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.

[Clinical and morphological variants of diverticular disease in colon].

Our own results of two-stage research are presented in the article. The first stage contains the retrospective analysis of 3682 X-ray examining of large bowel which were conducted in 2002-2004 to define the structure of colon disease and to determine gender differences. The second stage is prospective research which took place from 2003 to 2012 and 486 patients with diverticular disease were regularly observed. Following parameters were estimated: dynamics of complaints, life quality, clinical symptoms. Multiple X-ray and endoscopic examining were done with estimation of quantity and size of diverticula, changes of colon mucosa, comparison of X-ray and endoscopic methods in prognosis of complications. Two basic clinical morphological variants of diverticular disease (DD) of colon are made out as a result of our research. There are IBD-like and DD with ischemic component. The variants differ by pain characteristics, presence of accompanying diseases, life quality parameters and description of colon mucosa morphological research. We suppose that different ethiopathogenetic factors of development of both variants mentioned above influence the disease prognosis and selection of treatment.

Regeneration of colorectal epithelium in diverticulosis.

Excessive poorly differentiated epitheliocytes were detected in the crypts and subepithelial regions of the colorectal mucosa during the regeneration process in the majority of patients with diverticular disease. The compensatory reaction of the sigmoid mucosa decreased, which was seen from rarely detected cryptic hyperplasia. Disorders in the epitheliocyte proliferation and differentiation were paralleled by changes in tissue levels of proinflammatory cytokines (elevation of TNF-α and IFN-γ and reduction of IL-1ß and IL-8) and increase of IL-4, regulating lymphocyte activation.

[External respiratory function in patients with Crohn's disease].

This article presents the results of a study of respiratory function (SRF) in 56 patients with Crohn's disease (CD) who were hospitalized in the Department of intestine pathology in Central research institute of gastroenterology. SRF was determined by spirography and registration of the curve flow--volume forced exhale ("Eton-1, RF). Violations of pulmonary function in CD occurred in 44.6% of patients, which exceeded the rate of violations in the control group (60 healthy individuals) is about 5 times (p < 0.001). Identified breaches were presented in most cases with obstructive pathology of bronchial tubes, much less restrictive observed (8.0%) and mixed (16.0%), disorders of ventilation. The highest frequency of pulmonary function was observed during prolonged (more than 10 years) history of illness (81.2%) and in patients with ileocolitis (64.7%).

[The role of immune system in development of structural changes in colonic mucosa in diverticulosis].

AIM: To determine the role of immune response with production of auto- and heterologous antibodies (Ab) in development of the pathological process and in structural changes in colon mucosa (CM) in diverticulosis (Dv). MATERIAL AND METHODS: Of 219 Dv patients, 39 were newly diagnosed with x-ray-detected signs of previous inflammation (group 1), 180 had earlier detected Dv which was confirmed and endoscopic examination detected inflammation (group 2). The comparison group consisted of 25 patients with irritable colon syndrome. The immune status was assessed by concentration of immunoglobulins (Ig), auto- and heterologous Ab. Antibodies to catalytic cytoplasmic antigens to proteinase-3, myeloperoxidase, bactericide protein BPI, tissue transglutaminase (tTG) and antiglycanic Ab were detected with solid-phase enzyme immunoassay. RESULTS: IgA and IgG levels in group 2 were significantly higher than in group 1 and in the controls. Elevation of both IgA and IgG levels reflects activation of B-cell immunity. Group 2 patients had a higher level of Ab to endogenic peptides Saccharomyces cerevisiae (ASCA) of class IgG and IgA than group 1 and controls. The level of Ab to tissue molecules was elevated: antibodies to tTG IgG were detected in both groups--in group 2 twice more often than in group 1, while Ab to BPI--in 27% cases in group 1 and in 97%--in group 2. IgG Ab to antigens associated with phagocytic cells were detected in group 2, while Ab in group 1 were positive in single cases. CONCLUSION: Activation of immune response with a high concentration of IgA and IgG, Ab to tissue antigens (BPI, tTG) and IgGAb to catalytic antigens is characteristic of chronic course of Dv. Morphological changes in CM reflect different severity of inflammation-dystrophic process.

[Transplantation of allogeneic mesenchymal stem cells from the bone marrow increases duration of remission and reduces the risk of ulcerative colitis relapse].

The first results of allogeneic mesenchymal stem cells from the bone marrow transplantation to patients with ulcerative colitis demonstrated improved clinical course. We found an increasing in the duration of remission in patients with chronic recurrent and continuous recurrent course of ulcerative colitis. Also it was noted reducing the risk of relapse, and reducing the frequency of hospital admissions compared with medication therapy with only 5 aminosalicylic acid and glucocorticosteroid.

[Use of allogeneic mesenchymal stem cells in the treatment of intestinal inflammatory diseases].

AIM: to determine the whether mesenchymal stem cells (MSC) may be used in the treatment of patients with chrOnic intestinal inflammatory diseases (IID). SUBJECTS AND METHODS: Thirty-nine patients with ulcerative colitis (UC) (Group 1) and 11 with Crohn's disease (CD) (Group 2) were examined. Comparative groups included 30 patients with UC (Group 2) and 10 with CD (Group 4). Two-three days before MSC administration, immunodepressants were discontinued, the dosage of corticosteroids was reduced to 15-20 mg/day, and that of aminosalicylates remained to be 2 g/day. The results were quantified using the mean values of the Rachmilewich clinical activity index, the Crohn's disease activity index and the Mayo and Gebs scales. The patients were followed up for 4-8 months. Humoral immunological indices (cytokines, autologous antibodies) were determined. Bone marrow cells were obtained from the donor sternum or iliac crest. Cultivation at the end of weeks 5-6 provided a population of allogeneic donor MSC in a quantity of (1.5-2) x 10(8) tells required for transplantation to a patient. MSC cultures were once injected intravenously in a dropwise fashion. RESULTS: A statistically significant decrease in the indices of the clinical and morphological activities of an inflammatory process was noted in 39 patients with UC and in 11 patients with CD as compared with the comporison groups after MSC transplantation. Clinicomorphological remission occurred in 40 patients. Inclusion of MSC into the treatment program was ineffective in 8 patients with UC and in 2 patients with CD. The use of MSC made it possible to discontinue corticosteroids in 34 of the 50 patients with the hormone-dependent and hormone-resistant forms of UC and CD and to reduce the dose of prednisolone to 5 mg/day in 7 patients, by administering 5-aminosalicylic acid only. CONCLUSION: The use of MSC may be appreciated as a new strategic direction of therapy for IID. The intravenously administered stem cells exert a potent immunomodulatory effect, reduce the activity of autoimmune inflammation, and stimulate a reparative process in the intestinal mucosa.

[Peculiarities of respiratory function in elderly patients with ulcerative colitis].

This article presents a comparative analysis of the frequency and types of violations of respiratory function (RF) in ulcerative colitis (UC) in 29 elderly patients and in 108 patients younger than 60 years. Pulmonary function was studied by spirometry and record the flow curve--forced expiratory volume ("Eton-1"). Prescribe a higher rate of airflow obstruction in older compared with patients younger than 60 years (from 65.5 and 39.8% respectively, p < 0.05), which increased with the duration of the disease Yak (in the elderly to a greater extent than in patients younger than 60 years), had no clear connection with the extent of inflammation in the intestine, while staying within 60-71.4% at any site of inflammation.

[Allogeneic mesenchymal stromal cells in patients with ulcerative colitis: two years of observation].

UNLABELLED: The aim of the study was to determine the efficacy and safety of mesenchymal stromal cells (MSCs) of bone marrow in the treatment of patients with ulcerative colitis (UC). MATERIALS AND METHODS: The study included 44 patients with ulcerative colitis (UC), which was implemented MSC transplantation, 40 patients with UC who received standard therapy with mesalazane (salofalka) 4-6 g/day and corticosteroids (prednisone)--1-2 mg/kg, azathioprine--1.5 mg/kg methotrexate 20-50 mg/m2, and 12 patients who underwent induction and maintenance of infliximab therapy. 2-3 days prior to the induction of MSCs abolish immunosuppressive doses of corticosteroids reduced to 15-20 mg/day dose of aminosalicylates was left at 2.0 g/day. To quantify the results using the average values of indices of Rahmilevich clinical activity, indices of endoscopic and histological activity scales Mayo and Gebs. The patients were observed for 24 months after transplantation. Were studied parameters of the humoral immune status (immunoglobulin A, G, M, autologous antibody), cytokine profile. Bone marrow cells were obtained from the donor's sternum or the iliac crest. By culturing the end of 5 to 6 weeks received a population of allogeneic donor's MSCs in the amount of (1.5-2) x 10(8) cells needed for transplant patient. Culture of MSCs injected in the drip i/v, single dose. RESULTS: In 34 (72.7%) patients with UC after the induction of MSCs was statistically significant compared with the group of patients treated with drugs only 5-aminosalicylic acid and corticosteroids, reducing the clinical and morphological indices of inflammatory activity. In 12 patients with UC include MSCs in the treatment program did not have a therapeutic effect. Application of MSC allowed to cancel corticosteroids in most patients with hormone-dependent and steroid resistance forms of UC, and in 7 to reduce the dose of prednisolone to 5 mg/day, limiting the use of drugs 5-ASA. According to the anti-inflammatory effectiveness of combined therapy with MSCs comparable to infliximab therapy. CONCLUSION: The use of MSCs can be evaluated as a new strategic direction for therapy UC. MSC, introduced in I/O, have powerful immunomodulatory effects, reduce the activity of autoimmune inflammation and stimulate the reparative process in the intestinal mucosa, thereby increasing the duration of remission, reduces risk of recurrence of disease, reduces the frequency of hospitalizations.

[Application of allogeneic mesenchymal stem cells in complex patients treatment with ulcerative colitis].

Systemic transplantation of mesenchymal stem cells (MSC) is known to promote reparative process in a number of tissue damage as well as mucous healing one. It provided the basis for our study which was aimed to the effect of systemic transplantation of allogenic MSC (intravenous transfusion) in complex therapy of patients with Ulcerative Colitis.

[Clinical-functional and morphological changes in the large intestine in patients with chronic abdominal ischemia]. / Kliniko-funktsional'nye i morfologicheskie izmeneninia tolstoi kishki u bol'nykh s khronicheskoi abdominal'noi ishemiei

The article presents a study of clinical variants of ischemic lesions of the large intestine (ILLI) in patients with the chronic abdominal ischemia (CAI) syndrome. There was an examination of 42 patients with putative ILLI, who had a cardiovascular pathology at the background, which led to significant hemodynamic disorders of the blood flow in unpaired visceral branches of the abdominal aorta. The authors performed a complex diagnostics of ILLI including anamnestic and clinical data, laboratory and morphological assessment of the large intestine and vessels providing its blood supply. Based on the data collected, other functional and organic diseases of the large intestine (LI) were excluded. It was revealed that the final result of ILLI differed depending on the ischemia degree--from reversible functional disorders to high-grade organic lesions of the LI. Each clinical variant of ILLI has its own clinical manifestations as well as functional, organic and morphological peculiarities of changes in the LI revealed by a laboratory and histological examination of the LI.

[Immunosuppressive therapy of inflammatory diseases of the large intestine]. / Immunosupressivnaia terapiia vospalitel'nykh zabolevanii tolstoi kishki

The treatment of ulcerous colitis and Crohn's disease is based on suppression of various components of the immunoinflammatory cascade. In addition to aminosalicylates and glucocorticoids, drugs of primary immunosuppressive action are used for this purpose, which are adopted from clinical oncology and transplantation medicine: azathioprine, 6-mercaptopurine, methotrexate, cyclosporine A, tacrolimus, mycophenolate mofetil, thalidomide. Some of them are used for remission induction in case of hormonal dependence or resistance, while others are applied for its maintenance or at various stages of the inflammatory process course. The presented review discloses problems of clinical pharmacology of immunosuppressive drugs, side effects, results of pilot and clinical studies of ulcerous colitis and Crohn's disease. All this makes it possible to determine their role in the therapy of inflammatory diseases of the bowels.

[Comparative efficacy of mezakol and sulfasalazine in treating chronic relapsing ulcerative colitis]. / Sravnitel'naia éffektivnost' mezakola i sul'fasalazina v lechenii khronicheskogo retsidiviruiushchego iazvennogo kolita.

This research testifies to the fact that it is more preferable to use mesacol than sulfasalazine in treatment of common forms of ulcerative colitis of light and average severity. Mesacol acts faster in arresting inflammations in proximal parts of the larger intestine. One can assume that the pH-dependent release of 5-aminosalicylic acid in these forms of the disease suffers less than the destruction of the diazo link by the anaerobic microflora, due to which a higher concentration of the preparation is formed in the large intestine. Another alternative explanation can be the dose-dependent effect. Thus, 2.4. g of mesacol correspond to 6 g of sulfasalazine. The dose of sulfasalazine was smaller in our study. Mesacol had no advantages over sulfasalazine in treatment of distal colitis, which can and must be treated with rectal introduction of corticosteroids and 5-aminosalicylic acid preparations. Thus, mesacol must be reserved for treatment of patients with common ulcerative colitis of light and average severity in case of intolerance to sulfasalazine or impossibility to increase the preparation dose over 4 g/day. Its efficiency and price make the preparation available for most patients and patient care institutions.

[Hemorrhoids]. / Gemorroi.

Hemorrhoids is believed by right to be one of the most widely spread human sufferings ranking first among diseases of the rectum and large intestine. According to the data of numerous studies devoted to this problem, from 2.9 to 27.9%% of population of different countries suffer from hemorrhoids. Most authors agree that men suffer from hemorrhoids more often than women do and that its frequency increases with the aging. For the sake of justice, it is necessary to note that some researchers insist that men and women suffer from this disease equally often but that men ask for medical care 1.5 times more often.

[Disorders of hemostasis in clinical picture and pathogenesis of inflammatory diseases of the colon (literature review)]. / Narusheniia gemostaza v klinike i patogeneze vospalitel'nykh zabolevanii tolstoi kishki (obzor literatury).

Hemostatic disorders are involved in the pathogenesis of inflammatory large intestine diseases. Both thrombocytes and humoral coagulation factors are involved in this process. An attempt to correct these disorders will allow not only to declare a new approach to the treatment of inflammatory large intestine diseases but also to clarify their role in the occurrence and persistence of an active inflammation during these diseases.

[Absorption function of the large intestine in patients with nonspecific ulcerative colitis]. / Sostoianie absorbtsionnoi funktsii tolstoi kishki u bol'nykh nespetsificheskim iazvennym kolitom.

Colon absorption function was examined in twenty fife patients with active non-specific ulcerative colitis (15 persons with the distal form and 10 with left-side form investigate by rectal antipyrin test. The state of absorption was estimated on duration of antipyrin half-absorption, on attainment of its maximal concentration and on level of its salivary concentration. Most of patients (n = 19) with active non-specific ulcerative colitis had disorders of colon absorption. This was demonstrated by reduced antipyrin absorption and decreasing amount of absorbed material. But in 6 patients with expressed destructive-inflammatory processes the antipyrin absorption was intensified. In patients with ulcerative colitis the disorders of colon antipyrin absorption depend on activity of inflammatory processes.

[Morphometry in the diagnosis of colon villous polyps]. / Morfometriia v diagnostike vorsinchatykh polipov tolstoi kishki.

Endoscopic biopsies were carried out in 62 patients with colon villous adenomas and 28 patients with colon adenocarcinomas. Differential-diagnostic schemes of evaluation different morphological versions of colon villous adenomas were used for processing results of hystological investigations. These schemes were offered by G.G. Avtandilov et all. Multifactorial analysis of diagnostic features showed a possibility of transition from villous adenoma to adenocarcinoma.