[Modern concept of differential diagnosis of colitis: from G.F. Lang to the present day. A review].

The aim of the article is to improve the differential diagnosis of specific and nonspecific inflammatory bowel diseases. In Russia, this scientific direction is associated with the name of G.F. Lang, who performed in 1901-1902 the study "On ulcerative inflammation of the large intestine caused by balantidiasis". The etiology of specific colitis is associated with infection with parasites, bacteria and viruses that cause inflammation of the intestinal wall, diarrhea, often with an admixture of mucus, pus and blood. Specific colitis (SC) may be accompanied by fever, abdominal pain, and tenesmus. Bacterial colitis is commonly caused by Salmonella, Shigella, Escherichia coli, Clostridium difficile, Campylobacter jejuni, Yersinia enterocolitica, and Mycobacterium tuberculosis. Viral colitis is caused by rotavirus, adenovirus, cytomegalovirus, and norovirus. Parasitic colitis can be caused by Entamoeba histolytica and balantidia. In gay people, SC can cause sexually transmitted infections: Neisseria gonorrhoeae, Chlamydia trachomatis, and treponema pallidum, affecting the rectum. Stool microscopy, culture, and endoscopy are used to establish the diagnosis. Stool culture helps in the diagnosis of bacterial colitis in 50% of patients, and endoscopic studies reveal only nonspecific pathological changes. Differential diagnosis of SC should be carried out with immune-inflammatory bowel diseases (ulcerative colitis, Crohn's disease, undifferentiated colitis), radiation colitis and other iatrogenic bowel lesions. The principles of diagnosis and therapy of inflammatory bowel diseases associated with various etiological.

[Tuberculosis infection in patients with inflammatory bowel diseases. Clinacal cases].

In most cases Tuberculosis (TB) affects the lungs, but 10-15% of patients have extrapulmonary TB localisations, that is difficult to diagnose. TB is more spread among patients having the human immunodeficiency virus and among those who receive immunosuppressive therapy, specifically in patients with inflammatory bowel disease requiring long-term treatment with immunosuppressants and/or biologics. The symptoms of intestinal TB are nonspecific and may include chronic diarrhea, weight loss, fever and ascites. Differential diagnosis includes Crohn's disease, malignant neoplasms, periappendiceal abscesses, yersiniosis, etc. The article presents cases showing similarity of the intestinal form of TB with Crohn's disease, complexity dealing, diagnosing and treating patients with inflammatory bowel disease also having latent tuberculosis infection.

[Crohn disease: before and after 1932 year].

The article describes the historical milestones in the study of Crohn's disease from the time of its original description in the 17th century, the revolution in the medical community after the landmark paper in 1932, to the present day. The history of Crohn's disease testifies to the discoveries of the past years, which open up to us the advantages of a scientific approach to the diagnosis and treatment of this disease.

[CROHN'S DISEASE. TO THE 90th ANNIVERSARY OF THE DESCRIPTION].

The article describes the main achievements in the study of Crohn's disease, first described as a disease of the terminal ileum, affecting mainly young people, characterized by subacute or chronic necrotizing and scarring inflammation. In subsequent years, the inflammatory disease was also detected in other parts of the gastrointestinal tract. This disease affects the entire intestine and can involve every part of the gastrointestinal tract, from the mouth to the anus. The history of the study of Crohn's disease for 90 years has made it possible to delve deeply into the pathogenesis of inflammation, but has not yet come closer to revealing its etiology. Therefore, it is impossible to talk about the possibility of recovery from CD.

[Frequency and risk factors for thromboembolic complications in patients with inflammatory bowel diseases].

BACKGROUND: Inflammatory bowel diseases (IBD) are characterized by chronic immune inflammation of the mucous membrane and/or the thickness of the intestinal wall, and are also accompanied by disorders of the blood clotting system and the development of a hypercoagulation state. AIM: To identify the frequency of thromboembolic complications (TEC) in IBD patients and to determine the influence of acquired and inherited hypercoagulation factors that contribute to the development of TEС. MATERIALS AND METHODS: The clinical status of 1,238 IBD patients who were treated in 2019 was evaluated. Of these, 748 patients with ulcerative colitis (UC) and 490 patients with Crohn's disease (CD). Among UC patients, there were 369 (49.3%) men and 379 (50.7%) women. In 10.1% of patients with UC, there were clinically significant feasibility studies. There were 227 (46.3%) men and 263 (53.7%) women among patients with CD; 7.3% of patients with CD had clinically significant feasibility studies. RESULTS: In general 112 (9.0%) of 1,238 IBD patients had clinically significant feasibility studies. Among patients with UC (n=748), 76 (10.2%) showed clinically significant feasibility studies. Among patients with CD (n=490), 36 (7.3%) had a feasibility study. Of 112 IBD patients with clinically significant TEC, 45 (40.2%) had genetic polymorphisms that increase affinity for fibrinogen, increase platelet aggregation, and contribute to a decrease in the activity of folate cycle enzymes, including methylenetetrahydrofolate reductase, which may be manifested by a moderate increase in homocysteine levels. Of the 45 IBD patients with clinically significant TEC due to inherited factors, 30 (66.6%) patients had UC, 15 (33.7%) patients had CD (hazard ratio 1.038, 95% confidence interval 0.7461.444; 2=0.049; p=0.83921); 67 (59.8%) patients with IBD who had clinically significant TEC did not have genetic polymorphisms leading to hypercoagulation. CONCLUSION: Based on the analysis, we can conclude that such risk factors for the development of TEC as the status of a smoker, long bed rest, taking hormonal contraceptives, varicose veins of the lower extremities, high activity of the disease, glucocorticoids therapy, the extent of intestinal damage in patients with IBD, genetic factors, should be taken into account by gastroenterologists in the treatment of patients with UC and CD. The hereditary factor of hypercoagulation equally affects the development of TEC, both in patients with UC and CD.

[Loss of response and frequency of adverse events in patients with ulcerative colitis and Crohn's disease when switching from the original infliximab to its biosimilars].

AIM: To define the frequency of adverse events and loss of the response in patients with ulcerative colitis (UC) and Crohn's disease (CD), treated with original medicine infliximab (IFX) "Remicaide" and its biosimilars. MATERIALS AND METHODS: We included 154 patients with IBD: 78 UC patients (50.6%) и 76 CD patients (49.4%), treated with original medicine IFX Remicade and its biosimilars. In our study we did not include patients, who previously underwent induction treatment with IFX and its biosimilar. RESULTS: Among 78 UC patients, IFX was cancelled in 25 (32.0%) patients and they were switched to the other anti-TNF inhibitor or medicine with the another mechanism of action; in patients group, treated with biosimilar ­ 16 (20.5%) and 9 (11.5%) patients, who were interchanged biosimilar and/or original IFX. Among 76 CD patients IFX was cancelled in 20 (26.3%) patients: 11 (14.5%) patients in group, treated with similar trade name biosimilar, 8 (10.5%) patients, who were interchanged biosimilar and/or original IFX and 1 patient (1,3%), receiving original IFX. We found no difference in the secondary loss of response and adverse events in patients with CD and UC, switched from original IFX to biosimilar (p=0.6257 and p=0.6635, correspondingly). The frequency of the secondary loss of response or adverse events in patients with UC and CD, switched from original IFX to IFX biosimilar, was similar (p>0.05). CONCLUSION: Approximately 30% of IBD patients, receiving IFX biosimilar, will be switched to the other anti-TNF therapy or medicine with the another mechanism of action because of secondary loss of response or adverse events.

[Low adherence to treatment is a weak link in the problems of ulcerative colitis].

AIM: To determine factors of adherence to treatment in patients with ulcerative colitis (UC). MATERIALS AND METHODS: The study was performed in the department of treatment of inflammatory bowel diseases in Loginov Moscow Clinical Scientific Center from 2019 till 2021 years by surveying 1089 patients with UC. This analysis revealed patients with high adherence (HAP) and low adherence to treatment (LAP). RESULTS: In the survey analysis was determined, that there were more low-adherence patients, than high-adherence patients [596 (59.6%) and 404 (40.4%), respectively, (p0.001)]. In the group of HAP (100%) were 297 women (73.5%) and 107 (26.5%) men (p0.001). Also in this group prevailed patients with duration of disease more 5 years 305 (75.5%) and extraintestinal manifestations 261 (64.6%); p0.001. In the group of LAP (100%) were more patients younger 44 years, with bad habits and who did not follow diet (p0.001). The rate of UC reccurence more than 1 time per year was higher in LAP group 430 (72.1%), versus 137 (33.9%) patients in HAP (p0.001). The frequency of surgical procedures in UC patients was significantly higher in LAP 12 (2.0%) in comparison with 2 (0.5%) in HAP group (p0.001). CONCLUSION: In our study was determined, that among UC patients, examined in the department of inflammatory bowel diseases, 60% patients had low adherence to treatment. High adherence to the treatment is statistically significantly associated with female gender, family accommodation, non-working patients, extraintestinal manifestations, additional medical maintenance. Low adherence to the treatment is associated with steroids, male gender, age less than 44 year, bad habits (smoking, alcohol consumption), higher education, complicated UC and frequency of reccurences.

[Histological remission of ulcerative colitis with combined anti-cytokine and cell therapy].

AIM: To conduct comparative analysis of histological remission in patients with moderate and severe ulcerative colitis (UC), receiving biological therapy vedolizumab, mesenchymal stem cell (MSC) treatment and combined stem cells and vedolizumab therapy. MATERIALS AND METHODS: We studied biopsies of 75 patients with total or left-sided moderate and severe ulcerative colitis, divided into groups depending on treatment. The first group of UC patients (n=29) received stem cell therapy 2 mln per kg; the second group of UC patients (n=27) received vedolizumab and the third group (n=19) MSC and vedolizumab. The efficacy of treatment was assessed by C reactive protein (CRP), Mayo score (MS), fecal calprotectin (FC) and Geboes score (GS). RESULTS: We determined medium correlation between basic FC and MS before treatment (r=0.6605, p0.05). After 12 weeks of treatment in the first group of UC patients (n=29) CRP was 7.82.1 mg/l, FC 409.344.85 g/g, medium GS 1.20.1 points. After 12 weeks of treatment in the second group of UC patients (n=27) CRP was 8.41.4 mg/l, FC 435.547.3 g/g, medium GS 1.350.15 points. After 12 weeks of treatment in the third group of UC patients (n=19) CRP was 6.41.1 mg/l, FC 290.617.5 g/g, medium GS 0.90.1 points. We proved strong direct relationship between FC and GS after 12 weeks of treatment in UC patients, receiving MSC (r=0.8392, p0.05). The statistically significant majority of patients, achieved histological remission, have less than 5-year duration of disease. CONCLUSION: Our study showed that clinical and endoscopic remission in UC patients does not always correlate with histological remission. Combined anti-cytokine and stem cells therapy contributes to achieve deep remission and decrease mucosa inflammation rather than single MSC or vedolizumab treatment. Deep remission could be achieved by earlier start of biological therapy. FC could be a predictor and marker of mucosa healing and histological remission.

[Ulcerative colitis. To the 180th anniversary of the description by Karl Rokytansky].

The article describes the main historical milestones in the description and study of ulcerative colitis from the time of Hippocrates to the present day. The first description of the morphological picture of non-specific ulcerative colitis (NUC) was presented by the Viennese pathologist Karl Rokitansky in 1842. The term "ulcerative colitis" was coined by S. Wilks in 1859. A detailed description of the disease was presented in 1875 by S. Wilks and W. Maxon. In an independent nosological form, NUC was isolated in 1888 by the English doctor White. Boas in 1903. For the first time, he presented the differential diagnosis of NUC and chronic dysentery. The term "non-specific ulcerative colitis" in Russia was first introduced by A.S. Kazachenko in a report at the XIII Congress of Russian Surgeons in 1913.

[Is histological remission of ulcerative colitis achievable?]

Current conception of deep remission in patients with ulcerative colitis (UC) consists of clinical remission, endoscopic mucosal healing and normalization of laboratory markers. Histological remission should not be used as a primary end point for therapeutic efficacy, but instead should be considered as a marker of deep remission. The main goal of UC treatment should be focused on endoscopic healing of colon mucosa, decrease of inflammation activity, prolonged remission, absence of disease recurrence, and also histologic remission. Nevertheless, the term histologic remission has not yet been fully validated and no histologic indexes have been standardized. We need single unified definition for remission, based on multicentral studies analysis. One of important challenge is restoration of normal colon mucosal and results of multiple studies showed contradictory tests for assessing histologic remission, thus remaining an issue for further discussion.

[Systemic manifestations of inflammatory bowel diseases].

The article is devoted to the current data regarding the pathogenesis, classification and frequency of extraintestinal manifestations (EIMs) in inflammatory bowel diseases. We discuss two distinct theories of EIMs pathogenesis. First, EIMs arise from an extension of antigen-specific immune responses from the intestine to non-intestinal sites. Second, EIMs are independent inflammatory events initiated or perpetuated by the presence of IBD or by shared genetic or environmental risk factors in the host. These mechanisms are not mutually exclusive and may contribute to varying degrees in different EIMs. Early diagnosis of EIMs contributes to prevention disability and enhancement of quality of life of IBD patients. It is concluded that treatment of extraintestinal manifestations should be carried out taking into account the course of the IBD and the multidisciplinary approach, which requires close cooperation of doctors of various specialties. Assessment of prognostic markers and predictors for EIM in IBD will be part of a future investigation.

The use of fecal calprotectin in monitoring activity of inflammatory bowel diseases.

AIM: To compare fecal calprotectin (FC) concentration with laboratory and diagnostic methods in patients with inflammatory bowel diseases (IBD). MATERIALS AND METHODS: The level of FC was measured in 110 patients with established IBD. Crohn diseases (CD) was diagnosed in 50 patients, ileocolitis - in 38 and terminal ileitis in 12 individuals. Ulcerative colitis (UC) was diagnosed in 60 patients, total colitis in 35, left-side colitis in 21 and 4 patients have proctitis. Laboratory data include measurement of FC, leukocytes, erythrocyte sedimentation rate (ESR), C reactive protein (CRP), fecal occult blood. All patients underwent colonoileoscopy (CIS) at the start of disease flare and after 12 weeks of treatment. RESULTS: We found linear correlation between level of FCP and endoscopic activity of CD, analyzing FCP level and endoscopic activity of CD before (during disease flare) and after 12 weeks treatment (r=0.66, p<0.001). Linear correlation between FCP and SES-CD sustained after 12 weeks of treatment (r=0.77, p<0.001). We revealed correlation between FCP concentration. And CRP level (r=0.59, p<0.05). The linear correlation was detected between FCP and endoscopic activity of UC (r=0.88, p<0.001) before the treatment. After 12 weeks of treatment linear correlation was shown between FCP and Meyo scale (r=0.73, p<0.001). IBD patients with FCP more than 200 mcg/g have high risk of disease reccurence in short-term period of time (HR - 8.33; 95% CI 2.05-33.8; χ2 - 11.85; p<0.001) and (HR - 2.7; 95% CI 1.1-6.6; χ2 - 5.3; p<0.05), accordingly. CONCLUSION: Increased FCP level indicates poor effectiveness of treatment and high risk of reccurence. The level of FCP correlates strongly with recent laboratory and diagnostic indices of activity and enables to determine patients with high risk of reccurence. Thus, thorough monitoring, including additional procedures, contributes to just-in-time treatment modification.

[Evaluation of efficacy and comparative frequency of adverse events in patients with ulcerative colitis receiving the original infliximab and its biosimilar. One year of observation].

Real - life data on the effectiveness and safety of biosimilar and biologic drugs licensed for treatment of inflammatory bowel diseases (IBD) is lacking. AIM: To investigate efficacy of original Infliximab (IFX) and its biosimilar in treating patients with ulcerative colitis (UC) and determine the frequency of adverse events during 1 year follow - up period. MATERIALS AND METHODS: Our cohort consisted of 98 ulcerative colitis patients, treated with original IFX and its biosimilar since December 2017 till December 2018 years. Original Infliximab was prescribed in 56 UC patients (57.1%) during 5 years and longer; 16 patients (16.3%) were switched to IFX biosimilar; 13 UC bio - naïve patients (13.3%) received original IFX, 29 (29.6%) patients - biosimilar IFX. In 14 patients (14.3%) original infliximab was rotated with biosimilar. We picked out 42 patients to assess efficacy of original IFX and biosimilar. RESULTS AND DISCUSSION: Twelve patients, received original IFX and 28 patients, treated with its biosimilar, showed significant clinical improvement by decreasing Mayo index from 9.7±0.4 and 10.2±0.2 points to 1.9±0.09 and 2.1±0.1 points, accordingly. Also we noticed positive change in laboratory markers - CRP decrease from 89.6±8.7 mg/l and 77.5±8.0 mg/l to 6.5±0.8 mg/l and 6.9±0.8 mg/l (p>0.05), albumin increase from 30.1±4.7 g/l and 29.6±3.6 g/l to 34.1±6.3 g/l and 32.8±5.9 g/l (p>0.05), increase of serum iron levels from 6.4±0.5 mcg/l and 7.1±0.65 mcg/l to 14.6±4.4 mcg/l and 15.9±5.1 mcg/l (p>0.05), hemoglobin increase from 104.7±9.8 g/l and 102.2±8.8 g/l till 124±11.3 g/l and 121±10.9 g/l (p>0.05), and fecal calprotectin decrease from 1680±134 mcg/g and 1720±126 mcg/g till 245.5±33.4 mcg/g and 230.5±29.8 mcg/g (p>0.05). During 1 year follow - up 12 UC patients, treated with original IFX and its biosimilar, developed adverse events. The majority of adverse events (n=8) were registered in patients, rotating administration of original IFX and its biosimilar. CONCLUSION: IFX biosimilar is effective as well as original IFX. Frequency of adverse events, occurred in patients, treated with original IFX, was comparable with adverse events frequency in patients, received biosimilar IFX. Frequency of adverse events was significantly higher in UC patients, rotating original IFX and its biosimilar.

Personalized medicine in the treatment of inflammatory bowel diseases.

Personalized medicine (personalized medicine, individualized medicine) represents the totality of methods of prevention of a pathological condition, diagnosis and treatment in the event of its occurrence, based on individual patient characteristics. Such individual characteristics include genetic, epigenetic, and transcript, proteome, metabolomic and metagenomic markers, as well as a set of variable phenotypic traits - both of the patient's body and its separate tissues or cells. For example, treatment of inflammatory bowel diseases (IBD) can most clearly show the importance of applying personalized approaches. Currently in the treatment of patients with IBD paid great attention to genetic studies, monitoring of the concentration of the biological drugs and the level of antibodies to them, the role of microbiota as a predictor of effectiveness of therapy of IBD. Used clinical, laboratory, instru- mental methods, as well as new biomarkers to assess the forecasting efficiency of conservative therapy in IBD patient. In the future treatment of patients with IBD will include a number of personalized data in order to better predict outcomes of the disease in each patient and more ac- curately select the appropriate treatment regimen.

Mesenchymal stromal cells of bone marrow and azathioprine in Crohn's disease therapy.

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 an- ti-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) 1ß, 4, 10, tumor necrosis factor-α (TNF-α), interferon-γ (INF-γ), transforming growth factor-1ß (TGF-1ß), 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 pa- tients 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-1ß - in the 1st group, indicating potentiation of the immunosuppressive effect of MSCs and AZA, which provides a more pro- nounced 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.

Clostridium difficile in inflammatory bowel disease.

AIM: To study epidemiology and risk factors for Clostridium infection (CDI) associated with Clostridium difficile in patients with inflammatory bowel disease (IBD). MATERIALS AND METHODS: 1179 medical records were analyzed in a retrospective study of patients with IBD, of which 764 patients met the inclusion criteria. Patients were divided into 2 groups based on the presence of a preliminary diagnosis of CDI. Statistical analysis was carried out using Pearson Chi-square and two-sample t-test. RESULTS: The incidence of CDI in patients with IBD was 17.3%, with the same prevalence in patients with Crohn's disease (CD) (n=53/40.1%) and ulcerative colitis (UC) (n=79/59.9%). The mean age of occurrence of CDI in patients with IBD was 37.8±12.9, 84.8% of infections were community-acquired and only 4.5% occurred in medical institutions. Only 21.2% of all patients with CDI had a history of antibiotic use, and 24.2% had previously used steroids. Long-term immunosuppressive therapy in patients with IBD has an impact on the development of CDI: among patients with CDI 45.5% long-term received azathioprine/6-mercaptopurine, in patients without IBD - 17.7% (p<0.001). 18% of patients with CDI had control of the disease with salicylate therapy, while 62% of patients without CDI achieved remission by taking salicylates (p<0.05). CONCLUSION: The prevalence of CDI in UC and CD is comparable (p=0.16). The study shows that patients with IBD are more sensitive to the development of CDI at a young age, while not having such traditional risk factors as recent hospitalization or antibiotic use. Patients with IBD with CDI in history often noted the ineffectiveness of therapy with salicylates, often require the assignment of biological therapy. IBD patients with CDI have a lower average albumin, and a higher activity of the inflammatory process.

Adherence to therapy of patients with inflammatory bowel diseases.

Inflammatory bowel diseases are autoimmune systemic forms of pathology. The concept of continuous life-long drug intake is a cornerstone in their therapy. The review presents the factors that reduce patients adherence to treatment and ways to improve it. They include informing the patient about the disease and treatment, selection of individual therapy regimen, consolidation of achievements, provision of social support and interaction with other specialists.

Stem Cell Therapy for Perianal Crohn's Disease.

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.

Efficacy and tolerability of certolizumab pegol in Crohn's disease in clinical practice.

AIM: To assess the efficacy and tolerance of certolizumab pegol (CP) in patients with Crohn's disease (CD) treated in the Department of inflammatory bowel diseases of the A.S. Loginov Moscow Clinical Research Center and to determine the predictors of response to therapy. MATERIALS AND METHODS: All patients with CD who had received the treatment of CP were observed prospectively for at least 6 months or until the date of discontinuation of the drug. The effectiveness of the study was assessed response to therapy by the 6th week, maintaining the clinical response (6th and 26th weeks), the dynamics of endoscopic parameters by the 10th and 54th week of therapy, long-term maintenance of remission, healing fistula. Used univariant and multivariate analyses of predictors of response to treatment. RESULTS: The study included 39 patients: 12 (30.7%) men and 27 (69.3%) female, the average duration of observation was 104 weeks. The interdepartmental range was in the range from 28 to 158 weeks. Clinical improvement occurred in 38 out of 39 (97.4 %) patients with CD. Comparative analysis of response to treatment with CP have bionaive patients previously treated with another inhibitor of TNF-α. In the group of bionaive response to therapy in a month, 6 months and at the end of the observation period occurred at 100.0%, 95.0% and 95.0%, respectively. In the group of patients previously treated with GSI, the response rate was about 94.4 %, 88.9 % and 77.7% week 54 endoscopic response and endoscopic remission was maintained in 46,2% and 30,1% patients, complete healing of the mucosa on the background of maintenance therapy, CP, was preserved in 20.5% of patients with Crohn's disease. In the group of patients with perianal lesions (n=13) complete closure of all fistulas was observed in 5 (38.6 %) patients, partial response was observed in 4 patients (30,7%) patients, in 4 (30.7 %) closure of fistulas occurred. The frequency of adverse events was 0 cases (0.0%). The dose escalation was required in 3 patients (7,7%) patients with CD. Dose escalation in our study required patients with high initial CDAI and previous inefficiencies of the other two inhibitors of TNF-α. Reliable predictors of secondary loss of response and need for dose escalation of the drug has been the continued level of CRP >5 mg/l after 2 weeks initiation of therapy CP and smoking. CONCLUSION: The obtained results demonstrate the efficacy and tolerability profile of CP appropriate for long-term CD therapy in real clinical practice.

[Efficacy of adalimumab for Crohn's disease in real clinical practice]. / Effektivnost' adalimumaba pri bolezni Krona v real'noi klinicheskoi praktike.

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.