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Background: Infliximab is a monoclonal anti-TNF-alpha antibody that has been shown to be effective in Crohn's disease therapy. However, data are scarce about the mechanism of action and its efficacy in ulcerative colitis (UC). Aim: To assess intracellular changes of the colonic mucosa in patients with UC before and after infliximab treatment. Methods: 7 patients (18-65 years, 4 men) with active, refractory, moderate to severe UC (Lichtiger's Clinical Activity Index >6, Endoscopic Index >4) underwent colonoscopy before and 4 weeks after the initial infusion of infliximab 5mg/kg of body weight. Endoscopically obtained biopsy specimens were processed specifically, stained with uranyl-acetate and lead citrate and examined with a JEOL-1010 transmission electron microscope. Results: Before treatment we noticed severe alterations of the epithelium: microvilli depletion, shattering of the epithelial junctions, cytoplasmic vacuolization, dilatation of the endoplasmic reticulum, pycnotic nuclei, altered structure of mitochondria and Golgi complexes. Rarefaction of the goblet cells, and abnormal mucus formation and secretion were also observed. The corresponding chorion showed structural alteration of component cells, obstructed capillaries, erythrocyte extravasation, and many plasmocytes and neutrophils. After infliximab, improvement in morphology and function of the epithelial organelles, rich mucus secretion and recovery of the chorionic components were noticed. Conclusions: Our study revealed important intracellular alterations of the UC mucosa that were restored after infliximab therapy. These features may contribute to a better understanding of UC pathogenesis and mechanism of action of the anti-TNF-alpha therapies. [ABSTRACT FROM AUTHOR]

Background & Aims: Real-world assessments of efficacy and safety of advanced therapies used for inflammatory bowel disease (IBD) patients are limited. We aimed to report safety, efficacy and treatment persistence of new molecules (infliximab, adalimumab, vedolizumab, tofacitinib, ustekinumab) in a retrospective multicentric national Romanian analysis. Methods: We conducted a nationwide, retrospective observational multicentric study. Data were collected retrospectively from electronic and paper files. Patients who started on one of the five investigated molecules during December 2019-December 2021 were included. The main outcome measures were clinical remission, endoscopic healing, persistence on treatment and safety data. Results: A total of 678 adult patients from 24 Romanian IBD centers with a diagnosis of ulcerative colitis or Crohn's disease were included. Participants had previously failure to one (268, 39.5%), two (108, 15%) or more treatment lines and only 38% (259) were biologic naïve. In the 24 months study period, most patients were started on vedolizumab (192, 28%), followed by adalimumab, infliximab, ustekinumab and tofacitinib. In biologic-naïve patients, most physicians (72%) preferred anti-TNF treatment as first line biologic (93 patients started on infliximab, 92 on adalimumab), followed by vedolizumab, ustekinumab and tofacitinib. During follow-up, 71% (470, p=0.05) of patients achieved clinical remission and 36% (134, p=0.03) achieved mucosal healing. The 6 months milestone for persistence was reached in 78% (530) of cases. Almost half of patients (47%, 316 patients) persisted on their current treatment for over 12 months. Overall, an adverse reaction was reported for 67 (10.4%) patients, with no lethal events. Conclusions: Population of biologic-experienced IBD patients in Romania is increasing and is becoming more difficult to achieve long-term disease control. Discontinuation rates for advanced therapies are high. [ABSTRACT FROM AUTHOR]