Appropriateness of immunosuppressive drugs in inflammatory bowel diseases assessed by RAND method: Italian Group for IBD (IG-IBD) position statement
Appropriateness of immunosuppressive drugs in inflammatory bowel diseases assessed by RAND method: Italian Group for IBD (IG-IBD) position statement
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DOI：
10.1016/j.dld.2004.12.013
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发表时间：
2005-06-01
影响因子：
4.5
通讯作者：
Vecchi, M
中科院分区：
文献类型：
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作者：
Caprilli, R;Angelucci, E;Vecchi, M
导言。尽管生物疗法呈爆炸式增长，但旧的免疫抑制剂在炎症性肠病的治疗中仍发挥着关键作用。采用RAND/加州大学的适当性评价方法，评价免疫抑制剂硫唑嘌呤、6-巯基嘌呤、雷公藤甲酯、环孢素A、他克莫司(FK506)、霉酚酸酯和沙利度胺在炎症性肠病治疗中的适宜性。兰德方法结合了文献证据和专家意见。适当性被定义为预期的健康益处超过预期的负面后果的幅度足够大。意大利炎症性肠病小组的一个由10名专家组成的小组根据自己的临床经验，分两轮对促进者中心选择的每个适应症的适当性进行了从I到9的评分。如果小组成员的评分中值落在7-9区内，在1-3区不合适，在4-6区不确定，则认为这一指示是适当的。共有2781种适应症被分成13类(轻至中度克罗恩病；重度克罗恩病；瘘管性克罗恩病；类固醇依赖型和抗药性克罗恩病；克罗恩病内科治疗导致的持续缓解；克罗恩病手术导致的持续缓解；轻至中度溃疡性结肠炎；严重溃疡性结肠炎；类固醇依赖和抵抗性溃疡性结肠炎；溃疡性结肠炎的内科治疗保持缓解；炎症性肠病的肠外表现；妊娠和炎症性肠病；硫唑嘌呤抵抗或不耐受的炎症性肠病患者)。在2781个情景中，212个(7.6%)被评为合适，645个(23.2%)被评为不确定，1924个(69.2%)被评为不合适。最相关的结果是：在类固醇依赖或耐药的克罗恩病中，硫唑嘌呤、6-硫代嘌呤和甲氨蝶呤分别在29个方案中的25个(86.2%)和14个(48.3%)被定义为合适；在克罗恩病中，硫唑嘌呤和6-硫嘌呤被定义为合适的与英夫利昔单抗(桥接疗法)相结合；在类固醇依赖或耐药的溃疡性结肠炎中，在58个方案中有45个(77.6%)被定义为合适的硫唑嘌呤和6-巯基嘌呤，而甲氨蝶呤只有在先前的硫唑嘌呤失效后才被定义为合适；在严重溃疡性结肠炎中，环孢素A只有在激素治疗失败后才被定义为合适；在硫唑嘌呤不耐受或耐药的炎症性肠病患者中，甲氨蝶呤在30种情况中有20种(66.7%)是合适的；在存在活动性疾病的情况下，在受孕前停止硫唑嘌呤治疗是不合适的。FK506、霉酚酸酯和沙利度胺使用不当或不确定。本研究结果表明，只有硫唑嘌呤、6-巯基嘌呤和甲氨蝶呤是治疗炎症性肠病的合适药物。环孢素A被发现只适用于类固醇无效后的严重溃疡性结肠炎。FK506、霉酚酸酯和沙利度胺的结果是不合适的，但这些药物的经验有点有限。(C)2005年编辑意大利胃肠病学S.r.l.爱思唯尔有限公司出版。保留所有权利。
Introduction. Despite the explosion of biological therapies, the old immunosuppressants continue to play a pivotal role in the management of inflammatory bowel diseases.Aim. To assess the appropriateness of immunosuppressants-azathioprine, 6-mercaptopurine, rnethotrexate, cyclosporine A, tacrolimus (FK506), mycophenolate mofetil and thalidomide-in the treatment of inflammatory bowel disease by using RAND/University of California Appropriateness Method.Methods. The RAND method consists of a combination of evidence from the literature and experts' opinions. Appropriateness has been defined to mean that the expected health benefit exceeds the expected negative consequences by a sufficiently wide margin. A panel of 10 experts from the Italian Group for Inflammatory Bowel Disease has rated, in two rounds, on a scale from I to 9, the appropriateness of each indication selected by the Promoter Centre, on the basis of their own clinical experience. An indication was considered appropriate if the median of the panelists' ratings fell within the area 7-9, inappropriate in the area 1-3 and uncertain in the area 4-6. A total of 2781 indications were grouped into 13 categories (mild to moderate Crohn's disease; severe Crohn's disease; fistulizing Crohn's disease; steroid-dependant and -resistant Crohn's disease; maintenance of remission induced by medical treatment in Crohn's disease; maintenance of remission induced by surgery in Crohn's disease; mild to moderate ulcerative colitis; severe ulcerative colitis; steroid-dependant and -resistant ulcerative colitis; maintenance of remission induced by medical treatment in ulcerative colitis; extra-intestinal manifestations in inflammatory bowel disease; pregnancy and inflammatory bowel disease; azathioprine-resistant or -intolerant inflammatory bowel disease patients).Results. Of the 2781 scenarios, 212 (7.6%) were rated appropriate, 645 (23.2%) uncertain and 1924 (69.2%) inappropriate. The most relevant results were: in steroid-dependant or -resistant Crohn's disease, azathioprine, 6-mercaptopurine and methotrexate were defined as appropriate in 25 (86.2%) and 14 (48.3%) of the 29 scenarios respectively; in Crohn's disease, azathioprine and 6-mercaptopurine were defined as appropriate combined with Infliximab (bridge therapy); in steroid-dependant or -resistant ulcerative colitis, azathioprine and 6-mercaptopurine were defined as appropriate in 45 (77.6%) out of 58 scenarios, while methotrexate was defined appropriate only after previous azathioprine failure; in severe ulcerative colitis, cyclosporine A was defined as appropriate only after previous failure with steroids; in azathioprine-intolerant or -resistant inflammatory bowel disease patients, methotrexate was appropriate in 20 (66.7%) out of 30 scenarios; it is inappropriate to stop azathioprine treatment before conception in the presence of active disease. The use of FK506, mycophenolate mofetil and Thalidomide resulted as inappropriate or uncertain.Conclusions. Results of this study show that only azathioprine, 6-mercaptopurine and methotrexate are appropriate in the treatment of inflammatory bowel diseases. Cyclosporine A was found to be appropriate only in severe ulcerative colitis after the failure of steroids. FK506, mycophenolate mofetil and Thalidomide resulted as inappropriate but experience with these agents is somewhat limited. (c) 2005 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.