摘要
生物靶向药物如抗肿瘤坏死因子单抗、选择性黏附分子抑制剂等,给难治性炎症性肠病治疗带来了曙光。在诸多生物靶向药物中,英夫利昔单抗(infliximab,IFX,一种人-鼠嵌合体抗肿瘤坏死因子单抗)是近年研究与应用最深入的生物靶向药物。大量循证医学证据提示,IFX和类似的生物靶向药物可显著改进难治性克罗恩病和溃疡性结肠炎的疗效。然而,由于其固有的免疫原性,多次用药后疗效降低和药物输注反应在一定程度上影响了其疗效。提高剂量,缩短用药间隔或换用其他生物制剂可以恢复疗效。合并应用其他免疫抑制剂,或提前输入糖皮质激素可以减少输液反应的发生,但从根本上解决上述问题还需要改变抗体药物本身的免疫原性,如正在研制的纳米抗体便有望解决这些问题。药物诱发的机会感染,特别是结核感染是值得注意的问题。用药前认真进行结核杆菌筛查,如疑有结核病变活动,预先抗结核治疗是非常必要的。
Biological target drugs,such as anti-TNF monoclonal antibody and antibody against adhesion molecule,have opened new therapeutic horizons for inflammatory bowel disease（IBD）.Of series biological target drugs,infliximab（IFX）,a chimeric immunoglobulin（Ig）G1 monoclonal antibody to tumor necrosis factor,is the most advanced in use and development.A large number of evidence-based medicine data have suggested that IFX and other biological target drugs may dramatically improved the effects of treatment on patients with refractory Crohn＇s disease and ulcerative colitis.However,the drugs have also brought some issues related to immunogenicity after multiple administering,which compromise its long-term efficacy and safety.The therapeutic effects may be recovered by raising doses,shortening interval of infusion and changing to other biological target drugs.Concomitant immunosuppressive drugs and pre-infusion steroids can decrease serious adverse events related to the drugs.To avoid Immunogenicity,modifying drugs with current technique,such as the nanobodies that have been studied,might solve the problems.One of the main concerns is opportunistic infections during the course of therapy,especially tuberculosis（TB） activation.TB should be carefully screened before the therapy,and if TB activation is suspected anti-TB therapy will be necessary prior to the therapy.
出处
《中国新药杂志》
CAS
CSCD
北大核心
2010年第19期1750-1757,共8页
Chinese Journal of New Drugs
关键词
生物靶向药物
炎症性肠病
溃疡性结肠炎
克罗恩病
biological target drugs
inflammatory bowel disease
ulcerative colitis
Crohn＇s disease
