CD-related Surgery Research Articles

Real-world Clinical Effectiveness and Safety of Vedolizumab and Adalimumab in Biologic-naive Patients With Crohn's Disease: Results From the EVOLVE Study.

This study evaluated the real-world effectiveness and safety of vedolizumab versus adalimumab over 12 months of treatment in biologic-naive patients with Crohn's disease (CD), using data from the EVOLVE study. A comparison of vedolizumab and adalimumab may help to better position them in the therapeutic algorithm for moderate-to-severe CD. Data were collected from medical records of patients with CD aged ≥18 years initiating treatment with adalimumab or vedolizumab between May 2014 and July 2017. Adjusted analyses were performed using inverse probability weighting to account for differences in baseline characteristics. Cumulative rates for clinical effectiveness outcomes and treatment persistence were estimated using Kaplan-Meier analyses. Disease-related exacerbations, serious adverse events (SAEs), and serious infections (SIs) were also assessed. Data from 218 vedolizumab- and 144 adalimumab-treated patients were analyzed. Adjusted cumulative rates of clinical remission were greater with vedolizumab than with adalimumab (66.3% vs. 46.4%; P=0.006). Probability of treatment persistence was higher with vedolizumab (89.3% vs. 77.5%; P=0.024); probabilities of clinical response (68.5% vs. 61.1%; P=0.586) and mucosal healing (67.7% vs. 56.0%; P=0.562) were similar. SAEs were less likely to occur with vedolizumab [hazard ratio, 0.45 (95% confidence interval, 0.22-0.93)]; however, the likelihood of SIs [0.27 (0.06-1.20)], CD exacerbations [0.91 (0.56-1.47)], and CD-related surgeries [1.55 (0.21-11.15)] was comparable between the 2 groups. In a real-world setting, biologic-naive patients with CD treated with vedolizumab demonstrated a greater likelihood of drug persistence and achieving clinical remission, with equivalent rates of response and mucosal healing versus adalimumab-treated patients.

Early Biological Therapy Within 12 Months of Diagnosis Leads to Higher Transmural Healing Rates in Crohn’s Disease

Transmural healing (TH) is emerging as a potential Crohn´s Disease (CD) treatment target. Early biological treatment seems to be associated with improved disease outcomes, but its impact on TH remains unclear. We aimed to assess the impact of early biological treatment initiation on TH and its influence on CD prognosis. This multicenter retrospective study included adult CD patients starting biological therapy. TH was assessed using magnetic resonance enterography (MRE) at 12±6 months post-therapy initiation, with radiological examinations reviewed by blinded expert radiologists. TH was defined as complete normalization of all MRE parameters. Timing of biological therapy initiation was analyzed as a continuous variable, with optimal cut-off determined using the Youden index and clinical relevance. Logistic regression with propensity score-adjusted analysis was used to assess the association between early biological therapy initiation and TH. Long-term outcomes (bowel damage progression, CD-related surgery, CD-flare hospitalization, and therapy escalation) were evaluated. Among 154 CD patients, early biological therapy initiation within 12 months of diagnosis was associated with significantly higher TH rates (aOR 3.23, 95% CI 1.36-7.70, p<0.01), which persisted after adjusting for previous biological therapy use (aOR 2.82, 95% CI 1.13-7.06, p=0.03). Time-to-event analysis demonstrated that TH was significantly associated with reduced time until bowel damage progression (aHR 0.28, 95% CI 0.10-0.79, p=0.02), CD-related surgery (aHR 0.21, 95% CI 0.05-0.88, p=0.03) and therapy escalation (aHR 0.35, 95%CI 0.14-0.88, p=0.02), independently of early biological therapy. Early initiation of biological therapy within 12 months of diagnosis significantly increases TH rates, leading to improved long-term outcomes in CD patients.

A Prediction Model for Successful Increase of Adalimumab Dose Intervals in Patients with Crohn’s Disease: Secondary Analysis of the Pragmatic Open-Label Randomised Controlled Non-inferiority LADI Trial

BackgroundIn the pragmatic open-label randomised controlled non-inferiority LADI trial we showed that increasing adalimumab (ADA) dose intervals was non-inferior to conventional dosing for persistent flares in patients with Crohn’s disease (CD) in clinical and biochemical remission.AimsTo develop a prediction model to identify patients who can successfully increase their ADA dose interval based on secondary analysis of trial data.MethodsPatients in the intervention group of the LADI trial increased ADA intervals to 3 and then to 4 weeks. The dose interval increase was defined as successful when patients had no persistent flare (> 8 weeks), no intervention-related severe adverse events, no rescue medication use during the study, and were on an increased dose interval while in clinical and biochemical remission at week 48. Prediction models were based on logistic regression with relaxed LASSO. Models were internally validated using bootstrap optimism correction.ResultsWe included 109 patients, of which 60.6% successfully increased their dose interval. Patients that were active smokers (odds ratio [OR] 0.90), had previous CD-related intra-abdominal surgeries (OR 0.85), proximal small bowel disease (OR 0.92), an increased Harvey-Bradshaw Index (OR 0.99) or increased faecal calprotectin (OR 0.997) were less likely to successfully increase their dose interval. The model had fair discriminative ability (AUC = 0.63) and net benefit analysis showed that the model could be used to select patients who could increase their dose interval.ConclusionThe final prediction model seems promising to select patients who could successfully increase their ADA dose interval. The model should be validated externally before it may be applied in clinical practice.Clinical Trial Registration NumberClinicalTrials.gov, number NCT03172377.

Crohn's Disease Phenotypes and Associations With Comorbidities, Surgery Risk, Medications and Nonmedication Approaches: The MAGIC in IMAGINE Study.

We aimed to establish a cohort of persons with Crohn's disease (CD) enrolled from 14 Canadian centers to describe the contemporary presentation of CD in Canada. All enrollees were at least 18 years old and underwent chart review for phenotype documentation by Montreal Classification at time of enrollment, comorbidities, inflammatory bowel disease (IBD) and other surgeries, and use IBD and other therapies. Of 2112 adults, 59% were female, and the mean age was 44.1 (+/-14.9SD) years. The phenotype distribution was B1 = 50.4%, B2 = 22.4%, B3 = 17.3%, and missing information = 9.9%. Perineal disease was present in 14.2%. Pertaining to disease location, 35.2% of patients had disease in L1, 16.8% in L2, 48% in L3, and 0.4% in L4. There was no difference in phenotype by gender, anxiety score, depression score. Disease duration was significantly different depending on disease behavior type (B1 = 12.2 ± 10.1; B2 = 19.4 ± 12.9; B3 = 18.9 ± 11.8, P < .0001). Isolated colonic disease was much less likely to be fibrostenotic or penetrating than inflammatory disease. Penetrating disease was more likely to be associated with ileocolonic location than other locations. Perineal disease was most commonly seen in persons with B3 disease behavior (24%) than other behaviors (11% B1; 20% B2 disease, P < .0001) and more likely to be seen in ileocolonic disease (L3;19%) vs L2 (17%) and L1 (11%; P < .0001). Surgery related to IBD occurred across each behavior types at the following rates: B1 = 23%, B2 = 64%, and B3 = 74%. Inflammatory bowel disease-related surgery rates by location of disease were L1 = 48%, L2 = 21%, and L3 = 51%. In exploring this large contemporary CD cohort we have determined that inflammatory disease is the main CD phenotype in Canada and that CD-related surgery remains very common.

Defining Endoscopic Remission in Crohn’s Disease: MM-SES-CD and SES-CD Thresholds Associated With Low Risk of Disease Progression

ObjectiveWe assessed Modified Multiplier Simple Endoscopic Score for Crohn’s disease (MM-SES-CD) and SES-CD thresholds that are best associated with low likelihood of long-term disease progression. DesignData from 61 patients with early CD who participated in the CALM long-term extension study were used as the derivation cohort and validated using the McMaster IBD database (n=99). The primary outcome was disease progression (new internal fistula/abscess, stricture, perianal fistula or abscess, CD-related hospitalization or surgery) since the end of the CALM trial. Optimal MM-SES-CD and SES-CD thresholds were determined using the maximum Youden index. Receiver operating characteristic curve analyses compared threshold scores of remission definitions on disease progression. ResultsIn the derivation cohort, based on the maximum Youden index, the optimal thresholds associated with a low likelihood of disease progression were MM-SES-CD <22.5 and SES-CD <4. A significantly greater proportion of patients with a MM-SES-CD ≥22.5 had disease progression as compared to patients in the derivation cohort with MM-SES-CD <22.5 [10/17 (58.8%) vs. 3/44 (6.8%), p<0.001]. Similarly, a significantly greater number of patients with SES-CD ≥ 4 had disease progression compared to those with a SES-CD <4 [11/25 (44.0%) vs. 2/36 (5.6%), p<0.001]. Compared to other clinical or endoscopic remission definitions, which demonstrated poor to fair accuracy, MM-SES-CD <22.5 performed the best for predicting disease progression [AUC: 0.81 (95%CI: 0.68-0.94), p<0.001]. These thresholds were confirmed in the validation cohort. ConclusionsAchievement of MM-SES-CD <22.5 or SES-CD <4 in patients with ileocolonic or colonic CD is associated with low risk of disease progression and may be suitable targets in clinical trials and practice for endoscopic healing.

Predictors of Complicated Disease Course in Adults and Children With Crohn’s Disease: A Nationwide Study from the epi-IIRN

Abstract Background Since data on predictors of complicated Crohn’s disease (CD) from unselected populations are scarce, we aimed to utilize a large nationwide cohort, the epi-IIRN, to explore predictors of disease course in children and adults with CD. Methods Data of patients with CD were retrieved from Israel’s 4 health maintenance organizations, whose records cover 98% of the population (2005-2020). Time-to-event modeled a complicated disease course, defined as CD-related surgery, steroid-dependency, or the need for &amp;gt;1 class of biologics. Hierarchical clustering categorized disease severity at diagnosis based on available laboratory results. Results A total of 16 659 patients (2999 [18%] pediatric-onset) with 121 695 person-years of follow-up were included; 3761 (23%) had a complicated course (750 [4.5%] switched to a second biologic class, 1547 [9.3%] steroid-dependency, 1463 [8.8%] CD-related surgery). Complicated disease was more common in pediatric- than adult-onset disease (26% vs 22%, odds ratio, 1.3; 95% confidence interval [CI], 1.2-1.4). In a Cox multivariate model, complicated disease was predicted by induction therapy with biologics (hazard ratio [HR], 2.1; 95% CI, 1.2-3.6) and severity of laboratory tests at diagnosis (HR, 1.7; 95% CI, 1.2-2.2), while high socioeconomic status was protective (HR, 0.94; 95% CI, 0.91-0.96). In children, laboratory tests predicted disease course (HR, 1.8; 95% CI, 1.2-2.5), as well as malnutrition (median BMI Z score −0.41; 95% CI, −1.42 to 0.43 in complicated disease vs −0.24; 95% CI, −1.23 to 0.63] in favorable disease; P &amp;lt; .001). Conclusions In this nationwide cohort, CD course was complicated in one-fourth of patients, predicted by laboratory tests, type of induction therapy, socioeconomic status, in addition to malnutrition in children.

Early Initiation of Biologics and Disease Outcomes in Adults and Children With Inflammatory Bowel Diseases: Results From the Epidemiology Group of the Nationwide Israeli Inflammatory Bowel Disease Research Nucleus Cohort

In this nationwide study, we explored whether early initiation of biologics is associated with improved outcomes in children and adults with Crohn's disease (CD) and ulcerative colitis (UC). All patients diagnosed with CD or UC in Israel (2005-2020) were included in the Epidemiology Group of the Israeli Inflammatory Bowel Disease Research Nucleus cohort, encompassing 98% of the population. We compared disease duration at biologics initiation (ie, 0-3 months, >3-12 months, >1-2 years, and >2-3 years) using the cloning, censoring, and weighting by inverse probabilities method to emulate a target trial, adjusting for time-varying confounders and selection bias. Of the 34,375 included patients (of whom 5240 [15%] were children), 7452 of 19,264 (39%) with CD and 2235 of 15,111 (15%) with UC received biologics. In CD, by 10 years postdiagnosis, the probability of CD-related surgery decreased gradually but modestly with earlier initiation of biologics; a significant difference was noted between >2-3 years (31%) and 0-3 months (18%; P= .02; number needed to treat, 7.7), whereas there was no difference between the 0-3-month and >3-12-month periods. The 10-year probability of steroid dependency for the 0-3-month period (19%) differed both from the >2-3-year (31%; P < .001) and 1-2-year periods (37%; P < .001). In UC, no significant differences in colectomy or steroid dependency rates were observed between the treatment initiation periods. Similar trends were noted in the pediatric population. Very early initiation of biologics was not associated with some outcomes except for a modest risk reduction of surgery and steroid dependency for CD, which requires confirmation in future studies. In UC, early introduction of biologics was not associated with reduced risk of colectomy or steroid dependency.

PHYSICAL ACTIVITY AND SOCIAL COGNITIVE THEORY CORRELATES AMONG POSTOPERATIVE PERSONS WITH CROHN'S DISEASE: PRELIMINARY RESULTS FROM A CROSS-SECTIONAL ANALYSIS

Abstract INTRODUCTION There is increasing research and clinical interest in physical activity (PA) behavior among persons with Crohn's disease (CD), but little is known regarding PA and its correlates among postoperative persons with CD. This is important as most patients with CD will require surgery within 10 years of diagnosis which may drastically alter PA levels and its benefits for CD. As found in past studies with other patient populations (e.g., colorectal cancer survivors), understanding the cognitive and behavioral factors associated with PA engagement among postoperative adults with CD is useful for informing the development of PA behavior change interventions for this population. This cross-sectional study examined self-reported PA levels and its associations with social cognitive theory (SCT) variables among postoperative persons with CD. METHODS Participants included 30 persons with CD who completed an online survey between November 2022 and June 2023. Of those participants, 18 reported a history of CD-related surgery. The survey assessed demographic and clinical characteristics, disease activity (Harvey-Bradshaw Index), leisure time exercise (Godin Leisure-Time Exercise Questionnaire and International Physical Activity Questionnaire), and related SCT variables (exercise self-efficacy, social support, outcome expectations, goal setting, and planning). Analyses included independent sample t-tests and non-parametric bivariate correlations (rs) for comparing PA levels and SCT survey scores among participants with and without a history of surgery. RESULTS There were differences in PA and SCT variables based on surgical history. Postoperative participants engaged in significantly more PA (t = 2.17, p = 0.04) and reported greater outcome expectations (t = 2.45, p = 0.02) and goal setting (t = 2.22, p = 0.04) scores compared with CD participants without a history of surgery. Among postoperative participants, only exercise goal setting was significantly correlated with PA (rs = .53, p = 0.03) such that postoperative participants with greater exercise goal setting behaviors reported higher levels of PA. None of the SCT variables were significantly associated with PA in the sample of participants without a history of surgery. CONCLUSIONS This study yielded novel findings regarding PA behavior and its SCT correlates in a small sample of postoperative persons with CD. The results suggest the need for further research into exercise goal setting as a potential target of behavior change interventions for increasing PA among postoperative persons with CD.

DEVELOPMENT OF CROHN'S DISEASE IN PATIENT PRESENTING WITH COMPLEX PERIANAL FISTULA TO A TERTIARY MEDICAL CARE CENTER

Abstract BACKGROUND Approximately 20% of patients with Crohn’s disease (CD) will develop a perianal fistula (PAF), most of which are complex fistulas1-4. Studies have shown that 4-5% of patients with CD present with perianal fistula without luminal disease, termed isolated perianal Crohn’s disease4,5,6. However, little is known about the natural history of isolated complex PAF (iPAF). We therefore aimed to evaluate the clinical course of patients who presented with iPAF including describing those who subsequently developed luminal CD. METHODS We performed a retrospective cohort study of patients seen within the Mount Sinai Health System (New York) with an ICD-10 diagnosis code for PAF between 7/22/2008 and 7/22/2022. Medical record review was conducted to identify patients with complex PAF who did not have evidence of luminal disease and had &amp;gt; 6 months of follow-up (Table 1). Luminal disease was defined as any evidence of ulcers, erosions, or strictures on endoscopic or video capsule exam or MRE with evidence of inflammation consistent with luminal CD. Demographics, comorbidities, imaging, endoscopy, surgeries, hospitalizations and medication data were collected. Descriptive and univariate analyses were performed. Complicated disease course was defined as a composite of any major CD-related surgery, PAF/IBD-related hospitalization or biologic use. RESULTS Among 887 patients with PAF, 62.2% (n=552) patients underwent luminal evaluation, of whom 80 patients (14.5%) were found to have no luminal disease (Table 1). Of these, 57 patients had &amp;gt;6 months of follow-up with 22.8% (n=13) going on to develop luminal disease. Luminal CD was diagnosed at a mean time of 4.2 (SD=3.8) years after iPAF presentation. Compared to patients who developed luminal CD, patients with solely iPAF were less likely to be &amp;lt;30 years old at PAF diagnosis (p=0.0225) or have concomitant autoimmune conditions (p=0.046) (Table 2). Patients with iPAF were less likely to have &amp;gt;2 fistulas (p=0.002) or have CD/PAF-related hospitalization (29.5% vs 61.5%, p =0.0356) compared to those who developed luminal CD (Table 2). Patients with iPAF were significantly less likely to have a complicated disease course than those who later developed luminal CD (2.3% vs 30.8%, p=0.007). CONCLUSION We observed that approximately 1 in 4 patients who presented with iPAF went on to develop luminal CD. Patients who went on to develop luminal CD were more likely to be &amp;lt;30 at PAF diagnosis, have concomitant autoimmune conditions and were more likely to have IBD-related adverse outcomes. The majority of patients with iPAF did not experience a complicated disease course and may represent a specific sub-phenotype of CD.

IMPACT OF TREATMENT RESPONSE WITH ADALIMUMAB ON RISK OF SERIOUS INFECTIONS IN PATIENTS WITH CROHN’S DISEASE: SECONDARY ANALYSIS OF THE PYRAMID REGISTRY

Abstract BACKGROUND AND AIMS Treatment efficacy and safety are primary factors in choosing therapies in patients with Crohn’s disease (CD). However, they can be perceived to be at odds with each other with more potent therapies associated with increased risk of infections. We evaluated the impact of treatment response on the risk of serious infections in adalimumab-treated patients with CD through secondary analysis of the PYRAMID registry. METHODS We included patients with CD who newly started adalimumab in the prospective PYRAMID registry (NCT00524537) and classified them as treatment responders (achieved steroid-free clinical remission based on patient-reported outcomes) vs. non-responders (not in steroid-free clinical remission) at 6m after treatment initiation (landmark). We compared the risk of serious infections between responders vs. non-responders between 6-36m after treatment initiation, through stabilized inverse probability of treatment weighted (IPW) Cox proportional hazards model. RESULTS Of 1515 adalimumab-treated patients with complete data at 6m, 763 (50.4%) were classified as responders (37±13y, 56% female, disease duration, 9.5y). At time of starting adalimumab (baseline), as compared with non-responders, responders were less likely to have moderate to severe symptoms (55.6% vs. 33%), require steroids (45.5% vs. 17.3%) or opiates (6.6% vs. 1.3%), have had prior CD-related surgery (46.5% vs. 35.1%), without any differences in disease location, perianal disease, and prior CD complications. On follow-up, between 6-36m (observation period after 6m landmark), 123 patients experienced a total of 162 serious infections. Of these, 52 responders (6.8%) experienced a serious infection vs. 71 non-responders (9.4%). Approximately, 58% infections were classified as gastrointestinal in origin. On stabilized IPTW through generalized boosting model, responders were 34% less likely to experience serious infections on follow-up compared with non-responders (HR, 0.66; 95% CI, 0.46-0.96). There was no significant difference in risk of serious infections between responders vs. non-responders based on organ site (gastrointestinal infections: HR, 0.61; 95% CI, 0.38-0.99; extra-intestinal infections: HR, 0.61; 95% CI, 0.46-1.30) (p-value for difference in groups = 1.00). Responders were significantly less likely to require corticosteroids on follow-up (1y: 4.4%, 2y: 8.9%, 3y: 9.6%), compared with non-responders (1y: 50.7%, 2y: 51.6% vs. 3y: 51%). CONCLUSIONS Patients with CD who respond to adalimumab have lower risk of developing serious infections, compared with non-responders, after accounting for disease severity. These findings underscore that initiation of advanced therapy for CD may lower the risk of serious infections through effective disease control and avoidance of corticosteroids.

P627 Real-world clinical effectiveness and safety of vedolizumab and ustekinumab in biologic-naïve patients with Crohn’s disease by disease location: Results from the EVOLVE Expansion study

Abstract Background Crohn’s disease (CD) location may affect disease course and treatment (Tx) decisions. This analysis compared real-world clinical effectiveness and safety of vedolizumab (VDZ) and ustekinumab (UST) in biologic-naïve patients (pts) by CD location. Methods Medical charts of biologic-naïve pts with CD aged ≥18 years initiating VDZ or UST in Australia, Belgium or Switzerland from 2016 to 2021 were analysed in a multicentre, observational, retrospective EVOLVE Expansion study (NCT05056441). Subgroup analysis evaluated outcomes with VDZ vs UST in pts with baseline ileal, ileocolonic and colonic CD (Montreal classification). Data were collected from Tx initiation to the first of chart abstraction initiation, Tx discontinuation, loss to follow-up or death. Inverse probability of Tx weighting (IPTW) was used to balance baseline characteristics between cohorts. Clinical outcomes (clinical response, clinical remission, mucosal healing), as assessed using published algorithms,1 and Tx persistence during 36 Tx months were analysed in time-to-event analyses (Kaplan-Meier method). Risks of safety (serious adverse events [SAEs], serious infections [SIs]) and healthcare resource utilisation (HCRU; CD exacerbations, CD-related hospitalisations, CD-related surgeries) outcomes with VDZ vs UST during 36 months were also compared. Results This analysis included 293 pts with ileal (VDZ:158, UST:135), 185 with ileocolonic (VDZ:91, UST:94) and 121 with colonic (VDZ:84, UST:37) CD. Baseline characteristics after IPTW were similar between VDZ and UST cohorts in all 3 subgroups. Cumulative rates during 36 Tx months were similar between VDZ and UST cohorts in ileal, ileocolonic and colonic CD subgroups for clinical response (p=0.67, p=0.94, p=0.22, respectively), clinical remission (p=0.51, p=0.20, p=0.52), mucosal healing (p=0.29, p=0.60, p=0.71) and Tx persistence (p=0.37, p=0.29, p=0.50) (Figure). There were no differences in the risks of SAEs, SIs, CD exacerbations and CD-related hospitalisations between cohorts across disease location; risk of CD-related surgeries was similar in pts with ileocolonic and colonic CD, and higher in VDZ vs UST cohort (p=0.02) in pts with ileal CD (Table). However, in ileal CD subgroup, CD-related surgeries during 36 months were reported only in 12/158 (7.6%) pts in VDZ and 3/135 (2.2%) pts in UST cohort. Conclusion During 36 Tx months, effectiveness, safety and HCRU outcomes were similar between VDZ and UST cohorts regardless of baseline disease location; risk of CD-related surgeries was higher with VDZ vs UST in pts with ileal CD and similar between cohorts in other subgroups. However, the absolute number of pts requiring CD-related surgeries was low. Reference: 1. Bressler B, et al. J Crohns Colitis. 2021;15(10):1694-1706.

P1100 A multivariate time-dependent proportional hazard model to predict development of intestinal failure from Crohn’s Disease

Abstract Background Intestinal Failure (IF) is a rare but severe complication of Crohn’s disease (CD). Advancement in therapy has not eliminated incident IF from CD (CDIF), and risk factors for developing IF from CD are not well characterised. The Copenhagen Intestinal Failure Database contains one of the largest, comprehensively described adult CDIF cohort1 from 1973 to 2018, which can be linked with a Danish nationwide CD cohort2 to explore healthcare utilisation patterns associated with developing IF from onset of CD. Methods CDIF patients from Copenhagen Intestinal Failure Database and a nationwide CD cohort without IF were followed from CD diagnosis until IF, death, or censoring on 31/12/2018. Hospital contacts, surgeries, medication use and employment status were extracted from multiple Danish population-based registries. Unplanned hospitalisation or emergency department attendance (inpatient-contact), CD-related abdominal surgery, and stopping work for 6 months or more (in working-age CD patients, excluding full-time study and parental leave) were considered time-dependent covariates and tested for significance (p&amp;lt;0.05) in univariate proportional hazard models. Significant covariates were then modelled together with additional non-time-dependent clinical and demographic variables in multivariate proportional hazard models. Backward variable selection was performed to derive a final predictive model. Results 175 CDIF and 22845 CD patients from whom data was available were followed for 2283.1 and 293536.5 patient-years, respectively. Univariate time-dependent proportional hazard models showed that every instance of unplanned IBD inpatient contact, CD-related abdominal surgery, and stopping work was significantly associated with increased hazard of developing IF, with a hazard ratio of 4.91 (95% CI 3.54-6.80, p&amp;lt;0.001), 29.79 (95% CI 9.70-91.48, p&amp;lt;0.001) and 1.61 (95% CI 1.15-2.26, p=0.005). In multivariate analysis, earlier decade of IBD onset, unplanned IBD inpatient contacts, length of stay of the inpatient contact, CD-related abdominal surgery, complicated surgery, number of previous admissions and surgeries and previous median-long term unemployment increased the rate of developing IF (Table), whereas age and comorbidity level at CD onset, non-IBD inpatient contacts, type of surgery, biologics use, and current employment status were not found to be significantly associated with IF development. Conclusion This is the first study to demonstrate significantly increased risks of developing IF from CD from increased healthcare utilisation patterns.

P259 Clinical characteristics and long-term disease course in patients with Crohn’s disease diagnosed by video capsule endoscopy; A retrospective multicentre matched case-control study

Abstract Background Video capsule endoscopy (VCE) is a non-invasive and accurate diagnostic modality that allows for direct visualization of the small intestinal mucosa in Crohn’s disease (CD). In rare cases, lesions not detected by other diagnostic modalities in patients suspected to have CD are solely identified through VCE. We aim to evaluate the clinical characteristics and long-term outcomes of these rare cases. Methods A retrospective multicentre matched case-control analysis was conducted in patients with CD across three hospitals in Korea, from January 2007 to April 2023. To perform a matched case-control study, we defined cases (VCE group) as patients with normal findings at colonoscopy and cross-sectional imaging, ultimately diagnosed with CD by VCE; the controls were patients with CD diagnosed with specific findings at endoscopy or cross-sectional imaging (non-VCE group). Controls were matched to cases with a ratio of 3:1 for sex, calendar year of diagnosis, and age at diagnosis. Clinical characteristics and outcomes between the two groups were compared. Results Of the 3,137 patients diagnosed with CD during the study period, 24 were diagnosed solely by VCE. When compared to 72 matched patients with CD, the mean duration from symptom onset to diagnosis did not significantly differ (27.2 months [SD 10.2] vs. 25.3 months [SD 8.9], p=0.394). There was a significant difference in the proportion of Montreal behaviour (p&amp;lt;0.001). In the VCE group, non-stricturing and non-penetrating (B1) type and stricturing (B2) type accounted for 91.7 and 8.3%, respectively. However, there was no significant difference in the perianal fistula modifier (25% vs. 33.3%, p=0.446). Within the VCE group, 45.8% underwent the examination due to abdominal pain with diarrhoea, followed by 25.0% with perianal disease, and 20.8% with unexplained iron deficiency anaemia. Regarding capsule findings, the ileum was mostly involved (87.5%), while the jejunum and duodenum were affected in 70.8 and 16.7% of cases, respectively. Fifteen patients had two or three segments affected. The Median Lewis score was 838 [IQR 393–1803]. Concerning the cumulative incidence of clinical outcomes over 10 years, complicated behaviour, need for biologics, and CD-related hospitalization and surgery were all significantly lower in the VCE group than in the non-VCE group (p&amp;lt;0.005). Conclusion Patients diagnosed with CD solely by VCE are rare. In this study, they exhibited different clinical characteristics and a more favourable long-term disease course compared to the general population of patients with CD. This included a lower incidence of complicated behaviour, reduced need for biologics, and CD-related hospitalization and surgery.

P452 Serum Amyloid A for Predicting Surgery and Disease Exacerbation in Patients with Newly Diagnosed Crohn’s Disease

Abstract Background Crohn's disease (CD) is characterized by relapsing-remitting course with highly heterogenous prognosis, ranging from quiescent disease to complicated course with stricturing, penetrating or need of abdominal surgery. Identifying biomarkers that determine their disease course can enable implementing more aggressive preventive strategies. Serum amyloid A (SAA) has been demonstrated to involve in the pathogenesis of Crohn’s disease (CD); however, its prognostic value is still uncertain. This study was determined to explore the prognostic value of SAA for CD-related surgery and disease exacerbation in newly diagnosed CD. Methods We conducted a retrospective cohort study and recruited newly-diagnosed CD patients at the First Affiliated Hospital of Sun Yat-sen University. Level of SAA was detected at diagnosis. The primary outcome was CD-related surgery. The secondary outcome was disease exacerbation, defining as newly developed structuring or penetrating lesions. Association between variables and outcome was evaluated through Kaplan–Meier method and Cox proportional hazard regression analysis. For continuous variables, the optimal cutoff values were determined by using the survminer R package in the analysis of primary outcome. The prognostic model was developed by cox proportional-hazards model. Concordance-index (c-index) was used to assess the predictive ability of the prognostic model. Results During 2187.6 person-years (median age, 28 years, 72.4% male), 87 surgery and 153 disease exacerbation events were documented. After adjustment, a 14% higher risk for surgery (adjusted hazard ratio, aHR [95% confidence interval]: 1.14 [1.05–1.23]; p=0.001) and a 12% higher risk for disease exacerbation (1.12 [1.05–1.19]; p&amp;lt;0.001) were observed with a 100-unit increase in SAA level. Patients with SAA levels ≥89.2 mg/L had aHRs of 2.08 [1.31–3.28] and 1.72 [1.22–2.41] for CD-related surgery and disease exacerbation, respectively. The association between SAA and outcomes was assessed as linear by the restricted cubic spline. Adding SAA into the model including known risk factors, including age at diagnosis ≥40 years, disease behavior, disease location, and initial biological treatment, led to significant improvement in its predictive ability for surgery (net reclassification index and integrated discrimination index, p&amp;lt;0.001) and disease exacerbation (net reclassification index and integrated discrimination index, p&amp;lt;0.001). Sensitivity analyses showed robust results. Conclusion Our study shows that higher serum SAA level at diagnosis was associated with poorer prognosis, including risk of surgery and disease exacerbation. And prognostic models based on SAA and known risk factors could better predict prognosis.

P411 Is transmural healing better than mucosal healing in pediatric Crohn’s disease?

Abstract Background While the long-term benefit of achieving mucosal healing (MH) in Crohn’s disease (CD) has been demonstrated, data on transmural healing (TH), assessed by non-invasive imaging modalities (i.e. magnetic resonance enterography, MRE) are scarce, particularly in the pediatric setting. Nonetheless it has been deemed as an adjunctive target for CD by the STRIDEII consensus. We aimed to investigate the outcomes of pediatric CD patients with TH comparing them to those with MH and with “no healing”. Methods Prospective, single-center, observational study conducted at the Pediatric Gastroenterology and Liver Unit of the Umberto I Hospital, Sapienza University of Rome. Children with an established diagnosis of CD and under biological therapy undergoing an MRE and an ileocolonoscopy performed within a 3-month interval were consecutively enrolled. Transmural healing was defined as the complete healing of both the mucosa at endoscopy (absence of ulceration) and of the bowel layers at the MRE. In the presence of a normal colonoscopy but an active MRE children were deemed as MH. The group “no healing” (NH) included children with an active endoscopy, regardless of the MRE classification. At 6, 12, and 24 months, the following outcomes were evaluated and compared in the three groups: disease flares, CD-related hospitalization, CD-related surgery, need for step-up treatment, and occurrence of complications. Results 93 children were included (30% female, mean age 11,2±3,8). Twenty-three (25%) were classified as TH, 27 (29%) as MH and 43 (46%) as NH. Overall, at the Kaplan Meier analysis, the risk of any unfavorable outcome was significantly lower in both TH and MH patients compared to NH (Log Rank p&amp;lt;0.0001 and p=0.002, respectively). Specifically, children with TH were at lower risk of hospitalization (p=0.02), and complications (p=0.007) compared to those with NH. No difference was found between MH and NH children for the same outcomes. Both TH and MH children were at lower risk of step-up treatment (p&amp;lt;0.0001 and p=0.0.0002, respectively) compared to NH. No difference was found between TH and MH patients for all the outcomes evaluated. Conclusion Achieving transmural healing in pediatric CD is associated with better long-term outcomes, although the additional benefit compared to reaching MH alone does not appear significant. However, the persistence of inflammation is associated with worse outcomes in all patients.

P553 The safety and efficacy of adalimumab 80mg weekly as maintenance therapy in pediatric Crohn’s Disease

Abstract Background Intensification of adalimumab (ADL) dosing to weekly 40 mg injections, in response to low drug levels, has been shown to provide beneficial outcomes in pediatric patients with Crohn’s disease (CD). Our study aimed to evaluate the safety and efficacy of weekly 80 mg ADL administration in children with CD. Methods In this retrospective cohort study conducted across five Israeli centers, we reviewed the medical records of pediatric CD patients who received a high dose of ADL 80 mg weekly injections between 2016 and 2023. Collected data included demographic characteristics, disease features, laboratory studies, and treatment outcomes. Results Thirty-two children with CD were included: mean age 15.8 (±1.7) years at intensification, 21 male (66%), 18 (56%) with L3 phenotype. The median time to ADL 80 mg intensification from ADL induction was 48.4 weeks (IQR 23.1-122.5). The mean weighted Pediatric Crohn's Disease Activity Index (wPCDAI) was 28.5 (±16.9) at the time of intensification and the median calprotectin and C-reactive protein levels were 937 μg/g (IQR 540-1410) and 1.3 mg/dL (IQR 0.6-5.2), respectively. Clinically active disease was the main reason for ADL intensification (30, 94%). Baseline ADL levels were available in 30 patients (94%) with a median of 3.8 μg/mL (IQR 2.4-7.2). Among these, 23 children (77%) failed to achieve a target of ≥ 7.5 μg/mL. The median follow-up duration from the intensification dose was 91.2 weeks (IQR 53.6-149.1). Corticosteroids were required in 5/32 (15.6%) children, with a median time of 32.3 weeks (IQR 10.7-51.3) from intensification. There was no statistically significant difference in steroid utilization rates between children who achieved a target baseline drug level of ≥ 7.5 μg/mL and those who did not (p=0.934). Thirteen individuals (41%) discontinued ADL treatment, within a median of 24.7 weeks (IQR 11.7-57.1) from intensification. CD-related exacerbation, hospitalization, and surgery rates were 9 (28%), 4 (13%), and 2 (6%), respectively. No statistically significant differences were found in exacerbation (p=0.406), hospitalization (p=0.322), or surgery rates (p=0.427) between children who achieved a baseline ADL trough concentration level of ≥ 7.5 μg/mL and those who did not. Overall, ADL intensification was safe, but 3 (9%) patients developed new-onset psoriasis. Conclusion Our findings support the safety and efficacy of administering ADL at a weekly dosage of 80 mg as maintenance therapy in pediatric patients with moderate to severe CD.

P409 Optimal endoscopic healing thresholds defined by MM-SES-CD &amp;lt; 22.5 and SES-CD &amp;lt; 4 are associated with low risk of disease progression in Crohn’s disease

Abstract Background After initiation of therapy in Crohn's disease (CD), it remains unclear what the optimal endoscopic healing (EH) threshold to target is using the SES-CD and the MM-SES-CD (Modified Multiplier Simple Endoscopic Score for Crohn’s disease). We assessed MM-SES-CD and SES-CD thresholds that are best associated with low likelihood of long-term disease progression. Methods Week 48 endoscopy videos from patients with CD who participated in the CALM long-term extension LTE study were obtained and re-read by central readers to obtain a SES-CD and MM-SES-CD score, which was used for the derivation cohort. A real-world validation was performed with data from 99 patients that had clinical response using a mixed cohort of biologic therapies from the McMaster IBD database. The primary outcome was disease progression, defined as a new internal fistula/abscess, stricture, perianal fistula or abscess, CD-related hospitalization or surgery since the end of the CALM trial for the derivation cohort, and over the observed period of follow-up for the validation cohort. The maximum Youden index was calculated to determine the optimal MM-SES-CD and SES-CD thresholds. Receiver operating characteristic curve analyses compared threshold scores of various remission definitions on disease progression. Kaplan-Meier survival curve analyses were performed to compare the time to disease progression from the end of study endoscopy in the derivation cohort. Results In the derivation cohort, the optimal thresholds associated with a low likelihood of disease progression were MM-SES-CD &amp;lt;22.5 and SES-CD &amp;lt;4. A significantly greater proportion of patients with a MM-SES-CD ≥22.5 had disease progression as compared to patients with MM-SES-CD &amp;lt;22.5 [10/17 (58.8%) vs. 3/44 (6.8%), p&amp;lt;0.001]. Similarly, a significantly greater number of patients with a SES-CD ≥ 4 had disease progression compared to those with a SES-CD &amp;lt;4 [11/25 (44.0%) vs. 2/36 (5.6%), p&amp;lt;0.001]. Compared to other clinical or endoscopic remission definitions, obtaining a MM-SES-CD &amp;lt;22.5 at the end of the CALM study performed the best for predicting disease progression [AUC: 0.81 (95% CI: 0.68-0.94), p&amp;lt;0.001](sensitivity 76.9% (95% CI: 46.2-95.0), specificity 85.4% (95% CI: 72.2-93.9)). Compared to those with lower scores, patients with MM-SES-CD ≥ 22.5 (log-rank p&amp;lt;0.0001) and SES-CD ≥ 4 (log-rank p=0.0002) had a significantly greater probability of disease progression (Figure 1A/B). These findings were confirmed in the validation cohort (Figure 1C/D). Conclusion Achievement of MM-SES-CD &amp;lt;22.5 and SES-CD &amp;lt;4 was associated with low risk of CD progression and may be a suitable target for EH in clinical trials and practice. Our findings support that targeting EH may modify the natural course of CD.

P1025 Analysis of the Clinical Characteristics of Elderly-onset Crohn's Disease

Abstract Background The prevalence of Crohn's disease in the elderly is increasing today. The purpose of this study was to analyze the clinical characteristics of elderly-onset patients with Crohn's disease and compare with non-elderly-onset adult patients. Methods All Crohn's disease patients with onset aged 60 years and older at our Inflammatory Bowel Disease Center in recently ten years were retrospectively included. The elderly were compared with adult patients aged 18-59 at the time of onset, who were matched according to diagnosis time and gender by a 1:3 ratio of propensity score matching. After matching, the clinical data were recorded and analyzed to compared between the two groups of patients. Results A total of 68 patients were included, including 17 patients in the elderly-onset group and 51 patients in the non-elderly-onset adult group. The mean age of diagnosis in the two groups was 30.3±8.7 years and 63.9±4.24 years, and the mean course of disease was 30.3 months and 63.9 months, respectively. According to the Montreal classification, most elderly patients presented with L3 (70.6%) and B1 (58.8%), no cases involving the upper digestive tract or multiple lesion sites, showed mild disease activity (76.5%). The elderly group had fewer intestinal complications and parenteral manifestations. The medication types of elderly are 5-aminosalicylates (52.9%), traditional immunosuppressive agents (45.6%) and enteral nutrition preparations (29.4%) being the more frequent types of medications used, and glucocorticoids and biologics being used less frequently. Exposure to two or more IBD medications was 31.4% and 52.9% in the non-elderly onset adult group versus the elderly onset group, respectively (p=0.110). During follow-up, symptoms such as diarrhea (11.8 vs 5.9%), abdominal pain (35.3% vs 17.6%) and weight loss (11.8% vs 3.9%) were more common in the elderly-onset group. Elderly patients had more hospitalizations on average (0.22 vs. 1.12). 40.7% of elderly patients underwent CD-related surgery during the duration of their disease, with 50.0% of patients undergoing reoperation. Conclusion Compared with non-elderly-onset adult patients, elderly-onset patients with Crohn's disease are more common in women, and the lesion mainly in the ileum and ilecolon; the disease behavior is mainly B1; nearly half of the patients have intestinal complications The elderly have atypical clinical manifestations, basically haven’t family history of IBD, take longer to diagnose, have more underlying diseases, more hospitalizations on average, and are more likely to have complications. They are more likely to receive conservative treatment, but with more frequent medication adjustments and a higher likelihood of undergoing CD-related surgery.

DOP68 Natural history of isolated Crohn's Disease perianal fistula

Abstract Background Approximately 20% of patients with Crohn’s disease (CD) have perianal fistulizing CD, which are most often complex PAF. Studies have shown that 4-5% of patients with CD present with PAF without luminal disease, termed isolated perianal CD (iPCD). Little is known about their natural history. Methods We performed a retrospective cohort study of patients seen within the Mount Sinai Health System (New York) with an ICD-10 diagnosis code for PAF between 7/22/2008 and 7/22/2022. Medical record review was conducted to identify patients with PAF, considered as possible iPCD, who did not have evidence of luminal disease and had &amp;gt; 6 months of follow-up (Table 1). Demographics, comorbidities, imaging, endoscopy, surgeries, hospitalizations and medication data were collected. These patients were reviewed to determine progression to luminal disease, which was defined as any evidence of luminal ulcers, erosions, or strictures on endoscopy, histology, video capsule exam, or MRE. Descriptive and univariate analyses were performed. Complex PAF was defined by American Gastroenterological Association criteria. Complicated disease course was defined as a composite of any major CD-related surgery, PAF/IBD-related hospitalization or biologic use. Results Among 887 patients who presented with PAF, 62.2% (n=552) patients underwent luminal evaluation, of whom 80 patients (14.5%) were found to have no luminal disease and considered as having iPCD (Table 1). 57 of these 80 patients had &amp;gt;6 months follow-up. Luminal disease developed in 13 patients (23%) with a mean time to diagnosis of 4.2 +/- 3.8 years after PAF presentation. Patients who developed luminal CD were more likely to be &amp;lt;30 years old at PAF diagnosis (p=0.0225), had &amp;gt;2 fistulas on imaging (p=0.002), and have concomitant autoimmune conditions (p=0.046) (Table 2). During the follow-up period, the patients who developed luminal CD were more likely to receive biological therapy (77% vs 16%, p&amp;lt;0.0001) or undergo CD/PAF-related hospitalization (62% vs 30%, p =0.0356) (Table 2). Overall, patients who developed luminal CD had a more complicated disease course (31% vs 2.3%, p=0.007) than those who did not. Conclusion Approximately 1 in 4 patients who presented with possible iPCD developed luminal CD at follow-up. Patients who developed luminal CD were more likely to be younger at diagnosis, had more fistula tracts, and had concomitant autoimmune conditions.

P1206 Mechanistic implications of the Mediterranean diet in patients with newly diagnosed Crohn’s disease- multi-omic analysis of a prospective cohort

Abstract Background The Mediterranean diet (MED) is hypothesized to play a protective role in Crohn’s disease (CD) etiology, yet the underlying mechanisms remain unclear. Here we explored the association between adherence to MED, CD course, clinical and inflammatory markers, and microbial and metabolite composition in patients with newly diagnosed CD. Methods Patients with newly diagnosed CD were recruited and prospectively assessed. Food frequency questionnaires (FFQ) were collected each visit and assessed for adherence to MED, using a predefined IBDMED score, alongside validated MED adherence screeners. The Crohn’s disease activity index (CDAI) was used to evaluate clinical activity and serum and fecal samples collected for fecal calprotectin, C-reactive protein (CRP), and microbial composition using 16S rRNA sequencing. Baseline serum and fecal metabolomics were analyzed using a targeted quantitative metabolomics approach. Patients were classified as having a complicated course if during follow-up, they were steroid dependent, switched ≥2 biologics, hospitalized or underwent CD-related surgery. Results We recruited and prospectively observed 271 consecutive patients with newly diagnosed CD (52% males, average age- 31±12 years, inflammatory phenotype, B1- 75%) and collected 636 FFQs (range 1-5 FFQ per patient). Adherence to MED was associated with a non-complicated course and was inversely correlated with CDAI, fecal calprotectin, CRP and microbial dysbiosis index (all p&amp;lt;0.05). Increasing adherence to MED over time was associated with decreasing CDAI and fecal calprotectin in patients with complicated and non-complicated courses (p&amp;lt;0.05). Diet microbial interactions revealed two microbial clusters, showing that adherence to MED and intake of its recommended foods positively correlated with commensals and short-chain fatty acid producers including Faecalibacterium. Conversely, adherence to MED inversely correlated with a cluster of members of the Proteobacteria and included Ruminococcus gnavus. Diet metabolomics interactions revealed two clusters showing that adherence to MED positively correlated with multiple serum and fecal organic compounds, vitamin derivatives, plant metabolites, amino acids and tryptophan metabolites and inversely associated with fecal triglycerides, ceramides and cholic acid, the major primary bile acid (FDR&amp;lt;0.1). Conclusion Adherence to MED is associated with lower levels of primary bile acids and microbial dysbiosis and with a beneficial microbial and metabolite composition in patients with newly diagnosed CD. This may drive the inverse association of MED with clinical activity, inflammatory markers and complicated course. Microbial and metabolite-targeted dietary approaches like MED, should play a role in CD management.