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1、环境/精神心理因素肠腔微生物抗原 免疫应答遗传易感性炎症性肠病药物治疗进展 -顺序性分步治疗方案应用 ： 最大限度缓解疾病活动性 最低限度发生激素依赖性Development and application of sequential protocols for treatment of inflammatory bowel disease (IBD) to maximize remission and minimize corticosteroid dependence in patients with IBD郑家驹M.D.,Ph.D. Zheng, Jia-ju, M.D., Ph.D.
2、嘉兴 JIA-xing 2012-04炎症性肠病病因与发病机制炎症性肠病治疗现状怎样？ -开始治疗前缺乏制订治疗方案(尤其是维持治疗方案) -诱导缓解不完全: 症状控制不彻底,炎症反复活动, 反复发作, 产生严重并发症 -维持治疗剂量不足 -维持治疗时间依从性欠佳 应对策略如何？ -治疗开始前即应制订一个可接受的个体化方案, 进行顺序性分步(序贯)治疗 -将临床常用药物拟定为相对固定方案可能有利于规 范化治病分会中华消化杂志2007; 夏冰.临床消化病杂志2007;19(1):3 What about the current state of IBD treatment ?- may not
3、receive effective therapy and their disease remains moderately active, leading to uncontrolled inflammation and potentially the development of complications.- optimal treatment outcomes are not often well defined and the duration of treatment is not addressed. As a consequence, patients undergo repe
4、ated cycles of corticosteroids (with or without immunosuppressive agents) without success as their disease remains active and progresses towards complications and the need for surgery. What are the optimal strategies to enable steroid free remission in IBD.-scientific literature was reviewed using M
5、edline and Chinese Database of Biology and Medicine (CBM) with a specific focus on medical therapies for inducing and maintaining remission of CD and UC. Therefore, treatment strategy algorithms are developed for use of suggested therapeutic protocols to enable steroid free remission in IBD. Panacci
6、one R, et al. Aliment Pharmacol Ther 28, 674688Aim: To seek evidence and provide direction for clinicians on optimal strategies to enable to maximize steroid free remission and minimize corticosteroid dependence in patients with inflammatory bowel disease. Methods: scientific literature was reviewed
7、 using Medline with a specific focus on medical therapies for inducing and maintaining remission of CD and UC.Therefore, treatment strategy algorithms are developed for use of suggested therapeutic protocols to enable steroid free remission in IBD. Panaccione R, et al. Aliment Pharmacol Ther 28, 674
8、688目的: 提供治疗 方向与方案，促使达到不用 激素状态下最大限度缓解IBD 活动性及最小限度激素依赖 性的最佳治疗效果。 方法: -搜集数据库诱导与维持溃疡 性结肠炎(UC)与克罗恩病 (CD)缓解的文献与科学依据 -分析并拟定有效与实用的顺序性治疗方案及其应用说明Results: Several therapies have demonstrated efficacy for the treatment of active, moderate-to-severe CD and UC. These include agents, which induce remission cortico
9、steroids, infliximab and adalimumab (CD only) or maintain remission and spare corticosteroids azathioprine, mercaptopurine, methotrexate (CD only), infliximab and adalimumab (CD only). Wide variability exists in the use of these agents. Panaccione R, et al. Aliment Pharmacol Ther 28, 674688结果: 研究证明有
10、多种药物 疗法对活动性UC或CD有效:具有诱导缓解 疗效的药物: 激素 英夫利西单抗（IFX） 阿达木单抗 （ADA, 仅用于CD)具有维持缓解与 减少激素剂量作 用的药物: 硫唑嘌呤(AZA)6-巯基嘌呤(6-MP) 甲氨蝶呤(MTX), IFX与ADA(仅适用于CD)-氨基水杨酸制剂是治疗炎症性肠病的基本药物 -不同个体间存在较大差病分会中华消化杂志2007; Rutgeerts P. Digestion 1998;59:453-69 Shanahan P. Gastrotenterol 2001;120:622-35治疗炎症性肠病的八大类常用药物 Drugs for medical tr
11、eatment of IBD1.氨基水杨酸盐 Aminosalicylates2.皮质类固醇 Corticosteroids3.免疫抑制剂 Immunosuppressive agents 4.生物学制剂 Biological agents 5.局部用制剂 Topical agent Traditional Chinese medicine (TCM)7.新药 Newly developed drugs8.其他 Other agents治疗标靶:1. 抗原呈递 抗体、益生菌 2. 抗原识别和细胞活化Aza, CyA, MTX 3. 细胞因子Anti-TNF (Infliximab), IL-1
12、1Corticosteroids 4. 趋化、黏附Antisense oligonucleo-tide to ICAM-1 5. 炎症和破损 Aminosalicylates,Corticosteroids 6. 修复和重建 Growth factors肠上皮细胞抗原细菌ICAM 1IL-12TNF IL-1 IL-8IFNIFN (-) IL-10 (-)+ 黏附分子+血管T-细胞巨噬细胞蛋白酶，NO， 白三烯类12 5634炎症性肠病的治疗标靶粒细胞、单核细胞表1.溃疡性结肠炎常用药物组合与顺序治疗方案-a 药物 方案 第一步:诱导缓解(黏 第二步:维持缓解（预 膜愈合)使用药物 防复发）
13、使用药物 5-氨基水杨酸 1.水杨酸偶氮磺胺吡 水杨酸偶氮磺胺吡 水杨酸偶氮磺胺 （5-ASA） 啶方案（SASP方案） 啶（SASP） 吡啶（SASP） 2.其它偶氮键前药方案：奥沙拉秦方案（Olz方案） 奥沙拉秦（Olz） 奥沙拉秦（Olz）巴柳氮方案（Blz方案) 巴柳氮（Blz) 巴柳氮（Blz)3.美沙拉秦方案（Mlz方案) 美沙拉秦(命)（Mlz）美沙拉秦(命)（Mlz）肾上腺糖皮质 4.传统激素联合方案 泼尼松（Prd）* 硫嘌呤类药物 类固醇（激素） （PrdAZA方案） （AZA/6-MP）5.布地奈德联合方案 布地奈德（Bud） 硫嘌呤类药物（BudAZA方案） （AZA/
14、6-MP）免疫抑制剂 6.环孢素联合方案 环孢素（CysA） 硫唑嘌呤（AZA） （CysAZA方案）7.他克莫司方案 他克莫司 他克莫司8.其它方案： 硫嘌呤类药物方案 硫嘌呤类药物 ? 硫嘌呤类药物?（AZA/6-MP） （AZA/6-MP）甲氨蝶呤（MTX）方案 甲氨蝶呤（MTX） 甲氨蝶呤（MTX）Table 1.Proposed stepwise protocols for treatment of ulcerative colitisDrugsProtocols1st step: agents using for remission induction (or mucosal he
15、aling)2nd step: agents using for remission maintenance (prevention of relapse)5- aminosali cylic acid （5-ASA ）1.SASP protocolSASPSASP2.Other prodrug protocols OLZ protocol BLZ protocolOlsalazine (OLZ) Balsalazide (BLZ)OLZ BLZ3.MLZ protocolMesalazine (MLZ)MLZCorticoste roids4.Combined PRDAZA protocol 5.Combined Bud protocolPrednisone (PRD)Budesonide (BUD)Azathioprine (AZA)/6-Mercapt
