Tsui Jonathan Jenkin, Huynh Hien Q
Edinburgh Medical School, University of Edinburgh, Edinburgh, UK (Jonathan Jenkin Tsui).
Department of Pediatrics, Stollery Children's Hospital, University of Alberta, Edmonton, Alberta, Canada (Hien Q. Huynh).
Ann Gastroenterol. 2018 Jul-Aug;31(4):413-424. doi: 10.20524/aog.2018.0253. Epub 2018 Mar 28.
The management of Crohn's disease involves immunosuppressive protocols in a step-up approach that progresses through a therapeutic pyramid with several tiers of medication. Medications at the top are considered more potent but present greater risk. A new top-down approach to therapy inverts this procedure, using top-tier drugs for initial treatment. A critical appraisal of the current literature relating to top-down therapy was performed to evaluate its merit. A literature search was conducted on PubMed, Ovid, and PubMed Central to identify studies of the efficacy of top-down therapy. Papers were appraised critically using the Scottish Intercollegiate Guidelines Network score to evaluate current evidence for the use of top-down therapy. Nineteen studies were identified, including six randomized controlled trials, thirteen cohort studies, and two cost-benefit studies. Early combined therapy involving both biologics and immunomodulators was found to be effective at improving patient outcomes; however, early biologics alone were not shown to have a clear benefit over step-up therapy. Likewise, the early use of immunomodulators alone showed inconsistent results with respect to efficacy in terms of both remission and surgical outcomes. Evidence for application in pediatric populations was also inconclusive. The cost-benefit analyses found that top-down therapy merits investigation, as it proved to be economical given current data. Top-down therapy has the potential of being a viable alternative to step-up therapy, but further studies are needed to determine the most appropriate patients to receive this treatment.
克罗恩病的治疗采用逐步升级的免疫抑制方案,通过一个包含多层药物的治疗金字塔逐步推进。位于金字塔顶端的药物被认为效力更强,但风险也更大。一种新的自上而下的治疗方法颠倒了这个过程,使用顶级药物进行初始治疗。对当前与自上而下治疗相关的文献进行了批判性评估,以评估其优点。在PubMed、Ovid和PubMed Central上进行了文献检索,以确定有关自上而下治疗疗效的研究。使用苏格兰跨学院指南网络评分对论文进行批判性评估,以评估当前使用自上而下治疗的证据。共识别出19项研究,包括6项随机对照试验、13项队列研究和2项成本效益研究。发现早期联合使用生物制剂和免疫调节剂可有效改善患者预后;然而,单独早期使用生物制剂并未显示出比逐步升级治疗有明显优势。同样,单独早期使用免疫调节剂在缓解和手术结局方面的疗效结果也不一致。在儿科人群中应用的证据也不确凿。成本效益分析发现,自上而下治疗值得研究,因为根据目前的数据,它被证明是经济的。自上而下治疗有可能成为逐步升级治疗的可行替代方案,但需要进一步研究以确定最适合接受这种治疗的患者。