Vedolizumab for inflammatory bowel diseasesI

Aim of review. To present literature data on administration of vedolizumab at inflammatory bowel diseases. Summary. The vedolizumab is anti-α4β7-integrin humanized class IgG1 antibodies which suppresses migration of leukocytes in intestinal tissue, interfering thereby with development of pathologic inflammation. GEMINI-1 study of ulcerative colitis has demonstrated efficacy of the drug in remission induction (clinical response rate of 47,1% of patients, clinical remission of 16,9% and endoscopic remission of 40,9% at the 6th week) and in remission maintenance (percent of patients in clinical remission at 52nd week at drug injection every 4 weeks - 44,8%). Similar efficacy was demonstrated for Crohn's disease (GEMINI-2) study in remission induction (clinical response rate - 31,4% of patients, clinical remission - 14,5%) and remission maintenance (percentage of patient in clinical remission by 52nd week at injection of the drug every 4 weeks - 39%). The results received in clinical trials were confirmed by clinical data in the different countries. Safety profile investigations demonstrated low system immune suppression due to specific action mechanism of the drug. Besides, due to α4β7 integrin heterodimer selectivity of vedolizumab, it provides selective block of intestinal leukocyte migration, without affection of central nervous system therefore the risk of the progressing multifocal leukoencephalopathy is not established. Conclusion. Present clinical trials has demonstrated that vedolizumab is effective and safe in treatment of inflammatory bowel diseases

Immunopathogenesis of inflammatory bowel diseases

The aim of review. To present analysis of data on immunopathogenesis of inflammatory bowel diseases.Key points. At genetically sensitive animals inflammatory bowel diseases (IBD) develop at various effects on innate and adaptive systems of immune defense (knock-out and transgenic mice), causing changes of expression of significant immunologic factors with distortion of pro- and anti-inflammatory cells and molecules ratio at their contact to microbiota structures. The physiological state of intestine is characterized by balanced interaction of effector (Th1, Th2, Th17) and regulatory (Treg) cells determining presence of immune tolerance to resident microflora antigens. Innate immunity changes revealed in last years, related to mutations of genes of bacterial structures receptors (NOD2, toll-like receptors, autophagy), cause disorder of endocellular signal processes and pathological activation of cells of adaptive immunodefense of intestinal mucosa and conforming profile of cytokines with development of chronic inflammation which will be mediated: at Crohn's disease – by Th1-and Th17-cells, cytokines IL-12, interferon-γ etc., at ulcerative colitis – by Th2-and NKT-cells, cytokines IL-4 and IL-3 in combination to incompetence of suppressor function of regulatory Т-cells and their cytokines TGF-β (transforming growth factor) and IL-10.Conclusion. Investigations of experimental enterocolites and human IBD confirm immunologic hypothesis of pathogenesis: relation of their development to defects of innate and adaptive immune system

Serum cytokines in ulcerative colitis of various clinical activity

Aim of investigation. To determine frequency of detection and level of circulating cytokines at ulcerative colitis (UC) and assess their interrelation with clinical activity and efficacy of conservative treatment. Material and methods. The serum level of IL-2, IL-4, IL-6, IL-8, IL-10, granulocyte-macrophage colonystimulating factor (GM-CSF), IFN-γ and TNF-α was studied in 37 ulcerative colitis patients. Investigation was carried out by «Bio-Plex» protein analyzer («Bio-Rad», USA). Moderately severe and severe forms of UC were diagnosed in 15 and 18 patients respectively, mild — in 4, resistance and sensitivity for conservative treatment were detected in 15 and 22 patients. Surgical treatment was carried out in 14 patients. The control group included 20 blood donors. Results. In patients with moderately severe, severe forms and in the control group IL-6 and IL-10 were revealed in 33,3, 61,1 (р<0,05), 5% of cases and 26,6, 50 (р<0,05), 10% of cases respectively. Substantial increase of IL-6 and IL-10 level was observed in severe form of UC (42,4±21,2 and 22,7±6,4 a pg/ml) as compared to the control group (1,5±1,8 and 5,2±4,1). In groups of patients, resistant and sensitive to conservative treatment, frequency of circulating IL-6 detection was 86,6 and 22,7% (р<0,05), level of IL-6 — 53,4±24,5 and 2,0±0,62 (р<0,05); detection rate of IL-10 — 66,6 and 9% (р<0,05), level of IL-10-31,6±7,4 and 7,1±6,9 (р<0,05) respectively. Three and more circulating cytokines were revealed in 80% of patients, resistant to conservative treatment and in 22,7% (р<0,05) of patients responded to treatment. The profile of IL-6, IL-8 and IL-10 was observed in 60 and 4,5% (р<0,05) patients of these groups respectively. Conclusions. Frequency of detection and level of circulating cytokines IL-6 and IL-10 is considerably higher at severe forms of UC and in patients, resistant to conservative treatment. Expansion of circulating cytokines spectrum, mainly IL-6, IL-8 and IL-10 profile in combination to 1–3 of the other studied cytokines (GM-CSF, IFN-γ, TNF-α) is typical for resistant form of disease

Раннее назначение генно-инженерных биологических препаратов при иммуновоспалительных заболеваниях: возможности и перспективы. Позиция экспертов

Psoriasis (Ps), psoriatic arthritis (PsA), and inflammatory bowel diseases (IBDs) are characterized by a progressive course and frequently lead to disability; therefore, their early diagnosis with the assessment of a clinical phenotype and unfavorable prognostic factors and the timely initiation of therapy are important tasks. The paper provides the experts agreed opinion on the definition of the early stage of Ps, PsA, and IBDs, the goals of therapy and main unfavorable prognostic factors for the course of these diseases and gives the rationale for the early use of biological agents in patients with immune-mediated inflammatory diseases.Псориаз (Пс), псориатический артрит (ПсА) и воспалительные заболевания кишечника (ВЗК) характеризуются прогрессирующим течением и нередко приводят к инвалидизации, поэтому важными задачами являются их ранняя диагностика с оценкой клинического фенотипа и факторов неблагоприятного прогноза и своевременное начало терапии. В статье приводятся согласованная позиция экспертов по определению ранней стадии Пс, ПсА и ВЗК, цели терапии и основные факторы неблагоприятного прогноза течения этих заболеваний, представлено обоснование раннего применения генно-инженерных биологических препаратов у пациентов с иммуновоспалительной патологией

Genome analysis of E. coli isolated from Crohn's disease patients

© 2017 The Author(s). Background: Escherichia coli (E. coli) has been increasingly implicated in the pathogenesis of Crohn's disease (CD). The phylogeny of E. coli isolated from Crohn's disease patients (CDEC) was controversial, and while genotyping results suggested heterogeneity, the sequenced strains of E. coli from CD patients were closely related. Results: We performed the shotgun genome sequencing of 28 E. coli isolates from ten CD patients and compared genomes from these isolates with already published genomes of CD strains and other pathogenic and non-pathogenic strains. CDEC was shown to belong to A, B1, B2 and D phylogenetic groups. The plasmid and several operons from the reference CD-associated E. coli strain LF82 were demonstrated to be more often present in CDEC genomes belonging to different phylogenetic groups than in genomes of commensal strains. The operons include carbon-source induced invasion GimA island, prophage I, iron uptake operons I and II, capsular assembly pathogenetic island IV and propanediol and galactitol utilization operons. Conclusions: Our findings suggest that CDEC are phylogenetically diverse. However, some strains isolated from independent sources possess highly similar chromosome or plasmids. Though no CD-specific genes or functional domains were present in all CD-associated strains, some genes and operons are more often found in the genomes of CDEC than in commensal E. coli. They are principally linked to gut colonization and utilization of propanediol and other sugar alcohols

Diagnosis and Treatment of Irritable Bowel Syndrome: Clinical Recommendations of the Russian Gastroenterological Association and Association of Coloproctologists of Russia

Aim. Current clinical recommendations accentuate current methods for the diagnosis and treatment of irritable bowel syndrome (IBS).Key points. IBS is a functional bowel disorder manifested with recurrent, at least weekly, abdominal pain with the following attributes (any two leastwise): link to defecation, its frequency or stool shape. The symptoms are expected to persist for at minimum three months in a total six-month follow-up. Similar to other functional gastrointestinal (GI) disorders, IBS can be diagnosed basing on the patient symptoms compliance with Rome IV criteria, provided the absence of potentially symptom-causative organic GI diseases. Due to challenging differential diagnosis, IBS can be appropriately established per exclusionem, with pre-examination as follows: general and biochemical blood tests; tissue transglutaminase IgA/IgG antibody tests; thyroid hormones test; faecal occult blood test; hydrogen glucose/ lactulose breath test for bacterial overgrowth; stool test for enteric bacterial pathogens and Clostridium difficile A/B toxins; stool calprotectin test; abdominal ultrasound; OGDS, with biopsy as appropriate; colonoscopy with biopsy. The IBS sequence is typically wavelike, with alternating remissions and exacerbations often triggered by psychoemotional stress. Treatment of IBS patients includes dietary and lifestyle adjustments, various-class drug agents prescription and psychotherapeutic measures.Conclusion. Adherence to clinical recommendations can facilitate timely diagnosis and improve medical aid quality in patients with different clinical IBS variants

Genetic diversity of Escherichia coli in gut microbiota of patients with Crohn's disease discovered using metagenomic and genomic analyses

© 2018 The Author(s). Background: Crohn's disease is associated with gut dysbiosis. Independent studies have shown an increase in the abundance of certain bacterial species, particularly Escherichia coli with the adherent-invasive pathotype, in the gut. The role of these species in this disease needs to be elucidated. Methods: We performed a metagenomic study investigating the gut microbiota of patients with Crohn's disease. A metagenomic reconstruction of the consensus genome content of the species was used to assess the genetic variability. Results: The abnormal shifts in the microbial community structures in Crohn's disease were heterogeneous among the patients. The metagenomic data suggested the existence of multiple E. coli strains within individual patients. We discovered that the genetic diversity of the species was high and that only a few samples manifested similarity to the adherent-invasive varieties. The other species demonstrated genetic diversity comparable to that observed in the healthy subjects. Our results were supported by a comparison of the sequenced genomes of isolates from the same microbiota samples and a meta-analysis of published gut metagenomes. Conclusions: The genomic diversity of Crohn's disease-associated E. coli within and among the patients paves the way towards an understanding of the microbial mechanisms underlying the onset and progression of the Crohn's disease and the development of new strategies for the prevention and treatment of this disease

Diagnosis and Treatment of Irritable Bowel Syndrome: Clinical Recommendations of the Russian Gastroenterological Association and Association of Coloproctologists of Russia

Aim. Current clinical recommendations accentuate current methods for the diagnosis and treatment of irritable bowel syndrome (IBS).Key points. IBS is a functional bowel disorder manifested with recurrent, at least weekly, abdominal pain with the following attributes (any two leastwise): link to defecation, its frequency or stool shape. The symptoms are expected to persist for at minimum three months in a total six-month follow-up. Similar to other functional gastrointestinal (GI) disorders, IBS can be diagnosed basing on the patient symptoms compliance with Rome IV criteria, provided the absence of potentially symptom-causative organic GI diseases. Due to challenging differential diagnosis, IBS can be appropriately established per exclusionem, with pre-examination as follows: general and biochemical blood tests; tissue transglutaminase IgA/IgG antibody tests; thyroid hormones test; faecal occult blood test; hydrogen glucose/ lactulose breath test for bacterial overgrowth; stool test for enteric bacterial pathogens and Clostridium difficile A/B toxins; stool calprotectin test; abdominal ultrasound; OGDS, with biopsy as appropriate; colonoscopy with biopsy. The IBS sequence is typically wavelike, with alternating remissions and exacerbations often triggered by psychoemotional stress. Treatment of IBS patients includes dietary and lifestyle adjustments, various-class drug agents prescription and psychotherapeutic measures.Conclusion. Adherence to clinical recommendations can facilitate timely diagnosis and improve medical aid quality in patients with different clinical IBS variants

USE OF 5-AMINOSALICYLIC ACID FOR TREATMENT OF ULCERATIVE COLITIS IN DIFFERENT DOSAGE MODES

Preparations of 5-ASA are the first line treatment of ulcerative colitis (UC). Today, in the market of drugs 5-ASA available for the treatment of UC, there are many dosage forms, varying in the coating, method of delivery of active substance and dosing regimens of the drug. The aim of this review is to compare these dosage forms by the main parameters: efficiency, safety and adherence to treatment

Adalimumab and azathioprine in the prevention of postoperative crohn’s disease recurrence

Introduction. Despite improvements in earlier diagnosis and the development of conservative therapy for Crohn’s disease (CD), approximately 70%–80% of patients undergo surgical treatment for complications. Surgical treatment is not a cure for this disease. The question of choosing therapy as a prevention of postoperative relapse of CD is still open. AIM. To compare the effectiveness of immunosuppressive and biological therapy as a postoperative preventive therapy.Materials and methods. The retrospective study included 125 patients with CD who underwent surgery in terms from 2010 to 2017. After the operation, patients were divided into 3 groups. Patients from the first group received azathioprine, from the second - adalimumab, and patients from the third group were prescribed combined therapy with azathioprine and adalimumab. Clinical, endoscopic, and laboratory data for analysis of disease activity was collected 3, 6, and 12 months after surgery.Results. During the year of therapy in all three groups relapses occurred in only 22 patients (22/125 17.6%). There were no statistically significant differences between the groups at any of the assessment stages. There was also no statistically significant correlation between the presence of risk factors and relapses.Conclusion. Our research has shown that the choice of anti-relapse therapy depending on risk factors is controversial. However, active endoscopic monitoring is important regardless of the treatment strategy. Also, our data allow us to conclude that the frequency of relapses of CD during the postoperative preventive therapy does not depend on the specific drug chosen, as well as on demographic and anamnestic parameters