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Abstract：
OBJECTIVE: The anti-inflammatory effects of the xanthine oxidase inhibitor, febuxostat, a urate-lowering agent, have been reported in animal studies. However, the anti-inflammatory effects of urate-lowering therapy and its associated cardiovascular protective effects have not been fully determined in actual clinical practice. This study aimed to investigate the effect of febuxostat on white blood cell (WBC) count in patients with asymptomatic hyperuricemia and to assess for potential correlations between changes in WBC count and inflammatory biomarkers and atherosclerosis in this patient population.
METHODS: This was a post hoc subanalysis of the PRIZE study, a multicenter, prospective, randomized, open-label clinical trial. In the PRIZE study, asymptomatic hyperuricemia patients were randomized to febuxostat group or control group with non-pharmacological therapy and evaluated the effect on vascular. The primary endpoints of this study were the assessment of the time course of WBC count over 24 months and its changes from baseline. Correlations of WBC count with high-sensitivity C-reactive protein (hs-CRP) and mean common carotid artery (CCA)-IMT were also exploratorily examined in the febuxostat group.
RESULTS: A total of 444 patients (febuxostat group, n=223; control group, n=221) with WBC measurements available at baseline and at least one of the follow-up time points of 12 or 24 months, were enrolled. Febuxostat modestly, but significantly, reduced WBC counts at 12 and 24 months compared with the baseline levels (P=0.002 and P=0.026, respectively). Notably, the WBC count in the febuxostat group at 12 and 24 months was significantly lower than that in the control group (P=0.007 and P=0.023, respectively). The changes in WBC count were associated with those of hs-CRP (P=0.038), but not with CCA-IMT (P=0.727).
CONCLUSIONS: Febuxostat therapy for 24 months modestly, but significantly, decreased WBC count in patients with asymptomatic hyperuricemia. This might potentially reflect a modest anti-inflammatory action of febuxostat in clinical settings.
METHODS: This was a post hoc subanalysis of the PRIZE study, a multicenter, prospective, randomized, open-label clinical trial. In the PRIZE study, asymptomatic hyperuricemia patients were randomized to febuxostat group or control group with non-pharmacological therapy and evaluated the effect on vascular. The primary endpoints of this study were the assessment of the time course of WBC count over 24 months and its changes from baseline. Correlations of WBC count with high-sensitivity C-reactive protein (hs-CRP) and mean common carotid artery (CCA)-IMT were also exploratorily examined in the febuxostat group.
RESULTS: A total of 444 patients (febuxostat group, n=223; control group, n=221) with WBC measurements available at baseline and at least one of the follow-up time points of 12 or 24 months, were enrolled. Febuxostat modestly, but significantly, reduced WBC counts at 12 and 24 months compared with the baseline levels (P=0.002 and P=0.026, respectively). Notably, the WBC count in the febuxostat group at 12 and 24 months was significantly lower than that in the control group (P=0.007 and P=0.023, respectively). The changes in WBC count were associated with those of hs-CRP (P=0.038), but not with CCA-IMT (P=0.727).
CONCLUSIONS: Febuxostat therapy for 24 months modestly, but significantly, decreased WBC count in patients with asymptomatic hyperuricemia. This might potentially reflect a modest anti-inflammatory action of febuxostat in clinical settings.
摘要：
目的：黄嘌呤氧化酶抑制剂的抗炎作用，非布索坦,尿酸降低剂,在动物研究中已经有报道。然而,尿酸盐治疗的抗炎作用及其相关的心血管保护作用在实际临床实践中尚未完全确定.本研究旨在研究非布索坦对无症状高尿酸血症患者白细胞（WBC）计数的影响，并评估该患者人群中白细胞计数变化与炎症生物标志物和动脉粥样硬化之间的潜在相关性。
方法：这是PRIZE研究的事后亚分析，一个多中心，prospective,随机化，开放标签临床试验。在PRIZE研究中,无症状性高尿酸血症患者被随机分为非布索坦组和非药物治疗的对照组,并评估对血管的影响.这项研究的主要终点是评估24个月内WBC计数的时程及其相对于基线的变化。在非布索坦组中，还探索性地检查了WBC计数与高敏C反应蛋白（hs-CRP）和平均颈总动脉（CCA）-IMT的相关性。
结果：总共444例患者（非布索坦组，n=223；对照组，n=221），在基线和至少一个随访时间点为12或24个月时可进行WBC测量，已注册。非布索坦适度，但重要的是，与基线水平相比,12个月和24个月时的白细胞计数减少(分别为P=0.002和P=0.026).值得注意的是,非布索坦治疗组12个月和24个月时白细胞计数显著低于对照组(分别为P=0.007和P=0.023)。白细胞计数的变化与hs-CRP的变化有关(P=0.038)。但与CCA-IMT无关(P=0.727)。
结论：非布索坦适度治疗24个月，但重要的是，无症状高尿酸血症患者白细胞计数减少。这可能潜在地反映非布索坦在临床环境中的适度抗炎作用。
方法：这是PRIZE研究的事后亚分析，一个多中心，prospective,随机化，开放标签临床试验。在PRIZE研究中,无症状性高尿酸血症患者被随机分为非布索坦组和非药物治疗的对照组,并评估对血管的影响.这项研究的主要终点是评估24个月内WBC计数的时程及其相对于基线的变化。在非布索坦组中，还探索性地检查了WBC计数与高敏C反应蛋白（hs-CRP）和平均颈总动脉（CCA）-IMT的相关性。
结果：总共444例患者（非布索坦组，n=223；对照组，n=221），在基线和至少一个随访时间点为12或24个月时可进行WBC测量，已注册。非布索坦适度，但重要的是，与基线水平相比,12个月和24个月时的白细胞计数减少(分别为P=0.002和P=0.026).值得注意的是,非布索坦治疗组12个月和24个月时白细胞计数显著低于对照组(分别为P=0.007和P=0.023)。白细胞计数的变化与hs-CRP的变化有关(P=0.038)。但与CCA-IMT无关(P=0.727)。
结论：非布索坦适度治疗24个月，但重要的是，无症状高尿酸血症患者白细胞计数减少。这可能潜在地反映非布索坦在临床环境中的适度抗炎作用。
