RA免疫抑制剂联合治课件

1、类风湿关节炎的免疫抑制剂联合治疗类风湿关节炎的免疫抑制剂联合治疗rara的新认识的新认识类风湿关节炎的治疗类风湿关节炎的治疗一般治疗一般治疗rara的药物治疗的药物治疗类风湿关节炎的治疗类风湿关节炎的治疗传统的药物疗法传统的药物疗法(dmard)(dmard)几种新的治疗方法几种新的治疗方法n产生对单抗的异蛋白的反应产生对单抗的异蛋白的反应n产生对单抗的抗体导致疗效减低产生对单抗的抗体导致疗效减低n生物反应生物反应n抗抗tnftnf单抗使用之后单抗使用之后 狼疮样反应狼疮样反应slesle，与（，与（nzbnzb nzw)f nzw)f 相似相似n干扰素干扰素 使用之后使用之后 自身免疫病自身

2、免疫病n近期疗效报告不一，如近期疗效报告不一，如infinf n远期疗效不详远期疗效不详n与与dmarddmard如何并用不详如何并用不详n昂贵昂贵rara治疗生物制剂存在的问题治疗生物制剂存在的问题(1)(1)dmardsdmards应用过程中普遍存在的问题应用过程中普遍存在的问题(2)table combination of disease-modifying antirheumatic drugs for the treatment of intractable ra author study type dmards findings sievers nonblind, nonrando

3、mized cq+ gold combination mroe efficacious than cq alone scott double-biind, randomized hcg+gold conbination more efficacious and more toxic than gold alone porter double-blind, radommized hcg+gold combination no mroe efficacious than gold alone mc kennal double-blind, randomized dp+gold conbinatio

4、n as efficacious as dp or gold alone bitter nonblinded, randomized dp+gold(high doses) combination more effective than dp gold alone bunch double-blind, randomized hcg+dp combination less efficacious than hcq alone, both less toxic than dp alone combination as toxic as hcq alone gibson nonblinded, r

5、andomzed cq+dp combination as efficacious as cq alone, both as efficacious as dp alone; more toxic than cq alone taggart nonblined, randomized sasp+dp combination more effective and more toxic than sasp alone furr uncontrolled study sasp+dp or gold combination moderated effective; conbination moderr

6、ately toxic author study type dmards findings brawer uncontrolled study gold+mtx combination effection williams doubl-blinded, randomized gold+mtx comoination as efficacious as mtx or gold alone reii nonblined, randomized mtx+sasp combination mroe efficacious than mtx alone clegg double-blinded, ran

7、domized mtx+hcq combination less effcacious than hcq alone wilikens double-blinded, randomized mtx+aza combination and mtx more efficasious than aza tugwell double-blinded, randomized mtx+cya combination more efficacious than mtx with moderately toxic bensen uncontrolled study mtx+cya conbination mo

8、re efficacious than cya or mtx alone mccarty uncontrolled study ctx+aza+hcq combination more effective but toxic csuka uncontrolled study ctx+aza+hcg combination more effective but toxic contd目前目前rara已普遍采用已普遍采用dmardsdmards联合治疗联合治疗我们应该如何选择联合治疗药物？我们应该如何选择联合治疗药物？联合治疗药物联合治疗药物 作用机理不太明确作用机理不太明确ngoldgoldna

9、ntimalarial agentsantimalarial agentsnd-penicillamined-penicillaminensulfasalazinesulfasalazine 作用机制明确作用机制明确nmtxmtxnaza aza n来氟米特来氟米特n骁悉骁悉n长春新碱长春新碱nctxctxa cell proliferation cycleg1s-phase s-phase synthesis of dna m-phase mitosis phaseg2m-phaseg0mtxaza来氟米特骁悉nmtxmtx，azaaza，来氟米特，骁悉：，来氟米特，骁悉： 周期特异性药物，

10、周期特异性药物，作用于作用于s s期，影响期，影响dnadna的合成，造成细胞成熟受阻的合成，造成细胞成熟受阻n长春新碱：周期特异性药物，作用于长春新碱：周期特异性药物，作用于m m期，抑制细期，抑制细胞的有丝分裂胞的有丝分裂nctxctx：周期非特异药物，作用于各细胞周期，直接：周期非特异药物，作用于各细胞周期，直接破坏破坏dnadna，杀伤细胞，杀伤细胞免疫抑制剂的细胞周期动力学免疫抑制剂的细胞周期动力学联合治疗方案联合治疗方案治疗治疗rara的新思路的新思路n首先选择联合的药物不适当：如首先选择联合的药物不适当：如mtx plus azamtx plus aza；mtx plus mtx

11、 plus 来氟米特等，它们有类似的作用机制，来氟米特等，它们有类似的作用机制，联合效率不高，甚至达不到相加作用联合效率不高，甚至达不到相加作用治疗治疗rara的新思路的新思路0 01010202030304040505060607070808090901001001 1weekweek3 3week week 6 6weekweek9 9weekweek1212weekweeknormal cellsnormal cellsabnormal cellsabnormal cellsgiven drugs every 3 weeks intermittent cycles of therapy联

12、合治疗降低副作用的途径联合治疗降低副作用的途径dmardsdmards联合用药的精髓联合用药的精髓联合治疗的结果联合治疗的结果n协同作用：协同作用： 1+121+12n相加作用：相加作用： 1+1=21+1=2n相减作用：相减作用： 1+12 1+10.5 there are no difference between two groups.table 2 times of morning stiffness ( hours )1.97 (0.992)1.03(0.61(0.51(0.44(2.01(0.929)1.08(0.43(0.43(0.34(0.8390.7630.0220.0430

13、.020-30-25-20-15-10-50疗后3周-基线疗后6周-基线疗后9周-基线疗后12周-基线疗后半年-基线疗后1年-基线疗后2年-基线图1 每一时窗血沉相对基线的变化图1 每一时窗血沉相对基线的变化mtxmtx+ctx00.511.522.5治疗前治疗前疗后12周疗后12周疗后半年疗后半年疗后1年疗后1年疗后2年疗后2年不同时间晨僵变化情况不同时间晨僵变化情况mtxmtx+ctxtable 3. time of morning stiffness baseline # ( hours)-0.939(-1.558(-1.458(-1.433(-0.931(-1.981(-2.182(-

14、2.567(0.88710.04570.0290.0012table 4 the cases of ra with joint pain 36(100.00)30(83.33)23(71.87)9(25.00)114(100.00)19(16.67)9(8.35)4(3.60)1.00000.00000.00000.000036(100.00)36(100.00)26(72.22)11(30.56)114(100.00)44(38.60)40(35.71)8(7.76)0.07420.00000.00000.0000table 5 the cases of ra with joint tend

15、erness36(100.00)36(100.00)32(88.89)6(16.67)114(100.00)44(38.60)40(35.71)15(13.51)0.27890.00000.00000.0098table 6 the cases of ra with joint swellingtable 7 esr chaning before and after treatment - baseline-8.583 (-13.306(-15.667(-16.472(-14.194(-15.528(-15.306(-11.175(-20.912(-25.140(-28.061(-26.254

16、(-27.623(-28.825 ( 0.05460.02860.02280.02510.02600.02670.0221table 8 the cases of ra with esr adnormal to normal4(11.11)7(19.44)7(19.44)9(25.00)11(30.06)13(36.11)8(22.22)24(21.05)35(30. 70)46(40.35)51(44.74)74(64.91)87(76.32)96(84.21) table 9 cases of complete remission0(0.00)8(22.22)7(19.44)21(18.4

17、2)46(40.35)78(68.42)0.00420.09770.0196远期疗效远期疗效 - 病例一病例一20022002年年20032003年年20032003年年远期疗效远期疗效 - 病例二病例二20022002年年20042004年年20052005年年远期疗效远期疗效 - 病例三病例三20012001年年20052005年年table 10 changing of peripheral blood leucocyte4(11.113(8.33)2(5.56)4(11.110(0.00)0(0.00)0(0.00)14(12.28)15(13.16)11(9.65)12(10.53)

18、0(0.00)0(0.00)0(0.00) 长期用药的副作用长期用药的副作用长期应用长期应用mtxmtx的副作用的副作用- -kevin gkevin g等等 长期应用长期应用mtxmtx的副作用的副作用- -kevin gkevin g等等 if ctx was given everyday, side effects is inevitableeffects of cyclophosphamide on the development of malignancy and on long-term survival of patients with rheumatoid arthritis.

19、 a 20-year followup study. arthritis rheum 1995 aug;38(8):1120-7 suarez-almazor me, et al. cyclophosphamide for rheumatoid arthritis. cochrane database syst rev 2000;(2):cd001157 长期应用长期应用ctxctx的副作用的副作用 hemorrhagic cystitis nausea, vomiting leucopenia thrombocytopenia alopecia amenorrhea herpes zoster infections if pulse cyclophosphamide was given, the side effects were mild in these studies长期应用长期应用ctxctx的副作用的副作用illei gg