scholarly journals Small Molecule Drugs in Inflammatory Bowel Diseases

2021 ◽  
Vol 14 (7) ◽  
pp. 637
Author(s):  
Inès Ben Ghezala ◽  
Maëva Charkaoui ◽  
Christophe Michiels ◽  
Marc Bardou ◽  
Maxime Luu
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Severe Disease ◽  
Standard Of Care ◽  
Mucosal Inflammation ◽  
Inadequate Response ◽  
First Line Therapy ◽  
Phosphodiesterase 4 Inhibitors ◽  
Bowel Diseases ◽  
Sphingosine 1 Phosphate ◽  
Inflammatory Bowel

Inflammatory bowel diseases (IBDs), mainly represented by Crohn’s disease (CD) and Ulcerative Colitis (UC), are chronic disorders with an unclear pathogenesis. This incurable and iterative intestinal mucosal inflammation requires the life-long use of anti-inflammatory drugs to prevent flares or relapses, which are the major providers of complications, such as small bowel strictures and intestinal perforations. The introduction of tumor necrosis factor (TNF)-alpha inhibitors and other compounds, such as anti-IL12/23 and anti-alpha4/beta7 integrin monoclonal antibodies, has considerably improved the clinical management of IBDs. They are now the standard of care, being the first-line therapy in patients with aggressive disease and in patients with moderate to severe disease with an inadequate response to conventional therapy. However, for approximately one third of all patients, their efficacy remains insufficient by a lack or loss of response due to the formation of anti-drug antibodies or compliance difficulties with parenteral formulations. To address these issues, orally administered Small Molecules Drugs (SMDs) that use a broad range of novel pharmacological pathways, such as JAK inhibitors, sphingosine-1-phosphate receptor modulators, and phosphodiesterase 4 inhibitors, have been developed for CD and UC. This article provides an updated and complete review of the most recently authorized SMDs and SMDs in phase II/III development.

Does Infliximab Short Infusion have a Beneficial Impact on the Quality of Life in Patients with Inflammatory Bowel Diseases? A Single Centre Prospective Evaluation

2015 ◽  
Vol 24 (2) ◽  
pp. 165-170 ◽  
Author(s):  
Mariabeatrice Principi ◽  
Giuseppe Losurdo ◽  
Rosa Federica La Fortezza ◽  
Pasquale Lopolito ◽  
Rosa Lovero ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Inflammatory Bowel Diseases ◽  
Adverse Reactions ◽  
Severe Disease ◽  
Sexual Life ◽  
Necrosis Factor Alpha ◽  
Short Infusion ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Background & Aims: Infliximab (IFX) is an anti-tumor necrosis factor alpha agent used in inflammatory bowel diseases (IBD) therapy. Usually, it is administered over a 2-hour intravenous infusion. However, shortening the infusion duration to 1 hour has proved to be feasible and safe. In the present study we evaluated whether shortening the IFX infusion could affect the patients' quality of life (QoL) compared to the standard protocol.Methods: Subjects affected by IBD receiving IFX were prospectively recruited. The main criterion to shorten the infusion was the absence of IFX-related adverse reactions during the previous three 2-h infusions. For each patient, demographic, clinical and anthropometric data were collected. A questionnaire investigating their overall/job/social/sexual QoL was administered. Ordinal regression was performed with odds ratios (OR) for significant independent variables.Results: Eighty-one patients were included (46 with ulcerative colitis - UC, 35 with Crohn's disease - CD). Sixteen received the 2-h infusion due to previous adverse reactions, and the remaining 65 underwent the 1-h schedule. Shortening the infusion to 1 hour determined a better QoL (OR=0.626). However, the QoL was negatively influenced by age (OR=1.023), female sex (OR=2.04) and severe disease activity (OR=7.242). One-hour IFX infusion induced a better outcome on work (OR=0.588) and social (OR=0.643) QoL. Long-standing disease was correlated with a slightly better sexual QoL (OR=0.93). Conversely, older age (OR=1.046), severe clinical score (OR=15.579), use of other immunomodulators (OR=3.693) and perianal CD (OR=3.265) were related to an unsatisfactory sexual life. The total number of infusions (OR=0.891), proctitis (OR=0.062) or pancolitis (OR=0.1) minimized the perception of infusion-related side effects.Conclusion: The 1-h short infusion improves overall, social and job QoL, so that, when indicated, it should be recommended.

scholarly journals Cytomegalovirus and Inflammatory Bowel Diseases (IBD) with a Special Focus on the Link with Ulcerative Colitis (UC)

2020 ◽  
Vol 8 (7) ◽  
pp. 1078
Author(s):  
Alexandre Jentzer ◽  
Pauline Veyrard ◽  
Xavier Roblin ◽  
Pierre Saint-Sardos ◽  
Nicolas Rochereau ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Diseases ◽  
Viral Reactivation ◽  
Steroid Resistance ◽  
Mucosal Inflammation ◽  
Special Focus ◽  
Close Relationship ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Cmv Colitis

Cytomegalovirus (CMV) infects approximately 40% of adults in France and persists lifelong as a latent agent in different organs, including gut. A close relationship is observed between inflammation that favors viral expression and viral replication that exacerbates inflammation. In this context, CMV colitis may impact the prognosis of patients suffering from inflammatory bowel diseases (IBDs), and notably those with ulcerative colitis (UC). In UC, the mucosal inflammation and T helper cell (TH) 2 cytokines, together with immunomodulatory drugs used for controlling flare-ups, favor viral reactivation within the gut, which, in turn, increases mucosal inflammation, impairs corticoid and immunosuppressor efficacy (the probability of steroid resistance is multiplied by more than 20 in the case of CMV colitis), and enhances the risk for colectomy. This review emphasizes the virological tools that are recommended for exploring CMV colitis during inflammatory bowel diseases (IBD) and underlines the interest of using ganciclovir for treating flare-ups associated to CMV colitis in UC patients.

scholarly journals Microbiota-independent immunological effects of non-digestible oligosaccharides in the context of inflammatory bowel diseases

2020 ◽  
Vol 79 (4) ◽  
pp. 468-478 ◽  
Author(s):  
Stefania Del Fabbro ◽  
Philip C. Calder ◽  
Caroline E. Childs
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Immune Cell ◽  
Intestinal Inflammation ◽  
Mechanisms Of Action ◽  
Mucosal Inflammation ◽  
Disease States ◽  
Inflammatory Conditions ◽  
Bowel Diseases ◽  
Inflammatory Bowel

The aim of the present paper is to review the effects of non-digestible oligosaccharides (NDO) on immunity, focusing on their microbiota-independent mechanisms of action, as well as to explore their potential beneficial role in inflammatory bowel diseases (IBD). IBD are chronic, inflammatory conditions of the gastrointestinal tract. Individuals with IBD have an aberrant immune response to commensal microbiota, resulting in extensive mucosal inflammation and increased intestinal permeability. NDO are prebiotic fibres well known for their role in supporting intestinal health through modulation of the gut microbiota. NDO reach the colon intact and are fermented by commensal bacteria, resulting in the production of SCFA with immunomodulatory properties. In disease states characterised by increased gut permeability, prebiotics may also bypass the gut barrier and directly interact with intestinal and systemic immune cells, as demonstrated in patients with IBD and in infants with an immature gut. In vitro models show that fructooligosaccharides, inulin and galactooligosaccharides exert microbiota-independent effects on immunity by binding to toll-like receptors on monocytes, macrophages and intestinal epithelial cells and by modulating cytokine production and immune cell maturation. Moreover, animal models and human supplementation studies demonstrate that some prebiotics, including inulin and lactulose, might reduce intestinal inflammation and IBD symptoms. Although there are convincing preliminary data to support NDO as immunomodulators in the management of IBD, their mechanisms of action are still unclear and larger standardised studies need to be performed using a wider range of prebiotics.

T-cell-directed therapies in inflammatory bowel diseases

2010 ◽  
Vol 118 (12) ◽  
pp. 707-715 ◽  
Author(s):  
Giovanni Monteleone ◽  
Flavio Caprioli
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Inflammatory Bowel Diseases ◽  
Clinical Success ◽  
Mucosal Inflammation ◽  
Activated T Cells ◽  
Cell Accumulation ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Gut inflammation occurring in patients with IBDs (inflammatory bowel diseases) is associated with exaggerated and poorly controlled T-cell-mediated immune responses, which are directed against normal components of the gut flora. T-cells accumulate in the inflamed gut of IBD patients as a result of multiple mechanisms, including enhanced recruitment of cells from the bloodstream, sustained cell cycling and diminished susceptibility of cells to undergo apoptosis. Activated T-cells produce huge amounts of cytokines, which contribute to amplify and sustain the ongoing mucosal inflammation. Strategies aimed at interfering with T-cell accumulation and/or function in the gut have been employed with clinical success in patients with IBDs. In the present article, we review the available results showing that T-cell-directed therapies are useful to dampen the tissue-damaging immune response in IBDs.

Mo1723 Role of CCL20-CCR6 Axis and MMP9 in the Mucosal Inflammation and Fibrosis in Inflammatory Bowel Diseases

2015 ◽  
Vol 148 (4) ◽  
pp. S-694-S-695
Author(s):  
Orsolya Inczefi ◽  
Tamas Molnar ◽  
Anita Balint ◽  
Raffaella Dainese ◽  
Mathilde Leveque ◽  
...  
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Mucosal Inflammation ◽  
Bowel Diseases ◽  
Inflammatory Bowel

scholarly journals Quality of Life Impact and Special Issues in Women with Inflammatory Bowel Diseases

2021 ◽  
Author(s):  
Gabriel Constantinescu ◽  
Gina Gheorghe ◽  
Ecaterina Rinja ◽  
Oana Plotogea ◽  
Vasile Sandru ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Inflammatory Bowel Diseases ◽  
Standard Of Care ◽  
Cross Sectional ◽  
Men And Women ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
The Impact ◽  
Gender Specific

Abstract Background: The impact of inflammatory bowel diseases (IBD) on quality of life (QoL) of patients is significant and has important social and professional consequences. Methods: We aimed to describe the patients’ perspective regarding the impact of IBD on their overall QoL and to evaluate the differences between men and women. An observational cross-sectional study, that included 180 patients with IBD in clinical remission, was conducted. All the patients completed a number of 3 questionnaires in order to evaluate the general aspects of their QoL. A separate questionnaire was created regarding gender-specific issues in women with IBD encounter. Also, particular features such as the incidence of anemia and osteoporosis among IBD patients were documented. The data obtained were analyzed and compared between the two gender-classified groups. Results: According to the Short Inflammatory Bowel Disease Questionnaire (SIBDQ), patients had a general perception of a good QoL, but the impact was higher in women. Fatigue and tiredness were severely perceived almost to the same degree regardless of gender, whereas anxiety and unemployment were more present in men. No significant differences in women with IBD during active disease and during disease remission were found. Conclusions: The overall quality of life of IBD patients is affected in many aspects, leading to the deterioration of their social and professional lives, for both men and women, but some aspects remain gender-specific and require a personalized standard of care.

Ultrasensitive molecular imaging of intestinal mucosal inflammation using leukocyte-mimicking particles targeted to MAdCAM-1 in mice

2020 ◽  
Vol 12 (560) ◽  
pp. eaaz4047
Author(s):  
Antoine P. Fournier ◽  
Sara Martinez de Lizarrondo ◽  
Adrien Rateau ◽  
Axel Gerard-Brisou ◽  
Maximilian J. Waldner ◽  
...  
Keyword(s):  
Adhesion Molecule ◽  
Intestinal Mucosa ◽  
Inflammatory Bowel Diseases ◽  
Intestinal Inflammation ◽  
Mucosal Inflammation ◽  
Molecular Mri ◽  
Mucosal Tissues ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Chronic Intestinal Inflammation

Mucosal tissues play critical roles in health and disease as the primary barrier between the external world and the inner body, lining the digestive, respiratory, urinary, mammary, and reproductive tracts. Clinical evaluation of mucosal tissues is currently performed using endoscopy, such as ileocolonoscopy for the intestinal mucosa, which causes substantial patient discomfort and can lead to organ damage. Here, we developed a contrast agent for molecular magnetic resonance imaging (MRI) that is targeted to mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1), an adhesion molecule overexpressed by inflamed mucosal tissues. We investigated the diagnostic performance of molecular MRI of MAdCAM-1 to detect mucosal inflammation in several models of acute and chronic intestinal inflammation in mice. We demonstrated that molecular MRI of MAdCAM-1 reveals disease activity and can evaluate the response to inflammatory treatments along the whole intestinal mucosa in clinically relevant models of inflammatory bowel diseases. We also provide evidence that this technique can detect low, subclinical mucosal inflammation. Molecular MRI of MAdCAM-1 has potential applications in early diagnosis, longitudinal follow-up, and therapeutic response monitoring in diseases affecting mucosal tissues, such as inflammatory bowel diseases.

scholarly journals AN ADVANCED REVIEW ON DIAGNOSIS AND TREATMENT AND EXTRA-INTESTINAL MANIFESTATIONS ASSOCIATED WITH INFLAMMATORY BOWEL DISEASE

2021 ◽  
Vol 10 (1) ◽  
pp. 99-113
Author(s):  
Deep Sharma ◽  
Rekha Rana ◽  
Kiran Thakur ◽  
Priyanka
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Inflammatory Bowel Diseases ◽  
Bowel Disease ◽  
Severe Disease ◽  
Clinical Pathology ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Inflammatory Bowel Diseases are mainly a group of bowel disorders which are generally associated with chronic inflammation of the intestinal tract due to the reason of an imbalance in the presence of the intestinal microbiota. Inflammatory bowel disease can have two different types based on their clinical pathology which are mainly Crohn’s Disease and Ulcerative Colitis. Both of these clinical sub-types are most likely to be focussed among all of the inflammatory bowel diseases due to their increasing risk of incidence as well as associated difficulties in their treatment. However, the main cause of inflammatory bowel disease has not been cleared till the date but from last three decades, there is a hub of researchnes being going on to get a clear idea about the cause of disease. Among these studies most of researchers have found the role of Nucleotide Oligomerization Domain 2 genes in the pathophysiology of disease. For the treatment of ulcerative colitis, there are severalapproaches available, based on the severity of the disease. Aminosalicylates are used to treat mild disease, use of corticosteroids is the effective treatment in the moderate case whereas use of cyclosporine in severe disease. In Crohn’s disease, drug choices are dependent on both location and behavior ofthe disease. Nowadays, the advanced treatments have been included such as use of monoclonal antibodiesor fusion proteins including anti-TNF drugs as biological therapy of disease. Also the post treatment remission of this disease makes it more complicated to be cured.

scholarly journals P243 Elevated presepsin levels are a marker of sepsis risk in patients with inflammatory bowel diseases receiving therapy of TNF-α blockers

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S286-S287
Author(s):  
O Knyazev ◽  
A Kagramanova ◽  
A Lishchinskaya ◽  
I Li ◽  
K Noskova ◽  
...  
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Severe Disease ◽  
Clinical Status ◽  
Predictive Marker ◽  
Immunosuppressive Drugs ◽  
Low Risk ◽  
Moderate Risk ◽  
Tnf Α ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Abstract Background Sepsis is a severe disease characterized by a systemic inflammatory response syndrome (SARS) associated with infection. Sepsis is registered in 1–2% of all hospitalized patients. IBD patients receiving immunosuppressive therapy have a high risk of developing sepsis. Diagnosis of sepsis is based on internationally agreed criteria. Predicting the course and outcomes of sepsis is evaluated on the MEDS (Mortality in Emergency Department Sepsis) scale. Clinical studies of a new biomarker called presepsin have shown that it is a promising early and predictive marker of sepsis Aim to establish the role of presepsin as a marker of sepsis development in patients with inflammatory bowel diseases (IBD) receiving therapy with genetically of TNF-α blockers. Methods The clinical status of 128 IBD patients receiving of TNF-α blockers therapy (without immunosuppressive drugs) was evaluated in the Department of IBD. 68 patients with ulcerative colitis (UC) and 60 patients with Crohn’s disease (CD). Presepsin level (PSP) was determined in all IBD patients (100.0%). To stratify patients, the following criteria were used for baseline PSP levels (pg/ml): < 200 – very low risk of sepsis; - 200 - 300– low risk of sepsis; - 300 - 500– moderate risk of sepsis; - 500 - 1000 – sepsis; - ≥ 1000-severe sepsis, septic shock Results The distribution among 128 IBD patients receiving of TNF-α blockers by presepsin level was as follows: < 200 -75 (58,6%); - 200 – 300 – 34 (26,6%); - 300 – 500 – 19 (14,8%); - 500 - 1000 – 0 (0%); ≥ 1000 – 0 (0%). Of the 75 IBD patients receiving gibp and having a very low risk, none of the patients developed sepsis; of the 34 IBD patients with a low risk, one patient developed septicemia (2.9%). Among 19 patients with IBD with a moderate risk, the development of a septic condition occurred in 4 (21.0%) patients (HR-0.140, 95% CI 0.017 - 1.162; x2-2,800; p= 0.04997). Conclusion IBD patients receiving of TNF-α therapy, it is advisable to determine the level of presepsin in order to identify risk groups for the development of sepsis. Patients with IBD who receive of TNF-α therapy and have presepsin values in the range of 300–500 pg/ml have a significantly higher risk of developing sepsis.

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