Response to Febuxostat in Elderly Gout Patients with Clinical Subtypes of Hyperuricemia: A Prospective Cohort Study

Purpose: Previous clinical studies have suggested potential differences in the response of different subtypes to febuxostat treatment. However, research on elderly gout patients, particularly those with chronic kidney disease (CKD) stage 3, remains lacking. This study aims to compare febuxostat response across subtypes in elderly gout patients. Methods: A prospective cohort study was conducted to compare the efficacy and safety of febuxostat (20 or 40 mg daily) in 490 gout patients with the clinical subtypes for 12 weeks. Hyperuricemia was defined as the renal underexcretion subtype when UUE ≤ 600 mg/d/1.73m 2 and FE UA < 5.5%, the renal overload subtype when UUE > 600 mg/d/1.73m 2 and FE UA ≥ 5.5%, the combined subtype when UUE > 600 mg/d/1.73m 2 and FE UA < 5.5%, or the normal subtype when UUE ≤ 600 mg/d/1.73m 2 and FE UA ≥ 5.5%, assessed from 24-h urine samples. The primary endpoint was the rate of achieving serum urate (SU) < 6 mg/dL at week 12. Results: Fewer participants with combined subtype achieved the SU target, 45.57% compared with 69.69% with renal overload subtype, 63.40% with renal underexcretion subtype and 64.06% with normal subtype. Participants with the normal subtype had the lowest baseline eGFR but showed the greatest improvement after treatment (an increase of 5.67 mL/min/1.73 m 2 at week 12, P < 0.001). Conclusion: Elderly gout patients with the combined subtype exhibit poorer response to febuxostat compared to other subtypes. Urate-lowering therapy improved renal function, particularly in patients with normal subtypes.