CT-P13 is the first biosimilar monoclonal antibody to infliximab (IFX); it has been approved for the same indications as its IFX counterpart in Hungary. The aim of this study was to assess the efficacy of CT-P13 induction therapy in patients with Crohn's disease (CD) and ulcerative colitis (UC).

Background and aims: Few data are available regarding the combination of biologics or small molecules in inflammatory bowel disease (IBD) patients. We report safety and efficacy of such combinations through a retrospective multicentre series.Methods: Combination therapy was defined as the concomitant use of two biologics or one biologic with a small molecule. Patient demographics, disease characteristics and types of combinations were recorded. Safety was evaluated according to the occurrence of serious infection, opportunistic infection, hospitalisation, life‐threatening event, worsening of IBD or immune‐mediated inflammatory diseases (IMID), cancer and death. Efficacy was evaluated as the physician global assessment of the combination and comparison of clinical/endoscopic scores of IBD/IMID activity prior and during combination.Results: A total of 104 combinations were collected in 98 patients. Concomitant IMID were present in 41 patients. Reasons for starting combination therapy were active IBD (67%), active IMID or extra‐intestinal manifestations (EIM) (22%), both (10%) and unclassified in 1. Median duration of combination was 8 months (interquartile range 5–16). During 122 patient‐years of follow‐up, 42 significant adverse events were observed, mostly related to uncontrolled IBD. There were 10 significant infections, 1 skin cancer and no death. IBD disease activity was clinically improved in 70% and IMID/EIM activity in 81% of the patients. Overall, combination was continued in 55% of the patients.Conclusions: Combination of biologics and small molecules in patients with IBD and IMID/EIM seems to be a promising therapeutic strategy but is also associated with a risk of opportunistic infections or infections leading to hospitalisation in 10%.

Background. Some of the most important questions relating to the use of biological therapy in inflammatory bowel diseases concern the duration of maintenance therapy. The RASH study revealed that previous use of biological therapy and dose intensification are associated with restarting of biological therapy in Crohn's disease. The aim of the study was to assess the disease course and frequency of relapse of ulcerative colitis (UC) following discontinuation of infliximab in patients with remission and to determine predictive factors for relapse. Patients and methods. Fifty-one UC patients who had achieved clinical remission following 1 year of infliximab therapy and for whom infliximab was then discontinued participated in this prospective observational study. 15.7% of the patients received infliximab before the 1-year period of biological therapy analyzed in the study. Biological therapy was restarted in case of recurrent clinical activity. Data were collected from four Hungarian IBD centers. Results. Thirty-five percent of the patients needed to be retreated with infliximab within 1 year after treatment cessation. Logistic regression analysis revealed that previous biological therapy (p = 0.021) was associated with the need of restarting infliximab. None of the data relating to patients' demographic and clinical characteristics, concomitant therapy and CRP level showed association with the need for restarting biological therapy. Conclusions. Biological therapy was restarted at a median of 4 months after discontinuation in more than every third UC patients who had been in clinical remission following 1 year of infliximab therapy. Response to retreatment with infliximab was favorable in the majority of the patients who relapsed.

Cytoplasmic lipid-droplets are common inclusions of eukaryotic cells. Lipid-droplet binding thalidomide analogs (2,6-dialkylphenyl-4/5-amino-substituted-5,6,7-trifluorophthalimides) with potent anticancer activities were synthesized. Cytotoxicity was detected in different cell lines including melanoma, leukemia, hepatocellular carcinoma, glioblastoma at micromolar concentrations. The synthesized analogs are non-toxic to adult animals up to 1 g/kg but are teratogenic to zebrafish embryos at micromolar concentrations with defects in the developing muscle. Treatment of tumor cells resulted in calcium release from the endoplasmic reticulum (ER), induction of reactive oxygen species (ROS), ER stress and cell death. Antioxidants could partially, while an intracellular calcium chelator almost completely diminish ROS production. Exogenous docosahexaenoic acid or eicosapentaenoic acid induced calcium release and ROS generation, and synergized with the analogs in vitro, while oleic acid had no such an effect. Gene expression analysis confirmed the induction of ER stress-mediated apoptosis pathway components, such as GADD153, ATF3, Luman/CREB3 and the ER-associated degradation-related HERPUD1 genes. Tumor suppressors, P53, LATS2 and ING3 were also up-regulated in various cell lines after drug treatment. Amino-phthalimides down-regulated the expression of CCL2, which is implicated in tumor metastasis and angiogenesis. Because of the anticancer, anti-angiogenic action and the wide range of applicability of the immunomodulatory drugs, including thalidomide analogs, lipid droplet-binding members of this family could represent a new class of agents by affecting ER-membrane integrity and perturbations of ER homeostasis.

One of the most common extraintestinal manifestations of inflammatory bowel disease is iron deficiency anemia. It is often an untreated condition that significantly impairs patients' quality of life and elevates mortality and morbidity. Although it is often accompanied by mild symptoms (e.g., fatigue, lethargy), it can provoke severe health conditions, such as dyspnea, palpitation, angina, and mental disorders, and increases hospitalization and mortality rate as well. As anemia develops through several pathomechanisms, such as occult bleeding, chronic inflammation, and medicines (e.g., methotrexate), treating anemia effectively requires to manage the underlying pathological changes as well. Based on international publications and data, it is a frequent condition and more frequent in pediatrics. According to Goodhand et al., iron deficiency is present in more than 60% of children, whereas only 14% of them received oral iron therapy. Compared to adult patients, 22% have iron deficiency, and 48% of them received oral and 41% intravenous iron therapy. Miller et al. also highlighted that among young patients iron deficiency anemia is a frequent condition, as almost 50% of the patients were anemic in their cohort. European Crohn's and Colitis Organisation's statements are clear regarding the diagnosis of iron deficiency anemia, and the iron supplementation as well. Third-generation parenteral iron supplementations seem to be safer and more effective than oral iron pills. Oral iron in many cases cannot replace the iron homeostasis as well; furthermore, it can provoke dysbiosis, which can potentially lead to relapse. As a result, we claim that both oral and parenteral should be used more frequently; furthermore, intravenous iron could replace oral medicines as well in certain cases. Despite the fact that iron deficiency anemia is examined by many aspects, further questions can be raised. Can it imply underlying pathological lesions? Are both oral and intravenous iron therapy safe and effective? When and how are they used? We demand that more studies should be conducted regarding these issues.

The usage of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for the diagnosis of solid pancreatic cancer is increasing, however mainly retrospective studies are available about the detailed methods of sampling. To compare prospectively the diagnostic yield of EUS-FNA samples obtained with slow-pull (SP) and with standard suction technique (SS). EUS-FNA sampling was diagnostic in 72 of 92 cases (78.3%). Diagnostic yield was 67.4% in the SS and 65.2% in the SP group. The number of smear pairs (1.84 vs. 3.56; p < 0.001) and blood contamination (1.50 vs. 2.19; p < 0.001) were significantly higher in the SS group, which resulted in lower rate of diagnostic samples (41.8% vs. 30.0%; p = 0.003). There was no difference in the cellularity (1.58 vs. 1.37; p = 0.2554), or in the sensitivity and specificity in the identification of malignancy between SP and SS subgroups (69.9, 100% vs. 73.5, 100%). Histological samples were obtained in 60 cases (with SP: 49 cases; with SS: 46 cases). There was no difference in the diagnostic yield of histological samples between the groups (63 and 58.7%). The diagnostic yield, the cellularity of smears and the rate of acquiring sufficient histological material are similar in the SP and SS group, but due to lower bloodiness and decreased number of slides, the pathological diagnosis is faster and more cost-effective.