03 类风湿关节炎的诊治进展2015继教班(胡建东)

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风湿科胡建东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)1972-2004AmericanCollegeofRheumatologyClinicalSlideCollection.Usedwithpermission.5DDiscomfortDisabilityDrugtoxicityDollarlostDeath病理机制诊断分类标准1987年ACR的RA分类标准注：以上7条满足4条或4条以上并排除其他关节炎可诊断RA，条件1～4必须持续至少6周(引自ArthritisRheum，1988，31：315-324)病情评估InstrumentsUsedtoMeasureRheumatoidArthritisDiseaseActivityClinicalMeasurementToolstoGuideTreatmentDecisionsAletahaD,etal.ClinExpRheumatol.2005;23(suppl39):S100-S108.CushJJ.ArthritisRheum.2005;52(9suppl):S686.LowDiseaseActivityModerateDiseaseActivityHighDiseaseActivityRemissionCDAI≤2.8222.9-1011-22DAS≤2.4SDAI225.53.6N/ASDAI≤3.33.4-1112-2626ACR/EULARDefinitionsofRemissioninRheumatoidArthritisClinicalTrials*Include28jointsplusfeetandankles.RA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RA确诊后尽快使用DMARD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）Whatistheevidenceforthepresenceofatherapeuticwindowofopportunityinrheumatoidarthritis?vanNiesJAB,etal.AnnRheumDis2014;73:861–870.doi:10.1136/annrheumdis-2012-203130Meta-analysisontheassociationbetweensymptomduration(inweeks)andachievingDMARD-freesustainedremissionovertimeinrheumatoidarthritis(RA).(A)Univariableanalysisonsymptomduration(B)Multivariableanalysisonsymptomduration,adjustedforage,genderandtreatment(C)Multivariableanalysisonsymptomduration,adjustedforage,gender,treatment,rheumatoidfactorandESR,vanNiesJAB,etal.AnnRheumDis2014;73:861–870.doi:10.1136/annrheumdis-2012-203130目标治疗（treattotarget)RemissionLowdiseaseactivity目标治疗(treattotarget)未达到治疗目标前，应严格控制（tightcontrol)，需定期（1-3个月）调整治疗方案，并密切监测•Progressionofstructuraldamage•Comorbidities•Safety调整治疗方案时除了上述疾病活动因素外，还应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•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（herbalmedicine)非甾体抗炎药(NSAIDs)EffectofNonsteroidalAntiinflammatoryDrugsontheC-ReactiveProteinLevelinRheumatoidArthritisHaemoglobindecreasesinNSAIDusersovertime:ananalysisoftwolargeoutcometrialsHaemoglobindecreasesinNSAIDusersovertime:ananalysisoftwolargeoutcometrialsHaemoglobindecreasesinNSAIDusersovertime:ananalysisoftwolargeoutcometrialsHaemoglobindecreasesinNSAIDusersovertime:ananalysisoftwolargeoutcometrialsAlimentPharmacolTher2011;34:808–816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≤7.5mg/d)仅适用于少数RA患者。•RA患者激素适用指征：①伴有血管炎等关节外表现的重症RA。②不能耐受NSAIDs的RA患者作为“桥梁”治疗。③其他治疗方法效果不佳的RA患者。④伴局部激素治疗指征(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(GC)糖皮质激素使用的指南改善病情抗风湿药(DMARDs)•传统DMARDs•生物制剂DMARDsDisease-ModifyingAntirheumaticDrugs生物制剂•Anti-TNF单抗人源单抗：adalimumab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•3/4为人源性，1/4为鼠源性，抗原结合区•可结合可溶性及细胞膜上的TNF，阻断炎症反应•单独使用或与MTX联用Infliximab(Remicade)Etanercept(Enbrel)•为一可溶性TNF受体，可中和TNF的体内活性•单独使用与MTX疗效相当，副作用小于MTXTEARRadiographicResultsIntensiveinterventioncanleadtoatreatmentholidayfrombiologicalDMARDsinpatientswithrheumatoidarthritisIntensiveinterventioncanleadtoatreatmentholidayfrombiologicalDMARDsinpatientswithrheumatoidarthritisIntensiveinterventioncanleadtoatreatmentholidayfrombiologicalDMARDsinpatientswithrheumatoidarthritisIntensiveinterventioncanleadtoatreatmentholidayfrombiologicalDMARDsinpatientswithrheumatoidarthritis草药（包括中药）•雷公藤制剂•青藤碱（Sinomenine）•姜黄（curcumalonga),姜黄素（Curcumin)•莪术（curcumaphaeocaulis)•姜（zingiberofficinale)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ComparisonofTripterygiumwilfordiiHookFwithmethotrexateinthetreatmentofactiverheumatoidarthritis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(12．5mg／周)、•单用雷公藤多甙组(20m∥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学会(ACR)推荐的RA疗效缓解50％(ACR50)标准。AnnRheumDis2015Jun;74(6):1078-86PMID:24733191ComparisonofTripterygiumwilfordiiHookFwithmethotrexateinthetreatmentofactiverheumatoidarthritis•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46．4％、55．1％、76．8％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=0．014)。同时探索性对比分析显示，两药联合治疗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(P0．05)，两药联合治疗疗效显著优于单用甲氨蝶呤(P0．05)。ComparisonofTripterygiumwilfordiiHookFwithmethotrexateinthetreatmentofactiverheumatoidarthritis•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RA的影响吸烟对RA的影响•Smokingasariskfactorfortheradiologicalseverityofrheumatoidarthritis:astudyonsixcohorts吸烟对RA的影响吸烟对RA的影响Meta-analysisontheeffectofsmoking(assessedaspastandpresentsmokersvsneversmokers)onjointdamageprogressioninsixcohorts.Depictedaretheresultsoftheindividualcohortsandofthemeta-analysis.(A)Meta-analysiswithoutadjustmentforanti-citrullinatedproteinantibodies(ACPA)status;Meta-analysisontheeffectofsmoking(assessedaspastandpresentsmokersvsneversmokers)onjointdamageprogressioninsixcohorts.Depictedaretheresultsoftheindividualcohortsandofthemeta-analysis.(B)theanalysesonallcohortswerealsoadjustedforACPA.吸烟对RA的影响•Thismulti-cohortstudyindicatedthattheeffectofsmokingonjointdamageismediatedviaACPAandthatsmokingisnotanindependentriskfactorforradiologicalprogressioninRA.谢谢！