines for patients with gout who do not meet treatment targets with XOI monotherapy alone. While the use of combination therapies has been investigated for many years, we reviewed data from the published studies to investigate the efficacy and safety of this approach.

Relevant published papers were identified by keyword search on PubMed and categorized according to the types of combination therapies included. Study methods and results were summarized. Outcomes of combination therapy were compared with respective monotherapies, where possible.

Efficacy was assessed by changes in serum urate (sUA), urinary uric acid, gout flare rates, and /or tophi. Safety assessments, where reported, included adverse events and, for more recent studies, laboratory assessments. Early studies in the 1960s based on case reports or open-label designs and more recent, well-designed studies with large patient numbers provided consistent outcomes: that combination therapy with a uricosuric and a XOI provides substantially greater sUA lowering than achieved by either monotherapy. Greater sUA lowering translated to greater gout symptom control, including improved tophus resolution.

Combination therapy with a uricosuric and an XOI offers additional sUA lowering compared to monotherapy alone and can provide benefit for achieving therapeutic targets in patients with gout who do not achieve target sUA or are intolerant of XOIs at appropriate monotherapy dosing.