Vedolizumab clearance (CL) outperforms serum trough concentrations in predicting therapeutic outcomes in Crohn's disease. Higher CL was significantly associated with reduced remission rates, supporting CL as a pharmacokinetic marker for optimizing vedolizumab therapy.

Abstract Background Limited comparative data is available on the real-world effectiveness and safety of tofacitinib (TOFA) and upadacitinib (UPA) in ulcerative colitis (UC). Methods We conducted an international, multicenter, real-life retrospective cohort study to assess and compare the short-term effectiveness of TOFA and UPA in bio-experienced, moderate-to-severe UC. The primary outcome was week 12 corticosteroid-free remission (CSFR) defined as clinical remission (CR; partial Mayo score [pMayo]<2 with a rectal bleeding subscore of 0) and C-reactive protein (CRP) ≤5 mg/L, as well as not receiving local and systemic steroids ≥30 days. The secondary outcomes were CR and biochemical remission (defined as CRP ≤5 mg/L and fecal calprotectin [Fcal] ≤ 250 mg/g) assessed at week 8 and week 12. Data was handled by intention to treat analysis. We performed multivariable logistic regression models with backward stepwise elimination to control potential confounders and to reduce bias. The most reliable models were selected based on ROC analyzes with highest area under the curve (AUC). Statistical power was calculated on the primary outcome with the number of subjects involved, resulting in 1-β=0.97. Results With the participation of 13 tertiary IBD centres, a total of 350 UC patients (Table 1.; mean age: 38.6 ± 13.8 years; 58.6% male) were enrolled in the study. Patients receiving UPA were more likely (OR=4.01 [95%CI: 1.49-10.82]) to achieve CSFR by week 12 compared to the patients on TOFA (47.1% vs. 22.4%). Additionally, higher baseline pMayo (OR=0.76 [95%CI: 0.59-0.98]) and baseline concomitant steroid use (OR=0.17 [95%CI: 0.08-0.40]) decreased the probability of reaching the primary outcome (AUC=0.80). Furthermore, UPA-treated UC patients were more likely to achieve CR at week 8 (54.8% vs. 26.4%; OR=4.06 [95%CI: 1.66-9.93; AUC=0.76]), and at week 12 (69.2% vs. 45.1%; OR=2.3 [95%CI: 1.04-5.13]; AUC=0.80), as well as biochemical remission at week 12 (43.3% vs. 27.3%; OR=6.96 [95%CI: 2.59-18.7]) than patients receiving TOFA. IBD-related hospitalisation was needed in 6.1% (15/246) of the patients on TOFA, as compared to 1.9% (2/104) of patients receiving UPA. Near-significant difference was observed in colectomy rates between the two patient groups (UPA vs. TOFA: 0% vs. 3.7%; p=0.066). Herpes zoster infection was reported in 1.6% (4/246) of the TOFA-treated patients, and in 1.0% (1/104) of the UPA-treated patients. No venous thromboembolism was observed. Conclusion Based on our real-life data, UPA might be associated with better short-term clinical outcomes compared with TOFA in refractory, moderate-to-severe UC.

Abstract Background Bowel urgency is one of the most bothersome symptoms of ulcerative colitis (UC). The Urgency Numerical Rating Scale (U-NRS) measures the degree of faecal urgency experienced over the past 24 hours by patients with UC on a scale of 0-10. We assumed that the scale has a large variance, as patients evaluate their own symptoms differently. The urge may be different quality for two patients with the same score. The score on the U-NRS may be influenced by the individual’s specific perception of symptoms (degree of pain, speed of urge). The objective of our study was to investigate the possible components of urgency using the U-NRS. Methods Patients with UC older than 18 years treated at our departments for at least 3 months and having complaints were enrolled in our study. The patients filled out our non-validated questionnaire with questions about fecal urgency (U-NRS), pain level, speed of urge, incontinence and lifestyle characteristics associated with incontinence. Statistical analysis was performed using SPSS program. Results 205 patients were enrolled, median age was 40 years, the mean of disease duration was 11.8±9.4 years. The mean U-NRS score was 3.2±3.2, 64 patients (31%) had 0 score and 8 (4%) had 10 score. 12% of the patients (n=24) felt most difficult to hold mucus, 38% (n=77) stool and 31% (n=63) other secretions. 9% (n=19) had urge with every stool in the last 24 hours, 35% (n=71) had less than half of defecations. Patient reported outcome (PRO2) had a significant but weak correlation with U-NRS (ͳb=0.348 p=0.000)(Figure 1). The speed of urge defined more the level of urgency than the pain level (R2=0.798, F(1, 203)=803.86 p<0.001, β=0.894 vs R2=0.805, F(2, 202)=417.98, p<0.001, β=0.117). The duration of faeces holding in the last 7 days had significant connection to U-NRS (R2=0.211, F(1, 203)=54.432, p<0.001, β=-0.46). Patients using public restroom at least once during the last week had significantly higher score on U-NRS than other patients (4.6±3.1 vs 2.4±3 p<0.0001). The usage of diapers was also significantly more often in patients with higher U-RNS score (5.2±3.2 vs 2.9±3.1,p<0.0001). Faecal leakage both during the day and night was significiantly higher with higher U-NRS score (p<0.0001 for both) Conclusion Urgency is more defined by the speed of urge than the pain. Using public restroom, usage of diapers and faecal leakage are associated with higher U-NRS. Bowel urgency greatly affects the daily life of UC patients, therefore, it has to be taken into count in therapy managing. Figure 1

Abstract Background Inflammatory Bowel Diseases (IBD) are chronic immune-mediated diseases of the gastrointestinal tract. Fibrosis is frequent in IBD driven by inflammatory cytokines. During fibrosis, extracellular matrix proteins accumulate in the tissue, causing loss of epithelial function and stenosis, leading to malabsorption and intestinal motility problems. This can ultimately lead to serious complications, strictures, fistulas, or ileus. Anti-inflammatory drugs cannot target fibrosis, only surgical intervention can be used. No relevant primary in vitro cell culture model is available for intestinal fibrosis modelling. Therefore, we aimed to establish and optimize human primary fibroblast cell culture from intestinal biopsies of control and IBD patients. We characterized and compared the fibrosis phenotype and gene expression as well. Methods Fibroblast cell cultures were generated from colonic biopsy samples by enzymatic digestion. In a suitable medium, the cells attach to the bottom of the vessel and proliferate, at 90% confluence the cultures were passaged. The phenotype was confirmed by immunofluorescent staining. Target proteins: COL1A1 (Collagen type 1 alpha 1), TGF-ß1 (Transforming growth factor beta), PAI-1 (Plasminogen activator inhibitor type 1), α-SMA (Alpha smooth muscle actin), and PHH3 (Phosphohistone H3). For gene expression analysis RNA was isolated and qRT-PCR technique was used for the following target genes: COL1A1, ACTA2 (Actin alpha 2), TGF-ß1, FN1 (Fibronectin 1), PAI-1, H3C4 (H3 clustered histone 4). We evaluated the collected data and performed statistical analysis. Results We can efficiently create and maintain human colon primary fibroblast cell cultures from colonic biopsies of healthy and CD origins. Cell morphology differences were observed from control and diseased patient samples. At the staining, the fluorescent intensity of fibrotic markers (COL1A1, TGF-ß1, PAI1) and the mitosis marker PHH3 were significantly higher in the CD samples, indicating that the cells maintained fibrotic phenotype, and the diseased fibroblasts had a higher proliferation rate. The myofibroblast marker, α-SMA didn’t show a significant difference. Interestingly, significant differences were not noted between the two groups in the qRT-PCR measurements. Conclusion In conclusion, we can generate primary human intestinal fibroblast cell cultures and maintain them to passage number 3. Fibrotic protein markers and morphology distinguish the diseased samples from the healthy subjects, therefore it could be useable for in vitro fibrosis modelling. However, the gene expression analysis doesn’t discriminate between the two groups at passage number 3. In the future, we would like to observe the fibrotic properties in earlier passage numbers.

Abstract Background Data suggest that patients’ knowledge about their chronic disease is associated with treatment adherence, and education may help improve disease outcomes. The effectiveness of educational activities depends on the source of the information. Our study aimed to compare the effectiveness of targeted educational activities in written and podcast formats for patients with inflammatory bowel disease (IBD). Methods In this nationwide randomized controlled trial, IBD patients were enrolled between December 2023 and May 2024. At baseline, enrolled patients completed an online questionnaire assessing general knowledge of their disease (Inflammatory Bowel Disease Knowledge [IBD-KNOW]) and health-related quality of life (Short Inflammatory Bowel Disease Questionnaire [SIBDQ] and Patient Health Questionnaire-9 [PHQ-9]). Patients were randomized (1:1) into a control and an intervention group and the latter received targeted telemedical educational material, either in podcast format or as a written version, covering topics on anatomy, medical and surgical therapy, quality of life, epidemiology, diet/lifestyle, reproduction, and vaccination. This content was developed by IBD experts. Two months after the educational material was distributed, intervention group was re-tested, and satisfaction was measured. Descriptive statistics, Welch’s test, and Fisher’s exact test were used, with p-values <0.05 considered significant. Results A total of 221 patients were recruited, among whom 129 (58%) had Crohn’s disease (median age was 42 years [IQR 34-49], and median disease duration was 10 years [IQR 4-19], Table 1). Higher baseline IBD-KNOW scores were associated with longer disease duration (95% CI for B: 0.08-0.22, p < 0.001) and lower PHQ-9 scores (95% CI for B: 0.23-0.001, p = 0.052). Of the 221 patients, 95 were randomized into the intervention group to receive educational content, with 46/95 receiving the written version and 49/95 the podcast. Baseline characteristics and overall IBD-KNOW scores did not differ significantly between groups, except for a clinically irrelevant age discrepancy. After the educational intervention, the intervention group had higher overall IBD-KNOW scores compared to the control group (26.7 vs. 23.7, p < 0.001), while the format of the educational activity or quality of life had no significant impact on scores (Figure 1). Patient satisfaction was high (mean score of 8 ± 1.98) and was not influenced by the format of the educational content. Conclusion Telemedical education may enhance disease knowledge among IBD patients, with both forms of educational materials proving equally effective. Although no clear predictors of educational efficacy were identified, disease duration was associated with higher baseline knowledge.

Abstract Background JAK inhibitors (JAKi) can induce and maintain remission in inflammatory bowel disease (IBD). Around 5% of IBD patients develop primary sclerosing cholangitis (PSC). Given the potential involvement of JAK/STAT signaling in PSC pathogenesis, JAKi may have a role in modulating IBD-related PSC. We aim to explore the course of PSC in IBD-PSC patients on JAKi for IBD. Methods Following a call-for-cases via ECCO CONFER (Round 10), we retrospectively collected baseline and outcome data for both PSC and IBD, before and after JAKi treatment, including laboratory tests, imaging and endoscopic findings, histopathology and adverse effects. The data were analyzed both descriptively and comparatively. A p-value of less than 0.05 was considered statistically significant. Results We collected data from 58 patients (53 ulcerative colitis), with a median of disease duration of 5.5 (IQR 2-9) years (Table 1). The median age at PSC diagnosis was 26 (18.25-40.5) years. Each patient had been treated with a median of 2.5 different types of drugs before starting JAKi; 57% received tofacitinib, 26% upadacitinib, 17% filgotinib. At the time of data analysis, the median time of JAKi exposure was 32 (15.75-69) weeks and we will refer to that median time of exposure when analysing each data related to JAKi exposure. At baseline, alkaline phosphatase (ALP) was elevated in 71% of patients (median, 292 U/L, 185-471). After JAKi exposure, ALP dropped to a median of 203.5 U/L (138.7-394.5), p=0.0004. Among this specific group, 30% of subjects reached normal ALP values. Gamma-glutamyl transferase (GGT) was elevated in 80% of patients (350 U/L, 164-552) and dropped to a median value of 127 U/L (95-270), p=0.0055; 13% of this specific group reached normal values of GGT after JAKi exposure. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were high in 58% and 50% of patients, respectively; following JAKi exposure, the median value of both went down significantly. After a median time of 32 weeks of JAKi treatment, 39,6% of patients had to change therapy: 23% due to primary non-response, 62% due to lack of response, 15% underwent colectomy. Patients who had to change therapy were divided into: switch group, treated with additional 40 (36-46) weeks with a different JAKi; swap group, swapped to biologic for additional 27 (24-40) weeks. Better control of liver biomarkers was observed in the switch group (Figure 1). Conclusion Treatment with JAKi can positively impact liver inflammation in terms of cholestasis and cytolysis indexes in patients with PSC and concomitant IBD. References Schregel I, Ramos GP, Ioannou S, Culver E, Färkkilä M, Schramm C; International PSC Study Group. Evaluation of Tofacitinib in Primary Sclerosing Cholangitis and Associated Colitis: A Multicenter, Retrospective Study. Clin Gastroenterol Hepatol. 2023;21(13):3448-3450.e3. doi: 10.1016/j.cgh.2023.01.014. Khrom M, Long M, Dube S, Robbins L, Botwin GJ, Yang S, Mengesha E, Li D, Naito T, Bonthala NN, Ha C, Melmed G, Rabizadeh S, Syal G, Vasiliauskas E, Ziring D, Brant SR, Cho J, Duerr RH, Rioux J, Schumm P, Silverberg M, Ananthakrishnan AN, Faubion WA, Jabri B, Lira SA, Newberry RD, Sandler RS, Xavier RJ, Kugathasan S, Hercules D, Targan SR, RB Sartor, Haritunians T, McGovern DPB. Comprehensive association analyses of Extraintestinal Manifestations in Inflammatory Bowel Disease. Gastroenterology. 2024;167(2):315-332. doi: 10.1053/j.gastro.2024.02.026. Dold L, Kalthoff S, Frank L, Zhou T, Esser P, Lutz P, Strassburg CP, Spengler U, Langhans B. STAT Activation in Regulatory CD4 (+) T Cells of Patients with Primary Sclerosis Cholangitis. Immune Inflamm Dis. 2024;12(4):e1248. doi: 10.1002/iid3.1248.

Abstract Background In clinical practice, vedolizumab (VDZ) is often considered a slow acting agent in Crohn’s disease (CD). However, a post-hoc analysis of the GEMINI trials revealed, that patients previously exposed to anti-TNF therapy already experienced less diarrhoea and abdominal pain already after respectively 2 and 4 weeks of VDZ treatment.1,2 We evaluated the rapidity of clinical and endoscopic benefit of VDZ treatment in the prospective, open-label LOVE-CD trial conducted in Belgium, the Netherlands and Hungary.3 Methods In the LOVE-CD trial, early and late CD patients with moderate-severe active CD (Crohn’s Disease Activity Index [CDAI] 220-450 and presence of ulcers at baseline endoscopy) received intravenous VDZ over a 52-week period. Early CD was defined as a diagnosis <24 months (treatment-naïve or prior corticosteroid and/or immunomodulator use), and late CD >24 months with prior anti-TNF exposure (and corticosteroids and/or immunomodulator use). Corticosteroids were tapered mandatorily and had to be discontinued by week 26. At every study visit, clinical remission (defined as a CDAI ≤150) and steroid-free clinical remission (no corticosteroids and CDAI ≤150) were calculated. At baseline, week 26 and week 52 an endoscopy was performed with independent scoring. Endoscopic response was defined as a reduction in SES-CD score of ≥50% compared to baseline. Missing data were imputed as non-responders. Results In total, 86 early CD patients and 174 late CD patients were included in the LOVE-CD trial. Baseline median CDAI and SES-CD were similar between the early and late group (255 [IQR 236-287] vs. 259 [235-315] and 9 [6-17] vs. 12 [7-17], resp.). Patients in the early group were younger and had evidently shorter disease duration compared to the late CD group (median age 30 [24-45] vs 36 [28-48] years old, median disease duration 0 [IQR 0-1] vs 11 [6-16] years, resp.). From week 6 onward, clinical remission was reached in a significantly higher proportion of early CD than late CD patients. At week 14, more than half of patients with early CD were in clinical remission, compared to 31% in the late CD group (p<0.001) (Table 1). Week 14 corticosteroid free clinical remission results were comparable (47.7% vs 27.6%, p=0.001) (Figure 1A). The proportion of patients with an endoscopic response was significantly higher in the early CD group compared to the late CD group at week 26 (64% vs 34.5%, p<0.001) and at week 52 (57% vs 35.6%, p=0.001) (Figure 1B). No new safety signals were observed. Conclusion Vedolizumab induced (steroid-free) clinical remission and endoscopic response more often in early than in late CD. Based on these observations, vedolizumab may be considered as a potential first line treatment for CD patients. References 1.Sandborn, et al. (2013). Vedolizumab as induction and maintenance therapy for Crohn's disease. The New England journal of medicine, 369(8), 711–721. https://doi.org/10.1056/NEJMoa1215739 2.Feagan, et al. (2019). Rapid Response to Vedolizumab Therapy in Biologic-Naive Patients With Inflammatory Bowel Diseases. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association, 17(1), 130–138.e7. https://doi.org/10.1016/j.cgh.2018.05.026 3.D’Haens et al (2024). Vedolizumab treatment is more effective and safer in early versus late Crohn’s Disease: final results of the LOVE-CD trial. United European Gastroenterology Week, OP 2677.

Abstract Background Inflammatory bowel disease (IBD) patients with Clostridiodes difficile Infection (CDI) are at increased risk of disease exacerbations, therapy escalation, colectomy, and mortality. Data on fidaxomicin use in IBD patients with CDI are very limited. We aimed to assess the effectiveness and safety of fidaxomicin for CDI and its impact on IBD outcomes in a large retrospective multicenter cohort study. Methods Adult ulcerative colitis (UC) or Crohn’s disease (CD) patients with a CDI episode (positive toxin enzyme immunoassay or polymerase chain reaction for toxigenic C. difficile) treated with fidaxomicin for at least 7 consecutive days were included. The primary outcome was CDI recurrence rate, defined as C. difficile toxin detection and treatment with any antibiotic targeting CDI or faecal microbial transplantation within 8 weeks. Secondary outcomes included sustained response rate (no CDI treatment for 12 weeks), IBD therapy escalation, colectomy, and all-cause mortality at 30, 90, and 180 days. Pre-specified and any other adverse events were collected. Results A total of 96 patients (57 CD and 39 UC) were included from 20 European IBD centers. Patient demographics, IBD, and CDI characteristics are summarized in Tables 1 and 2. Most patients (73%) were on advanced IBD therapy, and 34% on steroids. Half of the patients were hospitalized, and 15% had a severe CDI episode. Half of the patients had a prior episode of CDI (30% with one, 21% with two or more), predominantly treated with vancomycin. Most patients (86%) received a fidaxomicin standard dose regimen, while 9 received extended-pulsed dosing. CDI recurrence occurred in 10 (10%) patients, while 79 (82%) patients achieved a sustained response. Compared to CDI-experienced patients, CDI naïve patients tended to have a lower recurrence (4.3 vs 16%; p=0.06) and higher sustained response (91 vs 75%; p=0.04) rate. Induction treatment with an IBD advanced therapy was required in 22 (24%), 18 (20%), and 11 (13%) patients at 30, 90, and 180 days, respectively. No difference in terms of CDI recurrence and sustained response was identified between CD and UC patients. Patients achieving, compared to not-achieving, CDI sustained response, showed a numerically lower need for IBD therapy escalation, with 2 (12%) vs 20 (26%), at day 30. Five UC patients underwent colectomy. A 79-year-old UC patient died unrelated to IBD or CDI. Mild episodes of rash, nausea, conjunctivitis, asthenia, hypokalemia, and hypocalcemia were reported. Conclusion In this large cohort of IBD patients with CDI, fidaxomicin was effective and safe for CDI resolution, with greater effectiveness for CDI first episodes. CDI resolution might influence short-term IBD-related outcomes, although further studies are required.

Abstract Background Inflammatory Bowel Diseases (IBD) require lifelong treatment and patient monitoring. Current predictors of relapse and therapeutic success have limitations, mostly invasive, time-consuming, and expensive. The faecal biomarker can help in disease activity and therapeutic response monitoring by simple and non-invasive way. Faecal Calprotectin (FC) is the gold-standard, but it has many disadvantages. We previously described that the correlation between the faecal Plasminogen activator inhibitor type 1 (PAI-1) (FP) level and the endoscopic activity and therapeutic response promote that it could be used as a novel non-invasive faecal biomarker in IBD diagnosis.1 To observe the exact faecal biomarker potential, we aimed to define the FP level of IBD patients and subjects with other gastrointestinal (GI) diseases and compare it with the FC. Methods Faecal samples were collected from 84 patients with IBD (CD-active: 12, CD-inactive: 10, UC-active: 9, UC-inactive: 10) and other GI diseases [colorectal cancer (CRC): 10, diverticulosis [DIV]: 9, irritable bowel syndrome [IBS]: 5, Polyp: 10) and 9 healthy subjects. ELISA method was applied to define FP level and it was validated for stool samples by us. In our previous study, 0.68 ng/g PAI-1 level was defined as the cut-off value. For FC observation diagnostic FC ELISA kit (Orgentec) was used. FC cut-off value was 50 mg/g. ROC analysis was applied to define Youden-index, specificity, and sensitivity of the measured values. Results FP level was significantly higher in patients with active IBD compared to inactive IBD and healthy subjects. No significant differences were observed between CD-active and UC-active groups. In addition, FP concentrations were significantly increased in active IBD patients compared to inactive IBD, CRC, DIV, IBS, Polyp, and healthy subjects. However, FC showed the same pattern as FP, except at the inactive IBD and DIV. In these groups, there were no significant differences compared to the active IBD subjects. ROC analysis defined high specificity (88.9%) and moderate sensitivity (47.6%) values (TP: 10, FP: 7, FN: 11, TN: 56, PPV: 0.588, NPV: 0.836) at the FP measurements. Nevertheless, at FC levels 34.9% specificity and 95.2% sensitivity were measured (TP: 20, FP: 41, FN: 1, TN: 22, PPV: 0.328, NPV: 0.957). Calculated Youden-index was higher at the FP (0.37) compared to the FC (0.3). Conclusion Our results suggest that the FP level selectively increased in the active IBD and discriminated more specifically from the other GI diseases compared to the FC. However, the sensitivity was lower, but it could be improved by the increasing patient numbers. Thus, the FP level could be useful in the diagnosis of IBD independently or combined with FC. References 1.Jójárt B, Resál T, Kata D, Molnár T, Bacsur P, Szabó V, Varga Á, Szántó KJ, Pallagi P, Földesi I, Molnár T, Maléth J, Farkas K. Plasminogen Activator Inhibitor 1 Is a Novel Faecal Biomarker for Monitoring Disease Activity and Therapeutic Response in Inflammatory Bowel Diseases. J Crohns Colitis. 2024 Mar 1;18(3):392-405. doi: 10.1093/ecco-jcc/jjad160. PMID: 37751311; PMCID: PMC10906952.

Abstract Background Dose intensification of anti-α4β7 integrin vedolizumab (VDZ) in Crohn’s Disease (CD) patients with secondary loss of response has been reported to be effective. However, data on effectiveness of this intervention in primary non-responders is often inconsistent and retrospectively collected.1 Our aim was to investigate the effect of vedolizumab dose intensification in endoscopic non-responders after 26 weeks of standard dosing on both clinical and endoscopic remission at week 52. Methods In the LOVE-CD trial, early and late CD patients with moderate-severe disease activity (Crohn’s Disease Activity Index (CDAI) 220-450) and presence of ulcers at baseline endoscopy were treated with VDZ for 52 weeks.2 Early CD was defined as diagnosis <24 months and late CD as diagnosis >24 months and previous exposure to anti-TNF. All patients received standard doses of vedolizumab (300 mg at week 0,2 and 6 and further every 8 weeks with an additional dose at week 10 in case of clinical non-response) and underwent an endoscopy at week 0, 26 and 52. Corticosteroids were mandatorily tapered and had to be discontinued by week 26. Halfway the trial, after 130 patients (50%) had been included, the study protocol was amended by introducing dose intensification from 300 mg IV every 8 weeks to every 4 week in patients without endoscopic response (DSES-CD drop <50%) at week 26. The primary outcome was deep remission, defined as clinical (CDAI ≤150) and endoscopic remission (SES-CD ≤3) at week 52. Results In LOVE-CD, eighty-two patients (31.5%) were endoscopic non-responders at week 26 (44 prior to and 38 after the dose intensification amendment). Four patients in the dose intensification group were excluded from analysis due to missing week 52 endoscopy data. Apart from previous biological exposure (90.0% vs 73.5% in the dose intensification and standard dosing group, resp.), baseline characteristics were similar between the dose intensification and continued standard dosing groups (median SES-CD at baseline 11 (IQR 7-17) vs 13 (IQR 8-18) resp.). At week 52, the dose-intensified group had significantly higher VDZ serum concentrations at trough (mean 46.4 vs 16.3 ug/ml, p<0.001). However, there was no significant difference in endoscopic remission, clinical remission and deep remission rates at week 52 between the two groups (table 1). No significant differences in severe adverse events were observed between both groups (9.7% vs 13.6%, p=0.344). Conclusion In the LOVE-CD trial, dose intensification of vedolizumab in endoscopic non-responders with Crohn’s Disease after 6 months of standard dosing was not effective. References 1.Samaan, et al. (2019). Effectiveness of vedolizumab dose intensification to achieve inflammatory bowel disease control in cases of suboptimal response. Frontline gastroenterology, 11(3), 188-193. https://doi.org/10.1136/flgastro-2019-101259 2.D’Haens et al (2024). Vedolizumab treatment is more effective and safer in early versus late Crohn’s Disease: final results of the LOVE-CD trial. United European Gastroenterology Week, OP 2677.

Abstract Background Achieving deep remission, encompassing clinical, endoscopic, and biological remission, is a long-term goal in Crohn's disease [CD] according to the STRIDE-2 guidelines. The role of histological remission in CD remains unclear. We evaluated the efficacy of vedolizumab [VDZ] for inducing histo-endoscopic remission in early versus late CD in the prospective, open-label LOVE-CD trial conducted in Belgium, the Netherlands and Hungary. Methods In the LOVE-CD trial, patients with moderate-to-severe disease (Crohn’s Disease Activity Index 220-450 and presence of ulcers at baseline endoscopy) received intravenous vedolizumab over a 52-week period. Early CD was defined as a diagnosis <24 months (treatment-naive or history of corticosteroid and/or immunomodulator use), and late CD as a diagnosis >24 months with prior anti-TNF exposure. Ileocolonoscopies were performed at three timepoints (baseline, week 26, week 52) during which biopsies were systematically collected in the terminal ileum and colon. Both the endoscopies and biopsies were centrally scored by experienced readers for the simple endoscopic score for Crohn's disease [SES-CD], Robarts’ histopathology index [RHI], and Geboes score [GS]. Endoscopic remission, histo-endoscopic mucosal improvement [HEMI], and histo-endoscopic mucosal remission [HEMR] were defined as SES-CD <4, GS ≤3B.1, and GS <2B.1 respectively. The association between histologic and endoscopic scores was studied with Spearman’s correlation coefficient. Intention-to-treat analysis with non-responder imputation was used to handle missing data. Results Of the 260 patients included in LOVE-CD (Table), 440 biopsies (336 colon, 114 ileum) from 179 patients at week 26, and 435 biopsies (323 colon, 112 ileum) from 177 patients at week 52 were analysed. There was a strong correlation between the endoscopic and histological assessment (colon r 0.69, ileum r 0.64, total r 0.64, p<0.001). Patients with early CD were more likely to achieve histological remission than patients with late CD at week 52 (38.4 % vs. 14.9%, p=0.00004). Endoscopic and histological healing rates at week 26 (endoscopic remission 36.9%, HEMI 30.4%, HEMR 24.2%) and week 52 (endoscopic remission 35%, HEMI 30%, HEMR 22.7%) were comparable. When looking at disease location, histological remission rates in the colon and ileum did not significantly differ (35.2% vs. 27.8%, p=0.15). Conclusion Vedolizumab was more efficient at inducing histo-endoscopic remission in early CD as compared to late CD, with most of the histo-endoscopic healing occurring during the first 26 weeks. Histo-endoscopic healing rates under vedolizumab were comparable in colonic and ileal disease. Histological scores (RHI, GS) are also applicable for the evaluation of ileal and colonic CD.

Abstract Background Data are scarce on the deep remission of tofacitinib (TOFA) in moderate-to severe ulcerative colitis (UC), however, it can fundamentally change disease course and behaviour. Methods This was a prospective cohort study, assessing the short-term effectiveness of TOFA in UC patients. Baseline was the day of induction of TOFA. Clinical, biochemical, endoscopic and histological activities were assessed at baseline and at week 8 and 12, and we collected one-year treatment persistence. Primary outcome was week 12 histological remission (HR), defined as Nancy score<1 and endoscopic Mayo score (eMayo)≤1. Secondary outcomes were week 12 corticosteroid-free remission (CSFR), defined as clinical remission (CR; partial Mayo score [pMayo]<2 with a rectal bleeding subscore of 0) and C-reactive protein (CRP) ≤5 mg/L and endoscopic remission (eMayo score ≤1), furthermore, one-year treatment persistence were assessed. Data was handled by intention to treat analysis. We performed multivariable logistic, Cox-regression and linear regression models to control potential confounders and to reduce bias. The most reliable models were selected based on ROC analyzes with highest area under the curve (AUC). Results A total of 75 moderate-to severe UC patients (mean age 38.4 ± 12.1; male/female ratio 32/44) were involved in our prospective cohort study. In total, 7 patients (9.2%) achieved histological remission, while 20 patients (26.7%) achieved endoscopic remission. We found, that one-year treatment persistence was strongly influenced by week 12 endoscopic remission (β=3.79 [95% CI: 1.21 – 6.37]), but not by HR (β=1.58 [95% CI: -0.74 – 3.89]). In total, 34 patients (44.7%) were in CSFR at week 12, and higher baseline pMayo score decreased (OR=0.64 [95% CI: 0.43 – 0.94]), while albumin increased (OR=1.33 [95% CI: 1.01 – 1.76]) the chance of achieving the outcome (AUC = 0.93). Conclusion Based on our prospective cohort study, short-term HR is still a hard-to-reach endpoint in moderate-to-severe UC on TOFA. We found, that one-year treatment persistence is influenced by endoscopic mucosal healing, but not by HR, however, it should be enhanced, that as only a few patients achieved HR, the necessary statistical power was lacking.

Abstract Background High-quality endoscopy in IBD is associated with better clinical outcomes, while quality measurement supports effective quality control. The European Society of Gastrointestinal Endoscopy recommends using nine performance measures, depending on the indication for endoscopic examination in IBD. Our study aimed to compare colonoscopy quality between tertiary and secondary referral centers for IBD patients, based on endoscopic reports. Methods In this cross-sectional study, colonoscopy reports of IBD patients were analyzed. At our tertiary center, we consecutively enrolled patients over 18 years old with established IBD between July and October 2024, using their available colonoscopy reports. The secondary care group included patients referred to our tertiary center, with the last existing report from secondary care used for analysis, while the tertiary care group consisted of our patients whose most recent report was similarly used. Nine key performance measures (indication, bowel preparation, photo documentation, ileal intubation, biopsy, endoscopic activity score, high-definition and chromoendoscopy use, and neoplasia detection) were evaluated based on colonoscopy reports. Patients were stratified by procedure indication (diagnostic, activity assessment, or surveillance) as well. Descriptive statistics, Welch’s, and Fisher’s exact tests were used to compare groups, with p-values <0.05 considered significant. Results Overall, 207 colonoscopy reports were assessed, of which 68/207 were performed at secondary care level. A total of 78/207 patients were diagnosed with Crohn’s disease, while unclassified diagnoses were noted only at secondary centers. Activity control (88% vs. 38%, p<0.001) and surveillance (8% vs. 0%, p=0.02) examinations were more common at the tertiary level. Bowel preparation was better at tertiary centers (Boston Bowel Preparation Scale [BBPS] 8.3±2.3 vs. 7.2±1.2; p=0.003), and use of BBPS was more frequent at higher levels of care (p<0.001). Disease activity scores were more commonly used at the tertiary level during activity control examinations (51.2% vs. 19.2%, p=0.004), while ileal intubation was also more frequent at the tertiary level (53% vs. 28%; p<0.001). Procedure and withdrawal times did not differ between levels in diagnostic or activity control examinations. Neoplasia detection was low, and biopsy rates were similar. Conclusion Quality indicator targets were met in neither secondary nor tertiary centers; however, wider investigation is needed to verify these results. Broad education can help to improve the quality of colonoscopy in IBD care.

Abstract Background Crohn’s disease (CD) complicated with intra-abdominal abscess often requires surgical intervention. Image guided percutaneous drainage (PD) can help to avoid surgical interventions, however there is limited evidence on the optimal management after PD. Our study aimed to analyze the long-term outcomes of CD complicated with intra-abdominal abscess after intervention. Methods In this multicenter, multinational retrospective trial penetrating CD patients with simplex intra-abdominal abscess were enrolled and followed. Baseline was defined as the day of the first detection of simplex abdominal abscess, while follow-up period of 12-24 months was set. Patients with urgent resection were excluded. Patients were grouped based on elective surgical need during follow-up after a successful PD, while a control group of patients after resection without PD is created. Primary outcome was the abscess recurrence, while stoma rate, post procedural complications rate (<30 days), and postoperative luminal recurrence were analyzed as secondary outcomes. Logistic regression and Cox-regression models were created, while descriptive statistics, Welch’s test, and Fisher’s exact test were used to compare groups, with p-values <0.05 considered significant. Results A total of 131 CD patients from 7 countries were recruited (Table 1., 58% were male, the median age at inclusion was 31.4 [IQR25-40] years) and 74/131 patients had PD due to simplex abdominal abscess during a median follow-up of 104 (74-104) weeks. Abscess recurrence rates did not differ between groups (p=0.155, Figure 1.); however baseline SES-CD score was coupled with increased risk of recurrence (HR=1,17, 95% CI 0.993-1.389). Need for re-drainage was more common amongst PD patients (OR=0.092, 95% CI=0.012-0.732), while new stoma was created more frequently in patients without prior PD (OR=2.50, 95% CI=1.034-6.034). Postoperative luminal recurrence was similar between groups based on PD. Surgical complications were coupled with increased odds in patients without prior PD (OR=8.609, 95% CI=1.825-40.616), septic complications, perforation and new fistula formation were reported the most, while PD associated complication did not occur. Conclusion However, abscess recurrence did not differ between groups, PD prior to surgery strongly correlated with less stoma creature. Furthermore, surgical treatment of intra-abdominal abscess alone may be coupled with post procedural complications.

Abstract Background Perianal fistulas of Crohn’s disease (CD) create a significant burden on patient lives. However, the efficacy and safety of adipose-derived mesenchymal stem cell treatment are contradicting, and real-world evidence is lacking. We aimed to examine the usability of darvadstrocel therapy in managing perianal CD. Methods In this retrospective multicenter study CD patients with perianal fistulas were enrolled and followed. The primary outcome was perianal clinical remission (all treated fistulas have closed) at weeks 26 and 52, while the secondary outcomes were clinical response rates (≥ 1 fistulas have closed), perianal activity (PDAI), patient satisfaction, and adverse events. The data was recorded at the baseline and weeks 12, 26, and 52. Prediction of primary outcomes was performed by logistic regression. Results Overall, based on the data of 223 patients (Table 1., male/female ratio: 0.48), perianal clinical remission was achieved in 78.2% and 62.3% until week 26 and 52 (Figure 1.), whereas baseline PDAI score (OR 0.75), number of fistulas (OR 0.28), and the number of weeks after preparation for surgery (OR 0.98) were associated with treatment failure. The clinical response rates were 84.8% and 79.8% at week 26 and 52. Moreover, the improvement of subjective perianal symptoms was achieved in 77.8% and 78.4% of the patients, respectively. Adverse events occurred in 13.5% of the patients, with perianal abscesses and proctalgia reported the most. Conclusion Effectiveness data are higher than the clinical trials. The safety profile is reassuring, and patients’ satisfaction is high. Appropriate patient selection, fistula preparation and expertise may help to achieve treatment success.

Abstract Background Usability of subcutaneous vedolizumab (SC VDZ) in inflammatory bowel diseases (IBD, ulcerative colitis [UC], Crohn’s disease [CD]) have proved via clinical trials, while real-world data collection is ongoing. Experiences of Central-European population and assessment of patient’s perspectives are lacking. Our study aimed to evaluate the real-world efficacy, safety and patient’s preferences of SC VDZ maintenance treatment after switching from intravenous (IV) formulation in a Hungarian IBD cohort. Methods In this prospective, multicenter cohort study, IBD patients on maintenance IV VDZ treatment were enrolled, who switched to SC administration. Baseline was the day of the switch, while 52-week follow-up was set. Clinical and demographic data were collected, while serum VDZ level and CRP was measured at baseline and at w52. A non-validated questionary was filled by patients who were on drug at w12 recording patient’ satisfaction. Primary outcome was the drug survival rate at one year, while secondary outcomes were change in corticosteroid-free clinical (CSFR, based on physicians’ global assessment score PGA < 1), and biochemical remission (BR, 5 mg/l > CRP) rates to w52, safety issues and patients’ preferences and change in serum drug levels. Results In total, 37 IBD patients were followed (Table 1., 15 CD and 22 UC, male/female ratio 45.9 %, median age 42.0 [IQR 34-49] years). In CD group, 66.7 % were in CSFR and 60 % in BR, while in UC group 63.6 % were in CSFR and 68.2 % in BR (p = 0.55 and p = 0.61). Overall, 29.7 % of patients ceased SC VDZ treatment after a median of 20 (IQR 6-26) weeks. Cessation was due to secondary response losing in 3/6 and 4/5 patients in CD and UC group. In case of 2 and one patients, SC treatment was terminated due to local reactions. One patient was fear of needle. Severe adverse event did not occur. Factors associated with discontinuation did not identify. The mean serum VDZ level has higher at w52 compared to baseline in CD and UC patients (CD: 8.9 ± 6.9 to 30.6 ± 17.8 ug/mL, p = 0.047; UC: 13.6 ± 13.8 to 33.6 ± 17.6 ug/mL, p = 0.001, Figure 1.), while disease activity was stable. 84 % of the patients who filled the questionnaire were satisfied with injection, while only one patient found it difficult to inject. Conclusion Transition from IV to SC maintenance VDZ treatment is effective at one year, the overall survival rate is high presumably due to the elevated serum drug levels. Severe safety issue did not raise. Satisfaction of switched patients is high, which may improve treatment adherence and save resources.

Abstract Background Reproduction is an essential part of life. Our aim was to obtain a global perspective on IBD management by gastroenterologists (GIs) during preconception, pregnancy, lactation and neonatal period. Methods An anonymous survey (75 questions) was developed to investigate different aspects of clinical practice concerning the management of pregnancy and breastfeeding in patients with IBD. A national representative from each European country, USA, Latin America, Australia and New Zealand was selected to distribute the survey among their GI colleagues who treat patients with IBD (irrespectively of their experience). Results A total of 856 GIs from 36 countries participated in the survey. Among the participants, 63% had over a decade of experience as GIs, and 61% identified themselves as IBD specialist (IBDologists). The most relevant survey results and sub-analyses based on expertise are presented in tables 1 and 2. In the management of pregnant patients in remission, treatment discontinuation occurred either consistently or occasionally as follows: 20% thiopurines, 37% vedolizumab, 31% ustekinumab, and 96% small molecules. Notably, 13% did not always discontinue small molecules in patients contemplating pregnancy. Safety was the main reason for discontinuing IBD therapy during pregnancy. Contrary to the recommendations in clinical practice guidelines, many GIs avoid starting oral or rectal budesonide, anti-TNF, vedolizumab or ustekinumab during a disease flare. Further, a third of GIs would start thiopurines for a flare during pregnancy. Moreover, 13% will never perform a colonoscopy in a pregnant patient to guide decision making. Half of GIs implemented a dedicated outpatient follow-up program for pregnant patients in remission, with 87% enrolling all pregnant patients in this program. Concerning breastfeeding, 14% believed that all drugs can be used while breastfeeding. Regarding offspring’s vaccination, about 20% recommend against the administration of non-live vaccines and only 50% recommended avoiding live vaccines during the first 12 months for children exposed to anti-TNF in-utero. Among those GIs who recommended delaying vaccines in such cases, only 41% recommended testing the infant for detectable anti-TNF levels if live vaccines were required. Among the surveyed GIs, only a minority had a referral obstetrician, and only 35% referred patients with active or complicated IBD, while 45% had a referral paediatrician with expertise in IBD. Conclusion The management of IBD during pregnancy, lactation, and neonatal period is notably suboptimal, even among GIs specifically dedicated to IBD. It is crucial to address this current need and implement urgent educational measures in this area.

Abstract Background In contrast to the increasingly rigorous endpoints of clinical trials of ulcerative colitis (UC), Mayo endoscopic score (MES) ≤ 1 is mostly set as target during clinical follow-up, but long-term outcomes may differ according to different level of healing. Therefore, our study aimed to compare the long-term outcomes of UC patients in clinical remission with different MES and UCEIS scores in real-life condition. Methods UC patients in clinical remission (defined by pMayo<2 with no rectal bleeding) who underwent colonoscopy between 2016-2020 were consecutively enrolled in this multicenter retrospective study. Mayo and UCEIS endoscopic scores were evaluated and clinical and demographic data were collected at baseline. Clinical flare, colectomy, hospitalization and treatment modifications were recorded during at least 3 year of follow-up. Primary outcome was the clinical flare, while secondary outcomes were hospitalization, colectomy, new biological initiation and biological dose escalation during follow-up. Outcomes were compared with Log-rank test and survival characteristics were plotted. Results In total, 156 UC patients were enrolled with a median age of 46.0 (IQR 35.5-58.0), while male/female ratio was 49.4 % (Table 1.). Near to half of the patients (44.9%) had MES>0 endoscopic activity at baseline. Non zero baseline MES (Figure 1.; p = 0.002; MES 0 vs 1 p = 0.004) and UCEIS (p < 0.001; UCEIS 0 vs. 1 p = 0.016) scores were associated with higher rate of clinical flare. Higher baseline MES (p = 0.042) and UCEIS (p = 0.008) scores were coupled with increased risk of hospitalization. Colectomy rates were low. Increased baseline UCEIS (p = 0.003), but not MES score was coupled with new biological treatment initiation, while only UCEIS score was associated with biological treatment intensification (>4; p = 0.008). Conclusion Our study suggests differentiating between complete MH from MES 1 as long-term outcomes were more favorable in case of lower endoscopic scores. Consequently, targeting complete MH should be considered to achieve deep remission and disease clearance.