Panés Julián, Gomollón Fernando, Taxonera Carlos, Hinojosa Joaquin, Clofent Juan, Nos Pilar
Department of Gastroenterology, Hospital Clinic, Barcelona, Spain.
Drugs. 2007;67(17):2511-37. doi: 10.2165/00003495-200767170-00005.
Crohn's disease is a debilitating and expensive disease that is growing in incidence in both developing and developed countries. While conventional therapies, such as corticosteroids and immunosuppressants, continue to play a vital role in treating this condition, it is evident that many affected individuals do not respond to therapy or develop intolerable adverse effects. The addition of modern biological therapies to the Crohn's disease armamentarium is providing a change in expectations for disease outcome. Infliximab and adalimumab are currently the only biological agents approved for induction and maintenance treatment in adults (infliximab and adalimumab) and children (infliximab) with Crohn's disease. Furthermore, infliximab has a beneficial effect on perianal fistulas. Other tumour necrosis factor (TNF)-alpha inhibitors, such as certolizumab pegol, also demonstrate promising results in adults with moderate to severe active disease. In addition, adalimumab and certolizumab pegol have shown clinical efficacy in patients who are intolerant to or lose response to infliximab, suggesting that switching between agents may allow response to be maintained over time. The primary safety concerns with TNFalpha inhibitors include increased risk of serious infection (including reactivation of tuberculosis), malignancy (particularly lymphoma) and demyelinating disease. Other agents in development include recombinant human anti-inflammatory cytokines, agents that target pro-inflammatory cytokines and granulocyte-macrophage colony-stimulating factors. Further prospective studies will provide interesting insight into different mechanisms by which factors involved in the pathophysiology of Crohn's disease can be modulated.
克罗恩病是一种使人虚弱且费用高昂的疾病,在发展中国家和发达国家的发病率都在上升。虽然传统疗法,如皮质类固醇和免疫抑制剂,在治疗这种疾病中继续发挥着至关重要的作用,但显然许多患者对治疗没有反应或出现无法耐受的不良反应。现代生物疗法加入克罗恩病的治疗手段后,正在改变人们对疾病预后的期望。英夫利昔单抗和阿达木单抗是目前仅有的被批准用于成人(英夫利昔单抗和阿达木单抗)和儿童(英夫利昔单抗)克罗恩病诱导缓解和维持治疗的生物制剂。此外,英夫利昔单抗对肛周瘘管有有益作用。其他肿瘤坏死因子(TNF)-α抑制剂,如赛妥珠单抗,在中重度活动性疾病的成人患者中也显示出有前景的结果。此外,阿达木单抗和赛妥珠单抗在对英夫利昔单抗不耐受或失去反应的患者中已显示出临床疗效,这表明在不同药物之间切换可能使疗效得以长期维持。TNF-α抑制剂的主要安全性问题包括严重感染(包括结核病复发)、恶性肿瘤(特别是淋巴瘤)和脱髓鞘疾病风险增加。正在研发的其他药物包括重组人抗炎细胞因子、靶向促炎细胞因子的药物以及粒细胞巨噬细胞集落刺激因子。进一步的前瞻性研究将为调节克罗恩病病理生理学相关因素的不同机制提供有趣的见解。