A User’s Guide to De-escalating Immunomodulator and Biologic Therapy in Inflammatory Bowel Disease

De-escalation of immunomodulators and biologic agents in inflammatory bowel disease is frequently discussed with patients and must weigh the risk of continued medical therapy with the risk of disease recurrence. Risk factors for disease flare after withdrawal of inflammatory bowel disease medications such as disease activity at de-escalation, disease prognostic features, and prior course of disease have been identified predominately in retrospective studies, allowing for risk stratification of patients. This review evaluates the published literature regarding therapeutic de-escalation and provides a framework for physicians to apply this to clinical practice. Prospective trials are underway and planned, which should provide further insight into this treatment paradigm and better inform patient selection for this strategy.     

Immunomodulator Withdrawal From Anti-TNF Therapy Is Not Associated With Loss of Response in Inflammatory Bowel Disease

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英夫利昔单抗治疗炎症性肠病的研究进展

肿瘤坏死因子－α（TNF－α）是一种促炎细胞因子,在炎症性肠病（IBD）的发病过程中起重要作用。英夫利昔,单抗（infliximab）是一种人-鼠嵌合型TNF-αIgGl单克隆抗体,与体内多种形式的TNF-α有较强结合能力。美国食品药品管理局（FDA）于1998年批准该制剂用于治疗传统药物治疗无效的中重度或合并瘘管的克罗恩病（CD）,试验显示其对难治性活动性溃疡性结肠炎（UC）亦有一定疗效。英夫利昔单抗的使用已积累了10年的经验,本文对其作用机制、疗效、安全性方面的研究进展作一综述。     

炎症性肠病的药物治疗

近年来,炎症性肠病(IBD)的药物治疗进展较快,并强调在治疗开始前就制订一个长期顺序治疗方案(途径),治疗过程中进行阶段性疗效评估,必要时调整方案。本文通过复习国内外最新IBD诊治共识和指南以及近期发表的相关综述、随机对照试验和高质量荟萃分析,对IBD的药物治疗途径和治疗要点作一概述,以期促进和改善IBD患者的长期治疗结局。     

De-escalation of Therapy in Inflammatory Bowel Disease

Purpose of Review

Currently, inflammatory bowel disease treatment is based on immunomodulators (IM) and/or biologic as this strategy may prevent the development of irreversible damage. Nevertheless, long-term treatment may be associated with non-negligible side effects and with high costs, and therefore the question on whether therapy can be de-escalated is often posed in clinical practice.

Recent Findings

Recent studies have shown a predictable rate of relapse after stop biologic or IM therapy withdrawal. Overall, around 40–50% of patients will eventually relapse over the following year after drug withdrawal, and the rates will increase over time. Stratification of patients and therapeutic drug monitoring could be promising alternatives to guide therapeutic management.

Summary

We reviewed the current evidence on de-escalation strategy and summarised the recent results on discontinuation and dose reduction. Nowadays, de-escalation strategy is still a case-by-case decision in highly selected patients.

     

Medical Therapy for Pediatric Inflammatory Bowel Disease

Pediatric inflammatory bowel disease encompasses a spectrum of disease phenotype, severity, and responsiveness to treatment. Intestinal healing rather than merely symptom control is an especially important therapeutic goal in young patients, given the potential for growth impairment as a direct effect of persistent chronic inflammation and the long life ahead, during which other disease complications may occur. Corticosteroids achieve rapid symptom control, but alternate steroid-sparing strategies with greater potential to heal the intestine must be rapidly adopted. Exclusive enteral nutrition is an alternate short-term treatment in pediatric Crohn’s disease. The results of multi-center pediatric clinical trials of both infliximab and adalimumab in Crohn’s disease and of infliximab in ulcerative colitis (all in children with unsatisfactory responses to other therapies) have now been reported and guide treatment regimens in clinical practice. Optimal patient selection and timing of anti-TNF therapy requires clinical judgment. Attention must be paid to sustaining responsiveness safely.     

Drug Therapy of Inflammatory Bowel Disease in Fertile Women

Inflammatory bowel disease (IBD) is a disease that affects women of childbearing age. Active disease at conception increases the risk for adverse outcomes and thus postponement of pregnancy until the disease is in remission is the best advice that physicians can give their IBD patients. The majority of medications used to treat IBD are safe in pregnancy and breastfeeding; active, untreated, or undertreated disease is more deleterious than active therapy.     

干细胞治疗在炎症性肠病中的研究进展

我国炎症性肠病(IBD)发病率近年来呈明显上升趋势,危重病例也逐渐增多。现有的IBD治疗主要着眼于控制活动性炎症和调节免疫紊乱,常用药物有5-氨基水杨酸类制剂、糖皮质激素、免疫抑制剂等,对危重及难治性病例疗效有限,且存在许多不良反应。干细胞移植治疗是一种新兴的治疗方法,也是近年来IBD治疗领域的研究热点之一。本文对既往干细胞移植治疗IBD的临床和基础研究进行回顾,着重介绍近年来该领域的新进展。     

炎症性肠病伴慢性肠道炎症的新治疗

肠道持续性慢性炎症是炎症性肠病（IBD）难以治愈的关键所在。造成肠道慢性炎症的核心机制是肠道血循环中淋巴细胞和血管内皮细胞的黏附和渗出。本文就主要黏附分子靶向抗黏附治疗的应用和临床地位作一简介。     

Curcumin Therapy in Inflammatory Bowel Disease: A Pilot Study

Curcumin, a natural compound used as a food additive, has been shown to have anti-inflammatory and antioxidant properties in cell culture and animal studies. A pure curcumin preparation was administered in an open label study to five patients with ulcerative proctitis and five with Crohn's disease. All proctitis patients improved, with reductions in concomitant medications in four, and four of five Crohn's disease patients had lowered CDAI scores and sedimentation rates. This encouraging pilot study suggests the need for double-blind placebo-controlled follow-up studies. Kindly provided by R. Kane Products, Pennsauken, New Jersey.