P479 Biological therapies and bio-microbial dynamics in inflammatory bowel diseases

Abstract Background Therapeutic aims in IBDs are to induce remission through rapidly effective treatment. Conventional therapeutic methods including immunosuppression have been available for more than half a century with biological therapies the treatment of choice in patients who fail immunosuppressive drugs. There has been little attempt to longitudinally examine the differences in biopsychological factors and their associations with treatment modalities in IBD patients. Methods 50 IBD participants (24 UC, 26 CD) in clinical remission were followed for 12 months. Complete longitudinal datasets and monthly stool and blood samples for inflammatory biomarkers were collected for analysis of association. Microbiome analysis was performed using V4 16SrRNA for identification of microbial phylogenetic relationships. Patients were grouped on whether or not they were in remission and on biological agents. Results At the baseline there were similar ecological indices between the two treatment options in both disease classes; (Shannon, p = 0.380; Pielou’s, p = 0.246; Chao1, p = 0.934). At family level, the CD group showed significant differences (Wilcoxon, p ≤ 0.05) between the treatment received (biologics vs non-biologic) in the abundance of Barnesiellaceae, Bifidobacteriaceae, unclassified Clostridia, and Clostridiaceae (Figure 1A). Results showed similar ecological index values in samples from the two treatment options. Samples in UC groups on biological and non-biologic treatment modes were found to have significantly different microbial communities based on Bray-Curtis dissimilarity (PERMANOVA, p = 0.0031). Microbial family composition in UC group and on two treatment modalities showed a total of 12 families that were significantly different (Wilcoxon, p ≤ 0.05): Acidaminococcaceae, unclassified Bacteroidales, Barnesiellaceae, Christensenellaceae, Clostridiales vadinBB60 group, Coriobacteriaceae, Defluvitaleaceae, Eggerthelaceaem Fusobacteriaceae, Muribaculaceae, Prevotellaceae, and Streptococcaceae (Figure1B). Results identified significant differences in microbial diversity (Shannon index, p = 0.041), and evenness (Pielou’s evenness, p = 0.045) between the two treatment modes. No differences were identified in richness (Chao1) in UC participants. Conclusion Conclusion: Baseline biological indices were mostly similarly distributed between the two treatment options in remissive IBD patients, however biological therapy significantly influenced longitudinal trends of some microbiome dynamics, especially in UC. This suggests an underlying interrelationship between mode of treatment and biopsychological trajectories which might overshadow response to the treatment, requiring further assessment.

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Predictors and Early Markers of Response to Biological Therapies in Inflammatory Bowel Diseases

Journal of Clinical Medicine ◽

10.3390/jcm10040853 ◽

2021 ◽

Vol 10 (4) ◽

pp. 853

Author(s):

Giuseppe Privitera ◽

Daniela Pugliese ◽

Gian Ludovico Rapaccini ◽

Antonio Gasbarrini ◽

Alessandro Armuzzi ◽

...

Keyword(s):

Inflammatory Bowel Diseases ◽

Current Knowledge ◽

Real Life ◽

Response To Therapy ◽

Significant Heterogeneity ◽

Intestinal Damage ◽

Biological Therapies ◽

Early Markers ◽

Bowel Diseases ◽

Inflammatory Bowel

Inflammatory bowel diseases (IBD) are chronic conditions that primarily affect the gastrointestinal tract, with a complex pathogenesis; they are characterized by a significant heterogeneity of clinical presentations and of inflammatory pathways that sustain intestinal damage. After the introduction of the first biological therapies, the pipeline of therapies for IBD has been constantly expanding, and a significant number of new molecules is expected in the next few years. Evidence from clinical trials and real-life experiences has taught us that up to 40% of patients do not respond to a specific drug. Unfortunately, to date, clinicians lack a valid tool that can predict each patient’s response to therapies and that could help them in choosing what drug to administer. Several candidate biomarkers have been investigated so far, with conflicting results: clinical, genetic, immunological, pharmacokinetic and microbial markers have been tested, but no ideal marker has been identified so far. Based on recent evidence, multiparametric models seemingly hold the greatest potential for predicting response to therapy. In this narrative review, we aim to summarize the current knowledge on predictors and early markers of response to biological therapies in IBD.

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Malnutrition in Inflammatory Bowel Diseases. What do we know today?

Kompass Nutrition & Dietetics ◽

10.1159/000516279 ◽

2021 ◽

pp. 1-3

Author(s):

Christina N. Katsagoni

Keyword(s):

Disease Control ◽

Inflammatory Bowel Diseases ◽

Bone Development ◽

Treatment Modalities ◽

Growth Delay ◽

Refeeding Syndrome ◽

Exclusive Enteral Nutrition ◽

Pubertal Delay ◽

Bowel Diseases ◽

Inflammatory Bowel

Growth delay with height and weight impairment is a common feature of pediatric inflammatory bowel diseases (PIBD). Up to 2/3 of Crohn Disease patients have impaired weight at diagnosis, and up to 1/3 have impaired height. Ulcerative colitis usually manifests earlier with less impaired growth, though patients can be affected. Ultimately, growth delay, if not corrected, can reduce final adult height. Weight loss, reduced bone mass, and pubertal delay are also concerns associated with growth delay in newly diagnosed PIBD patients. The mechanisms for growth delay in IBD are multifactorial and include reduced nutrient intake, poor absorption, increased fecal losses, as well as direct effects from inflammation and treatment modalities. Management of growth delay requires optimal disease control. Exclusive enteral nutrition (EEN), biologic therapy, and corticosteroids are the primary induction strategies used in PIBD, and both EEN and biologics positively impact growth and bone development. Beyond adequate disease control, growth delay and pubertal delay require a multidisciplinary approach, dependent on diligent monitoring and identification, nutritional rehabilitation, and involvement of endocrinology and psychiatry services as needed. Pitfalls that clinicians may encounter when managing growth delay include refeeding syndrome, obesity (even in the setting of malnutrition), and restrictive diets. Although treatment of PIBD has improved substantially in the last several decades with the era of biologic therapies and EEN, there is still much to be learned about growth delay in PIBD in order to improve outcomes.

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Antioxidant Therapy in Inflammatory Bowel Diseases

Antioxidants ◽

10.3390/antiox10030412 ◽

2021 ◽

Vol 10 (3) ◽

pp. 412

Author(s):

Katarzyna Dziąbowska-Grabias ◽

Małgorzata Sztanke ◽

Przemysław Zając ◽

Michał Celejewski ◽

Katarzyna Kurek ◽

...

Keyword(s):

Inflammatory Bowel Diseases ◽

Nitrosative Stress ◽

Treatment Options ◽

Chemical Compounds ◽

Continuous Increase ◽

Public Health Burden ◽

Bowel Diseases ◽

Significant Public Health ◽

Inflammatory Bowel

Inflammatory bowel diseases (IBD) are a group of chronic, incurable diseases of the digestive tract, the etiology of which remains unclear to this day. IBD result in significant repercussions on the quality of patients’ life. There is a continuous increase in the incidence and prevalence of IBD worldwide, and it is becoming a significant public health burden. Pharmaceuticals commonly used in IBD management, for example, mesalamine, sulfasalazine, corticosteroids, and others, expose patients to diverse, potentially detrimental side effects and frequently do not provide sufficient disease control. The chronic inflammation underlies the etiology of IBD and closely associates with oxidative/nitrosative stress and a vast generation of reactive oxygen/nitrogen species. Relative to this, several substances with antioxidant and anti-inflammatory properties are now intensively researched as possible adjunctive or independent treatment options in IBD. Representatives of several different groups, including natural and chemical compounds will be characterized in this dissertation.

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Inflammatory Bowel Disease: An Overview of Immune Mechanisms and Biological Treatments

Mediators of Inflammation ◽

10.1155/2015/493012 ◽

2015 ◽

Vol 2015 ◽

pp. 1-11 ◽

Cited By ~ 69

Author(s):

Bruno Rafael Ramos de Mattos ◽

Maellin Pereira Gracindo Garcia ◽

Julia Bier Nogueira ◽

Lisiery Negrini Paiatto ◽

Cassia Galdino Albuquerque ◽

...

Keyword(s):

Ulcerative Colitis ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Severe Disease ◽

Biological Therapies ◽

Promising Alternative ◽

Biological Treatments ◽

Bowel Diseases ◽

Inflammatory Bowel ◽

And Behavior

Inflammatory bowel diseases (IBD) are characterized by chronic inflammation of the intestinal tract associated with an imbalance of the intestinal microbiota. Crohn’s disease (CD) and ulcerative colitis (UC) are the most widely known types of IBD and have been the focus of attention due to their increasing incidence. Recent studies have pointed out genes associated with IBD susceptibility that, together with environment factors, may contribute to the outcome of the disease. In ulcerative colitis, there are several therapies available, depending on the stage of the disease. Aminosalicylates, corticosteroids, and cyclosporine are used to treat mild, moderate, and severe disease, respectively. In Crohn’s disease, drug choices are dependent on both location and behavior of the disease. Nowadays, advances in treatments for IBD have included biological therapies, based mainly on monoclonal antibodies or fusion proteins, such as anti-TNF drugs. Notwithstanding the high cost involved, these biological therapies show a high index of remission, enabling a significant reduction in cases of surgery and hospitalization. Furthermore, migration inhibitors and new cytokine blockers are also a promising alternative for treating patients with IBD. In this review, an analysis of literature data on biological treatments for IBD is approached, with the main focus on therapies based on emerging recombinant biomolecules.

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Inflammatory bowel disease and COVID-19: A review

Journal of Clinical Images and Medical Case Reports ◽

10.52768/2766-7820/1323 ◽

2021 ◽

Vol 2 (5) ◽

Author(s):

Rabin Hamal ◽

◽

Rahul Pathak ◽

Brindeswari Kafle Bhandari ◽

Anurag Jha ◽

...

Keyword(s):

Immunosuppressive Drugs ◽

World Health ◽

Noncommunicable Diseases ◽

Severe Illness ◽

Infectious Risk ◽

The World ◽

Bowel Diseases ◽

Inflammatory Bowel ◽

Health Organization ◽

Chronic Inflammatory Bowel

The World Health Organization officially declared infection with severe acute respiratory syndrome coronavirus 2 (SARSCoV-2), leading to coronavirus disease 2019 (COVID-19) as a Public Health Emergency of International Concern (PHEIC) on 30 January 2020 and then as a pandemic on March 11, 2020 with reports of infection from most of the countries of the world [1]. COVID-19 has severely disrupted prevention and treatment for noncommunicable diseases. Severe illness can occur in otherwise healthy individuals of any age, but it predominantly occurs in adults with advanced age or certain underlying medical comorbidities [2]. Since the beginning of the health emergency, particular attention has been paid to the management of patients with chronic Inflammatory Bowel Diseases (IBDs) because they frequently are treated with immunosuppressive drugs and therefore potentially are exposed to a greater infectious risk than the general population [3].

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Biological Therapies for Inflammatory Bowel Diseases

Gastroenterology ◽

10.1053/j.gastro.2009.02.001 ◽

2009 ◽

Vol 136 (4) ◽

pp. 1182-1197 ◽

Cited By ~ 252

Author(s):

Paul Rutgeerts ◽

Severine Vermeire ◽

Gert Van Assche

Keyword(s):

Inflammatory Bowel Diseases ◽

Biological Therapies ◽

Bowel Diseases ◽

Inflammatory Bowel

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Challenges in screening for latent tuberculosis in inflammatory bowel disease prior to biologic treatment: a UK cohort study

Frontline Gastroenterology ◽

10.1136/flgastro-2017-100951 ◽

2018 ◽

Vol 9 (3) ◽

pp. 234-240 ◽

Cited By ~ 8

Author(s):

Aye Aye Thi ◽

Aula Abbara ◽

Sonia Bouri ◽

Simon M Collin ◽

Paul Wolfson ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Latent Tuberculosis ◽

Immunosuppressive Drugs ◽

Retrospective Case ◽

Biologic Treatment ◽

North West ◽

Ltbi Screening ◽

Interferon Gamma Release Assays ◽

Inflammatory Bowel

ObjectiveThe aim of this study was to determine the occurrence of latent tuberculosis infections (LTBI) and active TB in a cohort of patients with inflammatory bowel disease (IBD) treated with biologics. We also examined the effects of immunosuppressive drugs on indeterminate interferon-gamma release assays (IGRA) in LTBI screening.DesignRetrospective study of patients treated with biologics between March 2007 and November 2015.SettingSt Mark’s Hospital, North West London, UK.Patients732 patients with IBD who were screened for LTBI using either tuberculin skin test or IGRA before starting a biologic treatment.MethodsRetrospective case note review of all patients with IBD who were screened for LTBI prior to initiating biologics. Patients who developed active TB were identified from the London TB register.ResultsOf 732 patients with IBD, 31 (4.2%) were diagnosed with and treated for LTBI with no significant side effects. Six of 596 patients (1.0%) who received biologic treatment developed active TB. There was a higher proportion of indeterminate IGRA in the immunosuppressive medication group compared with the non-immunosuppressive group (33% (59/181) compared with 9% (6/66), p<0.001). The combination of steroids and thiopurines had the highest proportion of indeterminate IGRA (64%, 16/25). High and low doses of steroids were equally likely to result in an indeterminate IGRA result (67% (8/12) and 57% (4/7), respectively).ConclusionsThis study highlights the challenges of LTBI screening prior to commencing biologic therapy and demonstrates the risk of TB in patients who have been screened and who are receiving prolonged and continuing doses of antitumour necrosis factor.

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Echo Intima-Media Thickness (IMT) in the Evaluation of Early Atherosclerosis in Inflammatory Bowel Disease (IBD) Patients – a Prospective Study

Medicina Moderna - Modern Medicine ◽

10.31689/rmm.2021.28.3.281 ◽

2021 ◽

Vol 28 (3) ◽

pp. 281-289

Author(s):

Ana Maria NEGREANU ◽

◽

Simona BADIU ◽

Eugenia PANAITESCU ◽

Monica IONITA ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Doppler Ultrasonography ◽

Statistical Significance ◽

Intima Media Thickness ◽

Biologic Treatment ◽

Media Thickness ◽

Bowel Diseases ◽

Inflammatory Bowel ◽

Early Atherosclerosis

Introduction: Inflammatory bowel diseases (IBD) are accompanied by an early and accelerated atherosclerotic process. Previous studies showed that Doppler ultrasonography and intima media thickness (IMT) is a reliable marker for early atherosclerosis diagnosis. The aim of our study was to evaluate the presence of early atherosclerosis in a group of subjects with inflammatory bowel diseases, using Doppler ultrasonography and intima-media thickness (IMT) as a marker of subclinical atherosclerosis. Methods: A case-control study was conducted on 61 patients with inflammatory bowel disease and 19 healthy individuals. The included patients had an established IBD diagnosis, based on clinical, endoscopic, and histological criteria for at least 12 months. Results: In our study echo IMT was not significantly higher in IBD patients than in matched healthy controls. We found no difference between Crohn’s disease and ulcerative colitis patients or between conventional or biologic treatment regarding the echo IMT. Severity of the disease and its duration were predictors of an increased IMT. We found that disease activity (measured by the endoscopic scores and CRP) correlates with higher values of echo IMT. Also the presence of anemia reached statistical significance and was correlated with increased echo IMT in the biologic treatment group. Conclusions: In our study we found an increased echo IMT in IBD patients versus control, but the values did not reach statistical significance. We found no difference between Crohn’s disease and UC, conventional or biologic treatment. Age and duration of disease were corelated with increased IMT. Disease that was not controlled (high endoscopic, clinical and biological markers of activity) was correlated with increased echo IMT. The limitations of our study are that in our patients therapy was started early in the course of the disease and that the majority of the patients were in remission when echography was made. Further studies are necessary to evaluate factors correlated with early atherosclerosis in IBD and how echo IMT can be used as a tool in the proactive evaluation of these patients.

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Management of Acute Severe Colitis in the Era of Biologicals and Small Molecules

Journal of Clinical Medicine ◽

10.3390/jcm8122169 ◽

2019 ◽

Vol 8 (12) ◽

pp. 2169

Author(s):

Christine Verdon ◽

Talat Bessissow ◽

Peter L. Lakatos

Keyword(s):

Ulcerative Colitis ◽

Small Molecules ◽

Patient Monitoring ◽

Treatment Options ◽

Medical Emergency ◽

Bowel Diseases ◽

Inflammatory Bowel ◽

New Treatment ◽

Acute Severe Colitis ◽

Severe Colitis

Acute severe ulcerative colitis (ASUC) is a medical emergency which occurs in about 20%–30% of patients with ulcerative colitis during their lifetime, and does carry a mortality risk of 1%. The management of inflammatory bowel diseases has evolved with changes in objective patient monitoring, as well as the availability of new treatment options with the development of new biological and small molecules; however, data is limited regarding their use in the context of ASUC. This review aims to discuss the emerging data regarding biologicals and small molecules therapies in the context of ASUC.

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