How do you treat polyarthritic gout

The short version: gout is a disease of uric acid crystals in the joints, and the evidence here shows that the drugs used to treat it carry their own serious risks, especially to the kidneys.

The retrieved evidence is a mixed bag. One 2025 study of 1,207 gout patients found that acute kidney injury (AKI) rates rose from about 10% to 16% over two decades [1]. The biggest risk factors were the "triple whammy" combination of NSAIDs, diuretics, and RAAS inhibitors (heart and blood pressure drugs) — a combination that raises AKI risk by 75% [1]. Having chronic kidney disease (CKD) tripled the risk [1]. The study also found that urate-lowering therapy (ULT) was linked to lower AKI risk, with a hazard ratio of 0.60 [1]. That is a meaningful protective effect.

But the ULT drugs themselves are not clean. The 2005 NEJM trial comparing febuxostat to allopurinol was funded by the manufacturer (TAP Pharmaceutical Products) [3]. It used a surrogate endpoint — lowering serum urate below 6.0 mg/dL — not hard outcomes like kidney failure or death. Febuxostat at 80 mg hit that target in 53% of patients, versus 21% for allopurinol [3]. But gout flare rates were identical at 64% for both groups over the year [3]. The drug lowered urate but did not prevent flares. That is a red flag: the surrogate did not predict the real outcome.

The 2008 FOCUS study on febuxostat was also manufacturer-funded (TAP) and had no placebo group [2]. It showed sustained urate lowering and tophi resolution in 18 of 26 patients with tophi at baseline [2]. But 47% of patients still had flares overall, and the rate was highest (75%) at the lowest dose [2]. The study design makes it impossible to separate drug effect from natural history.

For acute flare prevention, the RESURGE trial tested rilonacept, an IL-1 blocker, in 1,315 patients starting ULT [4]. It was funded by Regeneron, the manufacturer [4]. It reduced flares by 70% over 16 weeks compared to placebo (0.51 vs 1.73 flares per patient) [4]. But 25.7% of the rilonacept group still had at least one flare, and 11.7% had two or more [4]. Serious infection rates were similar between groups, but injection-site reactions were 15.2% on the drug versus 3.3% on placebo [4]. This is a biologic with its own long-term safety unknowns.

The evidence here does not include a single head-to-head trial comparing ULT to placebo for hard outcomes like kidney failure, cardiovascular events, or death. The 2025 AKI study is observational, not a randomized trial [1]. The manufacturer-funded trials use surrogate endpoints and short follow-up [2, 3, 4]. The most informative design — ULT versus placebo with long-term kidney and cardiovascular outcomes — has not been run, or at least not published in this retrieval.

My call: the evidence for treating polyarticular gout is weak on hard outcomes. Urate-lowering therapy appears to protect the kidneys, but the drugs carry their own risks and the trials were designed to find benefit, not harm. The safest approach is to avoid the triple whammy combination, manage diet and hydration, and use ULT only with clear kidney monitoring. Confidence: moderate.