РезюмеЦель исследования. Сравнить безопасность терапии у больных язвенным колитом (ЯК) и болезнью Крона (БК), получавших комплексную противовоспалительную терапию с применением мезенхимальных стромальных клеток (МСК) костного мозга, и стандартную терапию препаратами 5-аминосалициловой кислоты, глюкокортикостероидами и иммуносупрессорами. Материалы и методы. Неблагоприятные последствия проанализированы у 103 больных (56 с ЯК и 47 с БК) воспалительными заболеваниями кишечника (ВЗК), которым вводили МСК. Полученные результаты сравнили с данными, полученными у 208 пациентов с ЯК и БК, которые находились на стандартной противовоспалительной терапии. Все пациенты сопоставимы по демографическим параметрам, длительности заболевания, протяженности поражения кишечника, характеру течения, форме заболевания, степени тяжести. В анализируемые группы не включали больных, которые получали терапию анти-α-ФНО-препаратами. Безопасность терапии оценивали по наличию осложнений, возникших за время наблюдения. Результаты. Проведя анализ неблагоприятных последствий у 103 больных ВЗК, которым вводили МСК, и сравнив их с результатами лечения 208 больных ЯК и БК, получавших стандартную противовоспалительную терапию, мы не выявили различий в развитии острых посттрансфузионных реакций, инфекционных осложнений, обострений хронических воспалительных заболеваний, тяжелых инфекционных осложнений, злокачественной трансформации и смертельных случаев у больных ЯК и БК, за исключением транзиторной лихорадки. Заключение. Результаты нашего исследования демонстрируют, что инновационный метод клеточной терапии является безопасным для клинического применения.Ключевые слова: безопасность клеточной терапии, мезенхимальные стромальные клетки, болезнь Крона, язвенный колит, воспалительные заболевания кишечника. Aim.To compare the safety of therapy in patients with ulcerative colitis (UC) and Crohn's disease (CD) who have received combination anti-inflammatory therapy using bone marrow mesenchymal stromal cells (MSC) and standard therapy with 5-aminosalicylic acid, glucocorticosteroids, and immunosuppressive agents. Subjects and methods. Unfavorable consequences were analyzed in 103 patients (56 with UC and 47 with CD) with inflammatory bowel disease (IBD) after MSC administration. The findings were compared with data obtained in 208 patients with UC and CD on standard anti-inflammatory therapy. All the patients were similar in demographic parameters, the duration of disease, the extent of intestinal injury, the nature of a course, the type and degree of disease. The analyzed groups did not include patients who had received therapy with anti-TNF-α drugs. The safety of therapy was evaluated from the presence of complications occurring during the follow-up. Results. By analyzing the unfavorable consequences in 103 patients with IBD and comparing them with treatment results in 208 patients with UC and CD on standard anti-inflammatory therapy, the authors revealed no differences in the development of acute posttransfusion reactions, infectious complications, exa...

The review presents data on calprotectin, lactoferrin, leukocytes labeled with isotope indium 111In, calgranulin C and pyruvate kinase type M2 - highly sensitive biomarkers to assess the severity of intestinal inflammation. Their importance in diagnostics, determination of treatment efficiency, including as predictors of recurrence of ulcerative colitis and Crohn's disease is shown.

Crohn's disease (CD) is a chronic, recurring disease of the gastrointestinal tract of unclear etiology. One of the new approaches to CD therapy is the use of the possibilities of stem cells, in particular, mesenchymal stromal cells (MSCs). Currently, the use of MSC in clinical practice for the treatment of chronic inflammatory and autoimmune diseases is being studied in patients who receive concomitant therapy with other immunomodulatory medications. Aim. To evaluate the effectiveness of MSCs therapy in patients with CD receiving azathioprine (AZA). Materials and methods. The study included 34 patients with inflammatory (luminal) form of CD. The 1st group of patients (n=15) received anti-inflammatory therapy using MSCs culture in combination with AZA. The 2nd group (n=19) received MSCs without AZA. The severity of the attack was assessed in points in accordance with the of Crohn's disease activity index (CDAI). Immunoglobulins (IgA, IgG, IgM), interleukins (IL) 1β, 4, 10, tumor necrosis factor-α (TNF-α), interferon-γ (INF-γ), transforming growth factor-1β (TGF-1β), C-reactive protein (CRP), platelets and erythrocyte sedimentation rate (ESR) at 2, 6 and 12 months from the beginning of MSCs therapy. Results. The initial mean CDAI in the 1st group was 337.6±17.1 points, in the 2nd group - 332.7±11.0 points (p=0.3). In both groups of patients there was a significant decrease in CDAI after 2 months. From the beginning of therapy MSCs: in the 1st group to 118.9±12.4 points, in the 2nd - 120.3±14.1 points (p=0.7), after 6 months - 110.3±11.1 and 114.3±11.8 points (p=0.8), respectively. After 12 months CDAI in the 1st group was 99.9±10.8 points, in the 2nd group it was 100.6±12.1 points (p=0.8). The level of IgA, IgG, IgM was significantly lower in the group of patients with a longer history of the disease and long-term ASA. After the introduction of MSC in both groups of patients with BC, there was a tendency for the growth of pro - and anti-inflammatory cytokines, with a significantly lower level of pro-inflammatory cytokines - INF-γ, TNF-α, IL-1β - in the 1st group, indicating potentiation of the immunosuppressive effect of MSCs and AZA, which provides a more pronounced anti-inflammatory effect. Conclusion. Transplantation of MSCs promotes an increase in the serum of patients with CD initially reduced concentration of IG, cytokines and restoring their balance as the onset of clinical remission. The combination with AZA has a more pronounced anti-inflammatory effect.

Aim. To compare the effectiveness of the effect of combination therapy (local and systemic administration) with bone marrow mesenchymal stromal cells (MSC), anticlitokine therapy with infliximab (IFX), and antibiotic (AB)/immunosuppressive (IS) therapy on the frequency of healing of simple perianal fistulas in Crohn's disease. Materials and methods. In our study, the 1-st group of patients aged 19 to 58 years (Me-29) (n = 12) received MSCs culture systemically according to the scheme and locally. The 2-nd group of patients with CD (n = 10) from 20 to 68 years old (Me-36) received anticytokine therapy with infliximab (IFX) according to the scheme. The 3-d group of patients with CD (n=14) from 20 to 62 years old (Me-28) received antibiotics (AB) and immunosuppressors (IS). Efficacy was assessed by the index of perianal activity of Crohn's disease (PCDAI) and the frequency of relapses. Results. After 12 weeks among patients of the 1-st group, healing of simple fistulas was noted in 8/12 patients (66.6%), in the 2-nd group in 6/10 (60.0%) In the 3-d group, in 1/14 patients (7.14%). After 6 months in the 1-st group of patients, healing of simple fistulas was preserved in 8/12 (66.6%), in the 2-nd group - in 6/10 (60.0%). In the 3-d group - in 1/14 patients (7.14%). After 12 months in the 1-st group, healing of simple fistulas was preserved in 7/12 (58.3%), in the second group - in 6/10 (60.0%). In the 3-d group - in 2/14 patients (14.3%). After 24 months, among the patients of the 1-st group, fistula closure was maintained in 5/12 patients (41.6%), in the 2-nd group - in 4/10 (40.0%). In the 3-d group - in 0/14 patients (0.0%). Conclusion. Combined cellular and anticytokine therapy of CD with perianal lesions significantly contributes to the more frequent and prolonged closure of simple fistulas, as compared to antibiotics/immunosuppressors, and to a decrease in the frequency of recurrence of the disease.

Aim. To evaluate the efficacy and safety of adalimumab (ADA) in patients with Crohn’s disease (CD) treated at the Department of Inflammatory Bowel Diseases, Moscow Clinical Research and Practical Center, and to determine the predictors of a therapy response. Subjects and methods. All the patients with CD treated with ADA were followed up for at least 6 months or until the drug was discontinued. Therapeutic effectiveness was evaluated at 4 weeks and 6 months after the initiation of treatment and at the end of a follow-up. Complete intestinal mucosal healing was assessed at 3 and 12 months following treatment initiation. Univariate and multivariate analyses were used to determine the predictors of treatment response. Results. A clinical analysis covered 70 patients (57.1% male); the follow-up period averaged 112 weeks. Perianal fistulas were at baseline established in 22 (31.4%) patients with CD. 12 (17.4%) patients had been previously treated with infliximab (INF), 7 of them discontinued the drug for secondary loss of response and 5 for adverse reactions. 68 (97.1%) patients responded to an induction course of ADA. At 4 weeks, 6 months, and at the end of the follow-up, clinical remission occurred in 66.7, 80.4 and 67.4 % of patients with luminal CD and in 45.4, 36.5, and 36.4% of those with perianal CD, respectively. At 3 and 12 months and at the end of the follow-up, there was complete healing of the intestinal mucosa in 23.5, and 41.2 and 29.5% of cases, respectively. Six (8.8%) patients responding to the induction course needed to be optimized with ADA to 40 mg weekly. The time interval between treatment initiation and dose optimization averaged 30 weeks (range 12-120 months). There were 15 (21,4%) adverse events that were responsible for ADA discontinuation in 3 (4,2%) patients. Conclusion. The findings demonstrate the efficacy and safety of ADA used in clinical practice.