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1、类风湿关节炎,北京协和医院风湿免疫科,美国欣凯公司 爱若华病友会,血管翳,RA骨破坏的机制：破骨细胞的分化,纤维母细胞样滑膜细胞,滑膜内有大量OC形成,a Georg Schett Cells of the synovium in rheumatoid arthritis-Osteoclasts , Arthritis Research 2010;69:631637,RA疾病活动和关节破坏的关系,Smolen, et al. Ann Rheum Dis; 2010;69:631637,EULAR Recommendations: Phase ,For internal Use Only For
2、 other usage subject to local regulatory review,The treatment target is clinical remission or, if remission is unlikely to be achievable, at least low disease activity,Phase ,Clinical diagnosis of rheumatoid arthritis,Start methotrexate,Combine with short-term low or high dose glucocorticoids,Start
3、leflunonmide, intramuscular gold or sulfasalazine,Achieve target* within 3-6 months,No,Failure phase : go to phase ,Yes,Continue,Smolen J et al. Ann Rheum Dis published online May 5,2010,No contraindication for methotrexate,Contraindication for methotrexate,第1步,诊断RA （ACR87或ACR/ EULAR2010),使用来氟米特、SAS
4、P或注射金,使用MTX,没有MTX禁忌证,有MTX禁忌证,第1步失败: 转入第2步,否,在3-6个月内达标,是,继续原方案,短期联合低或高剂量糖皮质激素,EULAR Recommendations: Phase ,For internal Use Only For other usage subject to local regulatory review,The treatment target is clinical remission or, if remission is unlikely to be achievable, at least low disease activity,
5、Phase ,Failure or lack of efficacy and/or toxicity in phase ,Add a biological drug (especially a TNF-inhibitor),Start a second Synthetic DMARD: Leflunomide, Sulfasalzine, MTX or Intramuscular gold as monotherapy or eventually as combination therapy (with or without addtion of glucocorticoids as abov
6、e),Achieve target* within 3-6 months,No,Failure phase : go to phase ,Yes,Continue,Prognostically unfavourable factors present,Prognostically unfavourable factors absent,such as RF/ACPA, esp. at high levels; very high disease activity; early joint damage,Achieve target* within 3-6 months,No,Smolen J
7、et al. Ann Rheum Dis published online May 5,2010,第2步,第1步治疗失败,单独使用第2种传统DMARD 或 联合治疗 (糖皮质激素),加用TNF拮抗剂,有预后不良因素,无预后不良因素,第2步失败: 转入第3步,无,在3-6个月内达标,是,继续治疗,高滴度RF/抗CCP 病情高度活动 早期骨破坏,否,在3-6个月内达标,Changes in Hand Bone Mineral Density are Associated with the Level of Disease Activity,Method Metacarpal bone minera
8、l density (mBMD) measurements were performed in 145 out of 508 patients from the BeSt study Results Continuous remission and age are independent predictors of mBMD gain Continuous higher disease activity is inversely associated with increase in mBMD (OR 0.5 95% CI: 0.3-0.8),BeSt,For internal Use Onl
9、y For other usage subject to local regulatory review,Increase in mBMD can occur, primarily in patients in continuous remission (DAS441.6), and therefore remission should be the treatment goal,Dirven L, et al. EULAR 10 FRI0162.,EULAR Recommendations: Phase ,For internal Use Only For other usage subje
10、ct to local regulatory review,Phase ,Failure or lack of efficacy and/or toxicity in phase ,Add a biological drug (especially a TNF-inhibitor),Start a second Synthetic DMARD: Leflunomide, Sulfasalzine, MTX or Intramuscular gold as monotherapy or eventually as combination therapy (with or without addt
11、ion of glucocorticoids as above),Achieve target* within 3-6 months,No,Failure phase : go to phase ,Yes,Continue,Prognostically unfavourable factors present,Prognostically unfavourable factors absent,such as RF/ACPA, esp. at high levels; very high disease activity; early joint damage,Achieve target*
12、within 3-6 months,No,Smolen J et al. Ann Rheum Dis published online May 5,2010,“Treatment should be aimed at reaching target of remission or low disease activity as soon as possible in every patient; treatment should be adjusted by frequent (every 1-3 months) and strict monitoring”,EULAR Recommendat
13、ions: Phase ,For internal Use Only For other usage subject to local regulatory review,Phase ,Failure or lack of efficacy and/or toxicity in phase ,Add a biological drug (especially a TNF-inhibitor),Start a second Synthetic DMARD: Leflunomide, Sulfasalzine, MTX or Intramuscular gold as monotherapy or
14、 eventually as combination therapy (with or without addtion of glucocorticoids as above),Achieve target* within 3-6 months,No,Failure phase : go to phase ,Yes,Continue,Prognostically unfavourable factors present,Prognostically unfavourable factors absent,such as RF/ACPA, esp. at high levels; very hi
15、gh disease activity; early joint damage,Achieve target* within 3-6 months,No,Smolen J et al. Ann Rheum Dis published online May 5,2010,“If a patient is in persistent remission, one can consider tapering biological DMARDs, especially if this treatment is combined with asynthetic DMARD” “In cases of s
16、ustained long-term remission, cautious titration of synthetic DMARD dose could be considered”,第2步治疗失败,转换其它生物制剂,在3-6个月内达标,是,继续治疗,否,第3步,生物制剂传统DMARD,药物选择 - MTX ：活动性RA首选之一,MTX：核心药物（Anchor Drug） 小剂量（7.5-15mg/w）每周使用是长期最有效和安全的药物 大剂量（2030mg/w）疗效更好，有细胞毒和其它副作用，根据个体差异决定是否使用大剂量 口服疗效不佳或胃肠副作用明显时可改皮下或肌注 快加：5mg/w；慢减：2.5mg/w 合并使用叶酸明显减少胃肠副作用,Chan ESL, Cronstein BN. Molecular action of methotrexate in inf
