Prediction of Relapse After Anti-Tumor Necrosis Factor Cessation in Crohn's Disease: Individual Participant Data Meta-analysis of 1317 Patients From 14 Studies.

BACKGROUND & AIMS: Tools for stratification of relapse risk of Crohn's disease (CD) after anti-tumor necrosis factor (TNF) therapy cessation are needed. We aimed to validate a previously developed prediction model from the diSconTinuation in CrOhn's disease patients in stable Remission on combined therapy with Immunosuppressants (STORI) trial, and to develop an updated model. METHODS: Cohort studies were selected that reported on anti-TNF cessation in 30 or more CD patients in remission. Individual participant data were requested for luminal CD patients and anti-TNF treatment duration of 6 months or longer. The discriminative ability (concordance-statistic [C-statistic]) and calibration (agreement between observed and predicted risks) were explored for the STORI model. Next, an updated prognostic model was constructed, with performance assessment by cross-validation. RESULTS: This individual participant data meta-analysis included 1317 patients from 14 studies in 11 countries. Relapses after anti-TNF cessation occurred in 632 of 1317 patients after a median of 13 months. The pooled 1-year relapse rate was 38%. The STORI prediction model showed poor discriminative ability (C-statistic, 0.51). The updated model reached a moderate discriminative ability (C-statistic, 0.59), and included clinical symptoms at cessation (hazard ratio [HR], 2.2; 95% CI, 1.2-4), younger age at diagnosis (HR, 1.5 for A1 (age at diagnosis ≤16 years) vs A2 (age at diagnosis 17 - 40 years); 95% CI, 1.11-1.89), no concomitant immunosuppressants (HR, 1.4; 95% CI, 1.18-172), smoking (HR, 1.4; 95% CI, 1.15-1.67), second line anti-TNF (HR, 1.3; 95% CI, 1.01-1.69), upper gastrointestinal tract involvement (HR, 1.3 for L4 vs non-L4; 95% CI, 0.96-1.79), adalimumab (HR, 1.22 vs infliximab; 95% CI, 0.99-1.50), age at cessation (HR, 1.2 per 10 years younger; 95% CI, 1-1.33), C-reactive protein (HR, 1.04 per doubling; 95% CI, 1.00-1.08), and longer disease duration (HR, 1.07 per 5 years; 95% CI, 0.98-1.17). In subanalysis, the discriminative ability of the model improved by adding fecal calprotectin (C-statistic, 0.63). CONCLUSIONS: This updated prediction model showed a reasonable discriminative ability, exceeding the performance of a previously published model. It might be useful to guide clinical decisions on anti-TNF therapy cessation in CD patients after further validation.

Effect of COVID-19 pandemic on workflows and infection prevention strategies of endoscopy units in Hungary: a cross-sectional survey.

BACKGROUND: Health care professionals in endoscopic labs have an elevated risk for COVID-19 infection, therefore, we aimed to determine the effect of current pandemic on the workflow and infection prevention and control strategies of endoscopy units in real-life setting. METHODS: All members of Hungarian Society of Gastroenterology were invited between 7 and 17 April 2020 to participate in this cross-section survey study and to complete an online, anonymous questionnaire. RESULTS: Total of 120 endoscopists from 83 institutes were enrolled of which 35.83% worked in regions with high cumulative incidence of COVID-19. Only 33.33% of them had undergone training about infection prevention in their workplace. 95.83% of endoscopists regularly used risk stratification of patients for infection prior endoscopy. While indications of examinations in low risk patients varied widely, in high-risk or positive patients endoscopy was limited to gastrointestinal bleeding (95.00%), removal of foreign body from esophagus (87.50%), management of obstructive jaundice (72.50%) and biliary pancreatitis (67.50%). Appropriate amount of personal protective equipment was available in 60.85% of endoscopy units. In high-risk or positive patients, surgical mask, filtering facepiece mask, protective eyewear and two pairs of gloves were applied in 30.83%, 76.67%, 90.00% and 87.50% of cases, respectively. Personal protective equipment fully complied with European guideline only in 67.50% of cases. CONCLUSIONS: Survey found large variability in indications of endoscopy and relative weak compliance to national and international practical recommendations in terms of protective equipment. This could be improved by adequate training about infection prevention.

Efficacy, tolerability and safety of a split-dose bowel cleansing regimen of magnesium citrate with sodium picosulfate - a phase IV clinical observational study.

BACKGROUND: There are contradictory results about the effect of magnesium citrate plus sodium picosulfate bowel cleansing agents on the fluid and electrolyte balance. Therefore, this study aimed to determine the efficacy, tolerability and safety of this medication in colonoscopy preparation. METHODS: 233 patients were enrolled in this phase IV prospective observational study. The effectiveness of bowel cleansing was assessed using the Boston Bowel Preparation Scale (BBPS). Adequate cleansing was defined as BBPS ≥ 6 and excellent cleansing as BBPS > 7. Tolerability was examined using a standardized questionnaire. In the safety analysis, the change of serum electrolytes levels and renal function during bowel cleansing was assessed. RESULTS: Adequate and excellent bowel cleansing were achieved 94.85% and 72.96% of cases, respectively. None or very mild symptoms were reported in 47.21% of cases. Statistically significant changes occurred in serum potassium (4.38±0.43 vs. 4.25±0.43 mmol/L, p<0.0001), urea (4.86±1.37 vs. 3.84±1.43 mmol/L, p<0.0001) and creatinine (male: 81.07±16.02 vs. 84.54±15.11 µmol/L; female: 69.32±12.22 vs. 72.96±12.11 µmol/L, p<0.0001) levels during the colonoscopy preparation. However, the number of patients with values outside of the normal range increased significantly only in the case of serum urea (3.95% vs. 26.97%, p<0.0001). CONCLUSION: Magnesium citrate with sodium picosulfate is outstandingly effective, well tolerated and a safe agent in colonoscopy preparation. It caused significant, but non-clinically relevant changes in serum electrolytes levels and renal function.

Slow-pull technique yields better quality smears: prospective comparison of slow-pull and standard suction techniques of endoscopic ultrasound-guided fine-needle aspiration.

BACKGROUND: Diagnostic accuracy and quality of smears obtained by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) are influenced by characteristics of suction and examined organ. AIMS AND METHODS: Efficiency of EUS-FNA and quality of smears obtained by slow-pull (SP) and standard suction (SS) techniques was prospectively compared in the sampling of pancreatic (N = 56) and extrapancreatic (N = 145) tumors. RESULTS: SS technique resulted in a higher number of smear pairs both in pancreatic (1.74 vs. 3.19; p < 0.001) and extrapancreatic tumors (1.62 vs. 3.28; p < 0.001); however, it decreased the proportion of diagnostic smears (46.69% vs. 36.52%; p = 0.002 and 49.17% vs. 30.67%; p < 0.001) and increased the bloodiness (1.51 vs. 2.07; p < 0.001 and 1.48 vs. 2.05; p < 0.001). In pancreatic cancers, no difference was observed in terms of diagnostic accuracy (81.38% vs. 83.45%) and cellularity (1.44 vs. 1.27; p = 0.067); however, they were substantially higher in extrapancreatic tumors using SP technique (71.41% vs. 60.71% and 1.34 vs. 0.77; p < 0.001). Only SP technique resulted in a significant difference between examiners in terms of technical success rate and quality of smears without any decrease of diagnostic accuracy. CONCLUSIONS: SP technique yields better quality smears independently from tumors characteristics; however, it shows significant examiner-dependency. SS technique reduces the diagnostic accuracy of sampling in extrapancreatic tumors.

Outcomes of Patients With Inflammatory Bowel Diseases Switched From Maintenance Therapy With a Biosimilar to Remicade.

BACKGROUND & AIMS: There is evidence that it is safe and effective for patients with inflammatory bowel diseases (IBD) to switch from maintenance therapy with an original infliximab drug to a biosimilar, but little is known about outcomes of reverse switches and/or multiple switches. We aimed to evaluate the effects of a reverse switch (from a biosimilar to Remicade) in a real-life cohort. METHODS: We performed a prospective observational study of 174 unselected and consecutive patients with IBD (136 with Crohn's disease [CD] and 38 with ulcerative colitis [UC]) who received maintenance therapy with the biosimilar in Hungary. In September 2017, patients were switched from the biosimilar (CT-P13) to Remicade, due to reimbursement policies. In our cohort, 8% (n = 14) patients had been previously exposed to the originator Remicade. We collected clinical and biochemical information from patients at baseline (time of the switch) and 16 and 24 weeks thereafter. Clinical remission was defined as a Crohn's disease activity index <150 points or no fistula drainage, or a partial Mayo score <3 points for patients with UC. Serum drug trough levels and anti-drug antibodies were measured at baseline and week 16. RESULTS: There was no significant difference in the proportion of patients in clinical remission at week 8 before the switch (82.5% with CD and 82.9% with UC), at baseline (80.6% with CD and 81.6% with UC), at week 16 (77.5% with CD and 83.7% with UC), or at week 24 (CD 76.3% with CD and 84.9% with UC) (P = .60 among groups for patients with CD and P = .98 among groups for patients with UC). For all patients, mean serum trough levels of infliximab were 5.33 ± 4.70 µg/mL at baseline and 5.69 ± 4.94 µg/mL at week 16 (P = .71); we did not find significant differences in prevalence of anti-drug antibody at baseline (16.2%) compared with week 16 (16.9%) (P = .87). Four infusion reactions occurred, until week 24 of follow up. There was no difference in outcomes or trough or antidrug antibody levels between patients with or without previous exposure to Remicade. CONCLUSIONS: We collected data from a real-life cohort of patients with CD or UC who were switched from maintenance therapy with a biosimilar to Remicade or were treated with only Remicade. No significant changes were observed in remission, trough levels, or antidrug antibodies in patients switched from the biosimilar to Remicade. No new safety signals were detected.

[Transfer of care of adolescent inflammatory bowel disease patients without longitudinal transition. Lesson from 10 years experiences]. / Gyulladásos bélbetegségben szenvedo gyermekek kezelésének átadása felnottszakrendelésre. 10 éves tapasztalataink összegzése.

INTRODUCTION: Transfer is a planned movement of patients and their medical records from one provider to another. Only a few data are available from real life in inflammatory bowel disease patients in this topic. AIM: Our aim was to retrospectively evaluate the results of the transfer of our patients without longitudinal transition. METHOD: Data of the transferred patients at the University of Szeged were analysed. Patients were diagnosed in paediatric care. Transfer strategy at our departments was detailed medical summary. RESULTS: 59 patients were enrolled in this study. 28.8% of the patients had mild to moderate disease activity and 71.2% was in remission at the time of transfer. Steroid therapy was initiated in 58% of the patients within an average of 9.1 months after the transfer. Anti-tumor necrosis factor therapy was given to 24% of the patients during the paediatric care and to an additional 23% in the adult care within an average of 28 months. Almost 70% of the patients received immunosuppressive therapy during paediatric and adult care. Surgery was required in 17% of the patients within an average 10.7 months after the transfer. CONCLUSION: Our results revealed that one-third of the paediatric patients have been transferred to adult care in active stage of disease. Shortly after the transfer 58% of the patients required corticosteroids and 17% surgery. Every fifth patient needed biological therapy to be initiated after the transfer. Longitudinal transition may have a potential to decrease the need for therapeutic change and the relatively high rate of surgery. Orv Hetil. 2018; 159(44): 1789-1793.

Plasminogen Activator Inhibitor 1 Is a Novel Faecal Biomarker for Monitoring Disease Activity and Therapeutic Response in Inflammatory Bowel Diseases.

BACKGROUND AND AIMS: Crohn's disease [CD] and ulcerative colitis [UC] require lifelong treatment and patient monitoring. Current biomarkers have several limitations; therefore, there is an unmet need to identify novel biomarkers in inflammatory bowel disease [IBD]. Previously, the role of plasminogen activator inhibitor 1 [PAI-1] was established in the pathogenesis of IBD and suggested as a potential biomarker. Therefore, we aimed to comprehensively analyse the selectivity of PAI-1 in IBD, its correlation with disease activity, and its potential to predict therapeutic response. METHODS: Blood, colon biopsy, organoid cultures [OC], and faecal samples were used from active and inactive IBD patients and control subjects. Serpin E1 gene expressions and PAI-1 protein levels and localisation in serum, biopsy, and faecal samples were evaluated by qRT-PCR, ELISA, and immunostaining, respectively. RESULTS: The study population comprised 132 IBD patients [56 CD and 76 UC] and 40 non-IBD patients. We demonstrated that the serum, mucosal, and faecal PAI-1 concentrations are elevated in IBD patients, showing clinical and endoscopic activity. In responders [decrease of eMayo ≥3 in UC; or SES-CD  50% in CD], the initial PAI-1 level decreased significantly upon successful therapy. OCs derived from active IBD patients produced higher concentrations of PAI-1 than the controls, suggesting that epithelial cells could be a source of PAI-1. Moreover, faecal PAI-1 selectively increases in active IBD but not in other organic gastrointestinal diseases. CONCLUSIONS: The serum, mucosal, and faecal PAI-1 concentration correlates with disease activity and therapeutic response in IBD, suggesting that PAI-1 could be used as a novel, non-invasive, disease-specific, faecal biomarker in patient follow-up.

Long-term outcomes after endoscopic removal of malignant colorectal polyps: Results from a 10-year cohort.

BACKGROUND: Choosing an optimal post-polypectomy management strategy of malignant colorectal polyps is challenging, and evidence regarding a surveillance-only strategy is limited. AIM: To evaluate long-term outcomes after endoscopic removal of malignant colorectal polyps. METHODS: A single-center retrospective cohort study was conducted to evaluate outcomes after endoscopic removal of malignant colorectal polyps between 2010 and 2020. Residual disease rate and nodal metastases after secondary surgery and local and distant recurrence rate for those with at least 1 year of follow-up were investigated. Event rates for categorical variables and means for continuous variables with 95% confidence intervals were calculated, and Fisher's exact test and Mann-Whitney test were performed. Potential risk factors of adverse outcomes were determined with univariate and multivariate logistic regression models. RESULTS: In total, 135 lesions (mean size: 22.1 mm; location: 42% rectal) from 129 patients (mean age: 67.7 years; 56% male) were enrolled. The proportion of pedunculated and non-pedunculated lesions was similar, with en bloc resection in 82% and 47% of lesions, respectively. Tumor differentiation, distance from resection margins, depth of submucosal invasion, lymphovascular invasion, and budding were reported at 89.6%, 45.2%, 58.5%, 31.9%, and 25.2%, respectively. Residual tumor was found in 10 patients, and nodal metastasis was found in 4 of 41 patients who underwent secondary surgical resection. Univariate analysis identified piecemeal resection as a risk factor for residual malignancy (odds ratio: 1.74; P = 0.042). At least 1 year of follow-up was available for 117 lesions from 111 patients (mean follow-up period: 5.59 years). Overall, 54%, 30%, 30%, 11%, and 16% of patients presented at the 1-year, 3-year, 5-year, 7-year, and 9-10-year surveillance examinations. Adverse outcomes occurred in 9.0% (local recurrence and dissemination in 4 patients and 9 patients, respectively), with no difference between patients undergoing secondary surgery and surveillance only. CONCLUSION: Reporting of histological features and adherence to surveillance colonoscopy needs improvement. Long-term adverse outcome rates might be higher than previously reported, irrespective of whether secondary surgery was performed.

Psychological characteristics of patients with inflammatory bowel disease during the first wave of COVID-19.

Introduction: Inflammatory bowel diseases (Crohn's disease (CD) and ulcerative colitis (UC)) are chronic, immune-mediated diseases with unclear aetiology, characterized by relapsing inflammation of the gastrointestinal tract. These conditions significantly impair patients' physical and mental condition and quality of life. Aim: To investigate the impact of the current pandemic situation on inflammatory bowel disease (IBD) patients' psychological status and to determine factors that mediate the level of depression, anxiety, and health-related quality of life. Material and methods: This was a multicentre, observational, cross-sectional, questionnaire-based study. A total of 206 participants (male: 34%) were involved. The online survey consisted of 8 different psychological measures (such as depression, anxiety, coronavirus distress, health-related quality of life, etc.) and other therapy-specific and sociodemographic factors. Results: 28.2% of respondents showed depressive symptoms and 11.2% indicated moderate to severe anxiety. Also, 27.7% revealed mild, moderate, or severe distress regarding the coronavirus situation. According to regression analysis, anxiety and coronavirus distress are mostly influenced by psychological factors. In contrast, the changes in quality of life and depression can be explained by disease-specific and psychological factors as well. Conclusions: Patients need more attention during this period to help them cope with psychological factors and prevent their IBD from becoming worse.

Conception and reality: Outcome of SARS-CoV-2 infection and vaccination among Hungarian IBD patients on biologic treatments.

Introduction: Inflammatory bowel disease potentially elevates the risk of infections, independently from age, while the disease activity and medical treatment(s) can also increase the risks. Nevertheless, it is necessary to clarify these preconceptions as well during the COVID-19 pandemic. Methods: An observational, questionnaire based study was conducted in Hungary between February and August 2021. 2 questionnaires were completed. The first questionnaire surveyed the impact of the pandemic on patients with biologic treatments and assessed the severity and outcome of the infection, whereas the second one assessed vaccination rate and adverse events. Results: 472 patients participated in the study. 16.9 % of them acquired the infection and 6.3 % needed hospitalization. None of them required ICU care. Male sex elevated the risk of infection (p = 0.008), while glove (p = 0.02) and mask wearing (p = 0.005) was the most effective prevention strategy. Nevertheless, abstaining from community visits or workplace did not have an impact on the infection rate. Smoking, age, and disease type did not elevate the risk. UC patients had poorer condition during the infection (p = 0.003); furthermore, the disease activity could potentially worsen the course of infection (p = 0.072). The different biological treatments were equally safe; no difference was observed in the infection rate, course of COVID-19. Azathioprine and corticosteroids did not elevate the infection rate. 28 patients (35.0 %) suspended the ongoing biologic treatment, but it had no impact on the disease course. However, it resulted in changing the current treatment (p = 0.004). 9.8 % of the respondents were sceptic about being vaccinated, and 90 % got vaccinated. In one case, a serious flare-up occurred. Discussion: Most patients acquired the infection at workplace. Biologic therapies had no effect on the COVID-19 infection, whereas male sex, an active disease, and UC could be larger threat than treatments. Vaccination was proved to be safe, and patient education is important to achieve mass vaccination of the population.

Possible genetical predictors of efficacy and safety of budesonide-MMX in patients with mild-to-moderate ulcerative colitis, and safety comparison with methylprednisolone.

BACKGROUND: Budesonide-MMX is a topically active corticosteroid degraded by cytochrome-P450 enzymes, resulting in favorable side-effect profile. We aimed to assess the effect of CYP genotypes on safety and efficacy, and make a direct comparison with systemic corticosteroids. RESEARCH DESIGN AND METHODS: We enrolled UC patients receiving budesonide-MMX and IBD patients on methylprednisolone in our prospective, observational-cohort study. Before and after treatment regimen clinical activity indexes, laboratory parameters (electrolytes, CRP, cholesterol, triglyceride, dehydroepiandrosterone, cortisol, beta-crosslaps, osteocalcin), and body composition measurements were assessed. CYP3A4 and CYP3A5 genotypes were determined in the budesonide-MMX group. RESULTS: 71 participants were enrolled (budesonide-MMX: 52; methylprednisolone: 19). CAI decreased (p<0.05) in both groups. Cortisol decreased (p<0.001), and the level of cholesterol was elevated in both groups (p<0.001). Body composition altered only following methylprednisolone. Bone homeostasis (osteocalcin; p<0.05) and DHEA (p<0.001) changed more prominently after methylprednisolone. Glucocorticoid-related adverse events were more common following methylprednisolone treatment (47.4% compared to 1.9%). CYP3A5(*1/*3) genotype positively influenced efficacy, but not safety. Only one patient's CYP3A4 genotype differed. CONCLUSIONS: CYP genotypes can affect the efficacy of budesonide-MMX; however, further studies would be needed with analyses of gene expression. Although budesonide-MMX is safer than methylprednisolone, due to glucocorticoid-related side effects, admission should require greater precaution.

Nationwide experiences with trough levels, durability, and disease activity among inflammatory bowel disease patients following COVID-19 vaccination.

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has complicated the management of inflammatory bowel diseases (IBD). Objectives: This study aimed to assess the efficacy of different anti-SARS-CoV-2 vaccines under different treatments in IBD patients and identify predictive factors associated with lower serological response, including anti-tumor necrosis factor (anti-TNF) drug levels. Design: A prospective, double-center study of IBD patients was conducted following messenger ribonucleotide acid (mRNA) and non-mRNA anti-SARS-CoV-2 vaccination. Methods: Healthy control (HC) patients were enrolled to reduce bias. Baseline and control samples were obtained 14 days after the second dose to assess the impact of conventional and biological treatments. Clinical and biochemical activity, serological response level, and anti-TNF drug levels were measured. Results: This study included 199 IBD (mean age, 40.9 ± 12.72 years) and 77 HC participants (mean age, 50.3 ± 12.36 years). Most patients (76.9%) and all HCs received mRNA vaccines. Half of the IBD patients were on biological treatment (anti-TNF 68.7%). Biological and thiopurine combined immunomodulation and biological treatment were associated with lower serological response (p < 0.001), and mRNA vaccination promoted better antibody levels (p < 0.001). Higher adalimumab levels caused lower serological response (p = 0.006). W8 persistence of anti-SARS-CoV-2 level was equal in IBD and HC groups. Vaccination did not aggravate clinical disease activity (p = 0.65). Conclusion: Anti-SARS-CoV-2 vaccination is considerably efficacious in IBD patients, with mRNA vaccines promoting better antibody levels. The negative impact of combined biological treatment, especially with high adalimumab drug levels, on serological response to vaccination should be considered. Although midterm durability of vaccination is encouraging, more data are needed to expand the existing understanding on this issue.

Adjustment of COVID-19 vaccination to adalimumab trough level is considerable due to the reduced serological response. mRNA vaccination should be preferred in case of IBD patients with an equal durability of anti-SARS-CoV-2 level of subjects and healthy control participants.

Effects of bowel cleansing on the composition of the gut microbiota in inflammatory bowel disease patients and healthy controls.

Background: In patients with inflammatory bowel disease (IBD), Crohn's disease (CD), and ulcerative colitis (UC), numerous cases of exacerbations could be observed after colonoscopy, raising the possible pathogenetic effect of colonic microbiota alterations in IBD flare. Objectives: We aimed to investigate the changes in the fecal microbiota composition in IBD patients influenced by the bowel preparation with sodium picosulfate. Design: We enrolled patients with IBD undergoing bowel preparation for colonoscopy in the prospective cohort study. The control group (Con) comprised non-IBD patients who underwent colonoscopy. Clinical data, blood, and stool samples were collected before colonoscopy (timepoint A), 3 days later (timepoint B), and 4 weeks later (timepoint C). Methods: Disease activity and gut microbiota changes were assessed at each timepoint. Fecal microbiota structure - at family level - was determined by sequencing the V4 region of the 16S rRNA gene. Statistical analysis included differential abundance analysis and Mann-Whitney tests. Results: Forty-one patients (9 CD, 13 UC, and 19 Con) were included. After bowel preparation, alpha diversity was lower in the CD group than in the UC (p = 0.01) and Con (p = 0.02) groups at timepoint B. Alpha diversity was significantly higher in the UC group than in the CD and Con (p = 0.03) groups at timepoint C. Beta diversity difference differed between the IBD and Con (p = 0.001) groups. Based on the differential abundance analysis, the Clostridiales family was increased, whereas the Bifidobacteriaceae family was decreased in CD patients compared to the Con at timepoint B. Conclusions: Bowel preparation may change the fecal microbial composition in IBD patients, which may have a potential role in disease exacerbation after bowel cleansing.

Ustekinumab is associated with superior treatment persistence but not with higher remission rates versus vedolizumab in patients with refractory Crohn's disease: results from a multicentre cohort study.

Background: Treatment with antitumor necrosis factor alpha (anti-TNF-α) is safe and effective as first-line therapy; however, its efficacy is limited due to primary nonresponse (PNR) and secondary loss of response (LOR), resulting in treatment discontinuation in approximately 40%-50% of cases. Vedolizumab (VDZ) and ustekinumab (UST) therapies could be good alternatives in patient with anti-TNF failure; however, no head-to-head randomized comparison of these drugs as second- or third-line treatments has been made. Objectives: This study aimed to assess the treatment persistence and comparative effectiveness of UST and VDZ in patients with refractory Crohn's disease (CD). Design: In this nationwide retrospective study, patients with CD on UST or VDZ maintenance therapy were enrolled. Clinical data at baseline, after induction, and at week 52 were obtained. Methods: Clinical and biochemical activities as well as corticosteroid-free remission (SFR) rates were assessed, while concomitant medications, comorbidities, hospitalizations, and surgeries were recorded during the follow-up to detect any predictors. Results: A total of 161 UST- and 65 VDZ-treated patients completed the follow-up. No significant difference in clinical or biochemical remission rates was observed after induction between the two treatment groups; however, clinical remission rate at week 52 was higher in UST group. UST showed superior drug persistence than VDZ (86.5%, 57.9%, p < 0.0001). The drug type was predictive of clinical SFR at week 52 [p = 0.011, odds ratio (OR) = 2.39 with UST]. Drug failure rates were higher for VDZ than those for UST (PNR rates: 21.54% and 4.97%, respectively, p < 0.001, OR = 8.267, p = 0.001). LOR and escalations were more common during UST treatment (61.5% versus 36.9%, p < 0.001; 64.2% versus 23.1%, p < 0.001). Hospital and surgical admission rates did not differ significantly. Only one adverse event occurred with VDZ at week 20, which led to drug cessation. Conclusions: VDZ and UST were safe and effective for treating patients with CD in whom anti-TNF therapy failed. UST showed superior drug persistence than VDZ, but dose escalation was more frequent. Biologicals used in lower treatment lines resulted in better drug persistence.

Clinical efficacy, drug sustainability and serum drug levels in Crohn's disease patients treated with ustekinumab - A prospective, multicenter cohort from Hungary.

INTRODUCTION: Although efficacy of ustekinumab (UST) has been demonstrated through randomized trials, data from real-life prospective cohorts are still limited. Our aim was to evaluate clinical efficacy, drug sustainability, dose intensification and results from therapeutic drug monitoring in UST treated patients with Crohn's disease (CD) using a prospective, nationwide, multicenter cohort. METHODS: Patients from 10 Inflammatory Bowel Disease centers were enrolled between 2019 January and 2020 May. Patient demographics, disease phenotype, treatment history, clinical disease activity (Crohn's Disease Activity Index(CDAI), Harvey Bradshaw Index(HBI)), biomarkers, and serum drug levels were obtained. Evaluations were performed at week8 (post-induction), w16-20, w32-36, and w52-56 follow-up visits. RESULTS: A total of 142 patients were included [57.4% female; complex disease behavior (B2/B3):48%, previous anti-TNF exposition:97%]. Clinical response and remission rates after induction(w8) were 78.1% and 57.7% using CDAI, and 82.5% and 51.8% based on HBI scores. The one-year clinical remission rate was 58%/57.3%(CDAI/HBI). Composite clinical and biomarker remission (CDAI<150 and C-reactive protein<10 mg/L) rates were 35.4%; 33.3%; 38.6% and 36.6% at w8/w16-20/w32-36 and w52-56. Drug sustainability was 81.9%(standard deviation(SD): 3.4) at 1 year(1y). Probability of dose intensification was high and introduced early, 42.2%(SD:4.2) at ~w32 and 51.9%(SD:4.4%) at 1y. CONCLUSION: Ustekinumab showed favorable drug sustainability and clinical efficacy in a patient population with severe disease phenotype and previous anti-tumor necrosis factor (anti-TNF) failure, however frequent dose intensification was required.

Does inflammatory bowel disease have different characteristics according to stage of adolescence?

BACKGROUND: There is a lack of data about demographic and treatment characteristics of adolescent patients with inflammatory bowel disease (IBD). The aim of this retrospective, epidemiological study was to evaluate characteristics and therapeutic features of Hungarian adolescents with IBD. METHODS: We analysed the social security databases of the National Health Insurance Fund. Adolescent patients with IBD for whom data from 2009 to 2016 were observable in the database were enrolled. Patients aged 14 to 17 years and 18 to 21 years were defined as middle and late adolescent patients. RESULTS: The incidences of IBD were 20.12 per 100,000 middle adolescent patients and 29.72 per 100,000 late adolescent patients. Admission to gastroenterology department was higher in both groups compared with admissions to surgery department. Mesalazine was used by a high proportion of Crohn's disease and ulcerative colitis patients. Rates of corticosteroid use were similar in both groups, with a tendency to decrease over time. The need for biologic agents was higher in the middle adolescent patients. The proportion of patients in the middle adolescent group who received anti-TNF therapy showed an increasing tendency. CONCLUSION: Our data suggest differences in the treatment strategies of gastroenterologists for these age groups. The greater need of anti-TNF therapy among the middle adolescent group indicates that adolescent patients before the transition to adult care may have a more severe disease phenotype. We expect that a strategy of early, effective treatment will significantly ameliorate the subsequent disease course, which is manifested in adult care.

The complex relationship between viruses and inflammatory bowel disease - review and practical advices for the daily clinical decision-making during the SARS-CoV-2 pandemic.

The coronavirus disease 2019 (COVID-19) outbreak emerged in December 2019 in China and rapidly spread worldwide. Inflammatory bowel disease (IBD) patients are likely to be more susceptible to viral infections, and this is significantly influenced by the type of therapy they receive. Thus, issues specifically concerning the medical treatment of IBD patients were shortly addressed at the beginning of the pandemic. However, recently available data on the occurrence and outcome of SARS-CoV-2 infection in IBD patients does not address the concerns raised at the beginning of the pandemic. Growing evidence and the rapid changes happening over the past few weeks have helped elucidate the current situation, contribute to our understanding of the disease, and many previously raised questions could now be answered. We hereby summarise available evidence regarding viral infections and IBD, focusing on SARS-CoV infections, and we provide practical recommendations related to patient management during the COVID-19 pandemic era.

Advances in the optimization of therapeutic drug monitoring using serum, tissue and faecal anti-tumour necrosis factor concentration in patients with inflammatory bowel disease treated with TNF-α antagonists.

INTRODUCTION: The relationship between clinical outcomes and serum anti-TNF levels is controversial. The aim of this study was to perform simultaneous analyses of serum, mucosal, and fecal anti-TNF-α levels. METHODS: Consecutive IBD patients who received maintenance anti-TNF-α therapy were enrolled. The number of TNF-α positive cells in the mucosa was detected using immunofluorescent labeling on biopsy samples. Serum, mucosal and fecal anti-TNF-α, serum anti-drug antibody, and fecal calprotectin levels were determined using ELISA. Each patient underwent body composition analysis as well. RESULTS: Data of 50 patients were analyzed. The number TNF-α positive cells was significantly higher in the inflamed part of the colon than in the un-inflamed part of the colon. Tissue and fecal drug levels did not show any association with serum drug levels; moreover, serum anti-TNF concentration did not correlate with endoscopic activity. Mucosal anti-TNF levels were higher only in IFX-treated patients in remission and IFX-treated patients with detectable fecal anti-TNF had lower tissue drug levels. Presence of the drug in the feces was significantly different according to disease activity. CONCLUSION: Fecal drug concentration is suggested to be a better predictor of endoscopic activity and loss of response, and fecal drug monitoring may improve the estimation accuracy of tissue drug levels.

Effect of COVID-19 pandemic on the workflow of endoscopy units: an international survey.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic poses a challenge to healthcare. Staff and patients are at increased risk during an examination or intervention, so certain restrictions ought to be introduced. Hence, we aimed to measure the effect of the pandemic on endoscopy units in real-life settings. METHODS: This was an observational, cross-sectional, questionnaire-based study, carried out between 7 April and 15 June 2020. Responds came from many countries, and the participation was voluntary. The survey contained 40 questions, which evaluated the effect of the COVID-19 pandemic on the endoscopy units and assessed the infection control. RESULTS: A total of 312 questionnaires were filled, 120 from Hungary, and 192 internationally, and 54 questionnaires (17.3%) were sent from high-risk countries; 84.9% of the gastroenterologists declared that they read the European Society of Gastrointestinal Endoscopy (ESGE) statement, while only 32.1% participated in any advanced training at their workplace. Overall, 92.1% of gastroenterologists realized risk stratification, and 72.1% claimed to have enough protective equipment. In 52.6% of the endoscopy units, at least one endoscopist had to discontinue the work due to any risk factor, while 40.6% reported that the reduced staff did not affect the workflow. Gastroenterologists considered that the five most important examinations both in low and high-risk patients are the following: lower/upper gastrointestinal (GI) bleeding with hemodynamic instability, endoscopic retrograde cholangiopancreatography (ERCP) in obstructive jaundice, foreign body in the esophagus, ERCP in acute biliary pancreatitis, and iron deficiency anemia with hemodynamic instability, which correlates well with the ESGE recommendation. Significant correlation was found in the usage of the necessary protective equipment in high-risk patients depending on the countries (p < 0.001). CONCLUSIONS: The survey found weak correlation in preliminary training depending on countries; nevertheless, in Hungary during the examined period, endoscopists considered the recommendations more strictly than in other countries. Although many physicians left the endoscopy lab, the workflow was not affected, probably due to the reduced number of examinations.

Endoscopic treatment of gastric antral vascular ectasia in real-life settings: Argon plasma coagulation or endoscopic band ligation?

OBJECTIVE: The efficacy of argon plasma coagulation (APC) on gastric antral vascular ectasia (GAVE) may be impaired over time and depends greatly on the application settings. Endoscopic band ligation (EBL) may be an alternative, but study on its efficacy is limited. This study aimed to evaluate and compare the clinical efficacy of APC and EBL in treating GAVE. METHODS: Changes in the need for blood transfusion, number of treatment sessions and hospitalizations were retrospectively assessed in 63 transfusion-dependent patients with GAVE (mean age: 67.1 y, 54.0% female) treated with either APC or EBL (45 and 18 patients, respectively) in four tertiary endoscopic centers. RESULTS: Both methods substantially increased hemoglobin levels and decreased patients' need for a transfusion (22.0 ± 4.0 g/L and -5.62 ± 2.30 units of packed red blood cells [RBC] with APC, and 27.4 ± 6.1 g/L and -4.79 ± 2.46 units of packed RBC with EBL), without a significant statistical difference between the methods. However, fewer EBL sessions were required both for the cessation of need for a transfusion compared with those for the resolution of GAVE lesions (0.90 ± 0.10 vs 1.69 ± 0.31, P = 0.028). CONCLUSIONS: Both APC and EBL are effective in GAVE treatment. EBL may be superior in terms of number of treatment sessions, but not in its influence on hemoglobin level and need for transfusion. Further prospective studies with large, homogeneous sample size and standardized APC settings are needed.