Novel Budesonide Suppository and Standard Budesonide Rectal Foam Induce High Rates of Clinical Remission and Mucosal Healing in Active Ulcerative Proctitis: a Randomised, Controlled, Non-inferiority Trial.

BACKGROUND AND AIMS: Proctitis is the least extensive type of ulcerative colitis, for which rectal therapy is rarely studied and is underused. This study evaluated the efficacy, safety, and patient's preference of a novel formulation of budesonide suppository 4 mg, compared with a commercially available budesonide rectal foam 2 mg, for the treatment of mild to moderate ulcerative proctitis. METHODS: This was a randomised, double-blind, double-dummy, active-controlled trial. Patients were randomly assigned in a 1:1 ratio to receive either budesonide 4 mg suppository or budesonide 2 mg foam once daily for 8 weeks. The co-primary endpoints were changes from baseline to Week 8 in clinical symptoms, for which clinical remission was defined as having a modified Ulcerative Colitis-Disease Activity Index [UC-DAI] subscore for stool frequency of 0 or 1 and a subscore for rectal bleeding of 0, and mucosal healing, defined as having a modified UC-DAI subscore for mucosal appearance of 0 or 1. Using a more stringent criterion, we additionally analysed deepened mucosal healing, which was defined as a mucosal appearance subscore of 0. Patient's preference, physician's global assessment, and quality of life were also assessed and analysed. RESULTS: Overall, 286 and 291 patients were included in the 4 mg suppository and 2 mg foam groups, respectively. Budesonide 4 mg suppository met the prespecified criterion for non-inferiority to the 2 mg foam in both co-primary endpoints of clinical remission and mucosal healing. Secondary endpoints consistently supported the non-inferiority of the suppository. Trends in favour of the suppository were observed in the subgroup of mesalazine non-responders. More patients reported a preference for the suppository over rectal foam. CONCLUSIONS: In patients with ulcerative proctitis, budesonide 4 mg suppository was non-inferior to budesonide 2 mg foam in efficacy, and both were safe and well tolerated.

Perception of COVID-19 Pandemic Among IBD Clinicians and IBD Surgeons in Black Sea Region: A Cross-Sectional Questionnaire Study.

BACKGROUND: Since December 2019, the COVID-19 pandemic has created an increasing challenge in managing inflammatory bowel dis- ease patients both medically and surgically. Although several international and national medical/surgical associations published guide- lines in this area, there is still a huge difference between daily practices and these guidelines, especially depending on regional practices and governmental policies. Therefore, we aimed to investigate and define gastroenterologists' and surgeons' fear of COVID-19 and how they have managed inflammatory bowel disease patients during this pandemic in the Black Sea region. METHODS: A 20-question survey was administered to 70 gastroenterology specialists and 80 general surgeons who are mainly focused on the management of inflammatory bowel disease in 5 countries in the Black Sea region. RESULTS: The majority of respondents (81.3%) mentioned that they have concerns that their inflammatory bowel disease patients were at risk of contracting COVID-19. In addition, the majority of respondents (80.3%) believed that inflammatory bowel disease itself, inde- pendent of medications, might increase the risk of contracting COVID-19. The majority of gastroenterologists told that they did not stop inflammatory bowel disease medications due to the COVID-19 pandemic unless patients had COVID-19 disease. Surgeons overwhelm- ingly reached a consensus on how to test patients for COVID-19 perioperatively and came to a conclusion on which of the patients can- not wait to be operated. Both gastroenterologists and general surgeons, usually have similar perceptions. CONCLUSION: Despite the increasing number of definitive studies, it seems that there are still regional differences in the perception of COVID-19 and inflammatory bowel disease patient care during the pandemic.

APPLICATION OF INTELLECTUAL MONITORING INFORMATION TECHNOLOGY IN DETERMINING THE SEVERITY OF THE CONDITION OF PATIENTS WITH INFLAMMATORY BOWEL DISEASES.

OBJECTIVE: The aim: Was to evaluate the effectiveness of the use of information technology of intelligent monitoring in solving the problems of assessing the morbidity of a patient with IBD during treatment. PATIENTS AND METHODS: Matherials and methods: 183 patients with IBD were observed. Among them 104(56.8%) patients suffered from Crohn's disease and 79(43.1%) patients had ulcerative colitis. For each patient and each disease, the formation of a list of signs, the extraction of information and knowledge will be carried out according to an individual method. At the lower level, tasks are performed: determination of the list of patient morbidity conditions, the formation of a list of indicators of the patient morbidity conditions, their identification as classes for machine learning models; formation of a list of signs, which identify the state of the patient's morbidity and whose characteristics obtained after results of medical tests. RESULTS: Results: The number of correctly classified points reached 92%. An analysis of the conditions of patients characterized by incorrectly classified points revealed the information content of this fact. In those cases when the classification results did not coincide with the expert assessment of the patient's condition, additional factors were found that influenced his condition and whose characteristics were not taken into account in the structure of classifier models. CONCLUSION: Conclusions: The results of the testing of classifier models indicate the effectiveness of the use of information technology of intelligent monitoring to assess the condition of patients with IBD.

Genetic polymorphism in patients with early and late onset of ulcerative colitis.

OBJECTIVE: The aim was to investigate SNPs of TLR-2,3,4, NOD2/CARD15, JAK-2, and IL-10 in patients with the early and late UC onset. PATIENTS AND METHODS: Matherials and methods: 126 patients with UC were investigated. To assess the predisposition of the early and late UC onset the incidence of the following SNPs: Arg753Gln TLR2 gene, Phe412Leu TLR3 gene, Asp299Gly and Thr399Ile TLR4 gene, C-819T, G-1082A and C-592A gene IL-10, Val617Phe gene JAK2, Gly908Arg gene NOD2/CARD15 were analyzed. RESULTS: Results: 76 patients had early disease onset and 50 had a late one. SNPs of TLR3 were observed in 50.8% cases. TLR4 polymorphism was more common than TLR3, and was observed in 81 (64.3%) UC patients. Polymorphism of NOD2/CARD15 and IL-10 genes were revealed with almost the same frequency 49 (38.9%) and 50 (39.9%) patients, respectively. CONCLUSION: Conclusions: Polymorphisms of TLR-2,3 genes and TLR4 Asp299Gly, NOD2/CARD15 prevailed in patients with the late UC onset that allows to suppose that bacterial flora plays one of the key roles in modification of immune response and UC development. In patients with early UC onset polymorphisms of the JAK2 and IL-10 genes prevailed responsible for the cytokine cascade activation and cause the immune mechanism that might lead to a more aggressive course of the disease.

Efficacy and safety of biosimilar CT-P13 compared with originator infliximab in patients with active Crohn's disease: an international, randomised, double-blind, phase 3 non-inferiority study.

BACKGROUND: The infliximab biosimilar CT-P13 was approved for use in Crohn's disease after clinical comparison with originator infliximab in ankylosing spondylitis and rheumatoid arthritis; however, concerns about such indication extrapolation have been expressed. This study investigated whether CT-P13 is non-inferior to infliximab in patients with Crohn's disease who were naive to biological therapy. METHODS: In this randomised, multicentre, double-blind, phase 3 non-inferiority study, we enrolled patients with active Crohn's disease who had not responded to, or were intolerant to, non-biological treatments. Patients were randomly assigned (1:1:1:1) to receive CT-P13 then CT-P13, CT-P13 then infliximab, infliximab then infliximab, or infliximab then CT-P13, with switching occurring at week 30. Patients received 5 mg/kg CT-P13 or infliximab at weeks 0, 2, 6, and then every 8 weeks up to week 54. The primary endpoint was the proportion of patients with a decrease of 70 points or more in Crohn's Disease Activity Index (CDAI) from baseline to week 6. A non-inferiority margin of -20% was set (CT-P13 was non-inferior to infliximab if the lower limit of the two-sided 95% CI for the treatment difference was greater than -20). This trial is registered with ClinicalTrials.gov, number NCT02096861, and is completed. FINDINGS: Between Aug 20, 2014, and Feb 15, 2017, 308 patients were assessed for eligibility, and 220 patients were enrolled: 111 were randomly assigned to initiate CT-P13 (56 to the CT-P13-CT-P13 group and 55 to the CT-P13-infliximab group) and 109 to initiate infliximab (54 to the infliximab-infliximab group and 55 to the infliximab-CT-P13 group). CDAI-70 response rates at week 6 were similar for CT-P13 (77 [69·4%, 95% CI 59·9 to 77·8] of 111) and infliximab (81 [74·3%, 95% CI 65·1 to 82·2] of 109; difference -4·9% [95% CI -16·9 to 7·3]), thereby establishing non-inferiority. Over the total study period, 147 (67%) patients experienced at least one treatment-emergent adverse event (36 [64%] in the CT-P13-CT-P13 group, 34 [62%] in the CT-P13-infliximab group, 37 [69%] in the infliximab-infliximab group, and 40 [73%] in the infliximab-CT-P13 group). INTERPRETATION: This study showed non-inferiority of CT-P13 to infliximab in patients with active Crohn's disease. Biosimilar CT-P13 could be a new option for the treatment of active Crohn's disease. FUNDING: Celltrion, Pfizer.

Association between body mass index and Firmicutes/Bacteroidetes ratio in an adult Ukrainian population.

BACKGROUND: Metagenomic studies confirm that obesity is associated with a composition of gut microbiota. There are some controversies, however, about the composition of gut microbial communities in obese individuals in different populations. To examine the association between body mass index and microbiota composition in Ukrainian population, fecal concentrations of Bacteroidetes, Firmicutes, Actinobacteria and Firmicutes/Bacteroidetes (F/B) ratio were analyzed in 61 adult individuals. RESULTS: The relative abundance of Actinobacteria was small (5-7%) and comparable in different BMI categories. The content of Firmicutes was gradually increased while the content of Bacteroidetes was decreased with increasing body mass index (BMI). The F/B ratio also raised with increasing BMI. In an unadjusted logistic regression model, F/B ratio was significantly associated with BMI (OR = 1.23, 95% CI 1,09-1,38). This association continued to be significant after adjusting for confounders such as age, sex, tobacco smoking and physical activity (OR = 1.33, 95% CI 1,11-1,60). CONCLUSIONS: The obtained data indicate that obese persons in Ukraine adult population have a significantly higher level of Firmicutes and lower level of Bacteroidetes compared to normal-weight and lean adults.