de Boer Nanne Kh, Löwenberg Mark, Hoentjen Frank
Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, the Netherlands.
Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, the Netherlands.
Clin Exp Gastroenterol. 2014 Apr 11;7:83-92. doi: 10.2147/CEG.S47627. eCollection 2014.
Anti-tumor necrosis factor therapy with adalimumab is an effective therapy for the induction and maintenance of remission in moderate to severe Crohn's disease. Although a large proportion of patients show a favorable clinical response to adalimumab, therapy failure is common. In this review, we provide a practical overview of adalimumab therapy in patients with Crohn's disease, with a specific focus on the clinical management of adalimumab failure. In the case of inadequate efficacy, a thorough assessment is required to confirm inflammatory disease activity and rule out noninflammatory causes. Evaluation may include biomarkers (fecal calprotectin and serum C-reactive protein), colonoscopy, and/or magnetic resonance enterography/enteroclysis. Furthermore, adalimumab trough levels and antibodies to adalimumab are informational after the confirmation of active inflammation. In the case of low or undetectable adalimumab trough levels, dose escalation to 40 mg weekly is recommended, whereas high antibody titers or adverse events frequently require switching to an alternative anti-TNF agent such as infliximab. Active inflammation despite therapeutic adalimumab trough levels requires alternative strategies such as switching to drugs with a different mode of action or surgical intervention.
使用阿达木单抗进行抗肿瘤坏死因子治疗是诱导和维持中度至重度克罗恩病缓解的有效疗法。尽管很大一部分患者对阿达木单抗表现出良好的临床反应，但治疗失败很常见。在本综述中，我们对克罗恩病患者的阿达木单抗治疗进行了实用概述，特别关注阿达木单抗治疗失败的临床管理。在疗效不足的情况下，需要进行全面评估以确认炎症性疾病活动并排除非炎症性原因。评估可能包括生物标志物（粪便钙卫蛋白和血清C反应蛋白）、结肠镜检查和/或磁共振肠造影/小肠灌肠造影。此外，在确认存在活动性炎症后，阿达木单抗谷浓度水平和抗阿达木单抗抗体具有参考价值。如果阿达木单抗谷浓度水平较低或检测不到，建议将剂量增加至每周40毫克，而高抗体滴度或不良事件通常需要换用另一种抗TNF药物，如英夫利昔单抗。尽管阿达木单抗谷浓度水平处于治疗范围但仍存在活动性炎症，需要采取替代策略，如换用具有不同作用方式的药物或进行手术干预。
