川草乌治疗类风湿性关节炎的效益-风险评价Aconitum in treatment of rheumatoid arthritis: benefit-risk assessment
张晓朦;金勇男;张冰;李宁;
ZHANG Xiao-meng;JIN Yong-nan;ZHANG Bing;LI Ning;Beijing University of Chinese Medicine;
摘要(Abstract):
类风湿性关节炎(RA)病势缠绵、较难治愈,常规治疗用药周期长、易诱发不良反应,特别需要考量患者的获益与风险。毒性中药川草乌作为RA治疗重要手段之一,用药存在一定争议。该研究切入临床用药的实际问题,基于多准则决策模型量化评估川草乌中药单独应用以及联用西药的效益与风险。采用Rev Man 5.2软件分别综合21项川草乌单独应用治疗RA的随机对照试验(RCT)、49项川草乌联用西药治疗RA的RCT各指标结果,显示相较于常规西药治疗,无论单独应用还是联用西药,川草乌均可提高疗效、降低不良反应/事件发生率。结合RA治疗的效益-风险评价指标决策体系,应用Hiview 3软件以及Crystal Ball蒙特卡洛模拟计算川草乌单独应用与联用西药的效益值、风险值、效益-风险总值。结果显示川草乌联用西药的效益高于其单独应用(效益差=15,95%CI[9.72,20.25]),但其风险也相对更高(风险差=23,95%CI[15.57,30.55]),当效益与风险对RA患者同等重要时,川草乌单独应用的效益-风险总值为58,联用西药为55,且单独应用优于联用西药的概率为81.07%。由此可见,川草乌是RA临床治疗手段的重要补充,且当患者对于风险的可接受性较低时,则不推荐中西药联用。
Rheumatoid arthritis(RA) has the characteristics of long course of disease and difficulty in treatment. The conventional therapy may easily induce adverse drug reactions or events( ADR/ADE) due to the long-time medication. Thus,it should be given special attentions to treatment benefit and medication risk of RA patients. Aconitum,a kind of toxic traditional Chinese herbs,is an important complement therapy for RA,with some controversy in clinical application. Coming straight to the practical problem of combined use of traditional Chinese medicines( TCM) and Western medicines( WM),this study conducted quantitative assessment on the benefits and risks of Aconitum using combined with WM or not,which was carried out by the method of multi-criteria decision analysis model. Rev Man 5. 2 software was used to separately analyze the results of every index of 21 random clinical trials( RCTs) of Aconitum exclusive use in the treatment of RA,and 49 RCTs of Aconitum combined use with WM. The merged results indicated that as compared with the conventional therapy of WM,no matter the exclusive use or the combined use of Aconitum could improve the efficacy and decrease the incidence of ADR/ADEs. Based on the benefit-risk assessment decision tree of RA treatment,Hiview 3 software and Crystal Ball Monte Carlo simulation were used to calculate the benefit value,risk value and benefit-risk value of Aconitum exclusive use and the combined use of Aconitum with WM. The results showed that the combination therapy had significantly better benefits than Aconitum exclusive using,difference value was 15,( 95 % CI[9. 72,20. 25 ]),but the risk of combined use was higher difference value =23,( 95 % CI[15. 57,30. 55 ]). In comprehensive consideration of the benefit and risk,the total benefit-risk value of using Aconitum alone was 58,while that of the combination therapy was 55,and the probability of the former superior to the latter was 81. 07 %.The study showed that Aconitum was the important therapy to supply RA treatment. In clinical application,the patient' s acceptability of benefit and risk need to be considered; if patients cannot bear the risk, the combination use of Aconitum and WM is not recommended.
关键词(KeyWords):
乌头;效益-风险评价;多准则决策;蒙特卡洛
Aconitum;benefit-risk assessment;multi-criteria decision analysis(MCDA);Monte Carlo
基金项目(Foundation): 药品评价中心项目(2020071420118);; 北京市中医管理局项目(2020071520049);; 北京中医药大学新奥优秀传承团队建设项目(1000062720028/001)
作者(Authors):
张晓朦;金勇男;张冰;李宁;
ZHANG Xiao-meng;JIN Yong-nan;ZHANG Bing;LI Ning;Beijing University of Chinese Medicine;
DOI: 10.19540/j.cnki.cjcmm.20171106.007
参考文献(References):
- [1]史晓飞,付建斌.应重视类风湿关节炎流行病学伴发疾病致残率及就医行为的研究[J].中华风湿病学杂志,2014,18(7):433.
- [2]曾小峰,朱松林,谭爱春,等.我国类风湿关节炎疾病负担和生存质量研究的系统评价[J].中国循证医学杂志,2013,13(3):300.
- [3]张义浜,刘志敏,熊凌霜.类风湿关节炎发病机制及其治疗方法研究进展[J].细胞与分子免疫学杂志,2005,21(Suppl):88.
- [4]黄帝内经·素问[M].崔应珉,王淼校注.郑州:中州古籍出版社,2010.
- [5]汉·张仲景.金匮要略[M].太原:山西科学技术出版社,2010.
- [6]张冰,林志健,张晓朦.基于“识毒-用毒-防毒-解毒”实践的中药药物警戒思想[J].中国中药杂志,2017,42(10):2017.
- [7]Filip Mussen,Sam Salek,Stuart Walker.Benefit-risk appraisal of medicines:a systematic approach to decision-making[M].New York:John Wiley&Sons,2009.
- [8]郑筱萸.中药新药临床研究指导原则(试行)[M].北京:中国医药科技出版社,2002.
- [9]黎建锋,唐纯志.祛风止痛胶囊治疗98例类风湿性关节炎患者的临床观察与分析[J].中国医药指南,2014,12(19):321.
- [10]胡瑞谦,智新丽,郑莉.那如三味丸治疗类风湿关节炎随访[J].中国伤残医学,2014,22(3):148.
- [11]郑新春,杨德才.痹痛舒胶囊治疗类风湿关节炎疗效观察[J].湖北中医杂志,2013,34(10):13.
- [12]徐小溪,刘桂娟,刘素彩,等.活络通痹汤治疗类风湿性关节炎临床观察[J].河北中医药学报,2012,27(4):25.
- [13]范海梅,袁宝华.桂枝芍药汤在类风湿关节炎治疗中的疗效观察[J].齐齐哈尔医学院学报,2012,33(19):2636.
- [14]陈汉玉,翁庚民.风湿3号胶囊治疗活动期类风湿关节炎的效果及对生活质量的影响[J].山东中医杂志,2012,31(10):721.
- [15]衣蕾,吉海旺.祛风止痛胶囊治疗类风湿性关节炎寒湿痹阻证20例[C].兰州:中国中西医结合风湿病西北学术会议,2011.
- [16]李勋.温通法治疗类风湿性关节炎寒湿痹阻证临床观察[J].辽宁中医药大学学报,2010,12(11):152.
- [17]王光权,晏明海.自拟中药风湿饮治疗类风湿关节炎30例[J].中国医学创新,2010,7(30):65.
- [18]张湘玲.地黄合剂治疗类风湿性关节炎的临床观察[J].中国医药导刊,2010,12(8):1383.
- [19]高立珍,孟彪.补肾通络丸治疗类风湿关节炎50例临床观察[J].中医杂志,2010,51(3):233.
- [20]王秀娟,王玉明,张秦,等.清热养阴除湿丸治疗活动期类风湿关节炎40例疗效观察[J].北京中医药,2009,18(7):521.
- [21]朱艺成,黄丽华.中药乌头治疗类风湿关节炎的疗效与护理[J].全科护理,2009,33(7):3023.
- [22]邱全.云南红药胶囊治疗类风湿性关节炎32例[J].中国现代医生,2008,46(8):96.
- [23]王广东,杨静,侯凯.散寒除湿通络法治疗类风湿性关节炎50例[J].现代中医药,2008,28(2):13.
- [24]庞学丰,蒙宇华.热痹康胶囊治疗湿热型类风湿关节炎86例疗效观察[J].广州中医药大学学报,2003,20(2):106.
- [25]何东仪,周嘉陵,朱琦.精方风湿骨痛胶囊治疗类风湿关节炎临床观察[J].上海中医药杂志,2001,35(10):35.
- [26]石正敏,张淑娟.克痹散联用甲氨蝶呤与单用甲氨蝶呤治疗类风湿性关节炎疗效观察[J].宁夏医学杂志,2000,22(9):552.
- [27]魏永军.自拟清痹汤治疗类风湿关节炎210例[J].邯郸医学高等专科学校学报,1999,12(5):354.
- [28]宫昭艳,刘晓伟.通痹汤治疗类风湿性关节炎80例[J].山东中医药大学学报,1998,24(4):295.
- [29]干磊.祛痹灵胶囊治疗类风湿关节炎活动期临床观察[J].中医药临床杂志,2007,19(4):317.
- [30]刘怀省,韩文朝.风湿骨痛丸联合小剂量甲氨蝶呤治疗类风湿关节炎临床观察[J].风湿病与关节炎,2017,6(3):26.
- [31]毕东敏,蔡江南,刘海涛,等.麝香乌龙丸联合甲氨蝶呤、美洛昔康治疗类风湿关节炎临床研究[J].承德医学院学报,2016,33(6):484.
- [32]谢鑫.乌附麻辛桂姜汤治疗类风湿关节炎(寒湿内蕴型)58例疗效观察[J].四川中医,2016,34(12):103.
- [33]姜丹,吴坚.中药自拟方联合抗风湿药治疗活动期类风湿关节炎疗效分析与评价[J].现代医药卫生,2016,32(22):3507.
- [34]苗柳,袁强,崔建美,等.麝香乌龙丸联合来氟米特片治疗寒湿痹阻型类风湿关节炎59例临床观察[J].中医杂志,2016,57(19):1666.
- [35]陈锋,闵重函,周瑛,等.蚁参蠲痹胶囊联合西药治疗肾气虚寒型类风湿关节炎35例临床观察[J].中医杂志,2016,57(12):1045.
- [36]胡强.蚁参蠲痹胶囊治疗类风湿关节炎老年患者临床研究[J].亚太传统医药,2016,12(9):131.
- [37]王莉莎.温痹汤治疗寒湿痹阻型类风湿关节炎的临床疗效研究[D].郑州:河南中医药大学,2016.
- [38]张攀科,张国胜,杨科朋.祛痹汤联合小剂量甲氨蝶呤治疗寒湿痹阻型类风湿关节炎临床观察[J].风湿病与关节炎,2016,5(4):25.
- [39]胡剑威,张聘年.中西医结合治疗寒湿痹阻型类风湿关节炎的疗效观察[J].临床合理用药杂志,2016,9(8):1.
- [40]于笑霞,王晓磊,章鹏,等.通痹胶囊治疗寒湿痹阻型类风湿关节炎疗效观察[J].现代中西医结合杂志,2015,24(34):3797.
- [41]陆亚岚,陈世明,汪玉芳,等.补肾蠲痹汤联合小剂量甲氨蝶呤治疗老年类风湿关节炎临床研究[J].中医学报,2015,30(11):1661.
- [42]李雪芬,钟诗婷,邓矢明.益肾蠲痹丸联合美洛昔康治疗活动期类风湿性关节炎的疗效观察[J].中医药导报,2015,21(17):81.
- [43]张成,韦嵩.双乌宣痹颗粒治疗类风湿关节炎29例临床观察[J].中医药导报,2015,21(11):25.
- [44]高焱.蚁参蠲痹胶囊联合西药治疗老年类风湿关节炎临床观察[J].中草药,2015,46(11):1653.
- [45]王洪涛.四生蠲痹汤治疗类风湿关节炎临床观察[J].中医临床研究,2015,7(9):79.
- [46]李小兰,邓国忠,李君.中西医结合治疗类风湿关节炎41例临床观察[J].中医药导报,2014,20(16):62.
- [47]张成,韦嵩.双乌宣痹颗粒治疗急性期类风湿关节炎临床观察[J].中国中医急症,2014,23(10):1786.
- [48]蒋薇,陈刚.复方夏天无片联合来氟米特治疗类风湿关节炎疗效观察[J].新中医,2014,46(10):121.
- [49]陆雯俊.温阳散寒益气通络法治疗类风湿关节炎临床研究[J].中医学报,2014,29(10):1525.
- [50]牛静虎.桂枝芍药知母汤合蠲痹汤化裁治疗类风湿关节炎疗效观察[J].陕西中医,2014,35(8):984.
- [51]于建伟,刘福东,张万标.中西医结合治疗类风湿性关节炎46例临床疗效观察[J].中国民族民间医药,2014(11):56.
- [52]成虎.风湿康冲剂联合甲氨喋呤治疗类风湿性关节炎40例临床研究[J].西部中医药,2014,27(6):1.
- [53]陈湘南,朱俊卿,冯知涛,等.小乌桂颗粒剂联合DMARDs治疗类风湿关节炎的临床研究[J].中药材,2014,37(4):710.
- [54]马旭,朱清,邵凤民.中西医结合治疗类风湿性关节炎68例疗效观察[J].时珍国医国药,2013,37(10):2528.
- [55]毛丽珠,黄丽华,吴定奇.二藤乌头汤治疗活动期类风湿关节炎的疗效及护理[J].黑龙江医学,2013,37(3):220.
- [56]王永强.48例生地马钱丸配合来氟米特治疗类风湿关节炎(RA)的疗效及安全观察[J].中外医学研究,2012,10(32):43.
- [57]黄子冬,黄崇平.乌头汤加味配合云克治疗类风湿性关节炎的疗效分析[J].中国现代医生,2012,50(25):114.
- [58]黎汉文,杜嫦燕.归芍地黄汤加减治疗类风湿性关节炎55例临床观察[J].湖南中医药大学学报,2012,32(6):20.
- [59]曾海坤,曾灶英,郭大敏,等.中药生地马钱丸配合来氟米特治疗类风湿性关节炎(RA)的疗效及安全性[J].当代医学,2012,18(16):153.
- [60]梁金梅.薏苡仁汤治疗类风湿关节炎的临床研究[D].武汉:湖北中医药大学,2012.
- [61]陈韦佐.新痹痛灵颗粒联合甲氨蝶呤治疗类风湿关节炎临床研究[D].南京:南京中医药大学,2012.
- [62]景嵘月.新痹痛灵颗粒剂治疗类风湿关节炎寒湿痹阻证的临床研究[D].南京:南京中医药大学,2012.
- [63]魏淑凤,梁丽娜,李秀峰,李丽杰.乌头汤加味治疗类风湿关节炎疗效研究[J].中国医药导刊,2012,14(1):161.
- [64]郑献敏,毛丽珠,麦桃香,等.二藤乌头汤治疗类风湿关节炎活动期临床研究[J].山东中医杂志,2012,31(9):636.
- [65]吴士杰.温经蠲痹汤治疗类风湿性关节炎108例[J].陕西中医,2011,32(9):1192.
- [66]孙智霞.生地马钱丸配合来氟米特治疗类风湿性关节炎50例[J].中国实验方剂学杂志,2011,17(14):272.
- [67]刘宇宁.三消饮子联合来氟米特治疗类风湿关节炎的疗效观察[J].湖南中医药大学学报,2011,31(6):17.
- [68]杨小丽,崔宏春,闫肃.愈痹方联用甲氨喋呤治疗类风湿性关节炎54例[J].陕西中医,2011,32(6):704.
- [69]刘通英.三九中药治疗类风湿关节炎24例临床观察[J].中医临床研究,2011,3(9):6.
- [70]唐蔚.益气散寒通络法治疗类风湿性关节炎30例临床观察[J].中医药导报,2011,17(4):67.
- [71]孙巍,孙妍.中西医结合治疗类风湿性关节炎48例疗效观察[J].中国现代医生,2011,49(12):58.
- [72]李国德.中西医结合治疗类风湿性关节炎的体会[J].辽宁中医杂志,2011,38(1):118.
- [73]马武开,钟琴,姚血明,等.金乌健骨汤对甲氨喋呤耐药类风湿关节炎患者的影响[J].中医杂志,2010,51(11):993.
- [74]马武开,钟琴,刘正奇,等.三乌胶囊联合甲氨喋呤、柳氮磺胺吡啶治疗类风湿关节炎的临床研究[J].新中医,2009,41(11):42.
- [75]罗试计.乌头汤加味治疗活动性类风湿关节炎的疗效观察[J].河南中医学院学报,2009,24(4):71.
- [77]刘汉顺,钟琴.三乌胶囊联合甲氨喋呤治疗类风湿性关节炎疗效观察[J].实用中医药杂志,2008,24(3):158.
- [78]石蕾.通痹2号治疗类风湿关节炎临床研究[D].武汉:湖北中医学院,2006.
- [79]何煜舟,温成平,曹灵勇,等.桂乌汤治疗类风湿性关节炎临床观察[J].浙江中西医结合杂志,2005,15(5):269.
- [80]明·王肯堂.证治准绳[M].上海:上海古籍出版社,1991.
- [81]黄小龙,陈明.川乌、草乌和附子治疗痹证探讨[J].中国中医基础医学杂志,2014,20(1):113.
- [82]沈映君.中药药理学[M].北京:人民卫生出版社,2000.
- [83]张红英.生物制剂在风湿免疫病治疗中的临床研究[J].中国医药科学,2013,3(9):86.
- [84]白云飞,林志健,张冰,等.祛风湿类中药饮片安全问题分析与用药警戒思考[J].中华中医药杂志,2016,31(10):4117.