CD-related Surgery Research Articles

S850 Obesity as Defined by Body Mass Index Is Not a Risk Factor for Post-Operative Recurrence in Crohn's Disease

Introduction: Obesity is a global epidemic and a condition which can lead to development of chronic illnesses such as diabetes, cardiovascular disease, and cancer, and has also been proposed as a risk factor for development and complications of inflammatory bowel diseases (IBD) such as Crohn’s disease (CD) and ulcerative colitis. In patients with CD, more than 70% require surgery due to stricturing and/or penetrating complications, and the risk for endoscopic recurrence within five years is as high as 60-90%. Obesity has not been studied extensively as a risk factor for postoperative recurrence (POR) of CD. We hypothesized that obesity as defined by BMI is a risk factor for POR. Methods: A retrospective study was performed at a university medical center following Institutional Review Board approval, and patients who had undergone CD-related surgery from January 2008 to July 2018 were included. Patients initiated on biologic therapy postoperatively were excluded. Data on patient demographics and covariates were collected, and the presence and timing of endoscopic, surgical, and/or radiographic recurrence were recorded. A Cox proportional hazard (PH) model was fitted to model the risk of POR of CD in obese patients, controlling for patient characteristics and risk factors. Results: A total of 82 patients were included in the analysis, one-fifth of whom were obese (n=18, 22%). Obesity as defined by a BMI ≥ 30 was not an independent risk factor for the development of POR in either the unadjusted or the adjusted model. Among the other examined variables, the risk of POR among males was 70% higher than in females (HR=1.70, 95% CI: 1.01, 2.86). Patients who smoked after surgery had a significantly higher risk of POR as compared to non-smokers (HR=1.74, 95% CI: 1.01, 3.01), while the presence of prior/current fistulizing disease reduced the recurrence of CD risk by more than 60% (HR=0.39, 95% CI: 0.20, 0.73). Cox PH models using BMI either as a continuous or categorical variable yielded similar results. (Table, Figure) Conclusion: Obesity as defined by BMI was not predictive of POR risk in our study, which may have been limited due to sample size and proportion of obese patients. The need to explore other measures of obesity in CD still exists, as identification of modifiable risk factors may help to prevent POR. Other measures of adiposity such as visceral fat area, visceral adipose tissue (VAT) and the ratio of VAT to total body fat mass have shown promise in predicting obesity-associated risks in the IBD population.Figure 1.: Six-year postoperative adjusted recurrence-free probabilities for each variable in the model. Table 1. - Hazard Ratios (HR) and Their 95% Confidence Intervals for Obesity, Demographic Characteristics and Covariates for Postoperative Recurrence Using Cox Proportional Hazard Modeling Characteristics Unadjusted HR (95% CI) Adjusted HR (95% CI) BMI Category Non-obese 1.00 1.00 Obese 1.28 (0.72, 2.27) 0.94 (0.49, 1.82) Gender Female 1.00 Male 1.70 (1.01, 2.86) Age at Surgery < 40 Years 1.00 ≥ 40 Years 1.35 (0.81, 2.25) Post-Surgery Smoking Non-smoker 1.00 Smoker 1.74 (1.01, 3.01) Fistulizing Disease No 1.00 Yes 0.39 (0.20, 0.73) Perianal Disease No 1.00 Yes 1.55 (0.84, 2.85) Prior Crohn's Disease Surgery No 1.00 Yes 1.14 (0.67, 1.92)

Sex-specific comparison of clinical characteristics and prognosis in Crohn's disease: A retrospective cohort study of 611 patients in China.

Background: Real-world data on the impact of sex on the disease progression and prognosis of Crohn’s disease (CD) from large-scale Chinese cohorts are lacking. Aims: This study aimed to evaluate sex disparities in the clinical characteristics of, disease progression behaviours of and surgery-related risk factors for CD. Methods: A retrospective cohort study comprising 611 patients consecutively diagnosed with CD at Peking Union Medical College Hospital from January 2000 to December 2020 was conducted. Multivariate Cox regression and survival analyses was performed to assess the risk factors for disease progression and CD-related surgery in sex subgroups. Results: Male sex was an independent protective factor against multisystemic extraintestinal manifestations [EIMs] (HR: 0.52, p = 0.03) and a risk factor for intestinal perforation (HR: 1.85, p = 0.01). Male patients had longer EIM-free survival (p = 0.024) and shorter intestinal perforation-free survival (PFS) than females (p = 0.012). Of the 397 patients with the A2 classification, male patients had a higher risk of CD-related surgery (HR: 1.80, p = 0.028) and shorter surgery-free survival (SFS) than female patients (p = 0.04). Conclusion: Sex disparities in disease progression and outcomes of CD were revealed in a single Chinese centre. Male sex was independently associated with worse disease progression and prognosis including multisystemic EIMs and perforation, which suggests the need for individualized management according to risk classification.

Comparative Effectiveness of Ustekinumab and Anti-TNF Agent as First-Line Biological Therapy in Luminal Crohn's Disease: A Retrospective Study From 2 Referral Centers.

Real-life data on the efficacy of ustekinumab as first-line therapy for the treatment of luminal Crohn's disease (CD) compared with anti-tumor necrosis factor (anti-TNF) agents are lacking. We compared the clinical response rates at 3 months in 2 cohorts of biologic-naïve patients treated by ustekinumab and anti-TNF agents. Biologic-naïve patients starting either ustekinumab or an anti-TNF agent for luminal CD between 2016 and 2019 in 2 tertiary centers were retrospectively included. The primary endpoint was clinical response at 3 months, defined as a Harvey-Bradshaw Index <4 or a 3-point drop in the score without steroids, need for CD-related surgery, or treatment discontinuation owing to failure or intolerance. Patients treated with ustekinumab were matched to patients receiving anti-TNF agents by a propensity score algorithm. We included 156 patients starting anti-TNF agents (95 adalimumab and 61 infliximab) and 50 ustekinumab. After matching, clinical response rates at 3 months were 64% and 86% in the ustekinumab and anti-TNF groups, respectively (P = .01). At 12 months, in multivariate analysis adjusted for disease duration, location, concomitant immunosuppressant and steroids, and symptoms, clinical remission was independently associated with the biological therapy received (odds ratio, 2.6 for anti-TNF agent vs ustekinumab; P = .02). With a median follow-up duration of 40 (interquartile range, 23-52) months, no difference was observed in terms of time to drug withdrawal (P = .29) or safety. This retrospective real-world data suggest that an anti-TNF agent as a first-line biological therapy is associated with higher rates of response at 3 months than ustekinumab in patients with CD.

Patients With Stricturing or Penetrating Crohn's Disease Phenotypes Report High Disease Burden and Treatment Needs.

Crohn's disease (CD) is a chronic autoimmune disease in which inflammation can progress to complications of stricturing and/or penetrating disease. Real-world data on burden of complicated CD phenotypes are limited. We analyzed cross-sectional data from the SPARC IBD (Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease) registry from 2016 to 2020. Four mutually exclusive phenotype cohorts were created: inflammatory CD (CD-I), complicated CD (stricturing CD, penetrating CD, and stricturing and penetrating CD [CD-SP]). Statistical analyses were performed using CD-I as the reference. A total of 1557 patients were identified: CD-I (n = 674, 43.3%), stricturing CD (n = 457, 29.4%), penetrating CD (n = 166, 10.7%), and CD-SP (n = 260, 16.7%). Patients with complicated phenotypes reported significantly greater use of tumor necrosis factor inhibitors (84.2%-86.7% vs 66.0%; P < .001) and corticosteroids (75.3%-82.7% vs 68.0%; P < .001). Patients with CD-SP reported significantly more aphthous ulcer (15.4% vs 10.5%; P < .05), erythema nodosum (6.5% vs 3.6%; P < .05), inflammatory bowel disease-related arthropathy (25.8% vs 17.2%; P < .01), liquid stools (24.2% vs 9.3%; P < .001), nocturnal fecal incontinence (10.8% vs 2.5%; P < .001), and CD-related surgery (77.7% vs 12.2%; P < .001). Patients with complicated CD phenotypes reported higher rates of active CD-related luminal and extraintestinal manifestations, and underwent more surgeries, despite being more likely to have received biologics than those with CD-I. The potential for early recognition and management of CD-I to prevent progression to complicated phenotypes should be explored in longitudinal studies.

Adalimumab Is Associated With Lower Healthcare Resource and Steroid Use Versus Vedolizumab in Biologic-Naive Crohn's Disease: A Retrospective Claims Database Analysis.

We compared real-world healthcare resource utilization (HRU), Crohn's disease (CD)-related complications, and time to systemic corticosteroid discontinuation between patients with CD treated with adalimumab versus vedolizumab as initial biologic. Biologic-naïve adults with CD and ≥2 claims between 05/20/2014 and 09/30/2019 for adalimumab or vedolizumab were identified in the IBM MarketScan research database. Patient characteristics were assessed during the 6-month baseline period before biologic initiation (index date). Adalimumab- and vedolizumab-treated patients were propensity score-matched 1:1 on demographics, disease characteristics, and comorbidities with ≥10% prevalence that differed significantly between groups. Categorical, continuous, and time-to-event outcomes between groups during the 12-month follow-up on/after index were compared with chi-square tests, Wilcoxon rank-sum tests, and Kaplan-Meier analyses, respectively. Adalimumab- and vedolizumab-treated patients were matched (n = 461 per group) and baseline characteristics balanced. Significantly fewer adalimumab- versus vedolizumab-treated patients had a CD-related emergency room visit (12-month proportion: 14.5% vs 21.0%; log-rank P < 0.01) or inpatient admission (14.9% vs 20.2%; log-rank P < 0.05). Rates of CD-related surgeries were similar (9.3% vs 11.5%; log-rank P = 0.282). Among patients without internal/perianal abscess or fistula or intestinal stricture at baseline (N ADA = 360, N VDZ = 364), numerically but not significantly fewer adalimumab- versus vedolizumab-treated patients had CD-related complications at 12 months (18.3% vs 22.3%; P = 0.171). Among patients with corticosteroid use at index (N ADA = 143, N VDZ = 139), significantly more adalimumab- versus vedolizumab-treated patients discontinued corticosteroids (12-month proportion: 90.2% vs 76.3%; log-rank P < 0.001). Patients with CD treated with adalimumab as their first biologic experienced significantly lower CD-related HRU and were more likely to discontinue corticosteroids compared to vedolizumab-treated patients.

Proactive infliximab optimisation using a pharmacokinetic dashboard versus standard of care in patients with Crohn’s disease: study protocol for a randomised, controlled, multicentre, open-label study (the OPTIMIZE trial)

IntroductionPreliminary data indicates that proactive therapeutic drug monitoring (TDM) is associated with better outcomes compared with empiric dose escalation and/or reactive TDM, and that pharmacokinetic (PK) modelling can improve the...

Toward transmural healing: Sonographic healing is associated with improved long-term outcomes in patients with Crohn's disease.

Background and AimsTransmural healing has emerged as a treatment target in Crohn’s disease (CD). We investigated whether transmural healing assessed with intestinal ultrasound (IUS) is associated with improved clinical outcomes in patients with CD in clinical remission.MethodsPatients with CD in clinical remission at baseline (HBI <4) having IUS between August 2017 and June 2020 with at least 6‐months’ follow‐up were retrospectively studied. Time to medication escalation, corticosteroid use and CD‐related hospitalisation or surgery were compared by the presence or absence of sonographic healing, defined as bowel wall thickness ≤3 mm without hyperemia on color Doppler, inflammatory fat, or disrupted bowel wall stratification. Factors associated with survival were analyzed by Kaplan–Meier analysis using Cox proportional‐hazard model.ResultsOf 202 consecutive patients (50% male), sonographic inflammation was present in 61%. During median follow‐up of 19 (IQR 13–27) months, medication escalation occurred in 52%, corticosteroid use in 23%, hospitalisation in 21%, and CD‐related surgery in 13%. Sonographic healing was significantly associated with a reduced risk of medication escalation (p = 0.0018), corticosteroid use (p = 0.0247), hospitalisation (p = 0.0102), and surgery (p = 0.083). On multivariable analysis, sonographic healing was significantly associated with an increased odds of medication escalation‐free survival (hazard ratio [HR]:1.94; 95% CI 1.23–3.06; p = 0.004) and corticosteroid‐free survival (HR:2.41; 95% CI 1.24–4.67; p = 0.009), but not with hospitalisation or surgery.ConclusionIn patients with CD in clinical remission, sonographic healing is associated with improved clinical outcomes. Further studies are needed to determine whether sonographic healing should be a treatment target.

Enterogenous Microbiotic Markers in the Differential Diagnosis of Crohn's Disease and Intestinal Tuberculosis.

Crohn’s disease (CD) is a chronic intestinal disorder characterized by refractory gastrointestinal ulcerations. Intestinal tuberculosis (ITB) is one common intestinal disease in east Asia. The two diseases share similar clinical manifestations and endoscopic characteristics. Thus, it is difficult to establish a definite diagnosis of CD, CD concomitant with ITB (CD-ITB), and ITB in practice. Some enterogeneous microbiotic markers have been applied to differentiate CD and ITB, but it remains unknown how they work for the three groups of patients. The aim of our study was to explore the diagnostic values of these enterogeneous microbiotic markers (ASCA IgG, ASCA IgA, ACCA, Anti-I2 and AMCA) among CD, CD-ITB, and ITB patients. A total of 124 individuals were retrospectively enrolled in this study, namely, 103 CD patients, 10 CD-ITB patients, 9 ITB patients, and 68 healthy controls. The demographic and clinical characteristics of these patients were collected and analyzed. The values of these individual or combined enterogeneous microbiotic markers in diagnosis and classification were assessed in CD, CD-ITB, and ITB patients. ASCA IgG, ASCA IgA, and AMCA could accurately differentiate CD patients from healthy controls with an area under curve (AUC) of 0.688, 0.601, and 0.638, respectively. ASCA IgG was significantly higher in CD patients than in CD-ITB patients (P = 0.0003). The Anti-I2 antibody was appropriate for distinguishing CD-ITB from ITB patients (P = 0.039). In CD patients, ASCA IgG was higher in severe patients than in mild (P <0.0001) and inactive patients (P <0.0001), respectively. AMCA was significantly elevated in severe and moderate patients compared to inactive patients (P = 0.001, P = 0.003, respectively). AMCA was associated with a higher risk of CD-related surgery with a significant P-value of 0.0038. In our cohort, ASCAs and AMCA could accurately distinguish CD from healthy controls with an acceptable AUC. A combination of elevated ASCA IgG and AMCA antibodies established a higher sensitivity in differentiating CD from healthy controls. Elevated ASCA IgG demonstrated a differential diagnostic value between CD and CD-ITB. Anti-I2 could also distinguish CD-ITB from ITB. The level of AMCA was associated with both disease severity and CD-related surgery. Likewise, the level of ASCA IgG was also related to disease severity.

Treatment patterns, persistence with therapy, and outcomes of ustekinumab in Crohn's disease: Real-world data analysis.

Background and AimIn 2017, ustekinumab (UST) was included in Israel's National Basket of Health Services for treatment of biologic‐experienced Crohn's disease (CD) patients with moderately to severely active disease. This study aims to provide real‐world evidence on persistence and clinical outcomes among early users of UST.MethodsThis retrospective cohort study was conducted using data from Maccabi Healthcare Services (MHS; 2.5‐million‐member state‐mandated health provider, Israel). Adult patients with a CD diagnosis code who had ≥1 dispensed UST prescription in 2017–2018 and at least 12 months of prior continuous health plan enrollment were included. Outcomes, including treatment discontinuation, dose‐escalation (based on shortened intervals between purchases), CD‐related surgery, CD‐related hospitalization, corticosteroid (CS) discontinuation, and use of opioids were evaluated from the date of first dispensed UST through the end of 2019 using Kaplan–Meier analysis.ResultsA total of 162 eligible patients (81 [49.4%] female; median age 34.4 years [IQR 23.2–46.3]; median years since CD diagnosis 8.6 [IQR 4·8–16.0]) were enrolled in the study. Discontinuation rate after 365 and 540 days of follow‐up was 27.8% and 35.6%. Dose escalation was estimated at 15.4% and 28.6%, respectively. The first‐year cumulative rate of CD‐related surgery and CD‐related hospitalization were estimated at 4.7% and 9.8%, respectively.ConclusionIn this real‐world CD cohort of UST users, results suggest persistence is relatively high as compared to other biologics for CD. Comparative effectiveness of different biologic treatments for CD in this population should be further explored.

DOP90 Efficacy of the treat-to-target approach in modifying disease course with ustekinumab in patients with moderate-to-severe Crohn’s Disease: Results from the STARDUST trial

Abstract Background STARDUST is a phase 3b randomized trial comparing two therapeutic strategies with ustekinumab (UST) in patients (pts) with Crohn’s disease (CD): treat-to-target (T2T) using early endoscopic assessment vs standard of care (SoC). Results from the Week (W)48 and long-term extension (LTE) (W48 to W104) were published previously.1,2 Here we explore the efficacy of the T2T approach in modifying disease course with UST by analyzing time-to-disease modifying (DM) event up to W104. Methods Adult pts with moderate–severe active CD, received iv, weight-based UST ~6mg/kg at W0; then sc UST 90mg at W8. At W16, pts with ≥70-point reduction in CD Activity Index were randomized 1:1 to either T2T or SoC and received sc UST 90mg, every 12W/8W (up to 4W in the T2T arm), as per the protocol. From W48, eligible pts could continue to receive sc UST up to W104 with further protocol-guided dose adjustment. DM events were recorded through W48 and W104 starting at randomization, and time-to-event analysis was performed for pts in both arms. DM events are represented by combined bowel damage events (defined as the development of new strictures/fistulae or the occurrence of an intra-abdominal abscess) or CD-related hospitalizations or surgeries based on the adverse event analysis. Time-to-first bowel damage event, CD-related surgery, hospitalization, hospitalization or surgery was analyzed separately; Kaplan–Meier (K–M) curves with corresponding hazard ratios (HRs) and 95% confidence intervals (CIs) are shown here. Results Of 440 pts randomized to either T2T or SoC at W16, 74 discontinued before W48. Of the remaining 366 pts completing W48, 43 discontinued and did not enter LTE. At W48, 323 pts entered LTE; 20.1% of these pts discontinued before completing W104. HRs (95% CI) for time-to-first DM event from randomization through W48 and W104 are shown in Table 1, suggesting a numeric benefit in favour of the T2T arm. The separation of the K–M curves for time-to-first DM event between the two arms was apparent at W48 and continued up to W104, without significant difference (Figure 1a and b). Conclusion In STARDUST, with UST, starting at W48, numerically less DM events were observed in the T2T arm, mainly driven by the lower number of CD-related hospitalizations and bowel damage events, potentially linked to numerically higher proportion of endoscopic responders at W48.1 These results advocate for an optimized T2T approach using strictly defined targets like endoscopic response, on top of clinical and biomarkers, to facilitate decision making in clinical practice.

P380 Early improvement of endoscopic outcomes with risankizumab is associated with reduced hospitalisation and surgery rates in patients with Crohn’s disease

Abstract Background Control of endoscopic inflammation like endoscopic remission is an important treatment target in Crohn’s disease (CD), as suggested in the STRIDE II guidelines. This study evaluated the relationship of early improvement in endoscopic outcomes on hospitalisation and surgery rates at, 52 wks in patients with CD treated with risankizumab (RZB). Methods This post-hoc analysis uses data from three double-blind, randomised Phase, 3 induction (ADVANCE and MOTIVATE) and maintenance (FORTIFY) trials evaluating the efficacy and safety of RZB in patients with moderate to severe CD. Patients who responded to, 12-wk induction therapy with RZB IV (600 mg or, 1200mg) in ADVANCE or MOTIVATE and received up to, 52 wks of maintenance therapy with RZB SC (180 mg or, 360 mg) in FORTIFY were analysed. Incidence rates (events/100 person-years) of CD-related hospitalisation, CD-related surgery (surgical procedures due to adverse events or complications related to CD), all-cause hospitalisation, and all-cause surgery were evaluated from the beginning of maintenance to wk, 52 and compared between patients who achieved endoscopic outcomes at end of induction (wk, 12) and those who did not. Endoscopic response, endoscopic remission and ulcer-free endoscopy (absence of ulceration) were defined using the Simple Endoscopic Score for CD (SES-CD) (Figure, 1–3), as scored by a blinded central reviewer. Results A total of, 298 patients were included in the analyses. Patients who achieved endoscopic response (n=121) at wk, 12 had a significantly reduced incidence rate of CD-related hospitalisation, CD-related surgery, and all-cause hospitalisation by wk, 52 compared to those who did not achieve an endoscopic response (n=177) at wk, 12 (Figure, 1). Additionally, patients who achieved endoscopic remission at wk, 12 (n=83) had a significantly reduced incidence rate of CD-related hospitalisation, CD-related surgery, and all-cause hospitalisation by wk, 52, compared to those not achieving endoscopic remission at wk, 12 (n=215) (Figure, 2). Though not statistically significant, numerically lower rates of all-cause surgery were observed for patients who achieved endoscopic remission or endoscopic response at wk, 12. Significantly lower rates of CD-related hospitalisation, CD-related surgery, all-cause hospitalisation, and all-cause surgery by wk, 52 were observed among patients who achieved ulcer-free endoscopy (absence of ulceration) (n=70) vs those who did not (n=228) at wk, 12 (Figure 3). Conclusion Early improvement of endoscopic outcomes at wk, 12 is associated with significant reductions in hospitalisations and surgeries through, 52 wks for patients receiving RZB therapy.

P524 Compared efficacy of ustekinumab and anti-TNF agents as first-line biological therapy in luminal Crohn’s disease

Abstract Background Real-life data on the efficacy of ustekinumab as first-line therapy for the treatment of moderate to severe Crohn’s disease (CD) is lacking. The objective of this study was to compare the clinical remission rate at 3 months of patients treated by ustekinumab or anti-TNF agents as first-line biological therapy. Methods We conducted a two-center retrospective study including biologic-naïve patients starting either ustekinumab or an anti-TNF agent for CD between January 2016 and December 2019. The primary endpoint was clinical remission at 3 months after therapy initiation, defined as a Harvey Bradshaw Index (HBI) &amp;lt; 4 without steroids, need for CD-related surgery or treatment discontinuation due to treatment failure or intolerance. Secondary endpoints were remission at 12 months and time to drug withdrawal. Patients treated with ustekinumab were matched 1:3 to patients receiving anti-TNF agents using a propensity score including age, CD duration, smoking status, CD location according to the Montréal classification and history of perianal disease. Results 208 patients [104 (50%) female, median age (InterQuartileRange) 30 years (23–47)] were included, 156 (75%) patients starting anti-TNF (95 (45%) adalimumab and 61 (29%) infliximab) and 52 (25%) ustekinumab and followed for a median (IQR) duration of 39 (22–52) months. Median (IQR) CD duration was 21 (6–104) months and 45 (22%) patients had previously undergone a CD-related surgery. At inclusion, the median (IQR) HBI was 5 (2–8) and 83 (39%) patients were receiving oral corticosteroids. After matching, remission rates at 3 months were 25/45 (56%) patients in the ustekinumab group versus 102/135 (76%) in the antiTNF group [p=0.01, odds ratio (OR) 0.40 (Confidence Interval (CI) 95% 0.20, 0.82)]. At 12 months, remission rates were 26/41 (63%) patients in the ustekinumab group versus 99/123 (81%) in the antiTNF group (p=0.03). No difference was observed in terms of time to drug withdrawal (p=0.25). Rates of drug persistence at 12 months were 89% in patients treated with ustekinumab and 87% in those treated with antiTNF, respectively. Similar rates of adverse events were observed in the two groups (13% versus 13%, p&amp;gt;0.9). In the antiTNF group, 3/156 (2%) adverse events leading to hospitalization were observed compared to 0/52 (0%) in the ustekinumab group (p=0.6). Conclusion In this retrospective cohort, we found that anti-TNF agents as a first-line biological therapy led to higher rates of remission at 3 and 12 months in biologic-naïve patients with Crohn’s disease than ustekinumab.

P446 Long-term Clinical Effectiveness And Stoma Outcome Of Fecal Diversion In Refractory Crohn’s Proctitis

Abstract Background Proctectomy is often recommended when Crohn’s proctitis becomes refractory to medical therapy. However, some surgeons offer a temporary diverting stoma in an effort to avoid a permanent stoma. The long-term efficacy of this approach is not well-established. Our aim was to determine the long-term effectiveness of fecal diversion in patients with refractory Crohn’s proctitis. Methods This retrospective study included all patients with Crohn’s proctitis who underwent formation of a diverting ileostomy or colostomy for refractory disease from, 1998 to, 2019 in Mayo Clinic Rochester MN. Outcomes were disease recurrence, rate of stoma closure, and proctectomy. Univariate comparisons among categorical variables were performed with Pearson’s Chi-square and continuous variables using the student t-test. The cumulative probability of stoma closure was performed with a Kaplan Meier log-rank analysis. Multivariable analysis of risk factors for proctectomy and permanent stoma was achieved with logistic regression. Results Ninety-seven patients (55.7% female) were included. Ileostomy was the most common stoma type (88.7%, n=86), and colostomy was (11.3%, n=11) (Table.1). Median follow-up was, 4 years (range, 0–14). Active Crohn’s at follow-up was reported in, 68.1%. Only, 41.2% of patients underwent attempt at stoma reversal, and, 42.3% required a proctectomy (median, 19.5 months after diversion). At last follow-up, 29.9% were stoma-free, 42.3% had a new permanent stoma, and, 27.8% had the original diverting stoma (Fig.1). The multivariable predictors of proctectomy and permanent stoma were the recurrence of active CD after diversion and the need for other CD-related surgery following stoma creation (Table.2). The limitations of the study are its small sample size and its retrospective nature. The cumulative probability of stoma closure was performed with a Kaplan Meier log-rank analysis (Fig.2). Conclusion Diversion is effective at alleviating symptoms of Crohn’s proctitis in selected patients but does not significantly change disease outcome. Only a small number can avoid a long-term stoma.

P238 Symptom burden and indolent disease in newly diagnosed patients with ulcerative colitis and Crohn’s disease - a Copenhagen IBD Inception Cohort Study

Abstract Background The early course of ulcerative colitis (UC) and Crohn’s disease (CD) is difficult to predict, particularly regarding identifying patients for whom an indolent course might be expected. Therefore, we aimed to investigate the initial course of UC and CD and clinical predictors hereof in a generalizable population-based inception cohort. Methods We initiated a prospective population-based inception cohort of newly diagnosed patients with UC and CD between May 1st, 2021 and November 1st, 2021, according to the Copenhagen IBD Criteria within the geographical uptake area of Hvidovre University Hospital and Herlev University Hospital. All patients were examined systematically by IBD specialists at diagnosis using endoscopy, magnetic resonance (MR) enterography, and patient-reported measures including Simple Clinical Colitis Index (SCCAI) and Harvey-Bradshaw Index (HBI) for UC and CD, respectively. Indolent disease presentation was defined as the absence of UC or CD-related hospitalization, surgery, or decision to start steroid, immunomodulator, or biologic therapy within three months of follow-up. In addition, well-recognized predictors of long-term disease course of UC and CD were a priori defined and implemented in a univariate logistic model, and factors with a p-value smaller than 0.10 were included in the multivariate model. Results The study included 63 adult patients with UC and 50 with CD. At diagnosis, 23 (36.5%) and 13 (26.0%) patients with UC and CD were in clinical remission according to their SCCAI or HBI score, respectively (Table 1). The symptomatic disease burden is outlined in Table 2–3. Interestingly, well-recognized risk factors for the long-term disease course of UC and CD, including disease extent, behavior, baseline endoscopy, MR enterography, and serologic data, did not predict the initial disease course in a multivariable analysis (Table 4). However, C-reactive protein &amp;lt;10 mg/L were associated with an indolent course of UC (adjusted odds ratio=6.2 (95% confidence interval 1.3–38.9), p=0.03). Conclusion The preliminary data from the ongoing prospective population-based cohort study indicate that very heterogenous disease course patterns might be experienced very early. As initial disease control is considered critical for long-term outcomes, this study highlights the inapplicability of long-term predictors for the short-term disease course. It emphasizes the need for further development of simple clinical tools or biomarkers for early patient stratification.

P576 Real-world effectiveness and safety of risankizumab in patients with moderate-to-severe multi-refractory Crohn’s disease: a Belgian multi-centric cohort study

Abstract Background In recent phase 3 trials, risankizumab (RZB), a humanised monoclonal IgG1 antibody targeting the interleukin 23 p19 subunit, proved to be superior to placebo in inducing and maintaining clinical remission and endoscopic response in patients with moderate-to-severe Crohn’s disease. In this study, we aimed to evaluate the effectiveness and safety of RZB in a real-world cohort of multi-refractory CD patients. Methods Adult CD patients from six Belgian IBD centres who initiated RZB prior to May 2021 as part of a medical need program were prospectively followed. Patients with an ostomy were excluded for the main analyses. The primary endpoint was steroid-free clinical remission at week 24 (average daily liquid stool frequency [SF] ≤2.8 and average abdominal pain [AP] score ≤1, both not worse than baseline). Secondary endpoints included clinical response, endoscopic remission, endoscopic response, biological remission, biological response, need for CD-related hospitalisation or surgery, and serious adverse events (definitions in Figure 1). Given that a follow-up endoscopy has not yet been performed in some patients, results are shown for both “all patients” (with non-responder imputation) and “as observed”. Results A total of 27 patients started RZB of whom 19 patients were eligible for this study with a minimal follow-up of 24 weeks (Table 1). Eight patients were excluded as they had an ostomy at time of RZB initiation. Eighteen patients (95%) had been exposed to more than 3 biologicals and 13 (68%) previously underwent a CD-related intestinal resection. By week 24, 7/19 (37%) and 7/19 (37%) patients achieved steroid-free clinical remission and endoscopic response, respectively (Figure 1). In the “as observed” analyses, these rates were 7/18 (39%) and 7/9 (78%), respectively (Figure 2). Five patients used concomitant steroids at baseline and were all able to stop it after a median of 10 weeks. Eventually, three patients had to be hospitalized for bowel resection (2 with placement of an ostomy) after a median of 24 weeks, two of them required earlier an emergent hospitalization due to flares of abdominal pain and bloody diarrhea. None of the patients experienced serious infections or intolerance. Based on physician global assessment, three out of eight patients with an ostomy did achieve clinical remission, and two other achieved clinical response. Endoscopic follow-up data were available in six patients, and three of them experienced endoscopic response. Conclusion In this real-world, multi-refractory cohort, clinical remission and endoscopic response were both observed by week 24 in more than one third of CD patients initiating RZB. RZB was well tolerated with no safety issues.

P495 Perianal fistula closure in patients receiving ustekinumab: Results from the SEAVUE and STARDUST trials

Abstract Background Perianal fistulas are common and cause significant quality of life impairment in patients (pts) with Crohn’s disease (CD). In previous phase 2/3 studies, ustekinumab (UST) showed some evidence of efficacy on fistula resolution, with no clear dose-response relationship. Additional studies are needed to evaluate the role of UST in perianal fistula treatment. Here, we report fistula data from two recent studies of UST in CD, SEAVUE and STARDUST. Methods In SEAVUE, biologic-naïve pts with moderate-to-severe CD were randomized to receive blinded UST (⁓6mg/kg IV at baseline then 90mg SC q8w) or adalimumab (ADA; 160/80mg SC at baseline/W2, then 40mg SC q2w). In STARDUST, biologic-naïve and biologic-failure pts with moderate-to-severe CD received open-label UST ⁓6mg/kg IV at baseline and UST 90mg SC at W8. At W16, pts were randomized to maintenance treatment under standard of care (90mg SC q12w or q8w) or treat-to-target (90mg SC q12w or q8w with potential adjustment to q4w) regimens. In both trials, the number of open and draining perianal fistulas was evaluated at baseline and the end of maintenance (SEAVUE W52, STARDUST W48). Fistula resolution was defined as closure of all fistulas. Pts with missing data at W52/W48 were considered to not have been in fistula resolution. In SEAVUE, pts who had a prohibited CD-related surgery, discontinued for lack of efficacy or an adverse event of worsening CD, or had prohibited concomitant medication changes before W52 were considered not to be in fistula resolution. Results In SEAVUE, 7 of 13 pts (53.8%) with active perianal fistulas at baseline in the UST group had complete fistula resolution at W52, and 6 of 16 patients (37.5%) in the ADA group had fistula resolution. In STARDUST, 9 of 19 pts (47.4%) with active perianal fistulas at baseline had complete fistula resolution at W48. Of the 9 pts in fistula resolution, 2 were receiving q12w at W48, 6 were receiving q8w, and 1 was receiving q4w. Of the 10 pts without fistula resolution, 2 were receiving q12w at W48, 3 were receiving q8w, 1 was receiving q4w and 4 discontinued before W48. In both studies, among pts with evaluable samples for pharmacokinetic analysis, fistula closure at W52/48 was not associated with higher serum drug concentrations at either the early time point of W16 or at the end of maintenance (Figure). This result was consistent for UST in both studies as well as ADA in SEAVUE. Conclusion Of pts with perianal fistulas at baseline in SEAVUE and STARDUST who received UST (32 pts in total), half were in fistula resolution after ~1 year of maintenance treatment. No relationship was observed between fistula resolution and serum drug concentrations, but no definite conclusions can be drawn given the relatively small sample size.

P674 Predictors of response to biologics in Crohn’s Diseases: A population-based study from the epi-IIRN

Abstract Background Approximately one third of patients with inflammatory bowel disease (IBD) fail to response to anti TNF drugs, and another 25–50% loses response within one year. Identifying prognostic factors of therapeutic failure, may facilitate balancing the risks and benefits of this therapy. In this population-based study, we aimed to explore predictors of therapeutic failure of biologics in Crohn’s disease (CD). Methods We retrieved data from two of four Health Maintenance Organizations in Israel, covering 38% of the population as part of the validated epi-IIRN IBD cohort. We included an inception cohort of CD patients, diagnosed since 2005 who were commenced on biologics. Those who underwent CD-related surgery within 90 days from diagnosis were excluded. The primary outcome was therapeutic failure (i.e. discontinuation of treatment or need for surgery or &amp;gt;1 short steroid courses). The secondary outcome was primary non-response (PNR; i.e. therapeutic failure within 4 months of initiation). Predictors were sought through Cox proportional hazard model. Results A total of 2,805 patients were included (923 [33%] pediatric-onset, 1,882 [67%] adults) with a median follow-up of 7.5 years (IQR 4.4–11.5). The probability of of PNR was 11% and of therapeutic failure 29%, 52% and 62%, after one, three and five years after commencing biologics, respectively. Female sex (HR 1.2 [95%CI 1.1–1.4]), intestinal surgery prior to biologic treatment (HR 1.5 [95%CI 1.1–1.8]) and number of flares prior to biologic treatment (HR 1.1 [95%CI 1.1–1.2]) were associated with therapeutic failure. PNR was associated with intestinal surgery (HR 2.0 [95%CI 1.3–2.9]) and steroid use (HR 1.7 [95%CI 1.3–2.2]). Laboratory blood work, including CRP, ESR, albumin, hemoglobin, leukocytes and platelets, at diagnosis (HR 0.8 [95%CI 0.4–1.5]) and at initiation of biologics (HR 1.1 [95%CI 0.6–1.9]) did not predict therapeutic failure in the multivariable model. Conclusion Half of CD patients failed to response to biologic treatment within three years. Disease severity prior to biologic treatment, reflected by intestinal surgeries, number of flares and steroid use, predicted therapeutic failure. These results emphasize the importance of timely introduction of intensified treatment in patients at risk.

DOP47 Identification and characterization of T-cell receptor sequences associated with Crohn’s Disease

Abstract Background T cells, as part of the adaptive immune system, are a significant driver of inflammation in Crohn’s disease (CD), yet specific T-cell targets are largely unknown. Genetic factors contribute to a small portion of CD risk including several HLA alleles, such as DRB1*07:01 and HLA-DRB1*01:03, associated with CD. The involvement of HLAs suggests that studying specific T cells could lead to new insights into CD development and progression. In this study, we use established immunoSEQ® technology to profile T-cell receptors (TCRs) and identify TCRs associated with CD and CD characteristics. Methods We analyzed TCRs from blood of 1,738 CD cases and 4,970 healthy controls. TCRs that were statistically enriched in cases, but not healthy controls (p &amp;lt;0.001), were termed Enhanced Sequences (ES) associated with CD. An independent cohort of 434 CD cases was used for validation. We inferred associations between the ES and 145 common HLA alleles using data from a separate, HLA-typed dataset. We defined ES clusters by correlating TCRs with single amino acid substitutions. Results We identified 1,121 CD-associated ES in the exploratory cohort. These were also enriched in CD cases in our validation cohort (Fig 1A). Using intestinal tissue samples from a subset of cases, we found that a median of 14% ES from individual cases were shared between blood and tissue samples (Fig. 1B). ES breadth (ES diversity relative to total TCR diversity) was significantly associated with history of CD-related surgery (Fig 1C, p &amp;lt; 1x10-15), with stricturing or fistulizing phenotypes (Fig 1D, p &amp;lt; 1x10-5 for B1 versus B2 or B3), and with ileal or ileocolonic location (Fig 1E, p &amp;lt; 1x10-7 for L2 versus L1 or L3). We found that 202 ES formed clusters of similar sequences consisting of 2–23 members (Fig. 2A). We confidently (p &amp;lt; 0.0001) associated 398 ES to a specific HLA allele (Fig 2B), including 134 of the ES assigned to clusters (Fig 2A). Some clusters, including the largest, had no members that could be assigned to an HLA allele, raising the possibility that these ES clusters bind non-canonical HLAs. Conclusion Our discovery set of public TCRs associated with CD indicates that the immune system of CD patients responds to a consistent set of antigens. Importantly, CD ES were present in both tissue and blood, demonstrating that evaluating TCRs in blood may be a surrogate of TCRs in tissue. The HLA allele associations of these ES potentially point to new risk factors and disease insights, such as the involvement of DP and DQ alleles. The association of ES frequency with CD characteristics strongly suggested that further examination of these TCRs may impact CD patient care and advance understanding of the pathophysiology of the disease.

P315 High symptom burden and impact on health-related quality of life in patients with Crohn’s perianal fistulas: results from a global burden of illness study

Abstract Background Perianal fistulas (PAF) are a common complication in Crohn’s disease (CD) and can be associated with an increased burden of illness. A global study was conducted to assess the burden of illness in patients with Crohn’s perianal fistulas (CPF) compared with patients with CD without PAF (non-PAF CD). Here we present patient symptom burden and impact on HRQoL. Methods This cross-sectional study was conducted in seven countries (France, Germany, Spain, UK, Canada, Australia and Japan) in patients aged ≥21 and ≤90 years with self-reported physician-diagnosed CD. Patients were classified as having non-PAF CD (cohort, 1) or CPF without PAF-related surgery (cohort, 2) or CPF with PAF-related surgery (cohort, 3). Customised questions and validated general and disease-specific patient-reported outcome data were collected via a, 45-min IRB/EC-approved web-enabled questionnaire. Symptom burden and impact on HRQoL were evaluated using the Short Inflammatory Bowel Disease Questionnaire (SIBDQ, scores, 1–7 [low–optimum] with, 2-week recall period) in all cohorts and Quality of Life in Patients with Anal Fistula (QoLAF, scores, 14–70 [low–high impact]) in cohorts, 2 and, 3. Data were analysed using descriptive statistics. Results Of, 929 patients recruited (cohort, 1, n=620; cohort, 2, n=174; cohort, 3, n=135), 58–69% were male and, 55–67% were aged, 21–40 years across all cohorts. Cohorts, 2 and, 3 experienced a significantly higher frequency of CD-related complications than cohort, 1 (mean [standard deviation, SD]:, 9.4 [4.5] and, 11.1 [5.2] vs, 6.0 [4.1], respectively; both p &amp;lt;0.05, Table, 1) and had a higher number of CD-related surgeries (other than PAF-related surgeries) in the past, 12 months (mean [SD]:, 1.8 [1.1], p =0.109 and, 2.2 [1.3], p &amp;lt;0.0001 vs, 1.5 [0.9], respectively). In patients with CPF, a smaller proportion in cohort, 2 had active PAF vs cohort, 3 (136 [78%] vs, 119 [88%], respectively; p =0.022) and a smaller proportion had experience with post-treatment PAF recurrence/persistence in cohort, 2 vs cohort, 3 (84 [48%] vs, 80 [59%], respectively; p =0.055). Overall SIBDQ scores were significantly lower (worse) in cohorts, 2 and, 3 than in cohort, 1 (3.8 and, 3.7 vs, 4.1 respectively; both p &amp;lt;0.001). In patients with CPF, total QoLAF scores were comparable between cohorts, 2 and, 3 (41 and, 42, respectively), although patients in cohort, 3 had a significantly higher (worse) score in the physical impact domain compared with cohort, 2 (21 vs, 19, respectively; p &amp;lt;0.05). Conclusion In this large global study, we observed that patients with CPF had incrementally higher symptom burden, owing to both CD and PAF, compared with patients with non-PAF CD. For patients with CPF, there was no difference in HRQoL irrespective of whether they had received PAF-related surgery or not.

Long-term Disease Behavior and Surgical Intervention Analysis in Hospitalized Patients With Crohn's Disease in China: A Retrospective Cohort Study.

There is lack of real-world data for disease behavior and surgery of Crohn's disease (CD) from large-scale Chinese cohorts. Hospitalized patients diagnosed with CD in our center were consecutively included from January 2000 to December 2018. Disease behavior progression was defined as the initial classification of B1 to the progression of B2 or B3. Clinical characteristics including demographics, disease classification and activity, medical therapy, development of cancers, and death were collected. Overall, 504 patients were included. Two hundred thirty-one (45.8%) patients were initially classified as B1; 30 (13.0%), 71 (30.7%), and 95 (41.1%) of them had disease progression at the 1-year follow-up, 5-year follow-up, and overall, respectively. Patients without location transition before behavior transition were less likely to experience behavior progression. However, patients without previous exposure to a corticosteroid, immunomodulator, or biological agent had a greater chance of experiencing behavior progression. When the long-term prognosis was evaluated, 211 (41.9%) patients underwent at least 1 CD-related surgery; 108 (21.4%) and 120 (23.8%) of these patients underwent surgery before and after their diagnosis, respectively. An initial classification as B1, no behavior transition, no surgery prior to diagnosis, and previous corticosteroid exposure during follow-up were associated with a lower risk of undergoing surgery. This study depicts the clinical features and factors associated with behavior progression and surgery among hospitalized CD patients in a Chinese center. Behavior progression is associated with a higher probability of CD-related surgery, and strengthened therapies are necessary for them in the early phase.