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生物分子在炎症性肠病治疗中的应用。

Use of biological molecules in the treatment of inflammatory bowel disease.

机构信息

Department of Gastroenterology, Medical Section, Herlev Hospital, University of Copenhagen, Herlev Ringvej 75, DK-2730Herlev, Denmark.

出版信息

J Intern Med. 2011 Jul;270(1):15-28. doi: 10.1111/j.1365-2796.2011.02344.x. Epub 2011 Mar 1.

Abstract

The introduction of biological agents (i.e. antitumour necrosis factor-α and anti-integrin treatments) for the treatment of inflammatory bowel disease (IBD) [i.e. Crohn's disease (CD) and ulcerative colitis] has led to a substantial change in the treatment algorithms and guidelines, especially in CD. However, many questions still remain about the true efficacy and the best treatment regimens. Thus, a need for further treatment options still exists as up to 40% of IBD patients treated with the presently available biologicals do not have positive clinical responses. Better patient selection might maximize the clinical benefit for those in most need of an effective therapy to avoid disabling disease whilst also minimizing the complications associated with therapy. Further, the 'trough-level strategy' may help clinicians to optimize therapy and to avoid loss of response and/or immunogenicity. The idea behind this dosage regimen is that correct dosing must ensure that the patient's lowest level of drug concentration (i.e. the trough level) occurring just before the next drug administration is high enough for the full effect to be seen. Controversy continues regarding the appropriate use of biologicals; therefore, in this review, we focus on considerations that might lead to a more rational strategy for antitumour necrosis factor-α agents in IBD, emphasizing the situations in which the risks may outweigh the benefits. Finally, the need for an appropriate strategy for stopping biological treatment is discussed.

摘要

生物制剂(即抗肿瘤坏死因子-α和抗整合素治疗)的引入用于治疗炎症性肠病(IBD)[即克罗恩病(CD)和溃疡性结肠炎],导致治疗算法和指南发生了重大变化,尤其是在 CD 中。然而,关于真正的疗效和最佳治疗方案仍有许多问题存在。因此,仍然需要进一步的治疗选择,因为高达 40%的接受现有生物制剂治疗的 IBD 患者没有积极的临床反应。更好的患者选择可能会最大限度地提高最需要有效治疗的患者的临床获益,以避免残疾疾病,同时最大限度地减少与治疗相关的并发症。此外,“谷底水平策略”可能有助于临床医生优化治疗,避免失去反应和/或免疫原性。这种剂量方案的理念是,正确的剂量必须确保患者在下一次药物给药前出现的最低药物浓度(即谷底水平)足够高,以产生全部效果。关于生物制剂的适当使用仍存在争议;因此,在这篇综述中,我们重点关注可能导致 IBD 中抗肿瘤坏死因子-α药物更合理策略的考虑因素,强调风险可能超过收益的情况。最后,还讨论了停止生物治疗的适当策略的必要性。

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