SES-CD Score Research Articles

Simplified magnetic resonance index of activity score versus simple endoscopic score in Crohn's disease: prospective study

BackgroundTo evaluate the correlation between simplified MR index of activity (sMaRIA) score and simple endoscopic score (SES-CD) in Crohn's disease activity assessment. A prospective study was done on established Crohn's disease patients referred to our institution. Magnetic resonance enterography and colonoscopy were performed as an activity assessment protocol searching for activity signs through calculation of sMaRIA score and SES-CD score and correlation between them. One hundred patients were enrolled in the study in period from July 2021 to July 2022. Patients with isolated upper gastrointestinal Crohn's disease (n = 4) or performed surgery before completion of activity assessment protocol (n = 9) or dropout (n = 18) were excluded. Patients with any age group, with ileal or colonic or ileo-colonic Crohn's disease and completed the protocol were eligible for the study (n = 69).ResultsSixty-nine patients with 345 bowel segments (five segments for each patient: ileum, right colon, transverse colon, left colon/sigmoid and rectum) were completely evaluated: 33 males and 36 females with mean age 29.16 ± 11.37 years. sMaRIA and SES-CD scores were calculated for each patient (global), and each bowel segment showed 97.50% sensitivity and 79.31% specificity at the level of global scores as well as significant positive correlation between the two scores at patient level/overall segments (rs = 0.816, p < 0.001), at ileal segments (rs = 0.704, p < 0.001) and colonic segments (right colon rs = 0.661, p ≤ 0.001, transverse colon rs = 0.586, p ≤ 0.001, left colon rs = 0.731, p < 0.001 and rectum rs = 0.786, p < 0.001). There were good inter-rater agreement between the two radiologists for the three parameters (wall thickness > 3 mm, mural edema and fat stranding) and moderate for mucosal ulcer detection with k value 0.666, 0.712, 0.712 and 0.565, respectively.ConclusionssMaRIA score is considered to be a reliable tool for Crohn's disease activity evaluation as compared to SES-CD.

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.

Empagliflozin in children with glycogen storage disease-associated inflammatory bowel disease: a prospective, single-arm, open-label clinical trial

Glycogen storage disease type Ib (GSD-Ib) is a rare inborn error of glycogen metabolism caused by mutations in SLC37A4. Patients with GSD-Ib are at high risk of developing inflammatory bowel disease (IBD). We evaluated the efficacy of empagliflozin, a renal sodium‒glucose cotransporter protein 2 (SGLT2) inhibitor, on colonic mucosal healing in patients with GSD-associated IBD. A prospective, single-arm, open-label clinical trial enrolled eight patients with GSD-associated IBD from Guangdong Provincial People's Hospital in China from July 1, 2022 through December 31, 2023. Eight patients were enrolled with a mean age of 10.34 ± 2.61 years. Four male and four female. The endoscopic features included deep and large circular ulcers, inflammatory hyperplasia, obstruction and stenosis. The SES-CD score significantly decreased at week 48 compared with before empagliflozin. Six patients completed 48 weeks of empagliflozin therapy and endoscopy showed significant improvement or healing of mucosal ulcers, inflammatory hyperplasia, stenosis, and obstruction. One patient had severe sweating that required rehydration and developed a urinary tract infection. No serious or life-threatening adverse events. This study suggested that empagliflozin may promote colonic mucosal healing and reduce hyperplasia, stenosis, and obstruction in children with GSD-associated IBD.

A226 NEUTROPHIL-TO-LYMPHOCYTE RATIO AT DIAGNOSIS PREDICTS COLONOSCOPIC ACTIVITY IN PEDIATRIC INFLAMMATORY BOWEL DISEASES (PIBD)

Abstract Background Neutrophil-to-lymphocyte ratio (NLR) has been recently identified as a potential biomarker for several autoimmune conditions. NLR predicts disease activity in adults with inflammatory bowel diseases (IBD) but had not been studied in pediatric IBD. Aims Investigate the link between NLR and baseline colonoscopic disease activity in UC and CD, the need for surgery or admission, and one-year therapy response in children. Methods Pediatric IBD patients were prospectively enrolled into the CIDsCaNN database [Canada-wide inception cohort for pediatric patients with IBD]. The cohort included patients diagnosed between 2003–2022 based on ileocolonoscopy, histopathology, and established diagnostic criteria. Patients were excluded if they had other conditions affecting NLR, such as neoplasms and autoimmune diseases. Endoscopic disease activity was assessed using the Mayo endoscopic score (MES; dichotomized as low (0, 1) or high activity (2, 3)) in UC and SES-CD score (as continuous variable) in CD. Logistic regression was used to test the link between predictors and binary outcomes. Simple linear regression was used to analyze the relationship between continuous variables. Results 576 UC and 1076 CD patients ampersand:003C18 years old were included. In UC, baseline NLR was significantly associated with baseline MES in univariate and multivariable logistic regression (multivariable OR= 1.5, 95% CI= 1.1–1.99, p= 0.019; Table). Patients with high-activity MES have significantly higher neutrophils (p= 0.0003), but lymphocytes wasn't different between the two groups. In CD, NLR was significantly correlated with SES-CD score in univariate and multivariable simple linear regression (multivariable coefficient= 1.4, 95% CI= 0.7–2.2, pampersand:003C0.0001; Fig1). Additionally, NLR predicted biologic-free remission in the CD cohort only in univariate analysis. NLR did not predict other the need for admission or surgery either in UC or CD. Conclusions Pediatric IBD patients with higher baseline NLR had a higher endoscopic disease activity. This establishes the significance of NLR as a non-invasive biomarker to help direct clinical decision making. This association suggests a role for neutrophils, as innate immunity cells in the acute stage of inflammation. Multivariable logistic regression of the relation between baseline labs in pediatric UC and Mayo endoscopic score Scatter plot demonstrating the relationship between baseline NLR and baseline SES-CD score Funding Agencies C.H.I.L.D.

FECAL URGENCY ASSOCIATED WITH POOR QUALITY OF LIFE IN QUIESCENT IBD: A CROSS-SECTIONAL STUDY OF SPARC IBD COHORT

Abstract BACKGROUND Fecal urgency (FU) is common in patients with active inflammatory bowel disease (IBD) and has been associated with reduced well-being and poor quality of life (QOL). Despite greater therapeutic options, clinical symptoms may persist in some patients. Data is lacking regarding FU in patients with objectively documented quiescent disease. OBJECTIVE Among endoscopic quiescent disease: (1) estimate prevalence of urgency, (2) assess predictors of FU, (3) describe its impact on validated QOL measures. METHODS This cross-sectional study used prospectively collected data from SPARC (Study of a Prospective Adult Research Cohort) IBD, a multicenter longitudinal study of well-phenotyped adult IBD patients initiated by the Crohn’s &amp; Colitis Foundation in 2016. Quiescent IBD was defined as Mayo endoscopy score &amp;lt;2 for ulcerative colitis (UC) and SES-CD score &amp;lt;3 for Crohn’s disease (CD). Patient reported outcomes (PROs) within 30 days of endoscopy were analyzed. Patients with ostomy or IPAA were excluded. Self-reported urgency was categorized as none, mild, or moderate/severe. Univariate statistics used Pearson’s Chi-square and Kruskal-Wallis tests. RESULTS A total of 943 patients with quiescent IBD (579 CD; 364 UC) were included in the study (Table 1). Fecal urgency was more commonly reported in quiescent CD (37.5% mild, 27.8% moderate/severe) as compared to quiescent UC (33.5% mild, 19.8% moderate/severe) (p&amp;lt;0.001). In the entire quiescent cohort, those with mild or moderate/severe FU were more likely to be female sex (58.4%; 63.2%), higher BMI (28.2; 29.5) and have an IBD-related surgery (p=0.030). Mild and moderate/severe urgency was associated with subjective abdominal pain, stool frequency, and bloody stool (all p&amp;lt;0.001). There was a trend towards ileocolonic involvement and penetrating disease in quiescent CD with moderate/severe urgency. General well-being was poorer for those with more severe urgency (p&amp;lt;0.001), and they were more likely to utilize the emergency department (p=0.016). Figure 1 depicts the PROMIS responses. There were significant differences across all domains, and notably those with moderate/severe urgency reported pain (38.8%) and fatigue (60.0%) interfered with enjoyment of life at least some of the time compared to those without urgency (3.9%; 10.0%) or with mild urgency (15.1%; 32,2%). CONCLUSION In this study of patients in SPARC IBD with endoscopic quiescent IBD the overall prevalence of fecal urgency was 65.2% for CD and 53.3% for UC. Fecal urgency was common in quiescent IBD and associated with poorer general well-being and quality of life. Further research is needed to elucidate the pathophysiology for presence of fecal urgency in quiescent IBD and develop personalized management approaches. Table 1 Demographics and IBD characteristics of SPARC IBD patients with quiescent Crohn’s disease (CD) and ulcerative colitis (UC) with symptoms of mild versus moderate/severe fecal urgency. Table 2 Severity of Fecal Urgency on Quality of Life for Patients with Endoscopic Quiescent IBD using PROMIS (Patient-Reported Outcomes Measurement Information System) Scores for Fatigue, Pain Interference† and Social Interference†*. †Responses indicate the degree and frequency of interference with each of the activities listed. *Polarity of Social Interference subscale reversed for consistency and interpretability of the figure.

P794 Relationship between Ustekinumab Trough Concentrations and Clinical, Biochemical and Endoscopic Outcomes in Crohn’s Disease; A Multi-Center Nationwide Study (TARGET STUDY)

Abstract Background Ustekinumab (UST) has been shown to be effective in inducing and maintain clinical and endoscopic remission in Crohn’s disease (CD). We aim to assess whether ustekinumab trough levels are associated with improved outcomes in CD in real life settings Methods We recruited patients with CD who were treated with ustekinumab for at least 6 months from January 2017 to June 2023. Patients received ustekinumab 6mg/kg intravenous induction followed by 90 mg every 4 or 8 weeks during maintenance were included. Clinical, biochemical, and endoscopic outcomes, trough concentrations of ustekinumab that was taken from week 42 to week 52 were included. Primary outcome was to assess if ustekinumab trough concentrations were associated with clinical remission, biochemical normalization, and endoscopic remission. Logistic regression was conducted to assess outcomes Results A total of 137 patients with CD. mean age of 34.1 years and 83 (60.6%) males. The mean serum levels of ustekinumab was 7.2 (SD 4.5). Using Spearman correlation analysis, a strong negative correlation was observed between ustekinumab drug levels and SES-CD score (r = -0.464, p &amp;lt; 0.001. Additionally, ustekinumab drug levels demonstrated substantial negative correlations with disease severity measured by HBI score (r = -0.582, p &amp;lt; 0.001), C-Reactive Protein(CRP) levels (r = -0.598, p &amp;lt; 0.001) and fecal calprotectin (FCAL) levels (r = -0.529, p &amp;lt; 0.001). A multivariate analysis adjusted for age, sex and 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 less than 3 (OR 1.24, CI 1.12-1.37, P&amp;lt;0.001), 44% more likely to achieve HBI score less than 5 (OR 1.44, CI 1.26-1.65, P&amp;lt;0.001), 52% higher likelihood of CRP less than 10 (OR 1.52, CI 1.31-1.77, p &amp;lt; 0.001), and 42% increased likelihood of FCAL less than 250 (OR 1.42, CI 1.24-1.62, p &amp;lt; 0.001). Conclusion Ustekinumab trough concentrations above 4.5 mcg/ml was associated with clinical, biochemical and endoscopic remission in Crohn’s disease. Prospective data is warranted to confirm these findings

P592 Higher predictive power of epigenetic signatures for response to vedolizumab and ustekinumab in anti-TNF naïve patients with active Crohn’s disease

Abstract Background Despite the significant progress in IBD care with biological therapies, the current 'trial-and-error' method remains suboptimal. Previous results from our EPIC-CD study demonstrated that two distinct epigenetic panels of 25 and 68 DNA methylation markers, respectively, were associated with (non-)response to vedolizumab (VDZ) and ustekinumab (USTE) in active Crohn’s disease (CD)1. Data from clinical trials have demonstrated that response rates in patients naïve to biological treatment are higher. We therefore aimed to evaluate the performance of our models in bionaive and anti-TNF exposed subpopulations. Methods We prospectively measured peripheral blood DNA methylation profiles from 184 adult CD patients prior to treatment with VDZ or USTE in a discovery (n=126) and independent validation (n=58) cohort using the Illumina EPIC BeadChip array. Between 26 and 52 weeks, patients were categorized as responders or non-responders based on a combination of endoscopic response (≥50% reduction in SES-CD score), steroid-free clinical response (≥3-point drop in Harvey-Bradshaw Index (HBI) or HBI ≤4 AND no systemic steroids), and/or biochemical response (≥50% reduction in C-reactive protein (CRP) and fecal calprotectin or a CRP ≤5 g/mL and fecal calprotectin ≤250 µg/g). Epigenetic biomarker identification and classification analyses were conducted through stability selection gradient boosting on the discovery cohort. Subsequently, the performance of the identified epigenetic biomarkers was assessed independently on the validation cohort, with patients stratified by prior anti-TNF exposure. Results Out of the 58 patients in the validation cohort, 25 received treatment with VDZ, and 33 with USTE, with 52% (n=13) and 36% (n=12) respectively naïve to anti-TNF treatment. Baseline characteristics between anti-TNF naive and anti-TNF exposed patients showed no significant differences, despite a slight significant age difference in the vedolizumab group, where anti-TNF exposed patients were significantly younger (table 1). In the overall independent validation cohort, the prediction models demonstrated an AUC of 0.75 for both VDZ and USTE. However, after stratification by prior anti-TNF exposure, we observed increased performance of our models among anti-TNF naive patients for both VDZ (AUCnon-exposed=0.85 versus AUCexposed=0.66) and USTE (AUCnon-exposed=0.97 versus AUCexposed=0.63 (figure 1). Conclusion Our findings demonstrate that prior anti-TNF exposure leads to somewhat reduced predictive power of our epigenetic models for Vedolizumab and Ustekinumab response. The predictive models may therefore find its optimal application in bio-naive patients, although they remain significant in anti-TNF exposed patients.

P1175 Abdominal Pain is Associated with Poor Quality of Life in Quiescent Inflammatory Bowel Disease: A Cross-sectional Study of the SPARC Inflammatory Bowel Disease Cohort

Abstract Background Abdominal pain (AP) is common in patients with active inflammatory bowel disease (IBD) and has been associated with poor quality of life (QOL). Despite greater therapeutic options, symptoms persist in a subset of patients. Data is lacking regarding AP in patients with objectively documented quiescent disease. Among endoscopic quiescent disease: (1) estimate prevalence of AP, (2) assess predictors of worse AP, (3) describe its impact on validated QOL measures. Methods This cross-sectional study used prospectively collected data from SPARC (Study of a Prospective Adult Research Cohort) IBD, a multicenter longitudinal study of well-phenotyped adult IBD patients initiated by the Crohn’s &amp; Colitis Foundation in 2016. Quiescent IBD was defined as Mayo endoscopy score &amp;lt;2 for ulcerative colitis (UC) and SES-CD score &amp;lt;3 for Crohn’s disease (CD). Patient reported outcomes (PROs) within 30 days of endoscopy were analyzed. Patients with ostomy or IPAA were excluded. Self-reported AP was categorized as none, mild, or moderate/severe. Univariate statistics used Pearson’s Chi-square and Kruskal-Wallis tests. Results A total of 973 patients with quiescent IBD (606 CD; 367 UC) were included in the study (Table 1). AP was more commonly reported in quiescent CD (31.2% mild, 15.5% moderate/severe) as compared to quiescent UC (23.4% mild, 10.1% moderate/severe) (p&amp;lt;0.001). In the entire quiescent cohort, those with mild or moderate/severe AP were more likely to be female sex (63.1% mild; 67.4% moderate/severe; p&amp;lt;0.001), higher BMI (28.4 mild; 30.0 moderate/severe; p=0.008) and have more recent tobacco use (p=0.004). Ileocolonic involvement was more commonly seen in moderate/severe AP. Mild and moderate/severe AP was associated with subjective fecal urgency, stool frequency, and bloody stool (all p&amp;lt;0.001). Disease behavior in CD was not associated with abdominal pain. General well-being was poorer for those with more severe AP (p&amp;lt;0.001), though this did not appear to result in more frequent recent ED visits or hospitalizations. Figure 1 depicts the PROMIS responses. Overall, worse AP was associated with universal worse scores on all PROMIS measures and subscales (all p&amp;lt;0.001). Data suggested that more severe AP had the greatest impacts on the "Fatigue" subscale. Conclusion In this study of patients in SPARC IBD with endoscopic quiescent IBD the overall prevalence of AP was 41.7% overall and more commonly reported in CD as compared to UC. AP was associated with a greater prevalence of other symptoms, worse general well-being, and poorer quality of life across all measures. Further research is needed to elucidate the pathophysiology for presence of AP in quiescent IBD and develop personalized management approaches.

P408 Complete endoscopic healing, the future therapeutic target in Crohn's disease? Results of a prospective multicenter study

Abstract Background The STRIDE II guidelines recognize endoscopic healing (EH), defined by an SES-CD score ≤2 or a CDEIS score &amp;lt;3, as one of the main therapeutic targets in Crohn's disease (CD). Nevertheless, complete endoscopic healing could reduce the risk of long-term complications in CD. The aim of this study was to assess the risk of long-term complications in CD according to the degree of endoscopic healing achieved. Methods We conducted a prospective multicenter study that included all patients with CD undergoing colonoscopy for EH assessment or dysplasia screening between September 2019 and September 2022 in one university hospital, one general hospital and one private center. Two groups were compared: patients with complete EH (CDEIS = 0) and those with partial EH (CDEIS &amp;lt;4). The primary endpoint was CD relapse, defined as the need for drug intensification and/or initiation of corticosteroid and/or CD-related hospitalization and/or development of a fistula (luminal or perianal) or abscess, and/or the need for bowel resection. Patients were followed up every 6 months for two years. Based on previously published data, 138 patients were expected to demonstrate a 13% difference with a two-sided alpha risk of 5% and a power of 80%. Results A total of 133 patients were included. The majority of patients were female (55%), non-smokers (63%), with a median disease duration of 10 (IQR, 4-19) years. Fifty-seven (43%) patients had ileocolonic location and 81 (61%) an inflammatory (B1) behavior. Patients had been on treatment for a median of 18.0 months (IQR 8.6-52) prior to colonoscopy, with no difference between the two groups. There was no significant difference between the two groups apart from BMI. Eighty-four (63%) patients had complete EH. After adjustment for BMI, the risk of relapse was significantly higher in the CDEIS&amp;gt;0 group (23% vs. 41%, HR = 2.05; IC95% = [1.09 - 3.87]; p=0.027). After a median follow-up of 23.3 months, the number of drug intensification, hospitalizations, use of corticosteroids, occurrence of abscess, fistula, or bowel resection in the CDEIS 0 and CDEIS &amp;gt; 0 and &amp;lt;4 groups were 20% and 35% (p=0.065), 2.4 and 16% (p=0.005), 2.4% and 10% (p=0.10), 3.6% and 18% (p=0.009), 7.1% and 18% (p=0.048), 7.1% and 18% (p=0.048) respectively. Conclusion This prospective multicenter study confirms that complete endoscopic healing is associated with better long-term outcomes than partial endoscopic healing in patients with CD, as well as fewer surgeries and hospitalizations and an overall decreased risk of treatment failure.

P1053 Ustekinumab trough concentration could predict the aggravation of endoscopic severity after de-escalation in the sub-analysis of CD-EXTEND study

Abstract Background De-escalation was a useful strategy for improving patient’s QOL and reduction of medical expenses. However, endoscopic data after de-escalation of ustekinumab (UST) has not been reported. The aim of this study was to elucidate UST trough concentration for the prediction of endoscopic aggravation after de-escalation of UST. Methods This CD-EXTEND study was a single-centre prospective observational study approved by the institutional review board of our hospital. Thirty CD patients who selected de-escalate UST treatment after administration of intravenous UST 6 mg/kg and subcutaneous UST 90mg every 8 weeks until 54 weeks were enrolled in this cohort. Endoscopic evaluation was performed at baseline and at one year. Endoscopic aggravation was defied as the increase of SES-CD score. Cut-off values of prediction for endoscopic aggravation was calculated by receiver operating characteristic (ROC) curve. Results Endoscopic evaluation could be evaluated in 25 patients. Endoscopic aggravation was recognized in 9 patients. There was no significant differences of patient’s characteristics and biomarkers including CRP, fecal calprotectin (FC) and Leucin-rich alpha-2-glycoprotein (LRG) between aggravated and non-aggravated groups at the baseline. However, trough concentration was significantly higher in aggravated group than non-aggravated group at the base line (1.5 ± 0.7 vs 2.8 ± 1.3 μg/mL, p=0.02). CRP, FC and LRG significantly increased in aggravated group, not in non-aggravated group. However, trough concentration significantly decreased in both aggravated and non-aggravated groups. Trough at one year was significantly lower in aggravated group than non-aggravated group (0.44 ± 0.3 vs 1.0 ± 0.71 μg/mL, p=0.02). Cut-off values of trough concentration of prediction for endoscopic aggravation at base line and at one year were 2.15 and 0.4 μg/mL, respectively. Conclusion UST trough concentration was a good prediction marker for endoscopic aggravation.

P779 Long term efficacy of azathioprine monotherapy in patients with Inflammatory Bowel Disease

Abstract Background ECCO guidelines recommend monotherapy with azathioprine (AZA) as maintenance therapy of patients with inflammatory bowel disease (IBD) mainly in steroid-dependent disease. However, in the era of the new advanced treatments AZA is not considered as a preferable option, mainly because of the referred side effects and its use is limited in combination with biologic agents. Methods This is a retrospective observational study using data from the longitudinal, prospective IBD registry of University Hospital of Heraklion, Greece. Our aim was to study IBD patients who started on monotherapy with AZA, the profile of adverse effects they developed, the treatment persistence in monotherapy, as well as the possible related factors of treatment success [including age, gender, smoking status, body mass index, disease type, disease phenotype for Crohn’s disease (CD), history of IBD related surgery and the presence of extraintestinal manifestations]. Results Of 168 IBD patients treated with AZA, 89 (53%) were under AZA monotherapy [38 (43%) female, 67 (74%) CD, median age (IQR) 47 (32-56) years, mean (±SD) disease duration 17 (±8.4) years, median (IQR) time receiving AZA 72 (7-120) months]. Thirty (34%) patients continue their treatment till now (23 CD, 7 ulcerative colitis-UC), with a median time (IQR) of 108 (81-132) months. Of these, 18 (60%) (15 with CD and 3 with UC) present endoscopic remission and 11 (36%) (8 with CD, 3 with UC) mild endoscopic activity (based on SES-CD Score for CD and Mayo endoscopic score for UC). Of the 59 who discontinued, 33 (37%) experienced adverse events, 5 (5.5%) developed malignancy, 5 (5.5%) did not respond at baseline, 6 (6.5%) had loss of response (at a median of 91 months), 3 (3%) discontinued due to advanced age, 3 (3%) discontinued their medication on their own and 2 because of treatment de-escalation due to deep remission. Using logistic regression analysis, patients who responded to AZA monotherapy were patients without a history of IBD surgery or any extraintestinal manifestation, P=0.001 and 0.004, respectively. In the multivariate analysis, these associations remained statistically significant (P=0.01 and 0.006 respectively). Conclusion About one third of patients with IBD under AZA monotherapy experience long term response and about two thirds of them prolonged disease remission. Patients without either a history of IBD surgery or extraintestinal manifestations seem to respond better to AZA monotherapy.

Efficacy and safety of 48 weeks of guselkumab for patients with Crohn's disease: maintenance results from the phase 2, randomised, double-blind GALAXI-1 trial

Many patients with moderately to severely active Crohn's disease do not respond to available therapies or lose response over time. The GALAXI-1 study previously found that three intravenous guselkumab dosages showed superior clinical and endoscopic outcomes over placebo at week 12 in patients with moderately to severely active Crohn's disease. We report the safety and efficacy of subcutaneous guselkumab maintenance regimens to week 48 in the GALAXI-1 study. We did a phase 2, randomised, multicentre, double-blind trial. Adult patients with moderately to severely active Crohn's disease were randomly allocated with a computer-generated randomisation schedule to receive one of five treatment groups, with regimens consisting of an intravenous induction phase transitioning to a subcutaneous maintenance phase starting at week 12 in a treat-through design: (1) guselkumab 200→100 mg group (200 mg intravenous at weeks 0, 4, and 8, then 100 mg subcutaneous every 8 weeks; (2) guselkumab 600→200 mg group (600 mg intravenous at weeks 0, 4, and 8, then 200 mg subcutaneous every 4 weeks); (3) guselkumab 1200→200 mg group (1200 mg intravenous at weeks 0, 4, and 8, then 200 mg subcutaneous every 4 weeks); (4) ustekinumab group (approximately 6 mg/kg intravenous at week 0, then 90 mg subcutaneous every 8 weeks); or (5) placebo group (placebo induction followed by either placebo maintenance [for those with CDAI clinical response at week 12] or crossover to ustekinumab [for those without CDAI clinical response at week 12]). Endpoints assessed at week 48 included CDAI remission (CDAI score <150), endoscopic response (≥50% improvement from baseline in SES-CD or SES-CD score ≤2), and endoscopic remission (SES-CD score ≤2) in the primary efficacy analysis population of all randomised patients who received at least one dose of study drug, excluding those discontinued during a temporary study pause. Safety analyses included all randomised patients who received at least one study drug dose. This trial is registered at Clinical Trials.gov (NCT03466411) and is active but not recruiting. Among 700 patients screened, 309 (112 biologic-naive; 197 biologic-experienced) were included in the primary efficacy analysis population: 61 in the guselkumab 200→100 mg group, 63 in the guselkumab 600→200 mg group, 61 in the guselkumab 1200→200 mg group, 63 in the ustekinumab group, and 61 in the placebo group. 126 (41%) women and 183 (59%) men were included, with median age 36·0 years (IQR 28·0-49·0). At week 48, the numbers of patients with CDAI clinical remission were 39 (64%) in the guselkumab 200→100 mg group, 46 (73%) in the guselkumab 600→200 mg group, 35 (57%) in the guselkumab 1200→200 mg group, and 37 (59%) in the ustekinumab group. The corresponding numbers of patients with endoscopic response were 27 (44%), 29 (46%), 27 (44%), and 19 (30%), respectively, and endoscopic remission was seen in 11 (18%), 11 (17%), 20 (33%), and four (6%) patients, respectively. In the placebo group, 15 patients were in CDAI clinical response at week 12 and continued placebo; of these, nine (60%) were in clinical remission at week 48. 44 patients in the placebo group were not in CDAI clinical response at week 12 and crossed over to ustekinumab; of these, 26 (59%) were in clinical remission at week 48. Up to week 48, adverse events frequencies in the safety population (n=360) were 46 (66%) of 70 patients (464·9 events per 100 patient-years of follow-up) in the placebo group, 163 (74%) of 220 patients (353·1 per 100 patient-years) in the three guselkumab groups combined, and 60 (85%) of 71 patients (350·7 per 100 patient-years) in the ustekinumab group. Among patients treated with guselkumab or ustekinumab, the most frequently reported infections up to week 48 were nasopharyngitis (25 [11%] of 220 guselkumab recipients, 12 [11%] of 114 ustekinumab recipients) and upper respiratory infections (13 [6%] guselkumab recipients, eight [7%] ustekinumab recipients). After week 12, one patient who responded to placebo induction and two guselkumab-treated patients had serious infections. No active tuberculosis, opportunistic infections, or deaths occurred. Patients receiving guselkumab intravenous induction and subcutaneous maintenance treatment achieved high rates of clinical and endoscopic efficacy up to week 48. No new safety concerns were identified. Janssen Research & Development.

Effectiveness of vedolizumab and ustekinumab as second biologic agent in achieving target outcomes in tumor necrosis factor antagonists experienced patients with inflammatory bowel disease (enroll-ex study).

Background: About a third of patients with inflammatory bowel disease (IBD) do not respond to anti-tumor necrosis factor (anti-TNF) therapy. In our study, we evaluated the effectiveness of vedolizumab and ustekinumab in achieving clinical and endoscopic outcomes in anti-TNF-experienced patients with IBD. Methods: We conducted a retrospective cohort study. Electronic medical records of patients with moderate to severe IBD, who were previously received anti-TNF therapies, were reviewed and evaluated retrospectively in a gastroenterology center. Outcomes of patients treated with ustekinumab or vedolizumab after failing one anti-TNF agent were evaluated. The primary outcomes were the percentage of hospitalization, surgery, mucosal healing and steroid-free remission. Mucosal healing was defined as a Mayo endoscopic score of 0 or 1 in ulcerative colitis (UC) and an SES-CD score of less than 3 in Crohn's disease (CD). Outcomes were quantified using descriptive analysis. Results: A total of 207 (130 CD: 77 UC) patients with IBD who had previously received one anti-TNF agent were included in the study. Of the total cohort, 62 (30.0%) patients were receiving vedolizumab, and 145 (70.0%) patients were on ustekinumab. 101 (77.6%) patients with CD who failed one anti-TNF therapy were on ustekinumab. Of these patients, 26 (19.7%) patients were hospitalized, and 12 (11.9%) patients had IBD-related surgery. 16 (16.1%) patients had at least one corticosteroid course. 60 (59.0%) patients with CD on ustekinumab achieved mucosal healing. 29 (22.3%) patients with CD who failed one anti-TNF therapy were receiving vedolizumab. Of those, 7 (25%) patients were hospitalized, and 11 (37.9%) patients had IBD-related surgery. 15 (51.0%) patients achieved mucosal healing. 44 (57.1%) patients with UC who failed one anti-TNF therapy were on ustekinumab. Of these 6 (14.1%) patients were hospitalized, 3 (7.0%) patients had IBD-related surgery and 13 (30%) patients had at least 1 corticosteroid course. 25 (57.0%) patients achieved mucosal healing. 33 (42.8%) patients with UC who failed one anti-TNF therapy were receiving vedolizumab. Of those, 6 (18.6%) patients were hospitalized, and 16 (49.6%) patients had at least 1 corticosteroid course. 17 (53.2%) patients achieved mucosal healing. Conclusion: Ustekinumab and vedolizumab were both effective in achieving clinical outcomes in patients with IBD after failing an anti-TNF agent. However, patients receiving ustekinumab had numerically higher percentages of reaching target outcomes than patients receiving vedolizumab. A prospective head-to-head trial is warranted to confirm these findings.

Early fecal calprotectin levels at week 8 may guide therapeutic decisions on Ustekinumab therapy in patients with Crohn’s disease

Background Response evaluation after induction therapy with ustekinumab (UST) in Crohn’s disease (CD) is important for decisions on maintenance therapy. We aimed to assess the potential of fecal calprotectin (FC) levels to predict endoscopic response at week 16. Methods CD patients with FC >100 µg/g and endoscopic active disease (SES-CD> 2, Rutgeerts’ score ≥ i2) at initiation of UST therapy were enrolled. FC was determined at weeks 0, 2, 4, 8 and 16 and patients underwent a colonoscopy at week 16. The primary outcome was an endoscopic response at week 16 (SES-CD score ≥50% decrease or a decrease of ≥1 points in Rutgeerts’ score). The optimal cut-off levels of FC and change in FC to predict endoscopic response were determined using ROC statistics. Results 59 CD patients were included. Endoscopic response was observed in 21/59 (36%) patients. The diagnostic accuracy for FC levels at week 8 to predict endoscopic response at week 16 showed a predictive value of 0.71. A decrease in FC levels ≥500 µg/g between baseline at week 8 indicates endoscopic response (PPV = 89%), whereas absence of any decrease indicates endoscopic non-response after induction (NPV = 81%). Conclusions Continuation of UST therapy without endoscopic response evaluation may be considered in patients with a decrease in FC levels of ≥500 µg/g at week 8. The decision on continuation of UST therapy or therapy optimization needs reconsideration in patients without a decrease of FC level. In all other patients, endoscopic response evaluation of induction therapy remains essential for therapeutic decisions.

A14 TRANSABDOMINAL BOWEL ULTRASOUND AND CLINICAL OUTCOMES OVER ONE YEAR IN CHILDREN WITH NEWLY DIAGNOSED CROHN’S DISEASE

Abstract Background Transabdominal bowel ultrasound (TABUS) is an emerging non-invasive tool for monitoring inflammatory bowel disease (IBD). Its use is particularly increasing in pediatric IBD, given the need for anesthesia during endoscopy. The assessment of TABUS in pediatric IBD has been limited to small numbers of patients with no long-term follow-up. Purpose To describe TABUS findings and its relationship with clinical, biochemical, and endoscopic assessments in pediatric patients with Crohn’s disease up to one year post-diagnosis. Method Patients (0-18 years) with suspected IBD were prospectively enrolled through the Edmonton Pediatric IBD Clinic. Those with Crohn’s disease were included. Patients underwent repeated TABUS, clinical assessments, blood work, fecal calprotectin (FCP) (baseline, 1-, 3-, 6-, 12-months), and endoscopy (baseline and 6-12 months). The weighted Pediatric Crohn’s Disease Activity Index (wPCDAI), Simple Endoscopic Score for Crohn’s Disease (SES-CD; rectum excluded), and Simple Ultrasound Activity Score for Crohn’s Disease (SUS-CD; rectum excluded) were used. Remission was defined as FCP&amp;lt;250mg/kg, CRP&amp;lt;4mg/L, wPCDAI&amp;lt;12, no upcoming surgery, and SES-CD score ≤2 for any bowel segment. Result(s) Fifty-six patients (68% male), median age 12.5 years (range 6-17), were followed for 6 months. Forty (71%) were followed up to 12 months. Median TABUS bowel wall thickness (BWT) and SUS-CD total scores improved in all bowel segments over time. SUS-CD total scores significantly correlated with SES-CD (baseline, 6-, 12-months), wPCDAI (baseline, 1-, 6-, 12-months), CRP (baseline, 1-, 3-, 6-months), ESR (baseline, 1-, 3-, 6-, 12-months), and FCP (baseline, 1-, 6-, 12-months) (rho ranged 0.302-0.732, p&amp;lt;0.05). Patients in remission had sustained significantly thinner BWT of their most affected bowel segment (Figure 1) starting at 1-month (median 3.1mm (IQR 2.7-3.7) vs. 4.1mm (IQR 2.9-5.6; p&amp;lt;0.05), and sustained significantly lower SUS-CD total scores starting at 6 months (median 0 (IQR 0-1) vs. median 2 (IQR 1-3); p&amp;lt;0.05). Seven patients had surgery (n=7/7 ileocecal, n=2/7 jejunal resection). All 7 patients had complex TI disease (n=6 strictures, n=1 long-segment disease &amp;gt;25cm) and proximal small bowel disease (n=2/2) on TABUS. Those with baseline ultrasound findings of a stricture with upstream bowel dilatation (n=7/56) had increased odds (OR=288, p&amp;lt;0.01) and relative risk (RR=42, p&amp;lt;0.01) of needing surgery (n=6/7 with baseline obstructive findings, n=1/49 without) within the first year. Image Conclusion(s) TABUS had significant correlations with clinical, biochemical, and endoscopic markers of Crohn’s disease activity in pediatric patients over one year. Bowel wall thickness of the most affected bowel segment is a helpful measurement, becoming significantly thinner as soon as 1-month post-diagnosis in those who obtain remission. Baseline findings of bowel narrowing and upstream dilation increase the odds and relative risk of needing surgery in the first year. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared

P318 Protein FingerPrint assays reflecting neutrophil activity, mucosal damage, and tissue fibrosis are surrogate biomarkers for mucosal healing in pediatric Crohn’s disease

Abstract Background Mucosal healing (MH) has become a treatment goal for inflammatory bowel disease (IBD), especially for ulcerative colitis. However, MH is less feasible to assess frequently in patients with Crohn’s disease (CD). In this study, we investigated Protein Fingerprint Assays (PFA) of collagen degradation and formation, and neutrophil and macrophage activity markers in the ImageKids study as non-invasive markers of MH. Methods This is a proteomics planned sub-study of the multi-center prospective ImageKids study which included serum samples from children with CD (n=178) undergoing MRE and ileocolonoscopy concurrently (ImageKids study: NCT01881490). Serum from healthy age and gender-matched controls were obtained from BioIVT (n=83). PFA panel for mucosal damage (C1M, C3M, C4M, C6M, ELP-3), Immune cell activity panel (CPa9-HNE, VICM, C4G), and tissue fibrosis panel (PRO-C1, PRO-C3, PRO-C4, PRO-C5, PRO-C6, PRO-C11, PRO-C22) were determined. MH was classified as having an SES-CD score of 0 and global radiologist assessment of inflammation in the MRE of 0, using a visual analogue scale (VAS) 0-100mm, and mucosal damage (MD) was defined as having SES-CD or MRE VAS&amp;gt;0. Spearman rho correlations, one-way ANOVA with Tukey correction, and receiver operator characteristics (ROC) curves were applied for statistical analysis. Results Some of the previous biomarkers demonstrated to correlate with the SES-CD score and ulcer size (C1M, C3M, C6M, PRO-C4, VICM, PRO-C1, PRO-C3). CPa9-HNE, ELP-3, and PRO-C22 also correlate with the SES-CD score (table 1). The combined SES-CD and MRE VAS score of MH correlated positively with CPa9-HNE (r=0.30, p&amp;lt;0.0001), VICM (r=0.39, p&amp;lt;0.0001), C1M (r=0.29, p=0.0001), C3M (r=0.22, p=0.0022), C6M (r=0.35 p&amp;lt;0.0001), PRO-C4 (r=0.2, p&amp;lt;0.0001), PRO-C22 (r=0.32, p&amp;lt;0.0001), (figure 1 and 2) and showed significantly lower serum levels in pCD patients with MH compared to patients with mild, moderate, or severe mucosal damage (p&amp;lt;0.001) (figure 2). PRO-C3 correlated negatively with the combined SES-CD and MRE VAS score (r=-0.17, p=0.0211). These PFA biomarkers were combined in a multivariate regression model, demonstrating increased accuracy to identify patients in MH healing compared to the individual biomarkers (p&amp;lt;0.001, MH vs. MD: AUC=0.82 [CI:0.69-0.95), MH+Mild MD vs. moderate+severe MD: AUC=0.77 [0.70-0.84], (figure 3). Conclusion PFA biomarkers of Neutrophil activity (CPa9-HNE), Macrophage activity (VICM), mucosal damage (C1M, C3M, C4M, C6M, ELP-3), and tissue fibrosis (PRO-C3, PRO-C22) are potential surrogate biomarkers for identifying pCD patients with mucosal healing and for monitoring of mucosal damage and stenosis.

P632 Etrasimod induction therapy in moderately to severely active Crohn’s disease: results from a phase 2, randomised, double-blind substudy

Abstract Background Etrasimod is an investigational, once-daily, oral, selective sphingosine 1-phosphate receptor 1,4,5 (S1P1,4,5) modulator in development to treat immune-mediated inflammatory disorders. CULTIVATE (NCT04173273) is a seamless phase 2/3 trial comprising 5 substudies designed to evaluate the efficacy, safety, and tolerability of etrasimod in subjects with moderately to severely active Crohn’s disease (CD). Here, we report the induction data from the first substudy (Substudy A). Methods Substudy A was a phase 2, randomised, double-blind study using a 14-week induction period followed by a 52-week extension period. Adults (18-80 years) with moderately to severely active CD and an inadequate response, loss of response to, or intolerance to ≥1 conventional or advanced treatments for CD were randomised 1:1 to once-daily etrasimod 2 mg or 3 mg. Subjects were stratified by baseline biologic failure status and oral corticosteroid use. The primary efficacy endpoint was achievement of endoscopic response (defined as endoscopic remission [SES-CD ≤4 and ≥2-point reduction from baseline with no subscore &amp;gt;1] or ≥50% decrease in SES-CD score) at week 14. Secondary/exploratory endpoints included achievement of endoscopic remission, clinical remission (CDAI &amp;lt;150), and IBDQ remission (IBDQ ≥170) at week 14. Outcomes were analysed in the Full Analysis Set (all randomised subjects treated with ≥1 dose) using NRI or observed data. Results Of 83 subjects randomised to etrasimod 2 mg or 3 mg, respectively, 32/42 (76.2%) and 36/41 (87.8%) completed week 14 (Table 1). Overall, 21.4% and 9.8% of subjects in the 2-mg and 3-mg groups, respectively, achieved the primary endpoint of endoscopic response, 14.3% and 7.3% achieved endoscopic remission, 31.0% and 43.9% achieved clinical remission, and 33.3% and 40.0% achieved IBDQ remission at week 14 (Figure 1). Most treatment-emergent AEs were mild or moderate, with more AEs reported in the 3-mg vs 2-mg group. The incidence of serious AEs (4.8% and 2.4%) and AEs leading to discontinuation (4.8% and 7.3%) was low in the 2-mg and 3-mg groups, respectively (Table 2). Two subjects in the 3-mg group experienced second degree atrioventricular block type 1 TEAEs (during 2-mg titration). Conclusion Data from this substudy of subjects with moderately to severely active CD suggest endoscopic and clinical improvement with both etrasimod 2 mg and 3 mg. However, the small sample size and lack of placebo arm limit the ability to draw conclusions about efficacy including comparison between the 2-mg vs 3-mg groups. Both doses were well tolerated and safety was consistent with other etrasimod clinical programmes. Data from the extension phase of Substudy A and the placebo-controlled, dose-ranging phase 2b Substudy 1 are forthcoming.

P576 Endoscopic healing with vedolizumab in Crohn's disease occurs predominantly in the first 6 months and is independent of serum concentrations: Data from LOVE-CD

Abstract Background Endoscopic healing is an important treatment goal in Crohn’s disease (CD). Vedolizumab (VDZ) was shown to induce endoscopic healing after 6 months in a significantly greater proportion of pts with early CD than in those with late CD (&amp;gt;2 years)(UEGW 2022). We investigated whether further endoscopic healing could be attained with 6 more months of VDZ treatment in those pts with no SES-CD worsening at month 6 compared to baseline. Methods Pts in the LOVE-CD study received standard doses of VDZ and had ileocolonoscopies at baseline, w26 and 52. We studied the kinetics of endoscopic improvement during continued VDZ treatment. Endoscopies were scored by independent readers. So far, 157 pts completed the LOVE-CD trial with available central reading results. We here report the results of 76 pts (48%) who had stable endoscopic diseases or any degree of endoscopic improvement at w26 with 3 centrally read endoscopy scores (baseline, w26 and 52) available at present. VDZ serum conc were also measured and correlated to endoscopic improvement. Results We studied 76 pts (mean age 36.7, 51 (67%) female, median baseline SES-CD 10 (range 3-30) who reached w52 and had no SES-CD worsening at w26. We identified 3 endoscopic improvement patterns: 1) 24 pts (32%, 12 early, 12 late CD) with median baseline SES-CD 7.5 (range 3-21) had a SES-CD score of 0 at w26. Three of these pts had again mild lesions at w52 (SES-CD 1-4), the rest maintained SES-CD=0 at w52 (endoscopic healing); 2) 20 pts (26%, 6 early, 14 late CD) with median baseline SES-CD 8 (range 3-27) had a SES-CD of 1-3 at w26 (endoscopic remission defined as SES-CD&amp;lt;4). At w52, 10/20 had a score of 0, 7/20 the same score as at w26 and only 3/20 a higher score; 3) 32 pts (42%, 5 early, 27 late CD) with median baseline SES-CD 14 (range 5-30) had no endoscopic remission at w26 (SES-CD &amp;gt;4) with a drop to median SES-CD 7 (range 5-20) at w26 and further to median SES-CD 5 (range 0-15) at w52. Figure 1 shows the evolution of the SES-CD. The mean VDZ serum conc was (1) 19.36 mg/l at w26 and 22.23 mg/l at w52 in the group with endoscopic healing, (2) 19.52 mg/l at w26 and 21.69 mg/l at w52 in the group with endoscopic remission, and (3) 17.38 mg/l at w26 and 20.09 mg/l at w52 in the group without endoscopic healing or remission. Conclusion In this subset of LOVE-CD pts with endoscopic improvement or unchanged SES-CD at w26, the majority of pts (44/76) reached endoscopic remission (SES-CD&amp;lt;4). Overall, endoscopic improvement in this subgroup of responders by SES-CD score was a median of 7 (range -1 to 25) SES-CD points between w0 and w26 and a median of 0 (range -10 to +15) SES-CD points between w26 and w52. The degree of endoscopic improvement beyond month 6 was unrelated to VDZ serum conc.

OP03 Highly stable epigenome-wide peripheral blood DNA methylation signatures accurately predict endoscopic response to adalimumab, vedolizumab and ustekinumab in Crohn’s disease patients: The EPIC-CD study

Abstract Background Despite the proven efficacy of biological treatments in Crohn’s disease (CD), many patients fail to respond or lose response over time. Therefore, predictive biomarkers for treatment efficacy would be of extreme value. Previous epigenome-wide association studies associated differential DNA methylation with CD-specific phenotypes, suggesting a potential use in classification and prediction of response to treatment. Methods We prospectively collected and measured longitudinal peripheral blood DNA methylation profiles of 184 adult CD patients prior to (T1) and after a median of 28 weeks (T2) following biological treatment with Adalimumab (ADA), Vedolizumab (VEDO) or Ustekinumab (USTE) in a discovery (n=88) and independently collected internal validation cohort (n=96) using the Illumina EPIC BeadChip array. Response (R) was defined as the combination of endoscopic response (≥50% reduction in SES-CD score) and steroid-free clinical response (≥3 point drop in HBI or HBI ≤4 AND no systemic steroids) and/or biochemical response (≥50% reduction in C-reactive protein (CRP) and fecal calprotectin or a CRP ≤5 g/mL and fecal calprotectin ≤250 µg/g). Biomarker identification and classification analyses were performed using stability selection gradient boosting on samples taken at T1 whereas samples taken at T2 and intraclass correlation (ICC) data were used to assess long-term stability of our identified CpG loci1. Results A total of 58 ADA-patients (NR=29, NNR=29), 64 VEDO-patients (NR=36, NNR=28) and 62 USTE-patients (NR=30, NNR=32) were included. Prior to treatment, at T1, we identified distinct panels of 100 ADA-, 22 VEDO- and 68 USTE-associated CpG loci that, in combination, predict clinical- and endoscopic response with high accuracy (AUC ADA=0.73, VEDO=0.89 and USTE=0.94) upon validation. Notably, for these CpG loci, methylation levels did not significantly differ between T1 and T2, implicating stability during both induction and maintenance treatment, irrespective of inflammatory status and therapeutic intervention. In addition, the majority of these CpG loci (&amp;gt;60%) demonstrated long-term hyper stability (ICC-values ≥0.90). Furthermore, genes annotated to the CpGs of interest suggest drug specific involvement in TNF-signaling, endothelial cell-cell adhesion, integrin dependent T-cell homing, the innate immune system and Th17/Treg differentiation, corroborating to the mode of action of each drug. Conclusion Here, we report on 3 validated panels of highly stable, epigenetic biomarkers that predict clinical and endoscopic response in CD patients treated with ADA, VEDO or USTE. Additional external- and clinical validation as part of EPIC-CD and the OMICROHN clinical trial are currently ongoing.

P648 Effectiveness of Biologic Therapies in Decreasing Risk of Hospitalization and Surgery, Maintaining Steroid Free Remission and Achieving Mucosal Healing in Inflammatory Bowel Disease; Real World Data.

Abstract Background Several biologic therapies are currently available for the management of inflammatory bowel disease (IBD) rendering the choice and sequencing between them as a first line under question. In our study, we evaluated the effectiveness of biologic therapies in achieving important clinical and endoscopic outcomes in biologic naïve patients with IBD. Methods Electronic medical records of patients with moderate to severe IBD, who were previously naïve to biologics, were reviewed and evaluated retrospectively in a tertiary care gastroenterology center, Haya Alhabib Center. Patients who were on infliximab, adalimumab, ustekinumab and vedolizumab for 12 months were included. The primary end points were percentage of hospitalization, surgery, steroid free remission, and mucosal healing, defined as Mayo score less than 1 in ulcerative colitis and SES-CD score less than 3 in Crohn’s disease. Descriptive analysis was performed to measure outcomes. Results A total of 335 biologic naïve patients with IBD were included; 262 (78.2%) patients with ulcerative colitis and 73 (21.8%) patients with Crohn’s disease. Regarding hospitalization, 25 (14.7%) out of 170 on adalimumab,12 (10.7%) out of 112 on infliximab, and one (6.25%) on vedolizumab were hospitalized. None of the patients on ustekinumab were hospitalized. 9 out of 171 (4.7%) patients on adalimumab underwent surgery, while none of the patients on the other biologics underwent IBD related surgery. Regarding steroid free remission, 29 (16.9%) out of 171 patients on adalimumab received steroid courses, 15 (13.3%) out of 113 patients on infliximab, 4 (11.4%) out of 35 patients on ustekinumab, and 1 (6.3%) out of 16 patients on vedolizumab. A total of 159 out of 171 patients (93.0%) on adalimumab achieved mucosal healing. While 100 out of 113 patients (88.5%) on infliximab, 26 out of 35 patients (74.3%) on ustekinumab, and 7 out of 16 patients (43.8%) on vedolizumab achieved mucosal healing. Conclusion Adalimumab, infliximab, and ustekinumab and vedolizumab were all effective in inducing steroid free remission. However, patients on vedolizumab had numerically lower percentages of mucosal healing than other biologics. Percentage of hospitalizations and IBD related surgeries were higher in patients on infliximab and adalimumab. Future Larger prospective comparative studies are needed.