Emerging role of biosimilars in the clinical care of inflammatory bowel disease patients

The increasing incidence of inflammatory bowel disease (IBD) globally has redirected the healthcare system's focus towards safe and affordable pharmacological interventions. The inception of anti-tumor necrosis factor-α (TNF-α) had resulted in a trend shift from surgical interventions. However, as the patents of approved anti-TNF-α drugs expire, biological copies of the many approved products are in the pipeline. The most commonly used biosimilar for IBD has been infliximab, followed by Adalimumab biosimilars which have been approved in major countries across the world. Although biosimilars are approved on the basis of similarity of their reference product, the lack of real-world evidence of its safety in ulcerative colitis and Crohn’s disease patients has contributed to physicians’ hesitancy. However, biosimilars are expected to reduce treatment costs and provide economic benefits.     

经腹肠道超声在炎症性肠病诊断中的应用及进展

炎症性肠病(IBD)是一种慢性炎症性疾病,病程漫长,症状发作与缓解反复交替,通常需要终身治疗。经腹肠道超声(TUBS)已成为临床IBD疑诊患者筛查的首选影像技术,对确定IBD病变的部位和范围、发现腹部并发症、评估炎症活动性及治疗后随访均有很高的敏感度和特异度。口服肠道超声造影、经静脉超声造影等超声新技术扩大了TBUS在IBD中的应用能力;而新兴的超声分子成像技术更有望使TBUS在疾病早期诊断上取得突破。     

肿瘤坏死因子样配体1A在炎症性肠病免疫调控中的作用

炎症性肠病包括溃疡性结肠炎和克罗恩病,目前多认为其发病机制是环境因素作用于遗传易感者,在肠道菌群的参与下,启动了难以停止的、发作与缓解交替的肠道免疫反应。然而,其发病机制尚不十分明确,因此,进一步探讨和阐明炎症性肠病的发病机制对于寻找新的治疗方法具有重要的意义。肿瘤坏死因子样配体1A(tumor necrosis factor-like ligand 1 aberrance,TL1A)是新近发现的一种肿瘤坏死因子家族新成员,是炎症性肠病的易感基因。TL1A在黏膜炎症的固有免疫和适应性免疫之间起到了关键的调控和连接作用,从而在炎症性肠病中发挥重要作用。现将TL1A在炎症性肠病免疫调控机制中的作用进行综述。     

MR colonography in inflammatory bowel disease

Colonography based on magnetic resonance imaging (MRI) appears to be a promising technique for polyp assessment in the colon. Several studies have evaluated this method for colonic assessment in patients with inflammatory bowel disease. We briefly review different methodologies such as dark lumen and bright lumen techniques for abdominal MRI. In addition, recently published studies concerning the sensitivity and accuracy in detecting inflammatory bowel changes in inflammatory bowel disease using MRI are discussed.     

Isoflavones and inflammatory bowel disease

Isoflavones constitute a class of plant hormones including genistein, daidzein, glycitein, formononetin, biochanin A, and irilone, and the major source of human intake is soybeans. Inflammatory bowel disease (IBD) is a chronic recurrent inflammatory disease including ulcerative colitis, Crohn’s disease, and indeterminate colitis, which seriously affects the quality of life of patients and has become a global health problem. Although the pathogenesis of IBD is not very clear, many factors are thought to be related to the occurrence and development of IBD such as genes, immunity, and intestinal flora. How to control IBD effectively for a long time is still a problem for gastroenterologists. Diet has an important effect on IBD. Patients with IBD should pay more attention to diet. To date, many studies have reported that isoflavones have both good and bad effects on IBD. Isoflavones have many activities such as regulating the inflammatory signal pathways and affecting intestinal barrier functions and gut flora. They can also act through estrogen receptors, as they have a similar structure to estrogen. Isoflavones are easy to get from diet for human. Whether they are valuable to be applied to the treatment of IBD is worth studying. This review summarizes the relationship between isoflavones and IBD.     

Chemiluminescence in inflammatory bowel disease patients: a parameter of inflammatory activity

Background: Reactive oxygen species (ROS) are produced in excess in the inflamed mucosa and peripheral blood of patients with inflammatory bowel disease. These species have emerged as a common pathway of tissue injury in a wide variety of inflammatory and other disease processes. The present study was conducted to assess ROS production and to correlate this with parameters of inflammatory activity. Methods: In 25 patients with Crohn's disease (CD), 20 patients with ulcerative colitis (UC) and 65 age- and sex-matched healthy volunteers ROS production was measured using the whole blood luminol enhanced chemiluminescence assay (LECA). Disease activity was assessed using the Crohn's disease activity index and the Ulcerative Colitis Symptoms Score (UCSS) for CD and UC, respectively. Furthermore, the effect of various scavengers, enzymes and enzyme inhibitors on LECA was studied to assess the contribution of different ROS. Results: LECA was significantly higher in CD and UC patients compared with healthy controls (7.1±4.7 and 9.8±6 vs. 5.2±2.8×10³ counts per minute (cpm), p<0.05 and <0.001). In CD, relative LECA (patient/control) was correlated with the Crohn's disease activity index and C-reactive protein (CRP) (r=0.54, p=0.001 and r=0.51, p=0.01). In UC, CRP but not LECA was correlated with the Ulcerative Colitis Symptoms Score (C-reactive protein: r=0.42, p=0.01). Addition of azide, superoxide dismutase, deferoxamine and dimethylthiourea resulted in a decrease of LECA values. Conclusion: Whole blood LECA is increased in patients with CD and UC. This parameter is correlated with disease activity in CD. The observed chemiluminescence is probably due to generation of superoxide and the hydroxyl radical.     

炎症性肠病患者脊柱关节炎的表现特点

目的 探讨炎症性肠病(IBD)患者的肠外表现—脊柱关节炎的发生情况,为后续炎症性肠病患者的诊断治疗提供借鉴.方法 分析2016年9月至2020年9月本院收治的210例炎症性肠病患者(其中溃疡性结肠炎/UC组138人,克罗恩病/CD组72人)肠道病变分布情况,并分析UC组及CD组患者脊柱关节炎各种分型的发生率及两组之间表...     

Therapeutic peptides in inflammatory bowel disease

Introduction: Therapeutic peptides in inflammatory bowel diseases essentially comprise cytokines affecting immune response, growth factors and monoclonal antibodies directed against key targets of mucosal inflammation, in particular, tumor necrosis factor-α (TNF-α). The latter have revolutionized standard medical treatment which previously was restricted to mesalamine, corticosteroids or classical immunosuppressants.

Areas covered: We review current evidence of the use of the so-called biologicals, including the well-established TNF-α antagonists and novel peptides and monoclonal antibodies developed for these diseases. The focus is on controlled clinical trials and meta-analyses, if available. Limitations and biases of these studies are important but tend to be ignored. Safety is also an important issue with opportunistic infections and lymphoma as relevant risks. There is significant heterogeneity between different countries, guidelines and opinions within the scientific community regarding clinical indications, even apart from pharmacoeconomics and reimbursement.

Expert opinion: TNF blockers have greatly extended medical options in inflammatory bowel diseases. Their more or less extensive use in nearly all patients or only a few selected indications is a matter of debate. It proved difficult to reproduce this success with other antibody targets as well as with immunomodulatory cytokines and growth factors. The most promising novel peptide is vedolizumab, an antibody against α4β7 integrin.     

CT colonoscopy in inflammatory bowel disease

Virtual colonoscopy is used worldwide for the detection of colon polyps, but this technique has not been used much for the evaluation of inflammatory bowel diseases. The advent of multidetector-computed tomography and the use of high quality 3D and virtual images opened up the opportunity to assess these patients with this non-invasive technique. Early and late colonic changes are illustrated.     

63例炎症性肠病经腹超声检查与结肠镜的对比分析

目的:探讨经腹超声检查在炎症性肠病诊断中的临床实用价值。方法:对临床诊断明确的克罗恩病17例,溃疡性结肠炎46例,与30例大肠癌对比观察超声图像特点,同步比较结肠镜所见。结果:炎症性肠病与大肠癌声像图上,肠壁均有不同程度的增厚,肠壁增厚≥1.2 cm的阳性例数比较,克罗恩病组明显高于溃疡性结肠炎组,差异有统计学意义(χ2=20.93,P<0.05),和大肠癌组比较差异无统计学意义(χ2=0.17,P>0.05);克罗恩病组肠管正常结构消失的比率明显高于溃疡性结肠炎组,差异有统计学意义(χ2=7.47,P<0.05),肠间淋巴结肿大例数克罗恩病与溃疡性结肠炎组和大肠癌组比较差异均无统计学意义(2χ=3.13,P>0.05,χ2=1.93,P>0.05);肠间积液例数克罗恩病与溃疡性结肠炎组和大肠癌组比较差异有统计学意义(2χ=8.74,P<0.05,χ2=8.57,P<0.05);而粘连包块多见于克罗恩病组,假肾征仅见于肠癌组。各肠段病变定位符合率:回盲部和升结肠为91.30%,降结肠和乙状结肠为86.49%,直肠71.43%,横结肠35.71%。结论:腹部超声检查简便易行,在声像图上克罗恩病和溃疡性结肠炎的表现有其各自特点,对于提示炎症性肠病存在、部位和性质有一定的临床实用价值。     

Kinetics of soluble TNF-receptors and soluble adhesion molecules ICAM-1, E-selectin and VCAM-1 under systemic rhTNFα therapy

Cytostatic as well as cytotoxic effects of tumour necrosis factor alpha (TNF-α) therapy have been shown in vitro and in experimental in vivo models. Nevertheless, the mechanism of anti-tumour activity in humans in vivo remains unclear. To determine the role of the vascular lining endothelial cells as important mediators of several immunological interactions, we investigated changes in the levels of the soluble endothelial cell adhesion molecules intercellular adhesion molecule 1, E-selectin and vascular cell adhesion molecule 1 as well as of soluble TNF receptors I and II during systemic therapy with recombinant human rhTNF-α (rhTNF-α). All tests were performed by enzyme-linked immunosorbent assays (ELISAs). The clinical efficacy of the intravenous rhTNF-α therapy was poor. Only one patient with isolated intra-arterial limb perfusion had a delayed, marked, but only temporary necrosis of tumour cells. In contrast, we found a marked, significant and (during therapy) undulating augmented increase in the levels of soluble adhesion molecules as well as of the soluble TNF receptors. Taken together, these data support the hypothesis that a sufficient tumour-specific cellular immunity is required to achieve a clinically apparent efficacy of systemic rhTNF-α therapy in addition to cytokine-dependent inducible activation mechanisms. In this context, the vascular lining endothelial cells might play an important role as mediators of the complex immunological antitumoral activity.     

血小板相关参数对评估炎症性肠病活动性的临床意义

目的探讨血小板相关参数评估炎症性肠病(IBD)活动性的价值。方法回顾性收集2010年1月至2019年6月九江学院附属医院消化内科住院的溃疡性结肠炎(UC)及克罗恩病(CD)患者共206例,另选取于九江学院附属医院健康体检50例健康人员作为对照;收集研究对象临床资料,并依据病史、Myao活动指数、蒙特利尔分级及克罗恩病活动指数(CDAI)对患者进行分组及疾病严重程度分级。收集患者首次诊断时的血常规检测指标。结果IBD患者的血小板相关参数除P-LCR外与对照组比较均有明显差异(P<0.05);CD患者PCT及PLT显著高于UC(P分别0.007、<0.001);IBD活动期患者血小板参数与对照组存在显著差异(P<0.05);且UC患者病情与血小板参数存在相关性,重度患者PLT高于轻度患者(P<0.05)、MPV低于轻度患者(P=0.001);将MPV、PDW、P-LCR、PCT、PLT联合诊断IBD的活动性,得到AUC=0.857,95%CI 0.803~0.912,P<0.05。结论MPV、PDW在IBD活动期降低;PLT、PCT则增高;血小板相关参数联合诊断可较好反映IBD活动性。     

炎症性肠病患者自我形象改变体验的质性研究

目的：了解炎症性肠病患者自我形象改变体验,以期为改善患者自我形象制定合理的干预策略提供参考。方法：采用现象学研究方法对天津市某三级甲等医院收治的11例炎症性肠病患者进行半结构式深入访谈,运用Colaizzi 7步分析法对资料进行整理分析。结果：共归纳提炼4个主题,存在多种负性情绪、难以有所追求、不被理解接受、患病后有所收获。结论：炎症性肠病患者存在积极自我形象和较为严重的负性自我形象,医护人员应注重负性自我形象患者心理疏导,加强健康教育,协助社会力量,改善其自我形象,促进疾病康复。     

间充质干细胞治疗炎性肠病的研究进展

炎性肠病（IBD）是一种病因不明确的疾病,有终生复发的倾向,重症患者迁延不愈,预后不良。IBD的传统治疗方式主要是运用抗炎和免疫抑制药物,长期治疗易致较多不良反应、效果欠佳。间充质干细胞（MSCs）具有多向分化能力和免疫调节功能,用于治疗IBD具有一定的理论和实验基础,是一种有前途的新型治疗方法。该文主要介绍MSCs移植治疗IBD的应用及其可能的机制。     

Fecal markers in the management of inflammatory bowel disease

Inflammatory bowel disease (IBD) is characterized by periods of symptomatic remission and relapse. Diagnosis and assessment of IBD are based on clinical evaluation, serum parameters, radiology, and endoscopy. Fecal markers have emerged as new diagnostic tools to detect and monitor intestinal inflammation. Fecal calprotectin (FC) and lactoferrin (FL) were identified decades ago as potentially revolutionary markers for IBD. Following these discoveries numerous additional markers, including S100A12, M2-PK, metalloproteinases, hemoglobin, myeloperoxidase, lysozyme, polymorphonuclear elastase, neopterin, and nitric oxide, have also been suggested as novel markers of IBD. But only FC and FL are used for the management of clinical IBD patients. The objective of this review is to introduce the clinical applications of fecal markers in the diagnosis, monitoring and prediction of outcomes of inflammatory bowel disease.     

Microbiota-gut-brain axis and its affect inflammatory bowel disease:Pathophysiological concepts and insights for clinicians

Despite the bi-directional interaction between gut microbiota and the brain not being fully understood,there is increasing evidence arising from animal and human studies that show how this intricate relationship may facilitate inflammatory bowel disease(IBD)pathogenesis,with consequent important implications on the possibility to improve the clinical outcomes of the diseases themselves,by acting on the different components of this system,mainly by modifying the microbiota.With the emergence of precision medicine,strategies in which patients with IBD might be categorized other than for standard gut symptom complexes could offer the opportunity to tailor therapies to individual patients.The aim of this narrative review is to elaborate on the concept of the gutbrain-microbiota axis and its clinical significance regarding IBD on the basis of recent scientific literature,and finally to focus on pharmacological therapies that could allow us to favorably modify the function of this complex system.     

Role of hospitalization for inflammatory bowel disease in the post-biologic era

Treatment for inflammatory bowel disease (IBD) often requires specialized care. While much of IBD care has shifted to the outpatient setting, hospitalizations remain a major site of healthcare utilization and a sizable proportion of patients with inflammatory bowel disease require hospitalization or surgery during their lifetime. In this review, we approach IBD care from the population-level with a specific focus on hospitalization for IBD, including the shifts from inpatient to outpatient care, the balance of emergency and elective hospitalizations, regionalization of specialty IBD care, and contribution of surgery and endoscopy to hospitalized care.