Physiological Basis for Novel Drug Therapies Used to Treat the Inflammatory Bowel Diseases I. Immunology and therapeutic potential of antiadhesion molecule therapy in inflammatory bowel disease

2005 ◽  
Vol 288 (2) ◽  
pp. G169-G174 ◽  
Author(s):  
Gert Van Assche ◽  
Paul Rutgeerts
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Adhesion Molecules ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Therapeutic Potential ◽  
Physiological Basis ◽  
Inflammatory Bowel

Adhesion molecules regulate the influx of leukocytes in normal and inflamed gut. They are also involved in local lymphocyte stimulation and antigen presentation within the intestinal mucosa. In intestinal inflammation, many adhesion molecules are upregulated, but α4-integrins most likely hold a key position in directing leukocytes into the inflamed bowel wall. Therapeutic compounds directed against trafficking of leukocytes have been designed and are being developed as a novel class of drugs in the treatment of Crohn's disease and ulcerative colitis. This review deals with the immunological aspects of leukocyte trafficking focused on gut homing of T cells. Second, the changes in adhesion molecules and T cell trafficking during intestinal inflammation are discussed. Finally, we review the clinical data that have been gathered with respect to the therapeutic potential and the safety of antiadhesion molecule treatment. Antegren, or natalizumab, a humanized anti-α4 integrin IgG4 antibody, has been most extensively evaluated and may be close to registration. A more specific humanized α4β7-integrin MLN-02 has shown preliminary clinical efficacy in ulcerative colitis, and both antergren and MLN-02 appear to be very safe. Trials with the anti-ICAM-1 antisense oligonucleotide ISIS-2302 in steroid refractory Crohn's disease have provided conflicting efficacy data. In the near future, some of these novel biological agents may prove valuable therapeutic tools in the management of refractory inflammatory bowel disease, although it is too early to define the patient population that will benefit most from these agents.

Prebiotics and Probiotics in Inflammatory Bowel Disease: Where are we now and where are we going?

2020 ◽  
Vol 15 (3) ◽  
pp. 216-233 ◽  
Author(s):  
Maliha Naseer ◽  
Shiva Poola ◽  
Syed Ali ◽  
Sami Samiullah ◽  
Veysel Tahan
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Clinical Trials ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Adverse Effects ◽  
Bowel Disease ◽  
Relapse Prevention ◽  
Remission Induction ◽  
Inflammatory Bowel

The incidence, prevalence, and cost of care associated with diagnosis and management of inflammatory bowel disease are on the rise. The role of gut microbiota in the causation of Crohn's disease and ulcerative colitis has not been established yet. Nevertheless, several animal models and human studies point towards the association. Targeting intestinal dysbiosis for remission induction, maintenance, and relapse prevention is an attractive treatment approach with minimal adverse effects. However, the data is still conflicting. The purpose of this article is to provide the most comprehensive and updated review on the utility of prebiotics and probiotics in the management of active Crohn’s disease and ulcerative colitis/pouchitis and their role in the remission induction, maintenance, and relapse prevention. A thorough literature review was performed on PubMed, Ovid Medline, and EMBASE using the terms “prebiotics AND ulcerative colitis”, “probiotics AND ulcerative colitis”, “prebiotics AND Crohn's disease”, “probiotics AND Crohn's disease”, “probiotics AND acute pouchitis”, “probiotics AND chronic pouchitis” and “prebiotics AND pouchitis”. Observational studies and clinical trials conducted on humans and published in the English language were included. A total of 71 clinical trials evaluating the utility of prebiotics and probiotics in the management of inflammatory bowel disease were reviewed and the findings were summarized. Most of these studies on probiotics evaluated lactobacillus, De Simone Formulation or Escherichia coli Nissle 1917 and there is some evidence supporting these agents for induction and maintenance of remission in ulcerative colitis and prevention of pouchitis relapse with minimal adverse effects. The efficacy of prebiotics such as fructooligosaccharides and Plantago ovata seeds in ulcerative colitis are inconclusive and the data regarding the utility of prebiotics in pouchitis is limited. The results of the clinical trials for remission induction and maintenance in active Crohn's disease or post-operative relapse with probiotics and prebiotics are inadequate and not very convincing. Prebiotics and probiotics are safe, effective and have great therapeutic potential. However, better designed clinical trials in the multicenter setting with a large sample and long duration of intervention are needed to identify the specific strain or combination of probiotics and prebiotics which will be more beneficial and effective in patients with inflammatory bowel disease.

scholarly journals The Changing Prognosis of Ulcerative Colitis and Crohn’s Disease by Decades

2021 ◽  
Author(s):  
Burton I Korelitz ◽  
Judy Schneider
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Medical Therapy ◽  
Bowel Disease ◽  
Surgical Intervention ◽  
Inflammatory Bowel

Abstract We present a bird’s eye view of the prognosis for both ulcerative colitis and Crohn’s disease as contained in the database of an Inflammatory Bowel Disease gastroenterologist covering the period from 1950 until the present utilizing the variables of medical therapy, surgical intervention, complications and deaths by decades.

scholarly journals Inflammatory bowel disease: a beast of burden

2011 ◽  
pp. 57-61
Author(s):  
Dawn Farrell
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Bowel Disease ◽  
Social Life ◽  
Symptom Burden ◽  
Complex Disorders ◽  
Inflammatory Bowel ◽  
The Uk

Imagine having to empty your bowel eight or ten times a day and experiencing constant panic and fear about the location of toilet facilities. Imagine experiencing constant tiredness that impacts on all aspects of your life including work, family and social life. These are just two examples of experiences commonly suffered by individuals with a condition called inflammatory bowel disease. These people are burdened with symptoms which impact on their daily lives. This research aims to provide healthcare professionals with an understanding of the extent to which individuals with inflammatory bowel disease experience symptom burden and to identify what symptoms are most problematic. Crohn’s disease and ulcerative colitis collectively termed as inflammatory bowel disease are complex disorders. In the United Kingdom, collectively Crohn’s disease and ulcerative colitis affects approximately one person in every 250 of the population. Ulcerative colitis affects up to 120,000 people in the UK, or every 1 ...

scholarly journals Immune system alterations in patients with inflammatory bowel disease during remission

Medicina ◽  
2008 ◽  
Vol 44 (1) ◽  
pp. 27 ◽  
Author(s):  
Jurgita Šventoraitytė ◽  
Aida Žvirblienė ◽  
Gediminas Kiudelis ◽  
Rimantas Žalinkevičius ◽  
Aurelija Žvirblienė ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Bowel Disease ◽  
Immune Homeostasis ◽  
Th2 Cytokines ◽  
Inflammatory Bowel ◽  
Anti Inflammatory ◽  
And Control

Objective. Perturbed immune homeostasis elicited by misbalanced production of proinflammatory and anti-inflammatory cytokines is characteristic of inflammatory bowel disease. The aim of this study was to evaluate cytokine profile in patients with different forms of inflammatory bowel disease – ulcerative colitis and Crohn’s disease – during clinical remission phase. Material and methods. Production of proinflammatory Th1 cytokines (tumor necrosis factoralpha (TNF-a), interferon-gamma (IFN-g)) and anti-inflammatory Th2 cytokines (interleukin- 10 (IL-10) and interleukin-13 (IL-13)) was analyzed in peripheral blood mononuclear cells of patients with inflammatory bowel disease (9 with ulcerative colitis and 9 with Crohn’s disease) and control subjects (n=11) by enzyme-linked immunosorbent assay (two-site ELISA). Results. The results of the study revealed that the level of TNF-a after stimulation with phytohemagglutinin in patients with Crohn’s disease was significantly higher in comparison to both patients with ulcerative colitis and controls (P<0.001 and P<0.01, respectively). The secretion of IFN-g both in patients with Crohn’s disease and ulcerative colitis was lower than that in controls (P=0.05 and P<0.01, respectively), but it normalized after stimulation with phytohemagglutinin. The levels of IL-10 and IL-13 were significantly (P<0.01) higher in patients with Crohn’s disease than in patients with ulcerative colitis and control group before and after stimulation with phytohemagglutinin. Conclusions. The results of our study provide evidence that in patients with inflammatory bowel disease, the imbalance between production of proinflammatory Th1 and anti-inflammatory Th2 cytokines persists even during remission of the disease, and disturbances of immune homeostasis are significantly more expressed in patients with Crohn’s disease than in patients with ulcerative colitis.

Validation of the “German Inflammatory Bowel Disease Activity Index (GIBDI)”: An Instrument for Patient-Based Disease Activity Assessment in Crohn’s Disease and Ulcerative Colitis

2018 ◽  
Vol 56 (10) ◽  
pp. 1267-1275 ◽  
Author(s):  
Angelika Hüppe ◽  
Jana Langbrandtner ◽  
Winfried Häuser ◽  
Heiner Raspe ◽  
Bernd Bokemeyer
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Bowel Disease ◽  
Activity Index ◽  
Disease Activity Index ◽  
Inflammatory Bowel ◽  
Activity Indices

Abstract Introduction Assessment of disease activity in Crohn’s disease (CD) and ulcerative colitis (UC) is usually based on the physician’s evaluation of clinical symptoms, endoscopic findings, and biomarker analysis. The German Inflammatory Bowel Disease Activity Index for CD (GIBDICD) and UC (GIBDIUC) uses data from patient-reported questionnaires. It is unclear to what extent the GIBDI agrees with the physicians’ documented activity indices. Methods Data from 2 studies were reanalyzed. In both, gastroenterologists had documented disease activity in UC with the partial Mayo Score (pMS) and in CD with the Harvey Bradshaw Index (HBI). Patient-completed GIBDI questionnaires had also been assessed. The analysis sample consisted of 151 UC and 150 CD patients. Kappa coefficients were determined as agreement measurements. Results Rank correlations were 0.56 (pMS, GIBDIUC) and 0.57 (HBI, GIBDICD), with p < 0.001. The absolute agreement for 2 categories of disease activity (remission yes/no) was 74.2 % (UC) and 76.6 % (CD), and for 4 categories (none/mild/moderate/severe) 60.3 % (UC) and 61.9 % (CD). The kappa values ranged between 0.47 for UC (2 categories) and 0.58 for CD (4 categories). Discussion There is satisfactory agreement of GIBDI with the physician-documented disease activity indices. GIBDI can be used in health care research without access to assessments of medical practitioners. In clinical practice, the index offers a supplementary source of information.

The Effect of Mesalamine and Nicotine in the Treatment of Inflammatory Bowel Disease

1997 ◽  
Vol 31 (7-8) ◽  
pp. 907-913 ◽  
Author(s):  
Charles R. Bonapace ◽  
David A. Mays
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Relapse Rate ◽  
Bowel Disease ◽  
Therapeutic Agent ◽  
Active Ulcerative Colitis ◽  
Steroid Dependence ◽  
Inflammatory Bowel

OBJECTIVE: To characterize the usefulness of mesalamine and nicotine in the treatment of active ulcerative colitis and inactive Crohn's disease. DATA SOURCES: Citations were selected from the MEDLINE database. Only those involving human subjects, inflammatory bowel disease, and available in English were selected. STUDY SELECTION: Selection criteria consisted of clinical trials and review articles assessing the effects of mesalamine and nicotine in active ulcerative colitis or inactive Crohn's disease and the utility of reducing steroid dependence or relapse rate. Less than 20% of the articles identified met the selection criteria. DATA SYNTHESIS: In patients with inactive Crohn's disease, mesalamine 2 g/d significantly reduced the risk of relapse in high-relapse-risk patients compared with placebo, reducing the relapse rate from 71% to 55%, but was ineffective in preventing recurrence of inactive Crohn's disease following surgical resection. Mesalamine 4 g/d was effective in decreasing weaning failure due to steroid dependence by 67%, although the relapse rate was not significant compared with placebo at the end of 12 months. Following surgical resection, mesalamine was unable to significantly reduce the incidence of recurrence compared with placebo at the end of 1 year. In patients with active ulcerative colitis, oral mesalamine 2 and 4 g/d was superior to placebo in inducing remission compared with placebo. Among patients with prior steroid or sulfasalazine treatment, rectal mesalamine 4 g hs achieved a remission rate of 78% in more than 12 weeks of therapy. Other studies have not found a dose—response relationship with lower dosages of mesalamine. Whereas nicotine 15–25 mg/d administered as a transdermal patch produced greater symptomatic improvement in active ulcerative colitis compared with placebo, nicotine 15 mg/16 h produced results no different from those with placebo in maintaining remission in inactive ulcerative colitis. Nicotine appears to have an adverse effect on the course of Crohn's disease and is not recommended. CONCLUSIONS: Mesalamine has demonstrated clinical effectiveness as a therapeutic agent in the treatment of active ulcerative colitis and inactive Crohn's disease. Although its relationship to inflammatory bowel disease has been known for many years, the usefulness of nicotine for the treatment of active ulcerative colitis requires further exploration before it can be recommended as a therapeutic agent.

scholarly journals Risk and outcomes of coronavirus disease (COVID-19) in patients with inflammatory bowel disease: a systematic review and meta-analysis

2020 ◽  
pp. 205064062097260
Author(s):  
Anupam Kumar Singh ◽  
Anuraag Jena ◽  
Praveen Kumar-M ◽  
Vishal Sharma ◽  
Shaji Sebastian
Keyword(s):  
Ulcerative Colitis ◽  
Intensive Care Unit ◽  
Inflammatory Bowel Disease ◽  
Intensive Care ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
General Population ◽  
Bowel Disease ◽  
Intensive Care Unit Care ◽  
Inflammatory Bowel

Background The risk of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) infection and clinical outcomes of coronavirus disease (COVID-19) in inflammatory bowel disease are unclear. Methods We searched PubMed and Embase with the keywords: inflammatory bowel disease, Crohn’s disease, ulcerative colitis and COVID-19, novel coronavirus and SARS-CoV-2. We included studies reporting the frequency of COVID-19 infection and outcomes (hospitalisation, need for intensive care unit care and mortality) in patients with inflammatory bowel disease. We estimated the pooled incidence of COVID-19 in inflammatory bowel disease and comparative risk vis-a-vis the general population. We also estimated the pooled frequency of outcomes and compared them in patients who received and did not receive drugs for inflammatory bowel disease. Results Twenty-four studies were included. The pooled incidence rate of COVID-19 per 1000 patients of inflammatory bowel disease and the general population were 4.02 (95% confidence interval (CI) 1.44–11.17) and 6.59 (3.25–13.35), respectively, with no increase in relative risk (0.47, 0.18–1.26) in inflammatory bowel disease. The relative risk of the acquisition of COVID-19 was not different between ulcerative colitis and Crohn’s disease (1.03, 0.62–1.71). The pooled proportion of COVID-19-positive inflammatory bowel disease patients requiring hospitalisation and intensive care unit care was 27.29% and 5.33% while pooled mortality was 4.27%. The risk of adverse outcomes was higher in ulcerative colitis compared to Crohn’s disease. The relative risks of hospitalisation, intensive care unit admission and mortality were lower for patients on biological agents (0.34, 0.19–0.61; 0.49, 0.33–0.72 and 0.22, 0.13–0.38, respectively) but higher with steroids (1.99, 1.64–2.40; 3.41, 2.28–5.11 and 2.70, 1.61–4.55) or 5-aminosalicylate (1.59, 1.39–1.82; 2.38, 1.26–4.48 and 2.62, 1.67–4.11) use. Conclusion SARS-CoV-2 infection risk in patients with inflammatory bowel disease is comparable to the general population. Outcomes of COVID-19-positive inflammatory bowel disease patients are worse in ulcerative colitis, those on steroids or 5-aminosalicylates but outcomes are better with biological agents.

Inflammatory Bowel Disease and Risk of Birth Defects in Offspring

2020 ◽  
Vol 14 (5) ◽  
pp. 588-594
Author(s):  
Nathalie Auger ◽  
Justin Côté-Daigneault ◽  
Marianne Bilodeau-Bertrand ◽  
Laura Arbour
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Central Nervous System ◽  
Nervous System ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Birth Defects ◽  
Bowel Disease ◽  
Inflammatory Bowel ◽  
Central Nervous System Defects

Abstract Background and Aims The relationship between inflammatory bowel disease in pregnancy and birth defects is not understood. We evaluated whether Crohn’s disease and ulcerative colitis in pregnant women were associated with the risk of birth defects in the offspring. Methods We undertook a retrospective cohort study of 2 184 888 pregnancies in Quebec, Canada, between 1989 and 2016. We calculated risk ratios [RR] and 95% confidence intervals [CI] for the association between inflammatory bowel disease and the risk of birth defects, using generalised estimating equations adjusted for maternal characteristics. We assessed associations in the period before 2000, when immunosuppressive biologic therapy and folic acid food fortification were not yet available, compared with the period after 2000 when these interventions were more widespread. Results This study included 13 099 women with Crohn’s disease and 7798 with ulcerative colitis. Crohn’s disease was associated with 1.90 times [95% CI 1.10–3.28] the risk of abdominal wall defects [gastroschisis, omphalocoele, and diaphragmatic hernia] and ulcerative colitis was associated with 1.53 times [95% CI 1.02–2.30] the risk of central nervous system defects. The association of Crohn’s disease with abdominal wall defects was stronger before 2000 [RR 3.62, 95% CI 1.71–7.67] than after 2000 [RR 1.23, 95% CI 0.55–2.75]. Ulcerative colitis was associated with central nervous system defects regardless of time period. Conclusions These findings suggest that inflammatory bowel disease is associated with the risk of abdominal wall and central nervous system defects, and that introduction of immunobiologic medications is unlikely to be associated with added risk. Podcast This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast

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