Van Assche Gert, Vermeire Séverine, Rutgeerts Paul
Division of Gastroenterology, University of Leuven, Leuven, Belgium.
Curr Opin Gastroenterol. 2005 Jul;21(4):443-7.
Despite the advent of the anti-TNF agent, infliximab, an important unmet medical need characterizes the medical treatment of inflammatory bowel diseases. This review aims to summarize recent progress in the field.
For Crohn's disease, the fully human IgG1 anti-TNF monoclonal antibody, adalimumab and the humanized anti-alpha4 integrin IgG4 antibody, natalizumab have yielded the most promising results in controlled trials, but agents inhibiting the crucial IL12/interferon-gamma feedback loop also suggest therapeutic potential. Maintenance treatment with azathioprine, although efficacious, is not tolerated by up to 25% of individuals, but 6-thioguanine, an active metabolite, is associated with liver toxicity and is no longer recommended. For severe ulcerative colitis, low intravenous cyclosporine doses have been demonstrated to be efficacious, and may serve to limit the toxicity with this agent. Biologic treatment is being developed to target severe ulcerative colitis. Efficacy of infliximab to stop fistula draining as a maintenance agent for fistulizing Crohn's disease has been demonstrated in a large controlled trial, but MRI imaging indicates that the improvement of inflammation in fistula tracks is delayed.
In conclusion, medical therapy of inflammatory bowel diseases is a constantly moving field and recent evolutions will undoubtedly change clinical practice in the years to come.
尽管抗TNF药物英夫利昔单抗已经问世,但炎症性肠病的医学治疗仍存在一项重要的未满足医疗需求。本综述旨在总结该领域的最新进展。
对于克罗恩病,全人源IgG1抗TNF单克隆抗体阿达木单抗和人源化抗α4整合素IgG4抗体那他珠单抗在对照试验中取得了最有前景的结果,但抑制关键的IL12/干扰素-γ反馈环的药物也显示出治疗潜力。硫唑嘌呤维持治疗虽然有效,但高达25%的个体无法耐受,而其活性代谢产物6-硫鸟嘌呤与肝毒性相关,不再被推荐使用。对于重度溃疡性结肠炎,低剂量静脉注射环孢素已被证明有效,且可能有助于限制该药物的毒性。针对重度溃疡性结肠炎的生物治疗正在研发中。一项大型对照试验已证明英夫利昔单抗作为瘘管性克罗恩病的维持药物在停止瘘管引流方面的疗效,但MRI成像表明瘘管通道内炎症的改善有所延迟。
总之,炎症性肠病的医学治疗是一个不断发展的领域,近期的进展无疑将在未来几年改变临床实践。