類風(fēng)濕關(guān)節(jié)炎的診治進(jìn)展繼教班胡建東2015

1、類風(fēng)濕關(guān)節(jié)炎的診治進(jìn)展,上海中醫(yī)藥大學(xué)附屬岳陽中西醫(yī)結(jié)合醫(yī)院風(fēng)濕科 胡建東,2015.9.17,RA臨床特點(diǎn),放射學(xué)破壞,(c) 1972-2004 American College of Rheumatology Clinical Slide Collection. Used with permission.,病理機(jī)制,診斷分類標(biāo)準(zhǔn),1987年ACR的RA分類標(biāo)準(zhǔn),注：以上7條滿足4條或4條以上并排除其他關(guān)節(jié)炎可診斷RA，

2、條件1～4必須持續(xù)至少6周(引自Arthritis Rheum，1988，31：315-324),病情評估,Instruments Used to Measure Rheumatoid Arthritis Disease Activity,Clinical Measurement Tools to Guide Treatment Decisions,Aletaha D, et al. Clin Exp Rheumatol. 2005;2

3、3(suppl 39):S100-S108.Cush JJ. Arthritis Rheum. 2005;52(9 suppl):S686.,Low Disease Activity,Moderate Disease Activity,High Disease Activity,Remission,,CDAI ≤ 2.8,,> 22,,2.9-10,11-22,,DAS ≤ 2.4,,SDAI >22,> 5.5,,

4、< 3.6,N/A,,,SDAI ≤ 3.3,,3.4-11,12-26,> 26,ACR/EULAR Definitions of Remission in Rheumatoid Arthritis Clinical Trials,* Include 28 joints plus feet and ankles.,RA的臨床緩解標(biāo)準(zhǔn),2013年版EULAR關(guān)于RA治療的推薦,2013年版EULAR關(guān)于RA治療的推薦,早期治

5、療,早期診斷,早期診斷,2010類風(fēng)濕關(guān)節(jié)炎早期分類標(biāo)準(zhǔn)配合MRI,早期治療（治療窗）,What is the evidence for the presence of a therapeutic window of opportunity in rheumatoid arthritis?van Nies JAB, et al. Ann Rheum Dis 2014;73:861–870. doi:10.1136/annrh

6、eumdis-2012-203130,Meta-analysis on the association between symptom duration(in weeks) and achieving DMARD-freesustained remission over time inrheumatoid arthritis (RA). (A)Univariable analysis on symptomduration (B

7、) Multivariable analysis onsymptom duration, adjusted for age,gender and treatment (C) Multivariable analysis on symptom duration,adjusted for age, gender, treatment,rheumatoid factor and ESR,,van Nies JAB, et al. Ann

8、 Rheum Dis 2014;73:861–870. doi:10.1136/annrheumdis-2012-203130,目標(biāo)治療（treat to target),,Remission,Low disease activity,目標(biāo)治療(treat to target),指南解讀,指南解讀,指南解讀,指南解讀,指南解讀,藥物治療,非甾體抗炎藥(NSAIDs)糖皮質(zhì)激素(GC)改善病情抗風(fēng)濕藥(DMARDs)生物制劑（Bio

9、logics)草藥（herbal medicine),非甾體抗炎藥(NSAIDs),Effect of Nonsteroidal Antiinflammatory Drugs on the C-Reactive Protein Level in Rheumatoid Arthritis,Haemoglobin decreases in NSAID users over time: an analysis of two large o

10、utcome trials,Haemoglobin decreases in NSAID users over time: an analysis of two large outcome trials,Haemoglobin decreases in NSAID users over time: an analysis of two large outcome trials,Haemoglobin decreases in NSA

11、ID users over time: an analysis of two large outcome trials,Aliment Pharmacol Ther 2011; 34: 808–816,,,糖皮質(zhì)激素(GC),重癥RA伴有心、肺或神經(jīng)系統(tǒng)等受累的患者，可給予短效激素，其劑量依病情嚴(yán)重程度而定。針對關(guān)節(jié)病變，如需使用，通常為小劑量激素(潑尼松≤7.5 mg/d)僅適用于少數(shù)RA患者。RA患者激素適用指征：伴有血管炎

12、等關(guān)節(jié)外表現(xiàn)的重癥RA。不能耐受NSAIDs的RA患者作為“橋梁”治療。其他治療方法效果不佳的RA患者。伴局部激素治療指征(如關(guān)節(jié)腔內(nèi)注射)。激素治療RA的原則：小劑量、短療程。使用激素必須同時應(yīng)用DMARDs。激素治療過程中，應(yīng)補(bǔ)充鈣劑和維生素D。,糖皮質(zhì)激素(GC),糖皮質(zhì)激素使用的指南,改善病情抗風(fēng)濕藥(DMARDs),傳統(tǒng)DMARDs生物制劑DMARDs,Disease-Modifying Antirheumati

13、c Drugs,生物制劑,Anti-TNF?單抗 人源單抗：adalimumab 鼠人嵌合單抗 : infliximab 可溶性受體: etanercept 作用機(jī)制： 拮抗TNF? 應(yīng)用：RA，SPACD20單抗 作用機(jī)制：去除前B細(xì)胞、B細(xì)胞 應(yīng)用：RA，ITP，SLE， ANCA相關(guān)性小血管炎,3/4為人源性， 1/4為鼠源性，抗原結(jié)合區(qū)可結(jié)合可溶性及細(xì)胞膜上的TNF?，阻斷炎癥反應(yīng)

14、單獨(dú)使用或與MTX聯(lián)用,Infliximab (Remicade),Etanercept (Enbrel),為一可溶性TNF?受體，可中和TNF?的體內(nèi)活性單獨(dú)使用與MTX療效相當(dāng)，副作用小于MTX,,TEAR Radiographic Results,Intensive intervention can lead to a treatment holiday from biological DMARDs in patients w

15、ith rheumatoid arthritis,Intensive intervention can lead to a treatment holiday from biological DMARDs in patients with rheumatoid arthritis,Intensive intervention can lead to a treatment holiday from biological DMARDs i

16、n patients with rheumatoid arthritis,Intensive intervention can lead to a treatment holiday from biological DMARDs in patients with rheumatoid arthritis,草藥（包括中藥）,雷公藤制劑青藤堿（Sinomenine）姜黃（curcuma longa),姜黃素（Curcumin)莪術(shù)（c

17、urcuma phaeocaulis)姜（zingiber officinale),草藥（包括中藥）,過山楓,貓爪藤,瑪卡,雷公藤,青口貝,大果漆樹腰果,,Comparison of Tripterygium wilfordii Hook F with methotrexate in the treatment of active rheumatoid arthritis,本研究共納入207例活動性RA患者，按1：1：1隨機(jī)分入3組

18、：單用甲氨蝶呤組(12．5 mg／周)、單用雷公藤多甙組(20 m∥次，3次／d)，兩藥聯(lián)合治療組(劑量同單藥組)，持續(xù)治療24周，主要療效終點(diǎn)為美國風(fēng)濕病學(xué)會(ACR)推薦的RA療效緩解50％(ACR50)標(biāo)準(zhǔn)。Ann Rheum Dis 2015 Jun;74(6):1078-86 PMID:24733191,Comparison of Tripterygium wilfordii Hook F with methot

19、rexate in the treatment of active rheumatoid arthritis,結(jié)果顯示，單用甲氨蝶呤組、單用雷公藤多甙組和兩藥聯(lián)合治療組分別有46．4％、55．1％、76．8％的患者達(dá)到ACR50。經(jīng)非劣效性檢驗分析，提示單用雷公藤多甙的療效不劣于單用甲氨蝶呤(P=0．014)。同時探索性對比分析顯示，兩藥聯(lián)合治療療效顯著優(yōu)于單用甲氨蝶呤(P<0，001)。在其他評價指標(biāo)(包括ACR20、ACR7

20、0、cDAI、疾病緩解率及低疾病活動度等)方面也顯示，單用雷公藤多甙的療效不劣于單用甲氨蝶呤(P<0．05)，兩藥聯(lián)合治療療效顯著優(yōu)于單用甲氨蝶呤(P<0．05)。,Comparison of Tripterygium wilfordii Hook F with methotrexate in the treatment of active rheumatoid arthritis,安全性分析顯示，3組間不良事件(包括胃腸反

21、應(yīng)、性腺抑制、肝腎功異常等)的發(fā)生率差異無統(tǒng)計學(xué)意義。,飲酒對類風(fēng)濕關(guān)節(jié)炎的影響,飲酒對RA的影響,吸煙對RA的影響,Smoking as a risk factor for the radiological severityof rheumatoid arthritis: a study on six cohorts,吸煙對RA的影響,吸煙對RA的影響,Meta-analysis on the effect of smoking (a

22、ssessed as past and present smokers vs never smokers) on joint damage progression in six cohorts. Depicted are the results of the individual cohorts and of the meta-analysis. (A) Meta-analysis without adjustment for ant

23、i-citrullinated protein antibodies (ACPA) status;,Meta-analysis on the effect of smoking (assessed as past and present smokers vs never smokers) on joint damage progression in six cohorts. Depicted are the results of the

24、 individual cohorts and of the meta-analysis. (B) the analyses on all cohorts were also adjusted for ACPA.,吸煙對RA的影響,This multi-cohort study indicated that the effect of smoking on joint damage is mediated via ACPA and th