Inflammatory Bowel Disease Therapy Research Articles

Bisdemethoxycurcumin and Curcumin Alleviate Inflammatory Bowel Disease by Maintaining Intestinal Epithelial Integrity and Regulating Gut Microbiota in Mice.

Curcuminoids, found in turmeric (Curcuma longa L.), include curcumin (CUR), demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC). Although CUR and DMC are well-studied, the anti-inflammatory effects of BDMC remain less explored. Recent studies highlight BDMC's stronger NF-κB inhibition compared to CUR and DMC in cell models, along with its ability to target pathways associated with inflammatory bowel disease (IBD) in DSS-induced colitis mice, reflected by lower disease activity scores and reduced inflammation. This study assessed CUR and BDMC in a DSS-induced colitis mouse model. Dietary administration of CUR or BDMC strengthened tight junction (TJ) proteins, reduced inflammatory cytokine secretion, and attenuated intestinal inflammatory protein expression, thereby alleviating DSS-induced IBD in mice. Furthermore, gut microbiota and short-chain fatty acid analyses revealed that CUR and BDMC effectively regulated gut microbial imbalance and promoted the relative abundance of butyrate-producing bacteria. Furthermore, CUR showed low absorption and was primarily excreted in feces, while BDMC had higher absorption levels. In conclusion, while both BDMC and CUR have potential as adjunct therapies for IBD, BDMC at a concentration of 0.1% showed strong anti-inflammatory effects and enhanced TJ proteins, suggesting that BDMC, even at lower concentrations than CUR, holds promising therapeutic potential and prospects.

From Evidence to Practice: A Narrative Framework for Integrating the Mediterranean Diet into Inflammatory Bowel Disease Management

Emerging evidence underscores the pivotal role of diet in preventing and managing inflammatory bowel disease (IBD). As our comprehension of the microbiome’s role in IBD expands, dietary modifications are increasingly recognized as potential adjuncts or primary therapeutic strategies. Key components of the Mediterranean diet (MD)—including microbiota-accessible carbohydrates, omega-3 fatty acids, polyphenols, and antioxidants—have demonstrated promise in enhancing gut microbiota diversity and reducing intestinal inflammation, making it a practical approach for managing IBD. Moreover, the MD offers additional benefits considering the rising prevalence of comorbid chronic inflammatory conditions such as diabetes, cardiovascular disease, and obesity in IBD patients. The purpose of this narrative review was to provide an overview of the feasibility and clinical outcomes of the MD and offer evidence-based guidance for researchers and practitioners on how to adapt the MD to patients with IBD. According to several cross-sectional and interventional studies, the MD is feasible for patients with IBD and confers several benefits, such as reduced inflammation, improved disease activity, and enhanced quality of life, with a strong adherence rate and minimal adverse effects. To facilitate knowledge translation, we provide a practical framework for integrating the MD as a nutritional therapy for IBD, including specific recommendations and messaging that researchers, practitioners, and patients can use. By synthesizing current evidence and offering actionable insights, the aim is to facilitate the integration of the MD into IBD management, with the potential to improve patient outcomes.

Anti-tumor Necrosis Factor Drug Concentration Is Not Associated with Disease Outcomes in Pouchitis: A Retrospective, International Study.

Therapeutic drug monitoring is important for optimizing anti-tumor necrosis factor-α (TNF-α) therapy in inflammatory bowel disease. However, the exposure-response relationship has never been assessed in pouchitis. To explore associations between anti-TNF-α drug concentration and pouchitis disease activity in patients with a background of ulcerative colitis. A retrospective, multicenter, cross-sectional study was conducted in adult patients with pouchitis requiring anti-TNF-α treatment. Rates of clinical and endoscopic remission were calculated, and drug concentrations during maintenance therapy were compared between remission and non-remission cohorts. Sixty-three patients were included: median age, 48years (IQR 36-59) and median time since pouchitis diagnosis, 7years (IQR 2-13). Patients received infliximab, n = 27 (43%), adalimumab, n = 29 (46%), or both n = 7(11%). Thirty-two (51%) patients received concomitant immunomodulation. Median infliximab trough concentrations (mg/ml) were similar between patients in clinical remission (n = 21) vs non-remission (n = 11), 5.3 vs. 4.4, p = 0.73. For adalimumab, median drug concentrations did not significantly differ between remission/non-remission groups based on clinical (n = 18/18), 11.4 vs 7.6, p = 0.32, or endoscopic assessment, (n = 7/29), 9.0 vs. 7.8, p = 0.78. Four patients had positive anti-drug antibodies with undetectable drug concentration. In a cohort of patients with pouchitis, higher anti-TNF-α drug concentrations were not associated with more clinical or endoscopic remission.

A Biomimetic Sweeping Microrobot for Active Therapy of Ulcerative Colitis

AbstractOverproduction of pathogenic cell‐free DNA (cfDNA) and reactive oxygen species (ROS) plays crucial roles in the onset and perpetuation of ulcerative colitis (UC). Inspired by sweeping robots, a magnesium@polylactic acid‐glycolic acid copolymer@polyethylenimine (Mg@PLGA@PEI) microswimmer capable of cleaning off deleterious disease triggers along its path of progress is designed. Mg@PLGA@PEI is successfully synthesized by adopting a core‐shell structure with a small opening which allows for Mg‐water reaction. The distinctive motility performance resulting from sustained detachment of the produced hydrogen not only contributes to strengthened hydrogen diffusion concomitant with potentiated ROS neutralization, but also facilitates the contacting probability with microenvironmental cfDNA and thus enhances the DNA binding efficiency. By integrating these merits, the developed Mg@PLGA@PEI confers desirable curative efficacy in a classical DSS‐induced acute colitis mouse model. Enema administration of Mg@PLGA@PEI microswimmers substantially alleviates the manifestations related to UC, as evidenced by the body weight recovery, colon length retention, colon tissue protection, and attenuated intestinal inflammation, which is attributed to the active scavenging of cfDNA and ROS. This work provides a paradigm for a drug‐free strategy competent in spontaneously eliminating causative triggers with minimal side effects, which presents a promising alternative for the active therapy of UC or other cfDNA‐ and ROS‐related diseases in the clinic.

Clinical and organizational features of ulcerative colitis and Crohn's disease differential diagnosis: the experience of the specialized City clinic for Inflammatory Bowel Diseases

Introduction. The initial diagnosis of ulcerative colitis and Crohn's disease – inflammatory bowel diseases (IBD) – is quite difficult, requiring a comprehensive evaluation of clinical and anamnesis data, the results of ilecolonoscopy with multifocal biopsy and, results of imaging diagnostic methods (in some cases).The aim of the study: to estimate the duration of the time period required to establish the IBD diagnosis of and to assess the potential consequences of untimely establishment of this diagnosis.Materials and methods. The data of 253 patients with ulcerative colitis and 263 patients with Crohn's disease who applied to the city center of St. Petersburg.Results. In 59 % of ulcerative colitis patients with and in 65 % Crohn's disease patients the diagnosis was established within 3 months from first clinical sighs appearance. Evaluation of the possible association between the duration of the period required to establish the diagnosis of IBD and features of the course of IBD after diagnosis did not reveal a statistically significant association with the rate of recurrence and the risk of developing non-life-threatening complications. When studying the development of life-threatening complications of IBD it was found that only 59 % of such complications occurred after the diagnosis of IBD, while in the remaining cases they occurred either before or caused the diagnosis. Untimely diagnosis of IBD increased the risk of life-threatening complications by 18 times in patients with ulcerative colitis, and by 13 times in patients with Crohn's disease, compared to the situation when the diagnosis was established timely and specific IBD therapy for was initiated. Conclusion. The majority of IBD patients, who suffered a life-threatening complication before the diagnosis was established, potentially had a temporary «window of opportunity», when on the basis of clinical data it was possible to suspect the presence of IBD, establish the diagnosis with the subsequent timely initiation of specific therapy to prevent a complicated course of the disease.

P1126 Patterns of conventional therapy use and drivers of initiation for advanced therapy in Inflammatory Bowel Disease: A European situational analysis

Abstract Background Data suggest limited use of advanced therapies (AT) in inflammatory bowel disease (IBD) despite the accumulating data for the benefits of early, broader AT use.1-3 We evaluated barriers to AT use in IBD using a multimodal approach. Methods Market research was conducted June-November 2023. Quantitative survey on prescribing trends amongst gastroenterologists (GEs) prescribing ATs was conducted to capture AT initiation drivers in Germany, Italy, UK and US; questions for this survey were identified in qualitative interviews. GEs cycling an average of 0-1 and ≥2 conventional therapies (CTs) before initiating AT were classified as low and high cyclers, respectively. The COM-B (Capability, Opportunity, Motivation and Behaviour) model was used for behavioural analysis.4 Results Qualitative analysis covered responses from 62 participants (28 patients [pts], 24 GEs, 7 nurses, 3 pt organisation representatives), and quantitative analysis – from 142 GEs (Germany, 30; Italy, 30; UK, 30; US, 52) currently prescribing ATs, with 559 pt report forms (ulcerative colitis [UC], 280; Crohn’s disease [CD], 279) collected. CT cycling was more prevalent in UC vs CD; AT treatment was less likely in pts with UC vs CD (Figure). Differences among GEs by geography were only partially explained by cost containment in highly regulated markets (eg, Italy, UK). High cycling variations were linked to behavioural and belief-driven factors as illustrated by the notable use (7-20%) of 5-aminosalicylates in CD despite the lack of clinical guideline support. In behavioural analysis, AT initiation barriers included a lack of awareness of AT value and prescribing approach of exhausting all CT options before initiating AT. Low vs high cyclers placed higher importance on patient preference (UC, +16%; CD, +19%) and peer recommendations (UC, +13%; CD, +20%). In UC, the belief of exhausting all CT options before initiating AT was more important for high vs low cyclers (+9%). Qualitative research showed that the lack of clear guidelines disproportionately impacted high cyclers as they had reduced academic interest and limited capacity as contributors. Physician-relevant AT initiation drivers were the perceived CT risks and the growing recognition of the AT clinical value and long-term impact on the quality of life. Pt-relevant drivers included improved AT awareness and the ability and confidence for pts to self-advocate. Conclusion Cost containment and guideline variations could partially explain the observed geographic variations in AT use. Within any given country, clinical beliefs play a determining role. In Europe, a tangible increase in AT vs CT share could be achieved by encouraging GEs to initiate AT in pts with poor prognostic factors as per guideline suggestions.

P0069 TP-317, a Novel BLT1 Agonist Oral Therapy for Inflammatory Bowel Disease, Exhibits Anti-Inflammatory and Epithelial Barrier Protective Efficacy in Murine DSS Colitis and TNFΔARE Ileitis

Abstract Background Resolvin E1 (RvE1) and leukotriene B4 (LTB4) are both BLT1 receptor agonists but elicit distinct biological outcomes through biased agonism. LTB4, a pro-inflammatory lipid mediator, initiates and regulates inflammatory responses by stimulating recruitment and activation of immune cells. In contrast, RvE1, a pro-resolution lipid mediator, selectively engages BLT1 to promote immune homeostasis and repair. TP-317, a stabilized RvE1 molecule, is being investigated as an oral therapy for inflammatory bowel disease (IBD). The subject studies describe the efficacy and mechanism of TP-317 in two preclinical colitis models. Methods DSS colitis: 8-wk old C57Bl6/J mice (n=12/group) were given two 5-day cycles of DSS (1%, 2%) separated by a 10-day recovery period, followed by 7 days of daily oral treatment starting on day 20 with TP-317 (0.04, 0.4 or 4 mg/kg), cyclosporin (25 mg/kg), the JAK1 inhibitor filgotinib (36 mg/kg), or vehicle. Colitis symptoms were scored daily using disease activity index (DAI). Mice were sacrificed on day 27 for histology. TNFΔARE Ileitis:8-10 wk old TNFΔARE mice were treated with daily oral TP-317 at 0.04, 0.4 and 4 mg/kg for 14 days (n=3/group). On Day 13, mice were administered FITC-Dextran (0.4 g/kg/d) by oral gavage and blood drawn after 4 hrs to measure intestinal permeability. Animals were sacrificed on day 14, intestinal tissue was harvested and cytokine levels were measured in whole tissue lysates by ELISA; disease activity was scored by histology. Results In DSS colitis, 0.4 mg/kg TP-317 showed similar efficacy to cyclosprin and filgotinib in reducing DAI scores. Overall histology scores (a composite of inflammation severity, inflammation depth and crypt loss) were reduced by 14% (NS), 22% (NS) and 33% (p<0.01) by 0.04, 0.4 and 4 mg/kg TP-317, respectively, compared to 33% (p<0.01) for cyclosporin and 44% (p<0.001) for filgotinib. All doses of TP-317 significantly reduced Crypt Damage score (34%, 37%, 39%), showing greater effects than cyclosporin or filgotinib. In TNFΔARE ileitis, TP-317 treatment was associated with reduced intestinal permeability and disease activity, while reducing pro- inflammatory IL-17 and increasing anti-inflammatory L-10 in mucosal tissue. Conclusion Oral TP-317 demonstrates anti-inflammatory, mucosal immuno-modulatory and epithelial barrier protective actions in preclinical colitis and ileitis. These findings align with reports of have exacerbated DSS colitis in BLT1-/- mice and RvE1’s promotion of BLT1-dependent wound repair in an in vitro model using human intestinal epithelial cells.1 2 Together, these studies support positioning of TP-317 as a novel, oral BLT1 agonist for treating ileal and colonic disease in IBD patients. References 1 Jala VR, Maturu P, Bodduluri SR, Krishnan E, Mathis S, Subbarao K, Wang M, Jenson AB, Proctor ML, Rouchka EC, Knight R, Haribabu B. Leukotriene B4-receptor-1 mediated host response shapes gut microbiota and controls colon tumor progression. Oncoimmunology. 2017 Aug 10;6(12):e1361593. PMID 29209564 2 Hayashi S, Muraleedharan CK, Oku M, Tomar S, Hogan SP, Quiros M, Parkos CA, Nusrat A. Intestinal epithelial BLT1 promotes mucosal repair. JCI Insight. 2022 Dec 8;7(23):e162392. PMID 36301666

P0725 The fragility of randomized clinical trials in evaluating novel therapies for Inflammatory Bowel Disease

Abstract Background Numerous randomized clinical trials (RCTs) have evaluated novel therapies for inflammatory bowel disease (IBD). However, these trials often rely solely on P values to determine treatment efficacy, which may not fully capture the robustness of the results. This study aimed to evaluate the fragility of these RCTs and to identify study characteristics that influence result stability. Methods A search for RCTs assessing the efficacy of novel IBD therapies, including biologics, small molecule inhibitors, fecal microbiota transplantation, and stem cell therapies, was conducted in PubMed and Web of Science from January 1, 2014, to November 10, 2024. Included RCTs were required to report at least one statistically significant result (P <0.05) and employ an equal randomization design. The FI and continuous FI (CFI) were computed for binary and continuous outcomes, respectively, as reported in previous studies1, 2. We used Wilcoxon rank-sum and Kruskal-Wallis tests for dichotomous and multi-categorical characteristics, respectively, and Spearman’s rank correlation for continuous characteristics. Multiple linear regression was used to further explore the impact of study characteristics on FI. Results A total of 129 trials from the 53 studies were analyzed. The median FI was 6, and the CFI was 14.8. FI varied significantly by treatment types, trial phases, outcome types, and reported P values. The total sample size (ρ = 0.734) and number of discontinuations (ρ = 0.479) exhibited strong and moderate positive correlations with FI, respectively, while publication year, impact factor, and events percentage showed weak positive correlations. CFI was significantly influenced by outcome types, and moderate and strong correlations were observed with journal impact factor (ρ = 0.426) and sample size (ρ = 0.757), respectively. After adjusting for other characteristics, the association between treatment type (biologics or small molecule drugs vs. fecal microbiota transplantation or stem cell therapy) and the natural logarithm of FI remained statistically significant (B = 0.283). Primary or coprimary outcome showed greater robustness compared to other outcomes in both the FI (B = 0.288) and CFI models (B = 0.459). Sample size was positively associated with both the natural logarithm of FI (B = 0.001) and CFI (B = 0.001), while the per protocol analysis demonstrated a negative association (B = -0.929). Conclusion RCTs evaluating novel IBD therapies show varying levels of robustness, influenced by multiple study characteristics. Fragility should be considered in future research when interpreting the efficacy.

P0922 Usefulness of Ustekinumab levels in clinical practice: a single center experience

Abstract Background Drug monitoring is a valuable resource in Inflammatory Bowel Disease (IBD) management. However, evidence regarding Ustekinumab (UTK) utility in clinical practice is scarce as the optimal therapeutic levels and strategy after their determination have not been clearly established so far. Methods Single-center retrospective study of IBD patients treated with UTK in whom drug levels were measured during maintenance, between October 2021-August 2024. UTK dose was defined as standard: 90 mg subcutaneously (sc)/8-12 weeks or intensified: 90 mg sc/<8 weeks or 130 mg intravenously (iv)/any frequency. UTK levels were measured using ELISA technique (μg/mL). Since there is no specific protocol in our center, patients were divided into two level determination strategies: reactive (patient with clinical and/or biochemical activity) and proactive (remission patients). The endpoint was to evaluate the utility of UTK levels in guiding therapeutic decisions. To guide our clinical decisions, we have based on the recommendations from the GETECCU 2024 consensus document. Results Seventy-four patients were included (Table 1). They had been on UTK therapy for a mean of 42 (±21) months (35% with intensified dose: 81% sc/19% iv). Level strategy was reactive in 74% (disease activity: 20% clinical, 22% biochemical, 58% both) and proactive in 26%. In reactive strategy, UTK was intensified in 65% of cases (56% with UTK level <1.5, 36% 1-3); unchanged in 20%, with UTK level >1.5 in 82% of them, considering acceptable disease control with therapeutic levels; and discontinued in 15%, all with UTK level >3, assuming that intensification would not provide benefit. Among patients with UTK intensification, response/remission was achieved in 39%/42%, after a median of 132 (110-172) days. In the proactive group, 68% of cases were on intensified UTK, measuring levels to assess whether UTK could be de-escalated. After level determination, UTK dose was modified in 58%: spaced out in 53% (all with UTK level >3) and intensified in 5.3% (UTK level <1.5) (Figure 1). Overall, level determination had a clinical impact in 70% of patients, influencing the therapeutic decision in 75% of reactive strategy and guiding the maintenance dose adjustment in 58% of proactive strategy. At the end of the study, 82% of patients remained on UTK (95%/78% on proactive/reactive strategy), after a median follow-up of 12 (5-28.5) months. Conclusion Drug level determination is a useful tool in optimizing UTK therapy in IBD, both guiding clinical decisions in active disease and monitoring during remission. It allows candidate selection for intensification and de-escalation, maintenance or treatment discontinuation. References Rodríguez-Moranta F et al. Therapeutic drug monitoring in inflammatory bowel diseases. Position statement of the Spanish Working Group on Crohn’s Disease and Ulcerative Colitis. Gastroenterología y Hepatología 2024.

P0276 Psoriasis is more frequently induced and displays a distinct phenotype in patients with Inflammatory Bowel Disease.

Abstract Background Specific psoriasis (Pso) phenotypes seem to emerge in inflammatory bowel disease (IBD) patients. Our study explored Pso phenotypes under and outside biologic therapy in IBD, comparing them to those in chronic inflammatory rheumatism (IRD). Methods From a prospective university hospital cohort of patients with IBD, IRD, and Pso, we selected those with IBD and/or IRD (axial and peripheral spondyloarthritis or rheumatoid arthritis) associated with Pso, excluding psoriatic arthritis cases. Each case was reviewed to classify psoriasis as therapy-induced or not, define prevalence with phenotype description, examine treatments responsible for induced Pso, and assess risk factors for therapy-induced Pso in IBD. Results Among 2,412 patients in the database, 237 (9.8%) had psoriasis associated with IBD and/or IRD: 98 with IBD, 110 with IRD, and 29 with both IBD and IRD. Pso prevalence was 12.1% in IBD vs. 8.5% in IRD (p=0.0056). After analysis, 92 (93.9%) IBD and 86 (78.2%) IRD patients had been exposed to systemic therapy (p=0.0013). The mean age for IBD+Pso and IRD+Pso was 46.4 (±15.8) and 52.8 (±15.5) years, respectively (p=0.0034); 62 (63.3%) and 49 (45%) were women (p=0.0083). Phenotypic details of Pso were available in 97/98 IBD and 90/110 IRD cases: 70 (71.4%) vs. 33 (30%) were therapy-induced Pso, respectively (p<0.0001). The main systemic therapy linked to induced Pso was biologics: adalimumab in 44 (62.9%) IBD and 15 (45.5%) IRD patients (p=0.0957). Plaque and inverse psoriasis were noted in 72 (73.5%) and 39 (39.8%) IBD vs. 53 (48.2%) and 6 (5.4%) IRD patients (p=0.0002 and p<0.0001). Lesions appeared on the face in 26 (26.5%) IBD vs. 6 (5.4%) IRD (p<0.0001), on the scalp in 40 (40.8%) IBD vs. 30 (27.3%) IRD (p=0.0391), and on nasal wings in 13 (13.3%) IBD patients only (p<0.0001), suggesting this as a specific site. In IBD, inverse and scalp Pso were more frequent in therapy-induced cases. Regarding Pso treatments, biologic therapy was discontinued in 13 (13.3%) IBD patients vs. 2 (1.8%) IRD patients (p=0.0014), and a swap out of biologic class was made in 32 (32.7%) IBD patients vs. 5 (4.5%) IRD patients (p<0.0001). Factors associated to therapy-induced Pso in IBD were active smoking (OR= 2.02, 95% CI [1.14–3.56], p=0.0193), inflammatory phenotype in Crohn’s disease (OR=1.94, 95% CI [1.21;3.10], p=0.0047), and female sex (OR=2.04 [1.25–3.31], p=0.0041). Conclusion In this large cohort, Pso prevalence in IBD was high, with therapy-induced Pso being more frequent among women and smokers. Specific phenotypes were observed (induced, inverse, scalp, nasal wings), suggesting a common pathophysiology with the underlying inflammatory disease.

P1158 Patients with refractory and difficult-to-treat Inflammatory Bowel Disease are underrepresented in randomized clinical trials

Abstract Background A significant proportion of patients with inflammatory bowel disease (IBD) do not respond to treatment. Recently, criteria to define difficult-to-treat (DTT) IBD have been proposed1. These include IBD refractory to at least 2 advanced therapies with different mechanisms of action. We aim to review the representation of patients with prior exposure to biologics, DTT-IBD, and other challenging phenotypes in randomized clinical trials (RCTs). Methods A scoping review was performed by reviewing all RCTs of advanced therapies in IBD. We updated the literature searches of two published systematic reviews of ulcerative colitis (UC)2 and Crohn’s disease (CD)3 searching MEDLINE, EMBASE, and the Cochrane Library up to December 2023. Results We included 140 RCTs, 73 in ulcerative colitis (UC), and 67 in Crohn’s disease (CD), comprising 44.799 patients. In UC, 53% (39/73) of studies included patients with prior exposure to other biologics, but only 19% (14/73) included patients exposed to two or more biologics. Moreover, only 5% (4/73) of studies included participants exposed to biologics with multiple mechanisms of action, or DTT, and these accounted for 2% of the total participants of UC RCTs. None of the trials reported efficacy results specific for DTT. In CD, 60% (47/67) of studies included patients with any prior biologic exposure, and 31% (21/67) allowed the participation of patients who received two or more biologics. Only one study (1.5%) reported efficacy results for patients exposed to multiple mechanisms of action, DTT-IBD, which accounted for 7.4% of the study participants and 0.1% of all those in CD trials. In CD, history of prior intestinal surgery was reported only in 28 of 67 studies (42%) for 2977 patients, or 14.5% of the total participants. Similarly, upper gastrointestinal involvement of CD was included only in 21 trials (31%) and present in 808 participants (3.9%). Instead, the majority of trials either excluded patients with locations proximal to the terminal ileum (35 RCTs; 52%) or did not report whether some participants had upper gastrointestinal locations (11 RCTs; 16%) In both UC and CD there was a trend towards greater inclusion of exposed and refractory patients in recent years. Conclusion Patients exposed to multiple advanced therapies and those with phenotypes of CD more challenging to manage remain underrepresented in clinical trials of IBD.

P0709 Patient Satisfaction with Subcutaneous versus Intravenous Vedolizumab: A Prospective Observational Study

Abstract Background Vedolizumab (VDZ) is a selective biologic agent that is available in both intravenous (IV) and subcutaneous (SC) forms for maintenance treatment. The SC route offers advantages such as the convenience of self-administration, although some patients may prefer the IV route. The aim of our study was to determine patients’ preferences and satisfaction with their treatment when switching to VDZ SC or continuing with an IV administration. Methods A prospective, observational study was conducted in patients with inflammatory bowel disease (IBD) receiving VDZ IV who were in clinical remission. Patients had the option to continue with VDZ IV or switch to SC and were grouped according to their preference. A baseline visit (before the switch) and another at 24 weeks were conducted. During both visits, patients completed the treatment satisfaction questionnaire (SATMED-Q) and quality of life questionnaire (IBDQ9). Clinical activity, treatment adherence, adverse effects, general bloodwork, and fecal calprotectin were also analyzed. Results Forty-one IBD patients were included, 43% of which were women, and 63% had ulcerative colitis. Almost half (41%) continued with VDZ IV while 59% switched to SC. There were no differences in gender, type, or characteristics of IBD between the groups. However, the age of patients in the SC group was significantly younger than that of the IV group (median 46 [32-63] vs. 66 [59-77] p=0.03). Fewer patients in the SC group had previously received IV biologics (SC 31% vs. IV 69%, p=0.012). The median SATMED-Q before the switch was lower in the SC group (SC 53 [40-61] vs. IV 61 [46-64], p=0.032), as was the IBDQ9 (SC 65.5 [59.4-68.5] vs. IV 70.8 [68.5-77.1], p=0.037). At 24 weeks, there were no differences in SATMED-Q or IBDQ9 scores or disease clinical activity. Drug persistence and frequency of adverse events were similar in both groups. Vedolizumab levels increased significantly in the SC group at 24 weeks (p=0.041). Conclusion Switching to VDZ SC showed similar treatment satisfaction to VDZ IV at 24 weeks in IBD patients, with comparable clinical outcomes and safety profiles. There was a clear preference for subcutaneous administration among younger patients and those without previous IV treatment. This suggests that patient demographics and prior treatment experiences can influence the choice of administration route. The lack of significant differences in clinical outcomes, quality of life scores, and treatment satisfaction between the SC and IV groups at 24 weeks highlights the clinical equivalence of these two administration routes for maintenance therapy in IBD.

P0953 Real world effectiveness and safety of filgotinib in Ulcerative Colitis: 1 year follow-up results of the ICC registry

Abstract Background Filgotinib is a preferential JAK1-inhibitor approved for the treatment of ulcerative colitis (UC). The ICC registry was developed to evaluate the effectiveness and safety of advanced therapies in inflammatory bowel disease (IBD). Here, we report the one-year follow-up results of filgotinib in patients with UC. Methods Fourteen hospitals prospectively enrolled UC patients initiating filgotinib in the Dutch ICC registry. Treatment persistence was assessed by Kaplan-Meier survival analysis. Clinical remission (i.e. Simple Clinical Colitis Activity Index [SCCAI] ≤ 2) and corticosteroid-free clinical remission rates were assessed at 12, 24 and 52 weeks for all patients who were not in remission at baseline, based on SCCAI score, faecal calprotectin and/or endoscopy. Patients lost to follow up were considered as treatment failure. Reasons for treatment discontinuation and adverse events were recorded. Results Eighty-three UC patients (47% females) were enrolled between January 2022 and October 2023. Mean age and disease duration at baseline were 41 [sd ± 16] and 12 years [sd ± 9], respectively. A total of 49 (59%) patients had used up to two advanced therapies and 34 (41%) patients had used three or more. At baseline, 75 patients (90%) had active disease of whom 24 (32%) used oral corticosteroids. After one year of follow-up, 58.8% of patients still used filgotinib (Figure 1). At week 12, 24 and 52, corticosteroid-free clinical remission rates were 57.1%, 32.7% and 34.6% respectively (Figure 2). Reasons for treatment discontinuation were primary non-response (n=17), secondary loss of response (n=13), side effects (n=3) or other reasons (n=4). Fifty-seven adverse events were recorded (19 infections). Ten infections required treatment with antibiotics or antiviral therapy, none of them led to hospitalization or therapy discontinuation. No thromboembolic events were reported. Conclusion The results of this real world study show that, even in a therapy-refractory UC population with an average disease duration of 12 years, more than half of the patients still used filgotinib and one third of patients was in corticosteroid-free clinical remission after one year of follow-up. No new safety signals were found.

P0858 Rate of participation in a second randomized clinical trial and factors associated with the likelihood of participation among inflammatory bowel disease patients who already experienced a randomized clinical trial

Abstract Background The development of new therapies in inflammatory bowel disease (IBD) has become increasingly difficult, partly due to challenges in recruiting patients for clinical trials. In the last 20 years, the average recruitment for IBD-trials has decreased to approximately 0.1 patients per site per month. The aim of our study is to assess the rate of participation in a second trial in IBD patients who already experienced a clinical trial and to investigate factors that are associated with a patient’s likelihood of participating in a second clinical trial. Methods This is a single-center, retrospective study. We included IBD patients who participated in at least one for-profit randomised clinical trial at the IBD centre of IRCCS Humanitas Research Hospital (Milan, Italy) between 2015 and 2024. Results 293 patients were included. Baseline demographic and clinical characteristics are shown in Table 1. After the end of the 1° trial, patients were followed for a median of 30 months (range 1-169). During the follow-up, 85 (29.0%) participated in a second trial. In the multivariate analysis, a distance from home to the IBD clinic > 100 km (OR 0.556, 95% CI 0.326-0.983, p=0.043) and being in clinical remission at the end of the first trial (OR 0.567, 95% CI 0.324-0.991, p=0.046) were significantly associated with a lower likelihood of participating in the second trial. Conclusion Approximately one third of patients participated again in a second clinical trial. Long distance from the IBD clinic and remission at the end of the first trail reduce the probability of participation in the second trial. Understanding the factors that hinder or promote participation in IBD clinical trials is crucial for enhancing patient involvement in research.

P0603 The real-world use of intravenous and subcutaneous Vedolizumab in IBD across Australia and New Zealand, Crohn’s Colitis Cure Data Insight’s Program

Abstract Background Vedolizumab, an established therapy for inflammatory bowel disease (IBD), has been proven to be effective in both intravenous (IV) and subcutaneous (SC) formulations. This study aims to understand the patterns of use of both formulations in real world clinical care. Methods Crohn’s Colitis Care (CCCare) is a cloud-based IBD-specific electronic medical record used in Australia (AUS) and New Zealand (NZ). Data feed into a de-identified clinical quality registry (CQR), which was interrogated in August 2024. We examined the real-world use of Vedolizumab in people with IBD under usual ambulatory care. People with Crohn’s Disease (CD) or Ulcerative colitis (UC) with a clinical assessment ever recorded were included. Results Of 8,724 eligible people with IBD, 13.6% (n=1,187) have ever received Vedolizumab, 734 (61.8%) of whom have UC and 453 (38.2%) have CD. The median age was 42 years (IQR 31 – 56), and the median disease duration was 11.1 years (IQR 5.6 – 19.1). There was an even gender distribution with 50.0% (n=593) male. The majority of people resided in AUS (n=1,117, 94.1%) with 5.9% (n=70) in NZ. A higher proportion of people with UC have received vedolizumab compared to those with CD (19.5% vs 9.1%, p<0.001). In those where residential location was documented, Vedolizumab was more frequently used in people residing in a metropolitan compared to a non-metropolitan area (n=875, 15.2% vs n=177, 10.7%, p<0.001). In those currently receiving Vedolizumab (n=541), there was no difference in the formulation used across metropolitan and non-metropolitan areas (72.9% IV vs 71.3% IV, p=0.75). Of those who ever received maintenance IV Vedolizumab (n=1,015), only 59 people (5.8%) have switched to SC Vedolizumab. The median duration on IV before switching was 97 weeks (IQR 59.5 – 217.8). There was no difference in the rate of IV to SC switching in CD compared to UC (4.9% vs 6.4%, p=0.34). Of those who ever received maintenance IV Vedolizumab, 161 (15.9%) were on dose escalated (DE) therapy. The proportion of people on DE Vedolizumab did not differ between CD and UC (13.2% vs 17.5%, p=0.07). Conclusion In this large, real-world data of people with IBD, Vedolizumab has been used in 13.6% of the cohort, more often in people with UC compared to CD. The majority of people receiving Vedolizumab remain on IV formulation with only a small subset of people changing to, or established on, SC route. SC formulations have the potential to reduce the patient’s burden of disease by reducing travel costs and time out of role, promoting autonomy and empowering people living with IBD. However, in the absence of economic incentive or policy change, there will remain inertia to change to SC formulation.

N28 The UK Inflammatory Bowel Disease Reasearch Network ; Preliminary results from advanced therapies in Inflammatory Bowel Disease a multi-centre evaluation of current practice

Abstract Background In early 2024, 25 research-ready nurses specialising in IBD joined the United Kingdom IBD Nurse Research Network (UK IBD NRN). This network is dedicated to collaborating on national service evaluation and research initiatives, aiming to enhance service delivery and improve patient experiences within IBD care. Each year, the network will undertake one project, with a ballot for ideas held towards the end of the project. The first initiative focuses on monitoring advanced therapies (AT-IBD) used in the UK for treating IBD. Current recommendations for monitoring advanced therapies in IBD remain ambiguous, and the efficacy of proactive therapeutic drug monitoring (TDM) is still uncertain. To address this, we sought to explore the variations in monitoring practices across IBD services in the UK, focusing on key areas such as access to medication, adherence to monitoring protocols, and the effectiveness of therapeutic drug monitoring. Methods Data collection instruments using REDCap were created and launched in November 2024. Data includes site demographics, a minimum of ten and a maximum of 25 reactively and proactively monitored cases. The case data is collected from retrospective monitoring events and anonymised. Descriptive statistics are used to report results. Results Seventeen unique users are entering data from 15 sites. The survey is open to all four nations of the UK. Responses have been received in England and Wales. Of the 17 users (15;82.4%) reported having had training to interpret blood results. IBD patient population was reported by seven out of eleven sites, with a total of 39,843 reported. Two sites shared the entire local population, and three were reported as unknown. The seven sites that reported the IBD patient population used an electronic health record. There is variance in the pre-screening undertaken (Figure 1); access to advanced therapies appears different, with some sites not having access to newer small-molecule medications (Figure 2). There is wide variation in routine and TDM frequency across all therapies. Conclusion The AT-IBD project is ongoing, with full results anticipated to provide insights into current practices for monitoring advanced therapies in the UK. The collected data may offer valuable insights regarding adherence and the effectiveness of advanced therapy monitoring, particularly concerning patient safety and outcomes. The UK IBD NRN remains committed to providing opportunities for training, collaboration, and research for IBD nurses across the UK.

P0523 Comparative analysis of two ELISA methods for measuring serum ustekinumab levels in Inflammatory Bowel Disease ¿Is interchangeability feasible?

Abstract Background Ustekinumab (UTK) is a recently introduced biologic therapy for inflammatory bowel disease (IBD), and consequently, the clinical use of UTK trough concentrations is less standardized compared to other biologic therapies. Therefore, accurate measurement of serum UTK levels is essential for adjusting treatment efficacy. The objective of the present study is to compare two enzyme-linked immunosorbent assay (ELISA) methods to evaluate their correlation, concordance, and systematic bias, given the variability between methods. Methods The study assessed the correlation and the agreement between two different methods available for UTK measurement. Thirty-six blood samples from different patients, which had a previous diagnosis of IBD, were analyzed. All patients were recruited from September to November 2024 from the autoimmunity laboratory of the Hospital Universitario 12 de Octubre, Madrid. Serum UTK levels were measured using the two ELISA techniques: IDKmonitor® ELISA assay (Immundiagnostik AG; Bensheim, Germany) (T1) and the alternative Promonitor® ELISA assay (Grifols; Barcelona, Spain) (T2). Measurements were further categorized into therapeutic ranges for response classification: non-responders (0–1 µg/mL), clinical response (1–4.5 µg/mL), and endoscopic response (>4.5 µg/mL). Results A strong linear correlation was observed between the two methods (Pearson’s r = 0.9693, p < 0.0001, R² = 0.9395), confirming a proportional relationship despite systematic differences. Lin’s concordance coefficient was moderate-to-good (0.7025), indicating agreement despite systematic differences. Bland-Altman analysis revealed a mean difference of 2.79, with increasing variability at higher concentrations, consistent with proportional error. Passing-Bablok regression revealed a systematic bias, indicating an overestimation by the Promonitor-Grifols ELISA: the slope was 1.4342 (95% CI: 1.2530–1.6387) and the intercept 1.2591 (95% CI: 0.7591–1.8309). Considering these results, a linear regression adjustment was conducted. Categorization into therapeutic ranges revealed poor concordance between the methods (Kappa index = 0.28), suggesting that systematic errors substantially affect clinical interpretation. T2 consistently assigned higher therapeutic ranges, potentially impacting treatment decisions. Conclusion While the two ELISA methods show strong correlation, moderate concordance and significant systematic biases limit their interchangeability. Adjustment strategies should be adopted to harmonize results and ensure reliable therapeutic decisions in IBD management. References - Kwon Y, Kang B, Kim ES, Choe YH, Kim MJ. Comparison of Ustekinumab Trough Concentrations Measured by 2 ELISA Kits and Evaluation of Clinical Response in Crohn’s Disease. Ther Drug Monit. 2022;44(4):535-542. doi:10.1097/FTD.0000000000000976 - Rodríguez-Moranta F, Argüelles-Arias F, Hinojosa Del Val J, et al. Therapeutic drug monitoring in inflammatory bowel diseases. Position statement of the Spanish Working Group on Crohn’s Disease and Ulcerative Colitis (GETECCU). Gastroenterol Hepatol. 2024;47(5):522-552. doi:10.1016/j.gastrohep.2024.01.007

P0837 Prevalence of the HLA-DQA1*05 phenotype in a cohort of Spanish patients with Inflammatory Bowel Disease, and its association with the response to first anti-TNF therapy in real-world settings

Abstract Background Anti-tumor necrosis factor (anti-TNF) drugs usually represent the first line of biological therapy in inflammatory bowel disease (IBD) patients. The presence of the HLA-DQA1*05 allele has been linked to a higher risk of immunogenicity and the development of anti-drug antibodies. This condition may increase the likelihood of primary treatment failure or loss of response to anti-TNF medications. However, clinical data on this topic are scarce and often contradictory. Methods Prospective, single-center cohort study in bio-naive IBD patients receiving the first anti-TNF medication for IBD activity from 1 January 2020 to 31 December 2023. PCR-SSP using the HLA-Ready Gene Coeliac Disease kit detected the DQA1*05 allele in a saliva sample. The result was positive if the DQA1*05:01:01,03 or DQA1*05:01:01,05,08 alleles were present. Patients were followed from first dose to discontinuation or last visit. The primary endpoint was anti-TNF persistence, considering as treatment failures, IBD patients with primary or secondary loss of response, and anti-TNF discontinuation due to adverse events. An appropriate statistical analysis was performed using survival Kaplan-Meier curves to assess anti-TNF persistence. Results We included 209 patients:108 men (51.7%), mean age 43.5 (17) and time since diagnosis 6.5 (10) years. Ulcerative colitis 39.2% and Crohn´s Disease 60.8%. As the first anti-TNF, 107 patients received adalimumab (51.2%) and 101 infliximab. Baseline demographics for the cohort are summarized in Table 1. At anti-TNF initiation, 29.2% and 58% of patients were on immunosuppressants and systemic steroids, respectively. HLA-DQA1*05 was determined in 205 patients with 38.8% (81) positive, 54.5% (114) negative and 4.8% (10) null results. HLA carriers did not differ according to gender, age or IBD clinical phenotype. A total of 87 patients (41.6%) discontinued treatment during a median follow-up of 22.3 (10-36) months, mostly infliximab 59,3% vs 41% (p=0.009). At 12 and 24 weeks, primary anti-TNF failure was reported in 24 (11.5%) and 34 (16.3%) patients, respectively. Anti-TNF was discontinued in another 23 patients (11%) because of loss of response and in 22 (10.5%) for serious adverse events, mainly infusion reactions (5.7%). The mean persistence of first anti-TNF was similar in allele carriers 36.7 CI95%(31.5-41.9) versus naive 33.8 CI 95%(29.6-38.1) months (Figure 1). Conclusion HLA-DQA1*05 ihaplotype is carried by 40%, of bio-naive Spahish IBD patients, a similar prevalence to that obtained in other western IBD populations. HLA-DQA1*05 carrier status was not associated with IBD clinical phenotypes or persistence on the first anti-TNF treatment. References Spencer EA, Stachelski J, Dervieux T et al. Failure to achieve target drug concentrations during induction and not HLA-DQA1∗05 carriage is associated with antidrug antibody formation in patients with Inflammatory Bowel Disease. Gastroenterology. 2022;162(6):1746-48. Pascual-Oliver A, Casas-Deza D, Cuarán C et al. HLA-DQA1*05 was not associated with primary nonresponse or loss of response to first anti-TNF in real-world Inflammatory Bowel Disease patients. Inflamm Bowel Dis.2024; 3:30 (6):922-929.

P0007 mAb-based targeting of the eAGR2-Fibrinogen interaction as a promising new therapy in Inflammatory Bowel Disease

Abstract Background Historically, Fibrinogen (Fg) is known to be crucial in IBD by aiding fibrin deposition, which leads to scar tissue formation and tissue remodeling. High Fg levels in IBD foster chronic inflammation, activate fibroblasts, stimulate extracellular matrix production, promote fibrosis, and hinder normal mucosal repair. Recently, Anterior Gradient 2 (AGR2), an endoplasmic reticulum chaperone protein that is expressed by mucin-secreting epithelial cells, is secreted (eAGR2) under stress and contributes to a plethora of pathogenic processes (e.g. epithelial integrity disruption, monocyte attraction, fibroblast activation, and oncogenesis). AGR2 overexpression in the colon of IBD patients correlates with disease severity and activity. The present report identifies the eAGR2-Fg physical interaction, which opens new therapeutic avenues in IBD care. Methods CoIP-MS was used to identify interactors of eAGR2 in Caco2 supernatant. The binding between AGR2 and interactors was orthogonally validated using ELISA and abrogated by proprietary anti-eAGR2 mAb (TH-009). The efficacy of TH-009 in preventing the development of fibrosis was assessed using a murine chronic DSS model of colitis. Results IP-MS identified the three Fg subunits as the most abundant eAGR2 interactors in the Caco-2 supernatant. This interaction decreased fourfold with anti-eAGR2 mAbs. ELISA confirmed the specific binding of Fg to AGR2 (p<0.01), which was abrogated by TH-009 in a dose-dependent manner (p<0.001). In a murine chronic DSS model of colitis, multiple features of inflammation and fibrosis went down significantly when treated with TH-009, and anti-inflammatory molecular signature was promoted. For example, fibrosis was decreased by two-fold in TH-009 treated mice compared to that in the untreated DSS group (p<0.001). Also, collagen deposition and aSMA were decreased by 2.4 and 17-fold, respectively (p<0.001). At the mRNA level, a 2-fold decrease of TGFb, and fibronectin and a 3-fold decrease of ColA1 were observed (p=0,05; p<0.05 and p<0.01). Conclusion We identified Fg as a central eAGR2 partner and showed that this interaction was disrupted by the anti-eAGR2 mAb. Our results may suggest that eAGR2 binding to Fg impairs the fibrinogen-fibrin maturation cycle, thus maintaining the deleterious signaling observed in IBD. Considering the TH-009 efficacy in preventing fibrosis in vivo, our results support the therapeutic interest of targeting the eAGR2-Fg complex in IBD and other mucosal inflammatory diseases.

P1181 Liver fibrosis predicts response to advanced therapy in inflammatory bowel disease: a new personalized treatment approach?

Abstract Background Crohn's disease (CD) and ulcerative colitis (UC) are chronic and progressive inflammatory bowel diseases (IBD). It is estimated that up to 30-50% of patients with IBD develop intestinal fibrosis leading to complications such as strictures. Liver fibrosis occurs up to 16.7% of patients with IBD. However, the impact of liver fibrosis on the response to therapy in patients with IBD is unknown. Our aim was to investigate the association between liver fibrosis before starting an advanced therapy and response to treatment in IBD. Methods We conducted a retrospective analysis of data that were prospectively gathered from consecutive patients with a confirmed diagnosis of UC or CD, spanning from November 2021 to December 2023. All patients who started an advanced therapy (biological therapy and small molecule drugs) and had transaminase concentrations, body mass index (BMI), history of diabetes, and platelet counts available were eligible. Several scores of liver fibrosis were measured including AST/ALT ratio (AAR), AAR platelet ratio index (AARPRI)1, AST to platelet ratio index (APRI), body mass index AST/ALT ratio and diabetes mellitus score (BARD), fibrosis index based on four factors (FIB -4)2, and modified FIB-4 (m-FIB4)3. All available clinical (partial Mayo score, PMS, for UC and Harvey-Bradshaw index, HBI, for CD), biochemical (fecal calprotectin, FC), and endoscopic (endoscopic Mayo score for UC and simple endoscopic score for Crohn's Disease (SES-CD) and Rutgeert’s score for CD) data at 6 months were collected. A logistic regression multivariate analysis was performed to identify any correlation between scores of liver fibrosis at baseline and response to advanced therapies. Analyses were subjected to correction using the false discovery rate (FDR) method. Results In total, 122 patients were included in the analysis. Patient key demographic and treatment information as well as clinical remission, FC normalization and endoscopic remission at 6 months are summarized in table. Two UC patients (2.7%) were hospitalized. Five patients (4.1%) underwent surgery (2 UC-related and 3 CD related). No cases of neoplasia or death occurred. In the multivariate analysis, mFIB-4 at baseline was a predictor of clinical activity at 6 months in CD (FDR=0.08), while AARPRI at baseline predicted clinical activity at 6 months in UC (FDR=0.08) (Figure). Conclusion Patients with IBD and concomitant liver fibrosis have a lower rate of clinical remission after 6 months of advanced therapy. Scores of liver fibrosis could predict the response to therapy. Further prospective studies are warranted to implement their use in clinical practice