强直性脊柱炎早期诊断与处理进展文档资料.ppt

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1、概 要,早期诊断的困难与对策CT-MR的应用与局限性生物制剂的应用、维持方法思考AS与RA在生物制剂反应的区别及可能的机制来自ACR的新信息,诊断强直性脊柱炎的纽约标准（1966年）,临床标准：1.腰椎在所有3个平面的活动均受限：前屈、侧屈、背伸 2.腰骶结合部或腰椎疼痛 3.在第4肋间隙水平测量的扩胸度 2.5cm肯定AS：至少1条临床标准+3级以上双侧骶髂关节炎；或3级以上单侧骶髂关节炎/双侧2级骶髂关节炎+临床标准第1条或同时具备临床标准第2，3条可能AS：3级以上双侧骶髂关节炎不具备临床标准,骶髂关节炎的X线分级,0级，正常（normal）1级，可疑骶髂关节炎（suspicious）2

2、级，轻度骶髂关节炎（minimal）3级，中度骶髂关节炎（moderate）4级，骶髂关节强直（ankylosis）,AS起病年龄与确诊年龄分布,X线骶髂关节炎是一种后期表现,出现X线骶髂关节炎的时间,A,B,C and D are 3 different group of AS patients,强直性脊柱炎的治疗目标,目前尚无特效治疗1）控制炎症，缓解症状2）防止脊柱、髋关节强直畸形或保 持最佳功能位置3）减缓病情的进展早期诊断和尽早使用控制病情药物是减少致残的关键,强直性脊柱炎的治疗手段,病人教育 药物治疗非甾体抗炎药肾上腺皮质激素控制病情进展药物：柳氮磺吡啶、甲氨喋呤、其它药物（反应停

3、、抗TNF治疗等）抗骨质疏松治疗手术治疗（融骨术、关节置换）,物理疗法,体育疗法（游泳）,吸烟对SpA的影响?A PROSPECTIVE LONGITUDINAL OBSERVATIONAL STUDY,结 论,在早期AS,吸烟者与高疾病活动性及高CRP水平相关，有功能和脊柱活动度更差的倾向 在AS以外的其他SpA也观察到类似倾向，但不如AS明显,何时开始用DMARDs治疗AS？,3个月规律NSAIDs治疗不能缓解症状无法耐受NSAIDs或其AE难以控制的关节外表现具有预后差的表现：髋受累、跗骨炎、严重的肌腱端炎、ESR在疾病早期明显增高、发病年龄小等,Refractory AS,其他国家、地

4、区研究证实该结果 Patricia Woo认为Tha的安全性足以支持它在JIA中应用,EULAR 2006,生物制剂治疗AS新进展,3种抗TNF-制剂已被EMEA/FDA批准用于治疗AS可以特异性干扰与RA/AS发病机制有关的免疫级联反应不仅明显改善患者关节炎的症状与体征，而且可能对关节的骨质结构具有某些修饰作用该修饰作用最好的例子是IFX与MTX合用治疗RA患者时的结果,对TNF抑制剂的争论,制剂的特征特异性(TNF/LT;可溶性/膜表面)对靶目标的亲和力 半衰期/给药途径并发症(靶目标与药物特异性)?感染(脓毒血症,机会感染,TB等)?恶性病变(淋巴瘤,实体瘤)?自身免疫反应/脱髓鞘病/骨

5、髓抑制致免疫性(影响因素包括:异物性/给药途径/剂量/给药次数/同时服用的免疫调节药物 局部与全身反应费用直接(药物,给药,监测,毒性)间接(治疗失败,其它难以确定的费用),Side effects of TNF-Inhibitors,Serious infectionsAnti-DNA antibodies and lupus-like syndrome(most in IFX)Demyelinating diseaseLymphomaPancytopenia and aplastic anemia Infusion reactions IFXCongestive heart failure

6、 IFXReactivation of latent tuberculosis:infliximab 181 cases(2/02)(4 x expected)many cases extra-pulmonary,33%disseminatedEarly,median 12 weeks,mSASSS Progression,*P 0.05 vs baseline,The mean change on infliximab:0.9(from 11.6 12.5)in first 2y;0.7(from 12.5 13.2)in the second 2y Total change=1.6(+/-

7、2.6)in 4y,Do TNF-Blockers Reduce Radiographic Progression of AS?,Baraliakos et al.Rheumatology(Oxford).2007;46:14501453.,N=33,N=133,Effects of 2-yrs of INF Rx on Spinal Mobility and Chest Expansion in Patients With AS,Randomized,placebo-controlled trial in patients with active AS to assess safety an

8、d efficacy of INF 5 mg/kg IV at weeks 0,2,6,then every 6 weeksDose increased if BASDAI 3 on 2 consecutive visitsPatients randomized to INF(n=201)or placebo(n=78)Placebo patients switched to INF at week 24Spinal mobility(BASMI)and chest expansion were measuredAt week 24,INF group showed improvement i

9、n spinal mobility(P 0.02)and chest expansion(P=0.03),sustained for 2 yearsINF treatment resulted in clinically meaningful and sustained improvement in spinal mobility in patients with AS,BASDAI=Bath AS Disease Activity Index;BASMI=Bath AS Metrology Index;INF=infliximab.Braun et al.Data presented at

10、the ACR meeting.2007.Presentation#1153.,ASspiMRI-a=AS spinal MRI core for activity;INF=infliximabBraun et al.Data presented at the ACR meeting.2007.Presentation#1154.,Placebo(switched to INF 5 mg/kg after week 24),INF 5 or 7.5 mg/kg,+0.38,-4.89,-4.4,-4.87,-5,-4,-3,-2,-1,0,1,Week 24,Week 102,Mean Cha

11、nge From Baseline in ASspiMRI-a Score,Baseline:6.21 5.91N=77 200,n=195,n=60,n=161,n=72,Greater Improvement,Effects of 2-yrs of INF Rx on MRI Spinal Inflammation in Patients With AS,Long-Term Efficacy and Safety of ETA Rx Over 4-yrs in Patients With AS,Patients,%,44/48,38/44,18/44,38/44,Efficacy,75%,

12、64%,31%,64%,0,20,40,60,80,ASAS 20,ASAS 40,ASAS 5/6,BASDAI 50,Safety24 serious adverse events reported in 12 patients in the final 2 years9 patients reported uveitis/iritis/iridocyclitis(2 new cases and 1 flare)Rate of 9/100 patient-years,ASAS=Assessment in AS International Working Group;BASDAI=Bath

13、AS Disease Activity Index.Dijkmans et al.Data presented at the ACR meeting.2007.Presentation#1161.,IFX in severe active AS with spinal ankylosisACR abstract#1174,Cheung PP,et al,Australia,27 B27+AS,mean BASDAI of 8.7,11(41%)had complete spinal ankylosis54-wk trial,compare at BL and 1 yrResults:older

14、 in age 47.6/37.3(P=0.01)82%achieved ASAS20,comp/w 100%similar in ASAS40,5/6,BASDAI50,QoLonly 18%achieved ASAS PRfull-time employment:4580%(3373%)at 1 yrConclusion:In real life clinical practice,pts w/established dis(spinal ankylosis)and high levels of inflammation/dis activity can achieve a major clinical response with IFX,