非布司他治疗高尿酸血症有效性及安全性的Meta分析
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摘要
目的系统评价非布司他对比别嘌醇治疗高尿酸血症的有效性和安全性。方法检索PubMed、Cochrane图书馆、EMBASE、CNKI、万方、维普等数据库,搜集非布司他和别嘌醇治疗高尿酸血症的随机对照试验,检索时限为建库至2017年2月。由2位评价员独立筛选文献、提取资料并评价纳入研究的偏倚风险后,采用RevMan5.3软件进行Meta分析。结果纳入23项随机对照试验,共计8 530个患者,Meta分析结果显示:在降尿酸效果方面,非布司他40 mg/d对比别嘌醇差异有统计学意义(风险比1.14,95%可信区间1.05～1.23,P=0.001),非布司他80 mg/d(风险比1.72,95%可信区间1.61～1.83,P<0.000 01)和120 mg/d(风险比2.04,95%可信区间1.85～2.26,P<0.000 01)都比别嘌醇更有效。随着非布司他剂量增加,其降尿酸能力也增加。在安全性方面,别嘌醇更易发生皮疹(比值比0.65,95%可信区间0.47～0.88,P<0.006),其他不良反应无明显差异。结论非布司他具有良好的降低血清尿酸作用,且皮疹发生率比别嘌醇低。
Objective To evaluate efficacy and safety of Febuxostat in hyperuricemic patients compared with Allopurinol by systematic review. Methods Electronic databases(PubMed,the Cochrane library,EMBASE,CNKI,Wanfang,CBM,ect)were searched for articles of all publication years(up to February 2017). According to the inclusion and exclusion criteria,tow reviewers independently selected articles,extracted data and evaluated quality. Randomized controlled trials(RCTs) were analyzed by meta-analysis. Results 23 RCTs were included. A significantly greater proportion of patients achieved the target serum urate level(sUA<6.0 mg/dL)at the final visit in the Febuxostat groups(40 mg/d:RR1.14,95%CI 1.05～1.23,P=0.001;80 mg/d:RR 1.72,95%CI 1.61～1.83,P<0.000 01;120 mg/d:RR 2.04,95%CI 1.85～2.26,P<0.000 01)compared with the Allopurinol groups. Conclusion Compared with Allopurinol(100～300 mg/d),Febuxostat(80～240 mg/d)showed more effective outcome and may reduce the incidence of rash.
Objective To evaluate efficacy and safety of Febuxostat in hyperuricemic patients compared with Allopurinol by systematic review. Methods Electronic databases(PubMed,the Cochrane library,EMBASE,CNKI,Wanfang,CBM,ect)were searched for articles of all publication years(up to February 2017). According to the inclusion and exclusion criteria,tow reviewers independently selected articles,extracted data and evaluated quality. Randomized controlled trials(RCTs) were analyzed by meta-analysis. Results 23 RCTs were included. A significantly greater proportion of patients achieved the target serum urate level(sUA<6.0 mg/dL)at the final visit in the Febuxostat groups(40 mg/d:RR1.14,95%CI 1.05～1.23,P=0.001;80 mg/d:RR 1.72,95%CI 1.61～1.83,P<0.000 01;120 mg/d:RR 2.04,95%CI 1.85～2.26,P<0.000 01)compared with the Allopurinol groups. Conclusion Compared with Allopurinol(100～300 mg/d),Febuxostat(80～240 mg/d)showed more effective outcome and may reduce the incidence of rash.
引文
[1]中华医学会内分泌学分会.高尿酸血症和痛风治疗的中国专家共识[J].中华内分泌代谢杂志,2013,29(11):913-920.
[2]王丽英,赵燕,郑毅,等.随机双盲三模拟对照多中心临床研究非布索坦降低痛风患者高尿酸水平的疗效和安全性[J].中华临床医师杂志(电子版),2013,7(7):2798-2803.
[3]魏斐菲.对痛风伴高尿酸血症患者采取非布司他治疗的效果研究[J].中国现代药物应用,2016,10(21):84-85.
[4]李文佳,李德.非布司他与别嘌醇治疗痛风伴高尿酸血症患者的有效性及安全性对比研究[J].东方食疗与保健,2016,(4):33.
[5]郑少玲,邓伟明,郭欣,等.非布司他与别嘌醇治疗病风患者的疗效与安全性比较[J].临床医学工程,2015,22(8):1069-1070,1073.
[6]覃文威.非布司他治疗痛风伴高尿酸血症的疗效观察[D].广西:广西医科大学,2016.
[7]汤艳华,江敏,刘玲,等.非布司他治疗痛风伴高尿酸血症患者的临床研究[J].中国当代医药,2016,23(21):40-42.
[8]陈翔,蔡吓明,陈国勇.非布司他治疗痛风伴高尿酸血症疗效观察[J].中外医学研究,2015,13(34):34-35,36.
[9]缪逸,朱建琴.非布司他治疗痛风的临床效果研究[J].中国现代医生,2016,54(26):103-105.
[10]万志红.非布司他治疗痛风及高尿酸血症的疗效及不良反应观察[J].中国实用医药,2016,11(1):112-113.
[11]邹国盛,黄志祥.非布索坦治疗痛风合并高尿酸血症50例[J].中国药业,2015,24(17):111-112.
[12]BECKER M A,SCHUMACHER H R,WORTMANN R L,et al.Febuxostat,a novel nonpurine selective inhibitor of xanthine oxidase:A twenty-eight-day,multicenter,phaseⅡ,randomized,double-blind,placebo-controlled,dose-response clinical trial examining safety and efficacy in patients with gout[J].Arthritis Rheum,2005,52(3):916-923.
[13]BECKER M A,SCHUMACHER H R,WORTMANN R L,et al.Febuxostat compared with Allopurinol in patients with hyperuricemia and gout[J].N Engl J Med,2005,353(23):2450-2461.
[14]SCHUMACHER H R,BECKER M A,WORTMANN R L,et al.Effects of Febuxostat versus Allopurinol and placebo in reducing serum urate in subjects with hyperuricemia and gout:A 28-week,phaseⅢ,randomized,double-blind,parallelgroup trial[J].Arthritis Rheum,2008,59(11):1540-1548.
[15]SCHUMACHER H R,BECKER M A,LLOYD E,et al.Febuxostat in the treatment of gout:5-yr findings of the FOCUSefficacy and safety study[J].Rheumatology(Oxford),2009,48(2):188-194.
[16]BECKER M A,SCHUMACHER H R,MACDONALD P A,et al.Clinical efficacy and safety of successful longterm urate lowering with Febuxostat or Allopurinol in subjects with gout[J].J Rheumatol,2009,36(6):1273-1282.
[17]BECKER M A,SCHUMACHER H R,ESPINOZA L R,et al.The urate-lowering efficacy and safety of Febuxostat in the treatment of the hyperuricemia of gout:The CONFIRMS trial[J].Arthritis Res Ther,2010,12(2):R63.
[18]KAMATANI N,FUJIMORI S,HADA T,et al.An Allopurinolcontrolled,randomized,double-dummy,double-blind,parallel between-group,comparative study of Febuxostat(TMX-67),a non-purine-selective inhibitor of xanthine oxidase,in patients with hyperuricemia including those with gout in Japan:Phase 3 clinical study[J].J Clin Rheumatol,2011,17(4Suppl 2):S13S-S18.
[19]KAMATANI N,FUJIMORI S,HADA T,et al.Placebocontrolled,double-blind study of the non-purine-selective xanthine oxidase inhibitor Febuxostat(TMX-67)in patients with hyperuricemia including those with gout in Japan:Phase 3clinical study[J].J Clin Rheumatol,2011,17(4 Suppl 2):S19-S26.
[20]KAMATANI N,FUJIMORI S,HADA T,et al.Placebocontrolled double-blind dose-response study of the non-purineselective xanthine oxidase inhibitor Febuxostat(TMX-67)in patients with hyperuricemia(including gout patients)in Japan:Late phase 2 clinical study[J].J Clin Rheumatol,2011,17(4Suppl 2):S35-S43.
[21]KAMATANI N,FUJIMORI S,HADA T,et al.An Allopurinolcontrolled,multicenter,randomized,open-label,parallel between-group,comparative study of Febuxostat(TMX-67),a non-purine-selective inhibitor of xanthine oxidase,in patients with hyperuricemia including those with gout in Japan:Phase 2exploratory clinical study[J].J Clin Rheumatol,2011,17(4Suppl 2):S44-S49.
[22]HUANG,X,DU H,GU J,et al.An Allopurinol-controlled,multicenter,randomized,double-blind,parallel betweengroup,comparative study of Febuxostat in Chinese patients with gout and hyperuricemia[J].Int J Rheum Dis,2014,17(6):679-686.
[23]XU S,LIU X,MING J,et al.A phase 3,multicenter,randomized,Allopurinol-controlled study assessing the safety and efficacy of oral Febuxostat in Chinese gout patients with hyperuricemia[J].Int J Rheum Dis,2015,18(6):669-678.
[24]YU K H,LAI J H,HSU P N,et al.Safety and efficacy of oral Febuxostat for treatment of HLA-B*5801-negative gout:Arandomized,open-label,multicentre,Allopurinol-controlled study[J].Scand J Rheumatol,2016,45(4):304-311.
[2]王丽英,赵燕,郑毅,等.随机双盲三模拟对照多中心临床研究非布索坦降低痛风患者高尿酸水平的疗效和安全性[J].中华临床医师杂志(电子版),2013,7(7):2798-2803.
[3]魏斐菲.对痛风伴高尿酸血症患者采取非布司他治疗的效果研究[J].中国现代药物应用,2016,10(21):84-85.
[4]李文佳,李德.非布司他与别嘌醇治疗痛风伴高尿酸血症患者的有效性及安全性对比研究[J].东方食疗与保健,2016,(4):33.
[5]郑少玲,邓伟明,郭欣,等.非布司他与别嘌醇治疗病风患者的疗效与安全性比较[J].临床医学工程,2015,22(8):1069-1070,1073.
[6]覃文威.非布司他治疗痛风伴高尿酸血症的疗效观察[D].广西:广西医科大学,2016.
[7]汤艳华,江敏,刘玲,等.非布司他治疗痛风伴高尿酸血症患者的临床研究[J].中国当代医药,2016,23(21):40-42.
[8]陈翔,蔡吓明,陈国勇.非布司他治疗痛风伴高尿酸血症疗效观察[J].中外医学研究,2015,13(34):34-35,36.
[9]缪逸,朱建琴.非布司他治疗痛风的临床效果研究[J].中国现代医生,2016,54(26):103-105.
[10]万志红.非布司他治疗痛风及高尿酸血症的疗效及不良反应观察[J].中国实用医药,2016,11(1):112-113.
[11]邹国盛,黄志祥.非布索坦治疗痛风合并高尿酸血症50例[J].中国药业,2015,24(17):111-112.
[12]BECKER M A,SCHUMACHER H R,WORTMANN R L,et al.Febuxostat,a novel nonpurine selective inhibitor of xanthine oxidase:A twenty-eight-day,multicenter,phaseⅡ,randomized,double-blind,placebo-controlled,dose-response clinical trial examining safety and efficacy in patients with gout[J].Arthritis Rheum,2005,52(3):916-923.
[13]BECKER M A,SCHUMACHER H R,WORTMANN R L,et al.Febuxostat compared with Allopurinol in patients with hyperuricemia and gout[J].N Engl J Med,2005,353(23):2450-2461.
[14]SCHUMACHER H R,BECKER M A,WORTMANN R L,et al.Effects of Febuxostat versus Allopurinol and placebo in reducing serum urate in subjects with hyperuricemia and gout:A 28-week,phaseⅢ,randomized,double-blind,parallelgroup trial[J].Arthritis Rheum,2008,59(11):1540-1548.
[15]SCHUMACHER H R,BECKER M A,LLOYD E,et al.Febuxostat in the treatment of gout:5-yr findings of the FOCUSefficacy and safety study[J].Rheumatology(Oxford),2009,48(2):188-194.
[16]BECKER M A,SCHUMACHER H R,MACDONALD P A,et al.Clinical efficacy and safety of successful longterm urate lowering with Febuxostat or Allopurinol in subjects with gout[J].J Rheumatol,2009,36(6):1273-1282.
[17]BECKER M A,SCHUMACHER H R,ESPINOZA L R,et al.The urate-lowering efficacy and safety of Febuxostat in the treatment of the hyperuricemia of gout:The CONFIRMS trial[J].Arthritis Res Ther,2010,12(2):R63.
[18]KAMATANI N,FUJIMORI S,HADA T,et al.An Allopurinolcontrolled,randomized,double-dummy,double-blind,parallel between-group,comparative study of Febuxostat(TMX-67),a non-purine-selective inhibitor of xanthine oxidase,in patients with hyperuricemia including those with gout in Japan:Phase 3 clinical study[J].J Clin Rheumatol,2011,17(4Suppl 2):S13S-S18.
[19]KAMATANI N,FUJIMORI S,HADA T,et al.Placebocontrolled,double-blind study of the non-purine-selective xanthine oxidase inhibitor Febuxostat(TMX-67)in patients with hyperuricemia including those with gout in Japan:Phase 3clinical study[J].J Clin Rheumatol,2011,17(4 Suppl 2):S19-S26.
[20]KAMATANI N,FUJIMORI S,HADA T,et al.Placebocontrolled double-blind dose-response study of the non-purineselective xanthine oxidase inhibitor Febuxostat(TMX-67)in patients with hyperuricemia(including gout patients)in Japan:Late phase 2 clinical study[J].J Clin Rheumatol,2011,17(4Suppl 2):S35-S43.
[21]KAMATANI N,FUJIMORI S,HADA T,et al.An Allopurinolcontrolled,multicenter,randomized,open-label,parallel between-group,comparative study of Febuxostat(TMX-67),a non-purine-selective inhibitor of xanthine oxidase,in patients with hyperuricemia including those with gout in Japan:Phase 2exploratory clinical study[J].J Clin Rheumatol,2011,17(4Suppl 2):S44-S49.
[22]HUANG,X,DU H,GU J,et al.An Allopurinol-controlled,multicenter,randomized,double-blind,parallel betweengroup,comparative study of Febuxostat in Chinese patients with gout and hyperuricemia[J].Int J Rheum Dis,2014,17(6):679-686.
[23]XU S,LIU X,MING J,et al.A phase 3,multicenter,randomized,Allopurinol-controlled study assessing the safety and efficacy of oral Febuxostat in Chinese gout patients with hyperuricemia[J].Int J Rheum Dis,2015,18(6):669-678.
[24]YU K H,LAI J H,HSU P N,et al.Safety and efficacy of oral Febuxostat for treatment of HLA-B*5801-negative gout:Arandomized,open-label,multicentre,Allopurinol-controlled study[J].Scand J Rheumatol,2016,45(4):304-311.