A prospective cohort study was conducted to compare the efficacy and safety of febuxostat (initially 20 mg daily, escalating to 40 mg daily if not at target) in 644 gout patients with the three major clinical subtypes for 12 weeks. Hyperuricemia was defined as the renal overload subtype, the renal underexcretion subtype, or the combined subtype based on UUE > or ≤ 600 mg/d/1.73 m2 and FEUA < or ≥ 5.5%. The primary endpoint was the rate of achieving serum urate (SU) < 6 mg/dL at week 12.
Fewer participants with combined subtype achieved the SU target, 45.5% compared with 64.8% with overload subtype (P = 0.007), and 56.6% with underexcretion subtype (P = 0.022). More participants with combined subtype (82%) had febuxostat escalated to 40 mg than those with overload (62%, P = 0.001) or underexcretion subtype (68%, P = 0.001). In all participants, combined subtype hyperuricemia (OR = 0.64, 95%CI 0.41-0.99, P = 0.048) and baseline SU (OR = 0.74, 95%CI 0.62-0.89, P = 0.001) were independently associated with lower rates of achieving SU target.
People with combined subtype have a lower response to febuxostat, compared to those with either overload or underexcretion subtype. Assessment of hyperuricemia subtype may provide useful clinical data in predicting febuxostat response.
方法:进行了一项前瞻性队列研究,以比较非布索坦的疗效和安全性(最初每天20mg,如果未达到目标,则在644名具有三种主要临床亚型的痛风患者中升级至每天40mg),持续12周。高尿酸血症被定义为肾超负荷亚型,肾排泄不足亚型,或基于UUE>或≤600mg/d/1.73m2且FEUA<或≥5.5%的组合亚型。主要终点是在第12周时达到血清尿酸(SU)<6mg/dL的比率。
结果:合并亚型的参与者达到SU目标的人数较少,45.5%,而过载亚型为64.8%(P=0.007),56.6%为排泄不足亚型(P=0.022)。合并亚型的参与者(82%)比超负荷的参与者(62%,P=0.001)或排泄不足亚型(68%,P=0.001)。在所有参与者中,合并亚型高尿酸血症(OR=0.64,95CI0.41-0.99,P=0.048)和基线SU(OR=0.74,95CI0.62-0.89,P=0.001)与较低的SU目标实现率独立相关.
结论:合并亚型的人对非布索坦的反应较低,与那些过载或排泄不足亚型相比。评估高尿酸血症亚型可能为预测非布索坦反应提供有用的临床数据。