1、类风湿关节炎的诊治进展类风湿关节炎的诊治进展上海中医药大学附属岳阳中西医结合医院上海中医药大学附属岳阳中西医结合医院风湿科风湿科 胡建东胡建东2015.9.17RA临床特点慢性侵蚀性关节炎进行性关节破坏功能丧失放射学破坏(c)1972-2004 American College of Rheumatology Clinical Slide Collection.Used with permission.诊断分类标准诊断分类标准19871987年年ACRACR的的RARA分类标准分类标准注：以上注：以上7条满足条满足4条或条或4条以上并排除其他关节炎可诊断条以上并排除其他关节炎可诊断RA，条件，
2、条件14必须持续至少必须持续至少6周周(引自引自Arthritis Rheum，1988，31：315-324)病情评估病情评估Instruments Used to Measure Rheumatoid Arthritis Disease ActivityClinical Measurement Tools to Guide Treatment DecisionsAletaha D,et al.Clin Exp Rheumatol.2005;23(suppl 39):S100-S108.Cush JJ.Arthritis Rheum.2005;52(9 suppl):S686.Low Dis
3、ease ActivityModerate Disease ActivityHigh Disease ActivityRemissionCDAI 2.8 222.9-1011-22DAS 2.4 SDAI 22 5.5 26ACR/EULAR Definitions of Remission in Rheumatoid Arthritis Clinical Trials*Include 28 joints plus feet and ankles.RARA的临床缓解标准的临床缓解标准2013年版EULAR关于RA治疗的推荐2013年版EULAR关于RA治疗的推荐早期治疗RARA确诊后尽快使用确
4、诊后尽快使用DMARDDMARD早期诊断是早期治疗的前提早期诊断是早期治疗的前提早期诊断早期诊断2010类风湿关节炎早期分类标准配合MRI早期治疗（治疗窗）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;73:861870.doi:10.1136/annrheumdis-2012-203130Meta-analysis on the association betwe
5、en symptom duration(in weeks)and achieving DMARD-freesustained remission over time inrheumatoid arthritis(RA).(A)Univariable analysis on symptomduration(B)Multivariable analysis onsymptom duration,adjusted for age,gender and treatment(C)Multivariable analysis on symptom duration,adjusted for age,gen
6、der,treatment,rheumatoid factor and ESR,van Nies JAB,et al.Ann Rheum Dis 2014;73:861870.doi:10.1136/annrheumdis-2012-203130目标治疗（treat to target)RemissionLow disease activity目标治疗(treat to target)未达到治疗目标前，未达到治疗目标前，应严格控制（应严格控制（tight controltight control)，需定期（需定期（1-31-3个月）调整治疗方案，并密切监测个月）调整治疗方案，并密切监测 Pro
7、gression of structural damageProgression of structural damage ComorbiditiesComorbidities SafetySafety调整治疗方案时除了上述疾病活动因素外，还应调整治疗方案时除了上述疾病活动因素外，还应考虑考虑指南解读指南解读指南解读指南解读指南解读药物治疗药物治疗 非甾体抗炎药(NSAIDs)糖皮质激素(GC)改善病情抗风湿药(DMARDs)生物制剂（Biologics)草药（herbal medicine)非甾体抗炎药非甾体抗炎药(NSAIDs)Effect of Nonsteroidal Antiinfl
8、ammatory Drugs on the C-Reactive Protein Level in Rheumatoid ArthritisHaemoglobin decreases in NSAID users over time:an analysis of two large outcome trialsHaemoglobin decreases in NSAID users over time:an analysis of two large outcome trialsHaemoglobin decreases in NSAID users over time:an analysis
9、 of two large outcome trialsHaemoglobin decreases in NSAID users over time:an analysis of two large outcome trialsAliment Pharmacol Ther 2011;34:808816糖皮质激素糖皮质激素(GC)重症RA伴有心、肺或神经系统等受累的患者，可给予短效激素，其剂量依病情严重程度而定。针对关节病变，如需使用，通常为小剂量激素(泼尼松7.5 mg/d)仅适用于少数RA患者。RA患者激素适用指征：伴有血管炎等关节外表现的重症伴有血管炎等关节外表现的重症RA。不能耐受不能耐
10、受NSAIDs的的RA患者作为患者作为“桥梁桥梁”治疗。治疗。其他治疗方法效果不佳的其他治疗方法效果不佳的RA患者。患者。伴局部激素治疗指征伴局部激素治疗指征(如关节腔内注射如关节腔内注射)。激素治疗RA的原则：小剂量、短疗程。使用激素必须同时应用DMARDs。激素治疗过程中，应补充钙剂和维生素D。糖皮质激素糖皮质激素(GC)糖皮质激素使用的指南糖皮质激素使用的指南改善病情抗风湿药改善病情抗风湿药(DMARDs)传统DMARDs 生物制剂DMARDsDisease-Modifying Antirheumatic Drugs生物制剂生物制剂 Anti-TNF单抗 人源单抗：adalimumab
11、鼠人嵌合单抗:infliximab 可溶性受体:etanercept 作用机制：拮抗TNF 应用：RA，SPA CD20单抗 作用机制：去除前B细胞、B细胞 应用：RA，ITP，SLE，ANCA相关性小血管炎 3/43/4为人源性，为人源性，1/41/4为鼠为鼠源性，抗原结合区源性，抗原结合区 可结合可溶性及细胞膜上可结合可溶性及细胞膜上的的TNFTNF，阻断炎症反应，阻断炎症反应 单独使用或与单独使用或与MTXMTX联用联用Infliximab(Remicade)Etanercept(Enbrel)为一可溶性为一可溶性TNFTNF 受体，可中和受体，可中和TNFTNF 的体内活性的体内活性单
12、独使用与单独使用与MTXMTX疗效相当，副作疗效相当，副作用小于用小于MTXMTXTEAR Radiographic ResultsIntensive intervention can lead to a treatment holiday from biological DMARDs in patients with rheumatoid arthritisIntensive intervention can lead to a treatment holiday from biological DMARDs in patients with rheumatoid arthritisInte
13、nsive intervention can lead to a treatment holiday from biological DMARDs in patients with rheumatoid arthritisIntensive intervention can lead to a treatment holiday from biological DMARDs in patients with rheumatoid arthritis草药（包括中药）雷公藤制剂雷公藤制剂 青藤碱青藤碱（Sinomenine）姜黄（姜黄（curcuma longa),姜黄素（姜黄素（Curcumin
14、)莪术（莪术（curcuma phaeocaulis)姜（姜（zingiber officinale)草药（包括中药）草药（包括中药）过山枫猫爪藤玛卡雷公藤青口贝大果漆树腰果Comparison of Tripterygium wilfordii Hook F with methotrexate in the treatment of active rheumatoid arthritis本研究共纳入207例活动性RA患者，按1：1：1随机分入3组：单用甲氨蝶呤组(125 mg周)、单用雷公藤多甙组(20 m次，3次d)，两药联合治疗组(剂量同单药组)，持续治疗24周，主要疗效终点为美国风湿病
15、学会(ACR)推荐的RA疗效缓解50(ACR50)标准。Ann Rheum Dis 2015 Jun;74(6):1078-86 PMID:24733191Comparison of Tripterygium wilfordii Hook F with methotrexate in the treatment of active rheumatoid arthritis 结果显示，单用甲氨蝶呤组、单用雷公藤多甙组和两药联合治疗组分别有464、551、768的患者达到ACR50。经非劣效性检验分析，提示单用雷公藤多甙的疗效不劣于单用甲氨蝶呤(P=0014)。同时探索性对比分析显示，两药联合治疗
16、疗效显著优于单用甲氨蝶呤(P0，001)。在其他评价指标(包括ACR20、ACR70、cDAI、疾病缓解率及低疾病活动度等)方面也显示，单用雷公藤多甙的疗效不劣于单用甲氨蝶呤(P005)，两药联合治疗疗效显著优于单用甲氨蝶呤(P005)。Comparison of Tripterygium wilfordii Hook F with methotrexate in the treatment of active rheumatoid arthritis 安全性分析显示，3组间不良事件(包括胃肠反应、性腺抑制、肝肾功异常等)的发生率差异无统计学意义。饮酒对类风湿关节炎的影响饮酒对类风湿关节炎的影
17、响饮酒饮酒对对RARA的的影响影响吸烟对吸烟对RARA的影响的影响 Smoking as a risk factor for the radiological severityof rheumatoid arthritis:a study on six cohorts吸烟对吸烟对RARA的影响的影响吸烟对吸烟对RARA的影响的影响Meta-analysis on the effect of smoking(assessed as past and present smokers vs never smokers)on joint damage progression in six cohort
18、s.Depicted are the results of the individual cohorts and of the meta-analysis.(A)Meta-analysis without adjustment for anti-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 coho
19、rts.Depicted are the results of the individual cohorts and of the meta-analysis.(B)the analyses on all cohorts were also adjusted for ACPA.吸烟对吸烟对RARA的影响的影响 This multi-cohort study indicated that the effect of smoking on joint damage is mediated via ACPA and that smoking is not an independent risk factor for radiological progression in RA.谢谢！谢谢！
