Declining use of combination infliximab and immunomodulator for inflammatory bowel disease in the community setting

AIM To describe trends of combination therapy (CT) of infliximab (IFX) and immunomodulator (IMM) for inflammatory bowel disease(IBD) in the community setting. METHODS A retrospective study was conducted of all IBD patients referred for IFX infusion to our community infusion center between 04/01/01 and 12/31/14. CT was defined as use of IFX with either azathioprine, 6-mercaptopurine, or methotrexate. We analyzed trends of CT usage overall, for Crohn's disease (CD) and ulcerative colitis (UC), and for the subgroups of induction patients. We also analyzed the trends of CT use in these groups over the study period, and compared the rates of CT use prior to and after publication of the landmark SONIC trial.RESULTS Of 258 IBD patients identified during the 12 year study period, 60 (23.3%) received CT, including 35 of 133(26.3%) induction patients. Based on the CochranArmitage trend test, we observed decreasing CT use for IBD patients overall(P 0.0001) and IBD induction patients,(P = 0.0024). Of 154 CD patients, 37(24.68%) had CT, including 20 of 77 (26%) induction patients.The Cochran Armitage test showed a trend towards decreasing CT use for CD overall(P 0.0001) and CD induction,(P = 0.0024). Overall, 43.8% of CD patients received CT pre-SONIC vs 7.4% post-SONIC (P 0.0001). For CD induction, 40.0% received CT preSONIC vs 10.8% post-SONIC(P = 0.0035). Among the 93 patients with UC, 19 (20.4%) received CT. Of 50 induction patients, 14 (28.0%) received CT. The trend test of the 49 patients with a known year of induction again failed to demonstrate any significant trends in the use of CT(P = 0.6). CONCLUSION We observed a trend away from CT use in IBD. A disconnect appears to exist between expert opinion and evidence favoring CT with IFX and IMM, and evolving community practice.     

Infliximab trough levels and persistent vs transient antibodies measured early after induction predict long-term clinical remission in patients with inflammatory bowel disease

BackgroundThe use of therapeutic drug monitoring has been proposed as a useful tool in the management of patients with loss of response to biological therapy in patients with inflammatory bowel disease.AimsTo evaluate whether early, post-induction anti-tumor necrosis factor trough levels and the presence of different types of anti-drug antibodies may impact long-term clinical remission in patients with inflammatory bowel disease.MethodsWe prospectively assessed anti-tumor necrosis factor trough levels and both persistent and transient anti-drug antibodies. The Harvey–Bradshaw Index and the partial Mayo score were evaluated at each visit or in case of relapse.ResultsAt week 14, median infliximab trough levels were significantly lower in patients who experienced loss of response at week 48 as compared to patients in stable remission (1.3 mcg/mL [range 0–10.2 mcg/mL] vs. 10.1 mcg/mL[range 0–42.8 mcg/mL], P < 0.0004). ROC curve identified an infliximab trough levels of 6.2 mcg/mL as the cut-off value with the highest accuracy (c-index = 0.864) for loss of response at week 48. At week 14 we observed a correlation between anti-drug antibodies concentration and infliximab trough levels (r_s = −0.513, P = 0.04).ConclusionsThe results highlight the usefulness of assessing early biological TL in order to predict patients’ long-term outcome.     

Effectiveness and safety of vedolizumab for maintenance treatment in inflammatory bowel disease—The Israeli real world experience

Introduction

Several real-world experience (RWE) studies with vedolizumab (VDZ) for induction of remission in inflammatory bowel diseases (IBD) have been published; however, long-term RWE data is scarce.

First United Arab Emirates consensus on diagnosis and management of inflammatory bowel diseases: A 2020 Delphi consensus

Ulcerative colitis and Crohn’s disease are the main entities of inflammatory bowel disease characterized by chronic remittent inflammation of the gastrointestinal tract. The incidence and prevalence are on the rise worldwide, and the heterogeneity between patients and within individuals over time is striking. The progressive advance in our understanding of the etiopathogenesis coupled with an unprecedented increase in therapeutic options have changed the management towards evidence-based interventions by clinicians with patients. This guideline was stimulated and supported by the Emirates Gastroenterology and Hepatology Society following a systematic review and a Delphi consensus process that provided evidence- and expert opinion-based recommendations. Comprehensive up-to-date guidance is provided regarding diagnosis, evaluation of disease severity, appropriate and timely use of different investigations, choice of appropriate therapy for induction and remission phase according to disease severity, and management of main complications.     

英夫力西单抗治疗难治性溃疡性结肠炎

目的分析14例英夫力西治疗难治性中重度溃疡性结肠炎的临床资料,探索英夫力西治疗国人溃疡性结肠炎的效果和安全性。方法对我院2006年-2011年经常规治疗失败的14例难治性中重度溃疡性结肠炎患者,行英夫力西单抗治疗,分别于0、2、6周按5 mg/kg全身用药,以后每8周给药1次,个别患者因用药效果、病情变化等增加了用药剂量或缩短了用药间隔。分析英夫力西单抗治疗8周有效率和缓解率,随访30周、54周缓解率及安全性等。结果治疗8周有效率为42.9%,缓解率为42.9%,无效率为14.3%;随访30周、54周缓解率分别为57.1%和42.3%。有2例患者达到黏膜愈合,至今分别随访35个月和28个月,病情均无复发。不良反应发生率为28.6%,无严重或危及生命的不良反应发生。随访54周,有效组和无效组前两次英夫力西单抗治疗有效者所占比例差异有统计学意义(P=0.015)。结论应用英夫力西治疗14例难治性中重度溃疡性结肠炎,取得了良好的治疗效果,前两次治疗有效可预示远期治疗效果好,近期的药物不良反应不影响程序性治疗的进行。英夫力西单抗可作为国人难治性溃疡性结肠炎的挽救治疗方法。     

Biosimilars in paediatric inflammatory bowel disease

The introduction of biological treatments has changed disease outcomes for patients with inflammatory bowel disease. Biologicals have high efficacy, and can induce and maintain remission after failed responses to conventional immunosuppressive and/or steroid therapy. The increasing occurrence of severe disease at diagnosis has resulted in infliximab being more often introduced as the firstline treatment in a "top-down" approach. Besides their favourable efficacy and safety profile, biologicals have one significant disadvantage, which is their high cost. This results in many patients stopping therapy prematurely, with the maintenance phase being too short. This often leads to disease exacerbation shortly after treatment cessation. Every newly started course of biological therapy can induce production of anti-drug antibodies, which can result in treatment failure and possible allergic/anaphylactic reactions. The introduction of biological biosimilars was intended to greatly reduce therapy costs thus increasing the availability of these agents to more patients. It was also anticipated that biosimilars would prevent premature termination of therapy. Analyses of paediatric data suggest that biosimilar infliximabs are equally effective as the reference infliximab. Safety patterns also seem to be similar. Paediatric experience places costtherapy reductions at around 10%-30%.     

英夫利昔治疗溃疡性结肠炎临床疗效的荟萃分析

目的采用荟萃分析的方法,探讨英夫利昔(Infliximab,IFX)治疗溃疡性结肠炎(ulcerative colitis,UC)的疗效。方法全面检索并收集研究IFX治疗UC的临床随机对照试验。纳入7篇文献,共有7个随机对照实验(RCT)。质量评价、独立提取资料后以RevMan 4.2分析。结果荟萃分析显示:比较IFX与安慰剂治疗UC的长期、短期疗效,结果均有显著差异。比较IFX 5 mg、10mg与安慰剂组短期、长期的疗效,结果有显著差异。IFX的短期及长期疗效与激素相比,结果无显著差异。IFX与安慰剂的不良反应结果无显著差异。结论 IFX可以诱导UC的临床缓解及维持,而且对于难治性中重度UC,IFX可以使患者减少结肠切除率,提高生活质量。但是仍然需要大样本多中心的随机对照试验来进一步验证。     

Mycophenolate mofetil is a valid option in patients with inflammatory bowel disease resistant to TNF-α inhibitors and conventional immunosuppressants

BackgroundFew studies investigated the role of mycophenolate mofetil in inflammatory bowel disease, and none of them had specifically focused on patients with previous multiple intolerances and/or nonresponses to conventional immunosuppressants and biologics.AimsTo evaluate clinical benefit and tolerability profile of mycophenolate mofetil in patients with inflammatory bowel disease and limited treatment options.MethodsAll consecutive patients with previous multiple intolerances and/or nonresponses to immunosuppressants and biologics who started an off-label treatment with mycophenolate mofetil from January 2014 to February 2016 were entered in a prospectively maintained database.ResultsTwenty-four patients were included. Four weeks after initiation of mycophenolate mofetil therapy, a steroid-free remission was achieved in 4 patients (16.7%), while a clinical response in 13 (54.1%). At the end of follow-up, 12 patients (50.0%) remained on mycophenolate mofetil. Six achieved and maintained steroid-free remission throughout the study period (25.0%), and a further 6 patients (25.0%) achieved a clinical response with complete discontinuation of steroids. Twelve patients (50.0%) were considered as treatment failure, and five of them underwent surgery.ConclusionsThis is the first experience reporting a clinical benefit and tolerability of mycophenolate mofetil in patients with inflammatory bowel disease and multiple previous failures to other immunosuppressants and/or biologics.     

Can a transition clinic bridge the gap between paediatric and adult inflammatory bowel disease care models?

Transition care in inflammatory bowel disease is increasingly recognized as challenging given the inherent differences between paediatric and adult health care models, disease characteristics and treatment strategies. Transition is a dynamic process involving adolescents and young adults that are moving from a paediatric to an adult health care setting, and it should be flexible, continually updated and tailored to each patient. The implementation of a transition clinic is essential given the increasing incidence of the paediatric population with inflammatory bowel disease and the lifelong impact of this disease.The key question is when and how to structure transition according to the adolescent's clinical, psycho-social, educational needs and expectations to ensure continuity of care.In the attempt to improve the management of transition in inflammatory bowel disease and address the wide gap between adult and child care, we provide an update of the transition clinic and we propose a “treat to target” approach in transition to facilitate an effective and successful transition programme. In the changing landscape of the treatment of inflammatory bowel disease, further studies are necessary to determine the role of the transition clinic in determining the choice and strategy of therapy and its monitoring and the adoption of newer strategies such as biomarkers guided treating to target.     

Epidemiology of inflammatory bowel disease in the Republic of San Marino: The “EPIMICI – San Marino” study

Background

The burden of Crohn’s disease (CD) and ulcerative colitis (UC) has never been estimated in the Republic of San Marino, the third smallest nation of the world.

溃疡性结肠炎患者Wnt9b的高表达及临床价值

目的研究溃疡性结肠炎和克罗恩病患者Wnt9b的表达,分析血浆Wnt9b水平与炎症性肠病患者内镜下疾病活动性的相关性以及对溃疡性结肠炎和克罗恩病的鉴别诊断价值。方法应用酶联免疫吸附试验(Enzyme-Linked ImmunoSorbent Assay,ELISA)对克罗恩病患者、溃疡性结肠炎患者和正常对照者血浆中Wnt9b的表达进行测定。分析血浆Wnt9b水平与炎症性肠病患者内镜下疾病活动性的相关性,通过受试者工作特征曲线(receiver-operating characteristic,ROC)分析血浆Wnt9b表达对溃疡性结肠炎和克罗恩病的鉴别诊断价值。结果溃疡性结肠炎患者血浆Wnt9b水平显著高于正常对照者(P=0.0324)和克罗恩病患者(P=0.0217),而克罗恩病患者血浆Wnt9b与正常对照者无显著差异(P=0.5919)。但是,溃疡性结肠炎患者血浆Wnt9b水平与内镜下疾病活动程度无显著相关性(Spearmanr=-0.2360,P=0.1102)。ROC曲线分析表明,血浆Wnt9b表达水平在区分溃疡性结肠炎和克罗恩病中具有显著意义(AUC=0.633,P=0.0228)。结论溃疡性结肠炎患者血浆Wnt9b表达水平增高,对于鉴别溃疡性结肠炎患者和克罗恩病患者具有一定意义。     

Factors Associated with the Immunogenicity of Anti-Tumor Necrosis Factor Agents in Pediatric Patients with Inflammatory Bowel Disease

Background/AimsAnti-drug antibodies (ADAs) can develop during treatment with anti-tumor necrosis factor (TNF) agents. We aimed to investigate the factors associated with immunogenicity of anti-TNF agents in pediatric patients with inflammatory bowel disease (IBD) and observe the clinical course of ADA-positive patients.MethodsPediatric IBD patients receiving maintenance treatment with anti-TNF agents who had been tested for ADAs against infliximab (IFX) or adalimumab (ADL) were included in this cross-sectional study. Factors associated with ADA positivity were investigated by analyzing clinicodemographic, laboratory, and treatment-related factors.ResultsA total of 76 patients (Crohn’s disease, 65; ulcerative colitis, 11) were included. Among these, 59 and 17 patients were receiving IFX and ADL, respectively. ADAs were found in 10 patients (13.2%), all of whom were receiving IFX. According to multivariable logistic regression analysis, the IFX trough level (TL) was associated with ADA positivity (odds ratio, 0.25; 95% confidence interval [CI], 0.08 to 0.51; p=0.002). According to the receiver operating characteristic analysis, the optimal cutoff of the IFX TLs for stratifying patients based on the presence of ADAs against IFX was 1.88 μg/mL (area under curve, 0.941; 95% CI, 0.873 to 1.000; sensitivity, 80.0%; specificity, 95.9%; p<0.001). Among the 10 patients with ADAs against IFX, five patients (50%) switched to ADL within 1 year, while five patients (50%) kept receiving IFX. Transient ADAs were observed in three patients (30%).ConclusionsIFX TL was the only factor associated with ADA formation in pediatric IBD patients receiving IFX. Future studies based on serial and proactive therapeutic drug monitoring are required in the future.     

半胱氨酸天冬氨酸蛋白酶-3在炎症性肠病中的差异表达

目的 研究血浆半胱氨酸天冬氨酸蛋白酶-3(cysteine-aspartic acid protease-3,caspase-3)与炎症性肠病患者临床疾病活动性的相关性及对疾病的诊断价值.方法 对克罗恩病患者、溃疡性结肠炎患者和正常对照者血浆中caspase-3的表达情况应用酶联免疫吸附试验(ELISA)进行分析.进一步分析血浆caspase-3浓度与内镜下疾病活动性的相关性.通过受试者工作特征曲线(receiver-operating characteristic,ROC)观察炎症性肠病患者中血浆caspase-3水平的潜在临床及科研价值.数据处理使用GraphPad Prism 5.结果 克罗恩病患者血浆caspase-3水平显著高于正常对照组(P=0.0022),但溃疡性结肠炎患者血浆caspase-3水平与对照组无显著差异(P=0.6377).easpase-3表达水平在区分克罗恩病患者和溃疡性结肠炎患者中诊断价值较低(AUC=0.6339,P=0.0039).克罗恩病患者血浆caspase-3水平与内镜下疾病活动性无显著相关性(r=-0.089,P=0.5172).结论 克罗恩病患者血浆caspase-3表达水平增高,与溃疡性结肠炎及正常对照者存在差异.     

Obesity and novel management of inflammatory bowel disease

Obesity is prevalent within the inflammatory bowel disease(IBD) population,particularly in newly developed countries.Several epidemiological studies have suggested that 15%-40% of IBD patients are obese,and there is a potential role of obesity in the pathogenesis of IBD.The dysfunction of mesenteric fat worsens the inflammatory course of Crohn’s disease and may induce formation of strictures or fistulas.Furthermore,obesity may affect the disease course or treatment response of IBD.Given the incr...     

Effects of anti–TNF-alpha therapy on hemoglobin levels and anemia in patients with inflammatory bowel disease

BackgroundTumor necrosis factor-α (TNF-α) is involved in inducing inflammatory anemia. The potential effect of anti–TNF-α agents on anemia in inflammatory bowel diseases (IBD) is still unknown.MethodsAnalytical data and disease characteristics from 362 IBD patients [271 CD/91UC) treated with anti-TNF-α drugs were retrospectively collected. Effects on disease activity, blood markers and prevalence of anemia were assessed after 6 and 12 months of therapy.Results29.3% patients presented anemia at baseline, and significantly reduced to 14.4% and 7.8% after 6 and 12 months of therapy, respectively. Mean ± SD Hb levels increased significantly at month 6, and this increase was sustained at 12 months. Serum markers of iron metabolism increased significantly compared to baseline, as disease activity measured by C-reactive protein (CRP) was reduced. All these effects were observed independently for CD and UC, and were independent of iron supplementation during treatment. Anemia at baseline (OR 4.09; 95%CI 1.98–8.45) and elevated CRP (OR 3.45; 95CI 1.29–9.22) were independently associated with risk of persistent anemia, as well as iron replacement during therapy (OR 4.36; 95%CI 2.07–9.16).ConclusionsControlling disease activity with anti-TNF- α therapy significantly and independently associated with resolution of anemia in IBD, with no relevant role for iron replacement therapy.     

Time-Dependent Changes in the Luminal Surface and Mass of the Rat Colon during Prolonged Systemic Treatment with Epidermal Growth Factor

Abstract

Background. In chronic inflammatory bowel disease (IBD) (Crohn’s disease [CD] and ulcerative colitis [UC]), symptoms from outside the gastrointestinal tract are frequently seen, and the joints, skin, eyes, and hepatobiliary area are the most usually affected sites (called extraintestinal manifestations [EIM]). The reported prevalence varies, explained by difference in study design and populations under investigation. The aim of our study was to determine the prevalence of EIM in a population-based inception cohort in Europe and Israel. Methods. IBD patients were incepted into a cohort that was prospectively followed from 1991 to 2004. A total of 1145 patients were followed for 10 years. Results. The cumulative prevalence of first EIM was 16.9% (193/1145 patients) over a median follow-up time of 10.1 years. Patients with CD were more likely than UC patients to have immune-mediated (arthritis, eye, skin, and liver) manifestations: 20.1% versus 10.4% (p < 0.001). Most frequently seen was arthritis which was significantly more common in CD (12.9%) than in UC (8.1%), p = 0.01. Pan-colitis compared to proctitis in UC increased the risk of EIM. Conclusion. In a European inception cohort, EIMs in IBD were consistent with that seen in comparable studies. Patients with CD are twice as likely as UC patients to experience EIM, and more extensive distribution of inflammation in UC increases the risk of EIM.     

Anemia at the time of diagnosis of inflammatory bowel disease: Prevalence and associated factors in adolescent and adult patients

BackgroundThe prevalence, characteristic and determinants of anemia, at the time of inflammatory bowel disease (IBD) diagnosis have yet to be fully elucidated.MethodsRetrospective cross-sectional study. Analytical data and disease characteristics obtained upon diagnosis of 1278 IBD patients [Crohn’s disease/ulcerative colitis (CD/UC): 718/560] were collected.ResultsAnemia was present in 41.2% of patients at diagnosis (47% and 33.8% of CD and UC patients, respectively; p < 0.001), being severe in 5.5%. Iron deficiency anemia represented 69.6% of cases, with no differences between CD and UC. Female sex was the strongest risk factor for anemia in both CD and UC (OR 7.11; 95%CI 4.18–12.10 and 6.55; 95%CI 3.39–12.63, respectively), followed by elevated (≥2 mg/dL) C-reactive protein (OR 4.08; 95%CI 2.39–6.97 and 4.58; 95%CI 2.26–9.27, respectively). Current smoking was a risk factor for anemia in CD (OR 2.23; 95%CI 1.24–4.02), but a protective one in UC (OR 0.36; 95%CI 0.14–0.92). A penetrating CD behavior increased the risk of anemia (OR 3.34; 95%CI 1.36–8.21); in UC, anemia increased with disease extension (E2 + E3) (OR 1.80; 95%CI 1.13–2.86).ConclusionsFemale sex and disease activity are major determinants of anemia at IBD diagnosis. Anemia is associated with disease behavior in CD and with disease extension in UC.     

Infliximab in pediatric inflammatory bowel disease rapidly decreases fecal calprotectin levels

AIM: To study the response to infliximab in pediatric inflammatory bowel disease (IBD), as reflected in fecal calprotectin levels. METHODS: Thirty-six pediatric patients with IBD [23 Crohn’s disease (CD), 13 ulcerative colitis (UC); median age 14 years] were treated with infliximab. Fecal calprotectin was measured at baseline, and 2 and 6 wk after therapy, and compared to blood inflammatory markers. Maintenance medication was unaltered until the third infusion but glucocorticoids were tapered off if the pat...