Harvey-Bradshaw Index Score Research Articles

Impact of Clinical Pharmacists in the Inflammatory Bowel Disease Clinic

Background: Limited evidence exists regarding pharmacist involvement and impact in inflammatory bowel disease (IBD) interdisciplinary clinic care models. The purpose is to describe pharmacist utilization in an interdisciplinary IBD clinic and evaluate clinical impact on patient quality of life. Methods: This was a retrospective cohort study comparing outcomes in patients with Crohn’s disease initiated on therapy when the implementation of pharmacy services began (Early Phase) to the expansion of pharmacy services (Recent Phase). The primary outcome compared the proportion of patients referred to a pharmacist and those achieving a Harvey-Bradshaw Index (HBI) reduction of ≥3 points after therapy initiation. Results: 50 patients were included in the Early Phase and 43 patients in the Recent Phase. Utilization in pharmacy referrals increased from 48% (n = 24) in the Early Phase to 72% (n = 31) in the Recent Phase (P = 0.03). The proportion of patients achieving a HBI reduction of ≥3 points increased from 35% (n = 14) in the Early Phase to 51% (n = 18) in the Recent Phase (P = 0.23). Results also found a greater proportion of patients remaining steroid free in the Recent Phase compared to the Early Phase (50% vs 63%; P = 0.01) and C-reactive protein (CRP) improved significantly in the Recent Phase (−11) compared to (−3) in the Early Phase (P = 0.006). Conclusion: The utilization of pharmacists in an interdisciplinary IBD clinic increased and showed to impact patient care through improving symptom relief as seen by the achievement rate of the HBI score reduction, reducing steroid use after therapy initiation, and making clinically significant interventions.

P1056 Effectiveness and Safety of Upadacitinib Induction Therapy in Real-World Setting for 234 Patients with Crohn’s Disease: A GETAID Multicentre Cohort Study

Abstract Background While upadacitinib has demonstrated its efficacy as an induction treatment for Crohn’s disease (CD) in two phase 3 randomized, placebo-controlled trials1, real-world data remain limited. Methods From September 2022 to September 2024, all consecutive patients with refractory CD treated with once-daily upadacitinib 45 mg in 30 French and Belgian GETAID centres were retrospectively included. The primary endpoint was steroid-free clinical remission (SFCR) at week 12, defined as a Harvey-Bradshaw Index (HBI) score of < 4. Secondary endpoints included clinical response (decrease of ≥ 3 points in the HBI score and/or an HBI score < 4), clinical remission, biological remission (calprotectin ≤ 250 µg/g, or CRP ≤ 5 if calprotectin was unavailable), endoscopic or radiological (IUS and/or MRI) response, and adverse events (AEs). Results 234 patients were included, all of whom had been previously exposed to at least one biologic (median 4, IQR[3-4]), and 125 (53.9%) had undergone prior intestinal resection (Table 1). At week 12, SFCR was observed in 107 patients (n=107/197, 54%), clinical response in 120 (n=120/190, 63%) and clinical remission in 111 (n=111/197, 56%). Ninety-two (n=92/179, 51%) achieved biological remission and endoscopic or radiological response was observed in 19 (n=19/40, 48%) patients (Figure 1). Respectively 28 (n=28/37, 76%) and 20 (n=20/37, 54%) of patients with articular EIMs achieved clinical response and remission. For cutaneous EIM, clinical response was achieved in 10 patients (n=10/11, 91%), and clinical remission was achieved in nine patients (n=9/11, 82%). In multivariate analysis, body mass index < 18.5 kg/m2 (OR=0.09, 95%CI: 0.01-0.33, p=0.002) and HBI > 7 (OR=0.24, 95%CI: 0.12-0.47, p<0.0001) were associated with lower rates of SFCR at W12 while the number of prior biologics did not influence SFCR (OR = 0.72, 95% CI: 0.35-1.48; p = 0.36). At week 12, 35 (15%) patients discontinued upadacitinib (lack of effectiveness, n=31; AEs, n=2 and other, n=2). CD-related hospitalization was needed in 18 (7.7%) patients, and 4 (1.7%) underwent intestinal resection. Sixty-eight AEs occurred in 61 patients (26%), including 19 serious AEs, corresponding to 18 cases of CD exacerbation and one case of colonic EBV-associated lymphoproliferative disorder. Acne was observed in 25 (10.7%), justifying treatment discontinuation in one (0.4%). Conclusion In this real-world cohort of highly refractory CD patients, upadacitinib induction resulted in a clinical response in about two-thirds of patients and SFCR in half of patients.

P0971 Effectiveness of Vedolizumab in Bio-Naïve Chinese Patients with Crohn’s Disease: A Subgroup Analysis of Second Interim Analysis of the VALUE Study

Abstract Background Vedolizumab (VDZ) is a humanized monoclonal antibody, that selectively targets α4β7 integrin and is approved for Crohn’s disease (CD) and Ulcerative colitis (UC). Previous studies demonstrated better efficacy of VDZ in bio-naïve pts with CD, however, there is lack of sufficient data in Chinese pts. VALUE study (NCT04872491) is a prospective, multicenter, single-armed observational study evaluating the safety and effectiveness of VDZ in UC and CD patients (pts). Methods This subgroup of bio-naïve pts with CD in second interim analysis of VALUE trial was assessed for clinical effectiveness (clinical response: ≥3 point-reduction in Harvey-Bradshaw index (HBI) score; clinical remission: HBI score ≤4; endoscopic remission: absence of any ulcers excluding aphthous ulcers.) on treatment of Vedolizumab, at week 14, 30, and 54. (Data cutoff: 21 Oct 23). Results Of the 91 pts with CD, 57 pts (62.64%) were bio-naïve, with a mean HBI score of 6.0±3.51 with the median duration of CD of 2.693 (4.1384) years. The majority of disease locations were Ileocolonic (49.12%) with 2 (3.51%) pts had history of Fistulas (Table 1). After treatment with VDZ, 44.44% (16/36), 52% (13/25) and 53.85% (7/13) achieved clinical response at week 14, 30 and 54, respectively. Overall, 83.33% (30/36), 96.15% (25/26) and 92.31% (12/13) pts achieved clinical remission at week 14, 30 and 54, respectively. Additionally, 100% of pts (13/13) achieved clinical response or remission, by 54 weeks (Figure 1). Further, 66.67% (4/6), 33.33% (2/6) and 0/1 pts achieved endoscopic remission at week 14 ,30 and 54, respectively. Conclusion This study demonstrated good effectiveness of VDZ in bio-naïve patients with CD in China.

DOP022 Shared and Distinct Features of the Gut Microbiome in Immune-mediated Inflammatory Diseases: Initial Analysis from the INTEGRATE Cohort Study

Abstract Background Inflammatory bowel disease (IBD) and ankylosing spondylitis (AS) share overlapping pathophysiological mechanisms as immune-mediated inflammatory diseases. While gut microbial dysbiosis has been implicated in both conditions, the shared and distinct features of the oral-gut microbiome axis remain poorly understood. This study aims to characterize the oral and gut microbial signatures and their relationship with environmental factors in IBD and AS to identify common pathogenic pathways and disease-specific patterns. Methods The INTEGRATE study is a nationwide prospective observational study in Korea targeting recruitment of 1,100 IBD patients, 700 AS patients, and 2,244 healthy controls over five years (Table 1). Systematic collection includes clinical data and biological samples (saliva, stool, blood, intestinal tissues) for multi-omics analyses. Microbial characterization employs full-length 16S rRNA gene sequencing and shotgun metagenomics for saliva and stool samples, complemented by metabolomic analyses of saliva, stool, and plasma. This initial analysis includes gut microbiome data from 254 IBD patients, 156 AS patients, and 194 healthy controls. Results Alpha diversity analysis revealed a gradient pattern, with IBD patients showing lowest gut microbiome diversity, AS patients intermediate, and healthy controls highest (p<1.0e-12 for all indices, Fig. 1). In IBD patients, alpha diversity significantly correlated with disease activity indices (Harvey-Bradshaw Index score in Crohn's disease, total Mayo score in ulcerative colitis) and inflammatory markers (CRP, r=-0.13, p=0.042). Blood urea nitrogen levels showed positive correlation with alpha diversity in both IBD (r=0.21, p=0.00062) and AS cohorts (r=0.20, p=0.015). Beta diversity analysis demonstrated distinct clustering patterns (UniFrac distance), with AS patients positioned intermediately between IBD patients and healthy controls (Healthy vs IBD: R²=0.0502, Healthy vs AS: R²=0.0148, IBD vs AS: R²=0.0198; all p=0.001). Species-level analysis through full-length 16S rRNA sequencing identified specific taxa (Clostridium bolteae, Blautia hansenii) significantly enriched in both IBD and AS patients compared to controls. Conclusion Our initial analysis demonstrates distinct gut microbiome signatures across IMIDs, with a clear diversity gradient and shared taxonomic features between IBD and AS. These findings, coupled with specific clinical correlations, provide a foundation for understanding common pathogenic pathways. Ongoing multi-omics analyses and quantitative microbiome profiling will further elucidate the role of the oral-gut microbiome axis in these IMIDs, potentially identifying novel microbial biomarkers for precision medicine.

P0601 Is advanced combination therapy effective in patients with refractory Inflammatory Bowel Disease?

Abstract Background Advanced combination therapy (ACT) involves combining two biological therapies or a biological drug with a small molecule, in order to complement their mechanisms of action inhibiting multiple inflammatory cascades. The primary aim of our study was to evaluate the effectiveness of combination therapies in Inflammatory Bowel Disease (IBD) Methods A prospective, single-centre observational study was conducted, including all patients diagnosed with ulcerative colitis (UC) or Crohn´s disease (CD) starting treatment with ACT from March to August 2024. Clinical and biological response and remission were assessed at week 16 and the last available visit. Clinical response was defined as a decrease ≥3 points from baseline Harvey-Bradshaw Index (HBI) in CD or baseline Partial Mayo Score (pMS) in UC. Clinical remission was considered as a HBI score ≤4 or pMs of 0-1. Biological response was determined as a ≥50% decrease from baseline C-reactive protein (CRP) and faecal calprotectin (FC) and remission as a CRP<5 and FC<250 Results A total of 20 patients were included, 70% (14/20) diagnosed with UC (Figure 1A). The most frequent combination was vedolizumab (VEDO) with upadactitinib (UPA) (Figure 1B) The median baseline HBI was 10.5 [IQR 6-15] decreasing to 6.5 at week 16 [IQR 3-11] and to 5.5 [IQR 2-10] at the last follow-up (p<0.001)(Figure 2A). The median baseline pMS was 7 [IQR 5-8] decreasing to 4 [IQR 2-4] at week 16 and to 2 [IQR 1-3] at the last visit (p<0.005) (Figure 2B) The median baseline FC was 1994 [IQR 805-3238], decreasing to 635 [IQR 183-222] at week 16 and to 387 [IQR 93-1115] at the last follow-up (p=0.047) (Figure 2C). Regarding CRP, the median baseline was 5.3 [IQR 1-31], decreasing to 2.4 [IQR 1-5] at week 16 and to 1.2 [IQR 1-4] at the end of follow-up (p=0.014) (Figure 2D) 65% of patients achieved clinical response and 20% reached clinical remission at week 16. At the end of follow-up, 80% achieved clinical response and 65% clinical remission (Figure 2E) At week 16, 45% and 20% of patients achieved biological response and remission, respectively. At the end of follow-up, 65% were in biological response and 45% in biological remission (Figure 2F) Treatment was discontinued in 3 patients, in 2 of them due to improvement and in the reimaining one due to lack of response. Treatment intensification was required in 7 patients. A total of 8 mild adverse effects were recorded, none of which led to discontinuation of the ACT Conclusion These results demonstrate adequate clinical and biological response in patients treated with ACT. Clinical and biological remission was achieved in 65% and 45% of patients at the end of follow-up, with good safety profile. Nevertheless, to confirm this results futher large prospective studies are needed

P0762 Early ustekinumab use improves clinical outcomes in biologic-naive Crohn’s Disease patients: A retrospective multicenter cohort study in Taiwan

Abstract Background Crohn’s disease (CD) is a progressive condition, and early treatment with infliximab combined with an immunosuppressant within six months has been shown to improve clinical outcomes. However, the impact of early ustekinumab (UST) use in biologic-naïve CD patients remains unclear. This study aims to address this gap by evaluating the clinical outcomes of early UST intervention in such patients. Methods In this retrospective cohort study, we included biologic-naïve CD patients treated with UST, with a clinical follow-up period of at least six months, from October 2020 to January 2024 across four medical centers in Taiwan. Patients who received UST within six months of CD diagnosis were categorized into the early-UST group, while the rest formed the control group. The primary endpoint was the improvement of clinical outcomes at six months. Results A total of 60 biologic-naïve CD patients were enrolled. Baseline characteristics were comparable between the two groups. At six months, the early-UST group (n=24) demonstrated significantly lower Crohn’s Disease Activity Index (CDAI) scores (73.03 vs. 112.42, p=0.038), lower Harvey-Bradshaw Index (HBI) scores (1.46±1.69 vs. 2.72±2.17, p=0.020), higher rates of clinical remission (91.7% vs. 63.9%, p=0.017), and higher rates of steroid-free clinical remission (79.2% vs. 50.0%, p=0.031) compared to the control group (n=36). Extending the evaluation to one year, the early-UST group continued to show lower CDAI scores (39.94 vs. 91.48, p=0.005). Adverse event rates were similar between the two groups. Conclusion Initiating ustekinumab within six months of CD diagnosis is associated with improved clinical outcomes and enhanced quality of life in biologic-naïve Crohn’s disease patients.

P0824 Patient-Reported Outcomes in Chinese Patients with Inflammatory Bowel Disease treated with Vedolizumab: A subgroup analysis of second interim analysis of VALUE study

Abstract Background Vedolizumab (VDZ), a gut-selective monoclonal antibody for α4β7 integrin, approved in China for treating inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD). Here, we assess the improvements in symptomatic relief and quality of life (QoL) by patient-reported outcomes (PROs) from the second interim analysis of VALUE study (NCT04872491). Methods VALUE study is a prospective, multicenter, single-arm observational study. Enrolled patients with UC/CD aged >18 years, were treated with 300mg VDZ at week 0, 2, 6, and every 8 weeks until 54 weeks. This second interim subgroup analysis was conducted 2 years after the first subject enrolment (data cutoff: 21 Oct’ 2023), which assessed the QoL using partial Mayo score [a composite index of rectal bleeding sub-score (RBS) and stool frequency sub-score (SFS)]for the patients with UC, and abdominal pain sub-score (APS), loose stool frequency sub-score (LSFS) for pts with CD at baseline, days 3, 7 and 14. IBD questionnaires (IBDQ), EuroQol - 5 Dimensions – 5 Levels index (EQ-5D-5L), EuroQol – Visual Analogue Scale (VAS) scores from baseline to week 14. Descriptive statistics summarized the effectiveness. Results Of 500 pts (UC: 409, CD: 91), 61.60% were males (61.60%) with a mean partial Mayo score of 5.2±2.09 and Harvey-Bradshaw Index (HBI) score of 5.6±3.35 in pts with UC and CD, respectively. After the treatment with VDZ in 315 pts with UC, the RBS and SFS score decreased(Figure 1), 34.92% (110 pts) achieved RBS=0 and SFS≤1 at baseline, which further increased to 51.69% (168 pts) and 64.19% (190 pts) by in day 7 and 14 respectively. Compared to baseline, the RBS = 0 and SFS≤1 scores improved by 30% (34.92% to 64.19%) at day 14, demonstrating the rapid onset effect of VDZ (Table 1A). In the pts with UC, mean IBDQ, EQ-5D-5L and EQ-VAS scores showed improvement from baseline (148.3 ±37.88, 0.890±0.157 and 76.1±15.56, respectively) to week 14 (186.7±26.30, 0.948±0.105 and 85.5±11.74, respectively) (Table 1B). The mean pro scores from baseline to day 14 in patients CD are presented in Figure 1. APS≤1 and LSFS≤3 scores in pts with CD treated with VDZ improved from 75% at baseline to 78.08%, 82.19% and 85.51% on days 3, 7 and 14, respectively (Table 1A). Improvement in IBDQ scores was observed from baseline (161.8±37.53) until week 14 (177.4±24.43). Similarly, the mean EQ-5D-5L and EQ-VAS scores from baseline (0.908±0.1126 and 77.2±15.68) to week 14 (0.942±0.0586 and 82.4±10.98) were also improved in CD pts (Table 1B) signifying improved QoL. Conclusion VDZ treatment was associated with significant symptomatic relief and improved quality of life in Chinese patients with IBD.

P0819 AIRIS-Crohn: Results on the Effectiveness and Safety of Risankizumab in the Medium Term in Real-World Clinical Practice

Abstract Background There is a lack of evidence on the effectiveness and safety of Risankizumab in Crohn’s disease in real-world clinical practice. This observational study aims to analyze these outcomes in patients with Crohn’s disease in Andalusia (Spain). Methods Retrospective clinical and biochemical data were collected from patients who initiated treatment with Risankizumab across 10 hospitals in Andalusia (AIRIS-Crohn registry). Clinical remission was defined as a Harvey-Bradshaw Index (HBI) score <5. Combined clinical-biochemical remission was defined as HBI <5, C-reactive protein (CRP) <5 mg/L, and fecal calprotectin <250 μg/g. Steroid-free remission was defined as HBI <5 and no corticosteroid use since week 12. An intention-to-treat analysis was performed. Results A total of 138 patients were included, with a mean age of 49 years (range 19-84), of which 50.8% were male. The disease distribution was ileocolonic in 46%, ileal in 45.7%, and colonic in 8.3%, with 5.9% having upper disease localization. The smoking status included 23% active smokers and 27% former smokers. Extra-intestinal manifestations were present in 31%, and 20.8% had associated perianal disease. The mean duration of disease was 15 years (range 0-55), and 39.7% had undergone resective surgery. The mean of previous advanced treatments was 3. At baseline, 9% were on 5-ASA, 3.6% on immunomodulators, and 32% were taking corticosteroids. The induction phase lasted 12 weeks for all patients. After 6 months, 84.6% continued on a 360 mg dose every 8 weeks, 9.6% required intensification to every 6 weeks, and 5.8% every 4 weeks. (Table 1.a) Clinical and Biochemical Effectiveness Results are shown in Table 1.b. Fifteen patients discontinued treatment before the 6-month mark (12.5%), primarily due to primary failure (60%). Three patients experienced skin reactions leading to treatment discontinuation: one due to hypersensitivity and another due to hepatotoxicity. Two mild, transient adverse events were reported: elevated transaminases and a skin reaction, both resolving without treatment discontinuation. Conclusion Risankizumab demonstrated both effectiveness and safety in a cohort of patients with refractory Crohn’s disease. References 1-de Souza HSP, Fiocchi C, Iliopoulos D. The IBD interactome: an integrated view of aetiology, pathogenesis and therapy. Nat Rev Gastroenterol Hepatol. 2017Dec;14(12):739–49 2-Ahmad T, Tamboli CP, Jewell D, Colombel JF. Clinical relevance of advances ingenetics and pharmacogeneticsof IBD. Gastroenterology. 2004 May;126(6):1533–49. 3-Feuerstein JD, Cheifetz AS. Crohn Disease: Epidemiology, Diagnosis, andManagement. Mayo Clin Proc. 2017 Jul;92(7):1088-1103. doi:10.1016/j.mayocp.2017.04.010. 4-Roda G, Chien Ng S, Kotze PG, Argollo M, Panaccione R, Spinelli A, Kaser A, PeyrinBiroulet L, Danese S. Crohn’s disease. Nat Rev Dis Primers. 2020 Apr 2;6(1):22. doi:10.1038/s41572-020-0156-2. Erratum in: Nat Rev Dis Primers. 2020 Apr 6;6(1):26. Erratum in: Nat Rev Dis Primers. 2020 May 20;6(1):42. Erratum in: Nat Rev Dis Primers. 2020 Jun 19;6(1):51. Kobayashi T, Siegmund B, Le Berre C, Wei SC, Ferrante M, Shen B, et al. Ulcerative colitis. Nat Rev Dis Primers. 2020 Sep 10;6(1):74 5-Flynn S, Eisenstein S. Inflammatory Bowel Disease Presentation and Diagnosis. SurgClin North Am. 2019 Dec;99(6):1051-1062. doi: 10.1016/j.suc.2019.08.001. Epub 2019Sep 11. PMID: 31676047. 6-Seyedian SS, Nokhostin F, Malamir MD. A review of the diagnosis, prevention, andtreatment methods of inflammatory bowel disease. J Med Life. 2019 Apr-Jun;12(2):113-122. doi: 10.25122/jml-2018-0075. PMID: 31406511; PMCID: PMC6685307. 7-Loftus EV Jr, Panés J, Lacerda AP, Peyrin-Biroulet L, D’Haens G, Panaccione R,Reinisch W, Louis E, Chen M, Nakase H, Begun J, Boland BS, Phillips C, Mohamed MF, Liu J, Geng Z, Feng T, Dubcenco E, Colombel JF. Upadacitinib Induction and Maintenance Therapy for Crohn’s Disease. N Engl J Med. 2023 May 25;388(21):1966-1980. doi: 10.1056/NEJMoa2212728 8-D’Haens G, Panaccione R, Baert F, Bossuyt P, Colombel JF, Danese S, Dubinsky M,Feagan BG, Hisamatsu T, Lim A, Lindsay JO, Loftus EV Jr, Panés J, Peyrin-Biroulet L, Ran Z, Rubin DT, Sandborn WJ, Schreiber S, Neimark E, Song A, Kligys K, Pang Y, Pivorunas V, Berg S, Duan WR, Huang B, Kalabic J, Liao X, Robinson A, Wallace K, Ferrante M. Risankizumab as induction therapy for Crohn’s disease: results from thephase 3 ADVANCE and MOTIVATE induction trials. Lancet. 2022 May28;399(10340):2015-2030.doi: 10.1016/S0140-6736(22)00467-6. PMID: 35644154. 10-Ferrante M, Panaccione R, Baert F, Bossuyt P, Colombel JF, Danese S, Dubinsky M,Feagan BG, Hisamatsu T, Lim A, Lindsay JO, Loftus EV Jr, Panés J, Peyrin-Biroulet L, Ran Z, Rubin DT, Sandborn WJ, Schreiber S, Neimark E, Song A, Kligys K, Pang Y,Pivorunas V, Berg S, Duan WR, Huang B, Kalabic J, Liao X, Robinson A, Wallace K,D’Haens G. Risankizumab as maintenance therapy for moderately to severely active Crohn’s disease: results from the multicentre, randomised, double-blind, placebocontrolled, withdrawal phase 3 FORTIFY maintenance trial. Lancet. 2022 May28;399(10340):2031-2046.doi: 10.1016/S0140-6736(22)00466-4. PMID: 35644155.

P0032 Human Extrachromosomal Circular DNA (EccDNA) is a Novel Biomarker in Inflammatory Bowel Disease

Abstract Background Inflammatory Bowel Diseases (IBD), comprising Ulcerative Colitis (UC) and Crohn’s Disease (CD), are chronic, relapsing-remitting disorders of the gastrointestinal tract with unclear etiology. Identifying reliable biomarkers for predicting disease progression and treatment response remains a priority. Extrachromosomal circular DNA (eccDNA) has shown promise as a diagnostic and prognostic biomarker in oncology, but its potential in IBD patients, including the gene fragments involved, has not been extensively studied. Methods This monocentric, observational case-control study enrolled IBD patients and healthy controls (HC) undergoing colonoscopy for colorectal cancer screening at our center. IBD disease activity was assessed using the Partial Mayo Score and Mayo Endoscopic Subscore (MES) for UC, and the Harvey-Bradshaw Index and Simple Endoscopic Score (SES-CD) for CD. Colonic biopsies were collected from both inflamed and healthy mucosa of IBD patients, and from HCs. eccDNA was purified using the Circle-Seq method; detection was performed with the Circle Finder pipeline. The study analyzed differences in eccDNA abundances between IBD patients and HCs, focusing on Differentially Produced per Gene eccDNAs (DPpGCs). Results In total, 93 IBD patients (38 CD, 39 UC) and 16 HC were included. IBD patients showed a significantly higher abundance of eccDNAs compared to HC, with this increase observed across all chromosomes, suggesting a global upregulation of eccDNA production throughout the human genome. There was also a statistically significant trend towards larger eccDNA fragments in IBD biopsies. Notably, even when considering only eccDNA derived from genic elements ("genic eccDNAs") IBD patients exhibited a significantly higher abundance of eccDNA compared to HCs. Analysis of DPpGCs (fold change >1 log2, p < 0.01) identified 152 genes enriched in IBD, including GRID2 and NRG1. In CD patients, 70 genes, such as FGF14, SOX5, and ZBTB20, were enriched, while UC patients had 123 enriched genes, including NRG1, SPOCK3, and ATP13A4. Patients in endoscopic remission (SES-CD< 3, MES 0-1) exhibited fewer eccDNAs, though this reduction was not statistically significant. Among identified DPpGCs, key genes included FARS2, HERC3, and PNK2. When analyzing UC and CD seperately, we found a statistically significant increase of eccDNA production in active UC, but not in CD, with NRG1 being notably overrepresented, suggesting its potential as a UC-specific biomarker. Conclusion Our study unveils a unique pattern of eccDNA production in IBD. We showed that circles harboring specific genes can distinguish UC and CD from HCs with statistical significance (p<0.01), indicating that eccDNA profiling may represent a novel diagnostic tool for IBD patients.

P0799 Efficacy and Safety of Dual Therapy for Refractory Inflammatory Bowel Disease in a Danish Cohort

Abstract Background Patients with Crohn’s disease (CD) and ulcerative colitis (UC) may become refractory to monotherapy with biologics or small molecules. Dual therapy, combining biologics and small molecules, has been proposed for this challenging population. While awaiting randomized studies, real-world data on its efficacy and safety are crucial. This study contributes to the evidence on dual therapy in a Danish adult IBD cohort. Methods Medical records from May 2018 to May 2023 were reviewed for CD and UC patients undergoing dual therapy with biologics and/or small molecules in outpatient gastroenterology clinics at Aarhus University Hospital and Regional Hospital Randers. Patients treated for at least three months were included and followed until treatment discontinuation or the end of the study period. Patient characteristics, clinical outcomes, adverse events, and efficacy data were collected at baseline and follow-up. Results Seventy-four patients (47 with CD and 27 with UC) received a total of 79 dual therapies. The median duration of dual therapy was 488 days for CD and 412 days for UC. The most common combinations were adalimumab and ustekinumab in CD (46%) and adalimumab and vedolizumab in UC (35%). Clinical remission was achieved in 56% of CD patients and 62% of UC patients. Steroid-free follow-up was observed in 81% of CD patients and 52% of UC patients (Table 1). In CD, dual therapy significantly reduced stool frequency, bloody stools, calprotectin levels, and Harvey-Bradshaw Index (HBI) scores. In UC, stool frequency, nighttime stools, abdominal pain, CRP, calprotectin, and Simple Clinical Colitis Activity Index (SCCAI) scores significantly decreased, while hemoglobin and albumin levels significantly improved. Serious adverse events (SAEs) occurred in 12% of UC patients and 14% of CD patients, consistent with prior studies of adult and pediatric cohorts [1, 2]. No UC patients required colectomy during the study period. Conclusion This retrospective study demonstrates a substantial rate of clinical remission and acceptable safety in refractory IBD patients receiving dual therapy. The findings highlight prolonged treatment duration, significant clinical improvements, and a manageable SAE profile. Dual therapy represents a promising approach for refractory and complex IBD, though the risk of SAEs must always be balanced against therapeutic benefits.

P0978 Effectiveness of risankizumab in moderate-to-severe Crohn’s Disease: A Canadian multicentric real-world study

Abstract Background Risankizumab is an interleukin-23 (IL-23) targeting monoclonal antibody, and has recently been approved for the treatment of moderate-to-severe Crohn’s Disease (CD). To this date, there is limited effectiveness and safety real-world data. Methods We performed a retrospective chart review at 5 inflammatory bowel disease centers in Canada between January 2023 and November 2023 to evaluate the safety and effectiveness of risankizumab in moderate-to-severe Crohn’s Disease. Adult patients with confirmed CD diagnosis on risankizumab for active clinical or endoscopic disease were included. Patients with indeterminate colitis, and patients treated for post-operative recurrence prophylaxis were excluded. Clinical, biochemical and endoscopic data was collected at 3, 6, and 12 months.We evaluated the rates of clinical remission (defined as Harvey-Bradshaw Index (HBI) <5) and response (decrease in HBI of >50%), biochemical remission (CRP<5mg/L and/or fecal calprotectin (FCAL) < 250ug/g), as well as endoscopic remission (SES-CD <4) and response (SES-CD decrease >50%) at each time point. If HBI or SES-CD scores were not available, treating physicians’ assessments of response and remission were used. Requirement for steroids, drug discontinuation, and drug-associated adverse events were also collected. Results A total of 335 patients were included in the study. Baseline data is presented in Table 1. Median age was 39, and 172 (51.3) of patients were female. Most patients (304, 90.7%) had previous biologic exposure, and 112 (33.4%) patients had been exposed to three or more biologics. Overall, 131/235 (55.7%) patients clinically responded at 3 months, and 121/233 (51.9%) were in clinical remission. At 12 months, rates of clinical response and remission were similar (73/129, 56.6% and 74/132, 56.1% respectively). Endoscopic remission was noted in 6/17 (35.3%), 13/41 (31.7%), and 29/72 (40.3%) at 3, 6 and 12 months respectively. Normalization of biochemical parameters at 12 months was found in 73/99 (73.7%) of patients for CRP, and 21/49 (42.9%) for FCAL. Patients were less likely to require steroids over time, with respectively 49 (14.6%), 25 (7.5%) and 15 (4.5%) of them with active steroid use at 3, 6 and 12 months. Forty-seven (16.1%) patients had discontinued risankizumab prior to 12 months of use. By 12 months, 28 (8.4%) had to undergo surgery for active disease, and 41 (12.2%) required hospitalization. Conclusion In this real-world, multicentric, Canadian study, risankizumab was an effective therapy in the management of Crohn’s Disease in a population with significant number of patients with refractory disease.

P0814 Transmural healing in Crohn’s disease: Real-world insights from the SUNRISE study on vedolizumab using intestinal ultrasonography

Abstract Background The use of patient-centric monitoring modalities for assessing therapies, such as vedolizumab (VDZ), are of growing interest to optimize disease outcomes in patients (pts) with Crohn’s disease (CD). Transmural healing is an emerging outcome assessed by intestinal ultrasonography (IUS), which allows frequent evaluation of CD.1,2 Real-world evidence on the effectiveness of current treatments to induce and maintain transmural response to inform treatment decisions is limited. The SUNRISE study aims to describe pts with CD treated with VDZ achieving a composite outcome of complete remission, and transmural response, utilizing IUS. Methods SUNRISE is an ongoing observational, prospective study (NCT05192863) being conducted across 10 sites in Canada, Israel and Italy. Adults with moderately to severely active CD, with a bowel wall thickness of >3 mm based on IUS, and who newly initiated intravenous VDZ are eligible. Complete remission (defined as a composite endpoint of clinically corticosteroid-free [Harvey–Bradshaw Index score of <5 points and no concomitant corticosteroids], biochemical [C-reactive protein and faecal calprotectin normalization] and transmural remission [assessed by IUS]), and transmural response after VDZ treatment are reported after induction with VDZ (Weeks 10/14) and every 6 months until Month 18 or early discontinuation. Methodological details are shown in the Figure. Results This interim analysis included 70 pts; median (interquartile range [IQR]) age was 50.0 (39.0–67.0) years, time since CD diagnosis was 4.0 (0.9–17.2) years and treatment duration (n=69) was 5.0 (3.2–6.1) months. At Month 6, the proportion of pts achieving complete remission, and transmural remission and response were 3/11 (27.3%), 9/28 (32.1%) and 12/28 (42.9%) pts, respectively; data at Weeks 10/14 are shown in the Table. Median (IQR) Short Inflammatory Bowel Disease Questionnaire total score was 4.3 (3.7–5.6) at baseline, 4.5 (3.4–5.3) at Week 10, 4.7 (3.9–5.6) at Week 14 and 5.0 (4.4–6.1) at Month 6. At Month 6, 10/21 pts (47.6%) ranked IUS as their preferred test over colonoscopy, magnetic resonance elastography and computed tomography enterography. Of 40 pts with available data at Month 6, 6 (15.0%) discontinued treatment, 5 (12.5%) switched to subcutaneous VDZ and 1 (2.5%) skipped ≥1 dose of VDZ. During the observation period, 2/70 pts (2.9%) had a CD-related hospitalization, and 1/70 pt (1.4%) each had a CD-related emergency room visit or CD-related surgery (fistula removal). Conclusion The SUNRISE study provides real-world evidence for the use of VDZ to achieve transmural healing in pts with CD and supports pt preference for IUS over other monitoring modalities. Additional follow-up data are required to confirm these findings.

P1101 Real-world effectiveness and safety of Risankizumab in Crohn’s Disease

Abstract Background Data on real-world therapy outcomes for the use of risankizumab in Crohn’s Disease (CD) remain limited. We aimed to assess the real-world effectiveness and safety of risankizumab therapy in CD. Methods A retrospective study was carried out at a tertiary referral centre on patients started on risankizumab for CD between February 2019 and November 2024. Primary outcomes included: rates of clinical response and clinical remission at weeks 12, 28, and 52, and rates of endoscopic improvement by week 52. Clinical response was defined as a treatment response recorded in the chart as “complete response” or “partial response”, clinical remission was defined as remission status recorded as “in remission”, and endoscopic improvement as an endoscopic assessment of normal, inactive or mild disease. Secondary outcomes included treatment persistence (patients who did not discontinue treatment during follow-up), changes in Harvey Bradshaw Index (HBI), SES-CD score, CRP, faecal calprotectin, and adverse events. Kaplan-Meier analysis was used for survival probabilities, and Mann-Whitney test compared group differences. Results The study cohort included 122 patients. The median duration of follow-up was 38.7 weeks (IQR 24.4-61.5). Clinical response rates at week 12, 28, and 52, were 78%, 69%, and 77% respectively. Clinical remission rates at week 12, 28, and 52 were 32%, 38%, and 37% respectively. Endoscopic improvement by week 52 was seen in 26% of patients who underwent endoscopy (n=35). There was no difference in rates of treatment persistence in the ustekinumab exposed group (n=45). In the overall cohort, there was no difference in median HBI score at baseline and the pre-defined time points. Median SES-CD score reduced from baseline (8 [IQR 6-11]) to week 12 (3 [0-3], p=0.009) and week 28 (6 [3-7], p=0.015). No differences between baseline SES-CD score and week 52 were seen. Median faecal calprotectin levels reduced from baseline (766μg/mg [IQR 318-1500]) to week 12 (427μg/mg [232-1096], p=0.04), week 28 (332μg/mg [59-1435], p=0.04), and week 52 (200μg/mg [54-900], p=0.048). There was a non-statistical trend towards reduction of CRP over the same time period. 13% (n=16) discontinued therapy in the follow-up period, 11 due to therapy failure, 3 due to adverse events and, 2 due to patient preference. There were 39 reported adverse events; 6 disease-related, 15 infectious (1 serious). There were 2 pregnancies during the follow-up period, with one early-term delivery and the second ongoing. Conclusion In a real-world setting risankizumab is an effective and safe therapeutic option in CD. Clinical effectiveness is comparable to other biologic therapies for CD. No new significant adverse events were identified.

Low Surgery Rates in Early Crohn's Disease: Results from a Prospective Population-Based Inception Cohort-The Inflammatory Bowel Disease in South-Eastern Norway III Study.

The emergence of biologic therapy has coincided with a decline in surgery rates for Crohn's disease (CD). This study aims to describe the disease course, including intra-abdominal surgery rates, biologic therapy use, and variables associated with biologic therapy initiation in a cohort of newly diagnosed CD patients. The Inflammatory Bowel Disease in South-Eastern Norway (IBSEN) III study is a population-based inception cohort study. From 2017 to 2019, newly diagnosed inflammatory bowel disease patients were included for prospective follow-up. The present study included CD patients ≥ 18 years. Clinical, endoscopic, and demographic data were collected at diagnosis and 1-year follow-up. Data were analyzed by using the Kaplan-Meier method and regression analyses. In total, 424 CD patients (median age 37.0 years (range 18-80), female 55.0%) were included. At diagnosis, 50.5% presented with ileal disease and 80.7% with inflammatory behavior. Within a 1-year follow-up, 39.6% of patients received their first biologic therapy and 5.2% required intra-abdominal surgery. Systemic steroid treatment, CRP ≥ 5.0mg dL-1, Harvey-Bradshaw Index score > 4, ileocolonic disease and penetrating disease behavior at diagnosis were independently associated with increased risk of initiation of biologic therapy, while age > 40 years was associated with decreased risk. A high proportion of patients had ileal disease and inflammatory behavior at diagnosis. Still, nearly 40% started biologic therapy within the 1-year follow-up, while only 5% required intra-abdominal surgery.

Estimation of the Harvey Bradshaw Index from the Patient-Reported Outcome 2 in Crohn's Disease: Results Based on a Large Scale Randomized Controlled Trial.

Many registrational trials in Crohn's disease assess treatment efficacy with the 2-item Patient-Reported Outcome (PRO2), while the Harvey-Bradshaw Index (HBI) is prominent in pragmatic trials and clinical practice. The translation between PRO2 and HBI has not been established. Data from a Phase 3 trial of vedolizumab in Crohn's disease were used to determine the Pearson correlation between PRO2 and HBI. Linear regression was used to fit equations that estimate between indices; 95% prediction intervals were determined for HBI scores corresponding to PRO2 thresholds for disease activity. Internal validation of the conversion equations was performed using the bootstrap methods. PRO2 and HBI were highly correlated at baseline (r = 0.75 95% confidence interval (CI) 0.73-0.78; P < .001), induction (r = 0.87; 95% CI, 0.85-0.88; P < .001), and maintenance (r = 0.88; 95% CI, 0.85-0.90; P < .001). PRO2 and HBI change scores were moderately correlated (r = 0.72; 95% CI 0.69-0.75; P < .001) in induction and more strongly correlated during maintenance (r = 0.81; 95% CI 0.78- 0.84; P < .001). Regression equations for conversion of PRO2 to HBI from all cohorts (induction, maintenance, randomized, open-label) support an approximate conversion where HBI = 0.5 PRO2. As expected from the imperfect correlation between scores, the prediction intervals were generally wide. No evidence of overfitting was seen in bootstrap internal validation. PRO2and HBI correlate strongly and conversion between them is possible. These findings facilitate the practical application of trial results and clinical guidelines.

The Role of Ultrasound in Assessment of Disease Activity in Inflammatory Bowel Disease Patients

Abstract Aim This study aim to evaluate the role of Ultrasound in assessment of disease activity in Inflammatory Bowel Disease patients (IBD). Patients and Methods The was performed at Radiology Department and involved a diagnosed cases of Inflammatory Bowel Diseases referred from the Gastroenterology Unit, Ain Shams University Hospitals. A total Thirty six patients inflammatory bowel disease patients (Ulcerative colitis and Chron's disease) were subjected to Intestinal Ultrasound assessment (IUS), Fecal Calprotectin (CP) analysis and calculation of the Clinical Activity Indices. Twenty five patients were subjected to Endoscopic Activity Assessment. Intestinal Ultrasound (IUS) parameters including intestinal wall thickness (BWT) and intestinal bowel wall vascularity, were compared with Endoscopic Activity, Fecal Calprotectin levels (CP) and Clinical Activity Indices. Results Among the thirty-six patients, there were fourteen diagnosed Chron`s cases (38.9%) and twenty-two Ulcerative Colitis cases (61.1%). Roc curve analysis revealed the ability of the ultrasound bowel wall thickness (BWT) to differentiate between mild and moderate disease activity in IBD patients with sensitivity of 90.91% and specificity of 100.0%, with area under curve (AUC) of 0.909 using the endoscopic activity as a gold standard. A statistically significant difference was found between the (BWT) measurements and Simple Endoscopic score (SES-CD) (P = 0.002) as well as between the (BWT) measurements and Endoscopic Mayo score (P = 0.001). A statistically significant correlation was found between the fecal CP levels and Intestinal bowel wall thickness among Ulcerative colitis and Chron's patients with (r = 0.708, P &amp;lt; 0.001) and (r = 0.736, P &amp;lt; 0.01) respectively. There was also statistically significant difference between the Clinical Activity Indices (Harvey-Bradshaw Index and Partial Mayo Score) and the (BWT) among both the Chron's and Ulcerative colitis patients with P-value (0.004) and (0.001) respectively. A statistically significant difference was found between Doppler (Limberg Score) and SES-CD endoscopic activity score (p = 0.009) as well as between Doppler (Limberg Score) and Endoscopic activity Mayo score (p = 0.005). Conclusion The results of the study suggest that the Bowel Wall Thickness (BWT) and Color Doppler Signal could serve as non-invasive parameters of detecting IBD activity. Intestinal US could be one of the promising methods for the detection of the disease activity as well as monitoring of IBD patients.

Short term effectiveness of ustekinumab versus vedolizumab in Crohn's disease after failure of anti-TNF agents: An observational comparative study design with a Bayesian analysis.

Crohn's disease (CD) is a debilitating gastrointestinal disease with complex etiology. Although effective, recipients of anti-tumor necrosis factor (TNF) agents may experience primary or secondary nonresponse, necessitating alternative treatments. This study is intended to compare the short-term effectiveness of ustekinumab and vedolizumab in treating CD after failure of multiple lines of anti-TNF therapy using real-world data. A retrospective study was conducted at a tertiary hospital in Dammam, Saudi Arabia, including adults (≥18 years old) with CD who did not respond to anti-TNF therapy. Primary endpoints were clinical improvement per the Harvey-Bradshaw Index (HBI) scores and remission at 12 weeks on an ordinal outcome scale. Secondary endpoints included clinical, biochemical, and endoscopic remission; clinical response; corticosteroid-free days; and cumulative steroid dose. Proportional odds and logistic regression Bayesian models were used to analyze outcomes, and the probability of treatment effectiveness was calculated from the posterior distribution. The study included 101 patients (ustekinumab, n = 71 and vedolizumab, n = 30) with a median age of 32 years (IQR: 26.0-38.0); 54.4% were male. At 12 weeks, the HBI endpoint showed an adjusted odds ratio (aOR) = 0.60 (95% confidence interval [CI]: 0.25-1.31), favoring ustekinumab, with a 75% probability of treatment effectiveness over vedolizumab. The clinical ordinal scale had an aOR = 0.61 (95% CI: 0.26-1.35) with a 73% probability of effectiveness for ustekinumab. Ustekinumab was also associated with favorable outcomes in secondary endpoints, reaching up to a 90% probability of effectiveness. In CD patients with anti-TNF failure, ustekinumab was more effective than vedolizumab in the short term. These real-world insights contribute to understanding CD management but require validation in larger prospective studies and randomized controlled trials.

Real-world clinical effectiveness of ustekinumab in the treatment of Crohn’s disease in the East Midlands UK

ObjectivesTo evaluate the effectiveness of ustekinumab in treating Crohn’s disease (CD) in a UK real-world setting.DesignThis was a multicentre, retrospective observational study of patients (aged ≥18 years) with CD or...

Relationship between Ustekinumab trough concentrations and clinical, biochemical and endoscopic outcomes in Crohn's disease: A multi-center nationwide retrospective study (TARGET STUDY).

Ustekinumab has been shown to be effective in inducing and maintain clinical and endoscopic remission in Crohn disease (CD). We aim to assess whether ustekinumab trough levels are associated with improved outcomes in CD in real-life. We recruited patients with CD who were treated with ustekinumab for at least 6 months from January 2017 to June 2023. Patients received ustekinumab 6 mg/kg intravenous induction followed by 90 mg every 4-, 8-, or 12-weeks during maintenance were included. We assessed clinical, biochemical, and endoscopic outcomes. Trough concentrations of ustekinumab that were taken from week 42 to week 52 were measured. Primary outcome was to evaluate the relationship between ustekinumab trough concentrations and clinical remission, biochemical normalization, and endoscopic remission. Logistic regression was conducted to assess outcomes. A total of 137 patients with CD, median age of 32 years and 83 (60.6%) males. The median serum levels of ustekinumab measured was 7.2 mcg/mL (interquartile range [IQR] 3.1-9.6). Using Spearman correlation analysis, a strong negative correlation was observed between ustekinumab drug levels and simple endoscopic score (SES-CD) (r = -0.464, P < .001). Additionally, ustekinumab drug levels demonstrated substantial negative correlations with disease severity measured by Harvey-Bradshaw index (HBI) score (r = -0.582, P < .001), C-Reactive Protein (CRP) levels (r = -0.598, P < .001) and fecal calprotectin (FC) levels (r = -0.529, P < .001). A multivariable analysis adjusted for age, sex and body mass index (BMI) showed a significant association between ustekinumab serum drug levels and predefined outcomes. Ustekinumab serum drug level above 4.5 mcg/mL was associated with 24% increase in the likelihood of having an SES-CD score <3 (OR 1.24, confidence interval [CI] 1.12-1.37, P value < .001), 44% more likely to achieve HBI score <5 (OR 1.44, CI 1.26-1.65, P value < .001), 52% higher likelihood of CRP more than 10 (OR 1.52, CI 1.31-1.77, P < .001), and 42% increased likelihood of FC more than 250 (OR 1.42, CI 1.24-1.62, P < .001). Ustekinumab trough concentrations above 4.5 mcg/mL were associated with clinical, biochemical and endoscopic remission in CD. Prospective data is warranted to confirm these findings.

A225 ASSESSMENT OF BEDSIDE INTESTINAL ULTRASOUND IN MONITORING CROHN’S DISEASE ACTIVITY

Abstract Background Bedside intestinal ultrasound (IUS) is an evolving modality in monitoring disease activity and assessing complications in inflammatory bowel disease (IBD). The easy-tolerability and immediate accessibility to results for expedited clinical decision-making contribute to the growing global attraction of IUS integration into IBD care. Fecal calprotectin (FC) is a known, non-invasive tool to assess disease activity in IBD. However, it comes with limitations. Aims To assess the efficacy of IUS in monitoring Crohn’s Disease (CD) compared to FC level. Methods We conducted a retrospective observational study in patients with confirmed CD at a certified IUS gastroenterologist’s outpatient clinic in Saskatoon. Patients’ charts undergoing IUS between February 2022 and April 2023 were reviewed. Patients with CD and available FC results within a month of IUS performance were identified. Age, gender, disease character, clinical symptoms (Harvey-Bradshaw Index (HBI)), FC levels, and IUS bowel wall thickening (BWT) were collected. The cut-off for FC levels and BWT for disease activity were ampersand:003E250 μg/g and ampersand:003E3 mm, respectively. The correlation between IUS BWT and FC levels was analyzed based on the Pearson correlation. Results Among a total of 178 chart reviews, 71 patients were identified. The median age was 49 years, 52.1% were males and 47.8% were females. 35 (49.3%) ileal CD, 35 (49.3%) ileocolonic and 1 (1.4%) colonic CD were identified. The HBI score verified 67.6% mild disease, 19.7% moderate, 11.2% in remission, and 1.4% severe disease. The Pearson correlation coefficient (r) between FC levels and BWT findings on IUS was r = 0.29 (P ampersand:003C0.0001), indicating a weak positive correlation. Conclusions A positive but weak correlation exists between bowel wall thickening in IUS and FC level in monitoring CD. Recognizing FC limitations, future multi-center, larger cohort studies need to be done to investigate this correlation further. Funding Agencies None