CD-related Surgery Research Articles

P240 Low surgery rates first year after diagnosis in Crohn’s disease; results from a large population-based inception cohort - the IBSEN III study

Abstract Background Surgery rates in Crohn’s disease (CD) have declined during recent years, in parallel with the introduction and increased use of biological treatment. The aim of this study was to describe the use of first-line biologic therapy and to estimate the intra-abdominal surgery rate during the first year after the CD diagnosis. Methods The Inflammatory Bowel Disease in South-Eastern Norway III (IBSEN III) study is a population-based inception cohort with a prospective follow-up of newly diagnosed inflammatory bowel disease patients from the South-Eastern Health Region of Norway included in the period 2017 to 2019. Five hundred and seven patients ≥18 years were diagnosed with CD and those attending the one-year follow-up visit were included in this study. Clinical data, including Montreal classification, were registered at time of diagnosis. At the one-year follow-up, use of biologic therapy and need for CD-related intra-abdominal surgery since diagnosis were registered. Kaplan-Meier plots estimated the cumulative incidence of first-line biologic therapy and intra-abdominal surgery. Results A total of 431/507 (85%) CD patients attended the one-year follow-up and were included, 54.8% female, median age 37 years (range 18-80). At diagnosis 218 (50.6%) presented with ileal disease location, 76 (17.6%) colonic and 137 (31.8%) ileocolonic disease location, while 11 (2.6%) also had upper gastrointestinal involvement. The majority, 351 (81.4%), had a non-stricturing non-penetrating disease behavior, 70 (16.2%) a stricturing and 10 (2.3%) a penetrating disease behavior, while 17 (3.9%) also had perianal disease. Within one year of follow-up, 165 (38.7%) received at least one biologic therapy (60.6% infliximab, 35.8% adalimumab and 3.6% vedolizumab). Seven patients (1.6%) underwent perianal surgery and 21 (4.9%) had intra-abdominal surgery within the first year. Three of these were diagnosed during their primary surgery. Time from diagnosis to start of first-line biologic therapy and first intra-abdominal surgery is shown in Figure 1 and Figure 2, respectively. Figure 1: Kaplan-Meier plot showing cumulative incidence of first-line biologic therapy. Figure 2: Kaplan-Meier plot showing cumulative incidence of Crohn's related intra-abdominal surgery. Conclusion In the IBSEN III cohort, the rate of intra-abdominal surgery during the first year of disease was low (4.9%) compared to a previous population-based study from the same geographic area during the pre-biologic era, the IBSEN study, where the surgery rate was reported as 15.9 %.1 We hypothesize that a large preponderance of patients presenting with milder phenotypes at diagnosis combined with high use of biologicals contribute to the low surgery rates.

P299 Disability in newly diagnosed patients with Crohn′s Disease: initial results from the prospective CROCO (Crohn′s Disease Cohort) Study

Abstract Background CD is classically seen as a progressive disease leading to bowel damage and disability. Disability has been proposed by the Spirit-IOIBD consensus1 as an endpoint in disease modification trials. However, there is a paucity of data regarding disability in CD patients at diagnosis. Methods The “Crohn′s Disease Cohort Study” (CROCO) is an ongoing prospective cohort aiming to study the longitudinal evolution of bowel damage and disability following diagnosis of CD. All patients are included within 12 months following CD diagnosis and will be followed over 5 years with serial assessments of bowel damage and disability. At recruitment patients completed an IBD disability score questionnaire (DS),2 comprising several domains: mobility, self-care, major daily life activities, gastrointestinal-related problems, mental health and interaction with the environment. We here describe the baseline DS and its association with disease features, disease activity score (Harvey-Bradshaw Index), and biomarkers of disease activity, on the first patients recruited into CROCO. Results Ninety-four patients were recruited, of which 66 filled at least 80% of the questions in the DS questionnaire; of those 55% were male and median age at diagnosis was 30.6 [IQR 24.2;38.8]. The baseline visit occurred at a median time of 6 months [IQR 2.6;9.2] after CD diagnosis. Ileal involvement (L1/L3) was reported in 82% of patients; 68% had B1 phenotype, and 26% presented extra-intestinal manifestations. Overall, 32% of patients had been hospitalised, and 6% had a history of CD-related surgery. Regarding medication [from diagnosis to baseline], 55% received steroids, 56% immunosuppressants, and 65% Anti-TNF therapy. The median DS was 79 [IQR 67;108.2] (range: 49;198); only 2 patients (3%) patients presented DS>162 (the central value of the DS), indicating no or mild disability. No correlations were found between clinical or analytical biomarkers of disease activity at the time of recruitment (Table 1). Associations between disease features and DS are displayed in Table 2. A history of CD-related hospitalisation was associated with a significantly higher DS (103 [IQR 79;157] versus 76.5 [65.5;97], p=0.013). No other associations were observed. Conclusion In a cohort of newly diagnosed CD patients, disability was mostly mild and independent of disease activity, disease location or behaviour; around 1/3 required hospitalisation within the first year of diagnosis, which was associated with increased disability. These data add to the growing concept that newly diagnosed disease represents a window of opportunity for intervention.

P638 Effectiveness and safety of risankizumab induction therapy for 100 patients with Crohn’s disease: a GETAID multicentre cohort study

Abstract Background Phase III trials have demonstrated the efficacy of risankizumab in moderate-to-severe Crohn’s disease (CD), but no real-world data are currently available. We aimed to assess the short-term effectiveness and safety of risankizumab in patients with CD. Methods From May 2021 to May 2022, all patients with refractory luminal CD treated with risankizumab in 22 French GETAID centers were retrospectively included. The primary endpoint was steroid-free clinical remission at week 12 (Harvey-Bradshaw (HB) score < 5). Secondary endpoints included clinical response (≥ 3-point decrease of HB score and/or (HB) score < 5), biological remission (CRP ≤ 5 mg/L), need for CD-related surgery, and adverse events. Results Among the 100 patients included, all have been previously exposed to anti-TNF agents, 94 to vedolizumab, 98 to ustekinumab (all exposed to at least three biologics) and 61 had previous intestinal resection. All but three (97%) received a 600 mg risankizumab intravenous induction at weeks 0-4-8. At week 12, steroid-free clinical remission was observed in 45.8% of patients, clinical remission in 58% and clinical response in 78.5%. Absence/mild abdominal pain with normal stool frequency was noted in 50% of patients at week 12. Biological remission was observed in 50% of patients. Six patients discontinued risankizumab before the week 12 visit due to lack of efficacy. CD-related hospitalization was needed in six patients, and three underwent intestinal resection. In multivariable analysis, only a history of ustekinumab loss of response (vs primary failure) (Odds Ratio (OR), 2.80 ; 95%CI, 1.07 – 7.82; p=0.041) was significantly associated with clinical remission at week 12. Twenty adverse events (AE) occurred in 20 patients including 7 serious AE corresponding to 6 CD exacerbation and one severe hypertension. Conclusion In a cohort of highly refractory patients with luminal CD and multiple prior drug failures including ustekinumab, risankizumab induction provided clinical response in about 3 out of 4 patients and steroid-free clinical remission in about half of patients.

P293 Correlation between clinical measures to capture disease burden and prediction of the initial course of Crohn’s disease - findings from a Copenhagen IBD Inception Cohort Study (IBD Prognosis Study)

Abstract Background The initial disease burden of Crohn’s disease (CD) is dissimilar across patients; however, the ability to capture and predict the disease burden at diagnosis is scarcely investigated. The aim of the current study was to describe the initial disease burden of Crohn’s disease. Methods IBD Prognosis Study is an ongoing prospective population-based inception cohort of newly diagnosed patients with CD between May 1st, 2021, and November 1st, 2022, according to the Copenhagen IBD Criteria.1 We defined an indolent disease presentation as no need for CD-related surgery, hospitalization, nor initiation of steroid, immunomodulatory, or biologic therapies within the first 30 days after diagnosis, while a complicated course was defined as the opposite. Results The study included 134 patients with adult-onset CD, of whom approximately one-third (44/134, 33%) had an early indolent course, with 26 patients (19%) not requiring any medication (Tables 1-2). In demographic factor adjusted analyses, a colonic phenotype (adjusted odds ratio (aOR) =4.5 (95% confidence interval (CI) 1.6-15) and a low symptom load measured with Harvey-Bradshaw Index (HBI) <5 (aOR = 3.1 (CI 1.0-10) were independently associated with an indolent course. In contrast, a C-reactive protein (CRP) level higher than 10 mg/L was the only parameter associated with a complicated onset of CD (aOR = 4.7 (CI 2.1-12)). Pearson’s correlation analyses demonstrated a significant, moderate correlation between fecal (F-) calprotectin, CRP, and endoscopic lesions, measured with Simple Endoscopic Score for CD (SES-CD) (Table 3). HBI and the International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) exhibited a significant but weak correlation with CRP. In a sensitivity analysis allowing exposure to anti-inflammatory therapy for only up to seven days, the platelet count, F-calprotectin, and bowel wall thickness measured in IBUS-SAS demonstrated a significant and moderate correlation with SES-CD. The total IBUS-SAS and CRP showed a significant but weak correlation, and other measures included in the IBUS-SAS did not yield significant correlations. Conclusion Preliminary data from the ongoing population-based cohort indicate that one-third of patients with newly diagnosed CD have an early indolent course. This study identified colonic disease location and CRP levels to be associated with the early course, while platelet count, bowel wall thickness, and CRP were correlated with endoscopic lesions at the onset of CD.

P494 Impact of early optimization of ustekinumab on mid-term targets in severe Crohn’s disease: THE MUST study

Abstract Background As a substantial proportion of patients with Crohn’s disease (CD) experiences a refractory disease course, immediate drug intensification may be an option to optimize the effectiveness of current biotherapies. Aim : to compare the one-year efficacy of immediate dose escalation of ustekinumab 90 mg to 4-weekly with that of 8-weekly dosing after intravenous (iv) induction in severe active CD patients. Methods The MUST (meta-optimization of Ustekinumab) study is a real-life multicenter observational French retrospective cohort study including patients with severe active CD. All patients from three academic IBD centers who received induction therapy with IV ustekinumab followed with subcutaneous (sc) UST 90 mg, either 4-weekly (MUST group) or 8-weekly (STD group) were included from Jan 2019 to Dec 2020. The choice of treatment regimen was left at the physician’s discretion. Severe active CD was defined by HBI > 16 and stool frequency (SF) ≥ 4 and abdominal pain (AP) ≥ 2 over one week and at least one objective evidence of inflammation (CRP ≥ 5 mg/L and/or FCal ≥ 250 μg/g and/or radiologic and/or endoscopic signs of disease activity). The primary endpoint was PRO-2 based clinical remission defined by SF≤2-8 and AP ≤1, and either FCal <250 μg/g and/or CRP <5 mg/L at week 52. Key secondary endpoints were PRO-2 remission, endoscopic improvement and steroid-free clinical remission at week 52. Results 203 adult patients were included, either in the MUST group (n = 59) or in the STD group (n = 144). Baseline patient demographics and disease characteristics were similar between groups. Median disease duration was 9 years (IQR: 5 – 14 yrs), 66% were females. Disease location according to the Montreal classification was L1 and L3 in 36% and 44 % of patients. All had previously been exposed to more than one biotherapy, 27% experienced perianal CD, and 35% had undergone previous CD-related surgery. At week 52, the adjusted difference between the two groups for the primary endpoint was 15.8% (95% confidence interval (CI) 0.21 – 0.94; p = 0.029) with significantly higher clinical remission in the MUST group. The adjusted difference for PRO-2 remission was 3.7% (CI 0.45 - 1.66; p = 0.64). All patients, except one in the STD group, were weaned off steroids at week 52. Endoscopic improvement was similar in both groups (61.9% vs. 61.5%, p=0.98). Adverse events were not significantly different in both arms (42.4% vs 34.7%, p=0.338). Conclusion In the treat-to-target era, our real-life study shows that immediate escalation of ustekinumab therapy to 4-weekly dosing could achieve higher clinical remission at one year than 8-weekly dosing in severe CD. These findings should be confirmed in a dedicated prospective randomized trial.

SUPERIOR PERSISTENCE WHILE ON LABELED MAINTENANCE DOSE AMONG BIO-NAÏVE PATIENTS WITH CROHN'S DISEASE INITIATED ON USTEKINUMAB COMPARED TO ADALIMUMAB

Abstract BACKGROUND Treatment of Crohn’s disease (CD) may require biologics. Dose escalation may be necessary to maintain efficacy, while adverse events or non-response may lead to treatment discontinuation. This analysis aimed to generate real-world evidence of persistence to ustekinumab versus adalimumab while on labeled maintenance dose (United States [US] prescribing information) among bio-naïve patients with CD in the US. METHODS Adults with CD initiated on ustekinumab or adalimumab from 09/23/2016 (approval of ustekinumab for CD in the US) to 08/01/2019 were selected from a de-identified health insurance claims database (IQVIA PharMetrics® Plus). Patients who used other biologics indicated for CD or had diagnoses for other autoimmune disorders in the 12 months before the initiation of the index agent (baseline) were excluded. Cohorts were balanced on baseline characteristics using inverse probability of treatment weights. Persistence to the index agent while on labeled maintenance dose was defined as (1) absence of gaps between days of therapy supply >120 days for ustekinumab (twice the 8-week on-label maintenance dosing interval) or >60 days for adalimumab (twice the mode of days of supply in claims) and (2) absence of any dose change during the maintenance phase relative to the dose per US label. It was assessed from the index date until the earliest of discontinuation (event), dose change during the maintenance phase (censoring), or the last day of index agent supply before the end of follow-up (censoring). Weighted Kaplan-Meier and Cox proportional hazards models were used to assess the outcome at 12 months post-index. RESULTS 948 bio-naïve patients with CD were included in the ustekinumab cohort (mean age 42.5 years old; 58.1% female) and 4,143 in the adalimumab cohort (mean age 42.3 years old; 56.7% female). During the baseline period, 8.4% and 9.2% previously had CD-related surgery, 66.6% and 67.7% used corticosteroids, and 25.9% and 26.3% used immunomodulators in the ustekinumab and adalimumab cohorts, respectively. At 12 months post-index, a higher proportion of patients in the ustekinumab cohort versus adalimumab cohort were persistent to the index biologic while on labeled maintenance dose (74.1% vs 65.4%; Fig. 1). Patients in the ustekinumab versus adalimumab cohort had a 47% higher rate of persistence while on labeled maintenance dose (hazard ratio [HR] 1.47; 95% confidence interval [CI]: 1.25-1.73; P-value: <0.001*). CONCLUSIONS Bio-naïve patients with CD initiated on ustekinumab were significantly more persistent while on labeled maintenance dose compared to patients initiated on adalimumab. These results are consistent with previous work, which demonstrated significantly higher persistence to the index agent and a trend of lower dose escalation rates among bio-naïve patients with CD initiating ustekinumab versus adalimumab.

MULTIDISCIPLINARY MANAGEMENT, ANTI-TNF THERAPY, AND CLINICAL OUTCOMES OF INTERNALLY PENETRATING CROHN’S DISEASE COMPLICATION IN PEDIATRICS: INTERIM ANALYSES OF A MULTICENTER RETROSPECTIVE COHORT

Abstract BACKGROUND Internally penetrating Crohn’s disease (CD) complications (IPCDC; i.e. abscess and/or inflammatory mass) confer significant morbidity to pediatric patients with CD. Management strategies are heterogenous. Anti-tumor-necrosis-factor-a biologics (anti-TNF) are the mainstay of penetrating CD therapy and are most effective early in the treatment course. However, anti-TNF use among patients with IPCDC is limited by hesitancy concerning infectious risk. Recent studies show that this risk may be overstated. We hypothesized that early anti-TNF following IPCDC diagnosis, in the context of infection control, is 1) safe and 2) effective in pediatric patients. Here, we present interim results of an observational multi-center study. METHODS We performed a retrospective cohort study of pediatric patients with IPCDC, across 12 tertiary children’s hospitals. Patients (age 6+ years) were identified via radiology, ICD-coding, and ImproveCareNow searches. Patients admitted for an IPCDC diagnosed via MRI or CT from 2007-2021, with 1+ year of follow-up were included. Patients were excluded if complications were due to a non-CD-related process, solely perianal, if admission followed outpatient or outside institution treatment failure, or if surgery was required within 7 days of IPCDC (n=7). First, we measured the safety effect of anti-TNF following IPCDC diagnosis, prior to IPCDC resolution, on infectious serious adverse events (SAE) (i.e. new or enlarging IPCDC, or infection, requiring hospitalization or surgery), within 30 days. Next, we measured the effectiveness of anti-TNF within 30 days of IPCDC diagnosis on CD-related SAEs (i.e. non-infectious CD-related hospitalization or surgery), within one year. Kaplan-Meier curves were generated to describe outcomes over time. RESULTS 95 patients were included. Cohort characteristics, multidisciplinary treatment strategies, and outcomes are presented in Table 1. Kaplan-Meier curves are presented in Figure 1. 80% of patients received anti-TNF within one year of IPCDC (median 37 days [IQR 7-68]). Infectious SAEs within 90 days of IPCDC occurred in 37% (median 20 days [IQR 10-26]). Among patients initiating anti-TNF prior to IPCDC resolution, 27% had an infectious SAE within 90 days, compared to 49% of those not initiating anti-TNF prior to IPCDC resolution. Non-infectious CD-related SAEs within one year occurred in 44% (median 51 days [IQR 27, 89]). Among patients initiating anti-TNF within 30 days of IPCDC, 47% had a CD-related SAE, compared to 43% in those not receiving anti-TNF within 30 days. CONCLUSION Among a large multicenter pediatric cohort, IPCDC are associated with high rates of both infectious and CD-related SAE. Further data collection, implementation of causal inference methods, and subgroup analyses will be critical in isolating the relationship between timing of anti-TNF post-IPCDC and SAEs. Values represent Number (Percent) for categorical variables and Median (Interquartile Range) for continuous variables. Kaplan-Meier Survival Analyses for A) Infectious Serious Adverse Events and B) Crohn's Disease-Related Serious Adverse Events, stratified by exposure status. No censoring for lost-to-followup occured, as all patients had at least 1 year of follow-up avaialble.

PERSISTENCE WHILE ON LABELED MAINTENANCE DOSE AMONG BIO-EXPERIENCED PATIENTS WITH CROHN'S DISEASE INITIATED ON USTEKINUMAB COMPARED TO ADALIMUMAB

Abstract BACKGROUND In Crohn’s disease (CD), dose escalation on biologic therapy may be required to maintain effectiveness, while adverse events or non-response, among other factors, may lead to lack of persistence. Understanding persistence while on labeled maintenance dose is particularly important in bio-experienced patients with CD, as they may have reduced response to subsequent lines of therapy. This analysis compared persistence while on labeled maintenance dose among bio-experienced patients on ustekinumab versus adalimumab in the United States (US). METHODS Adults with CD initiated on ustekinumab or adalimumab (index date) between 09/23/2016 (ustekinumab approval for CD in the US) and 08/01/2019 were selected from IBM® MarketScan® Commercial Database. Patients were bio-experienced (≥1 claim for another CD-indicated biologic in the 12 months baseline period pre-index date). Patients with other auto-immune diseases at baseline were excluded. Cohorts were balanced on baseline characteristics using inverse probability of treatment weights. Persistence to the index agent while on labeled maintenance dose was defined as (1) no gaps between days of therapy supply >120 days for ustekinumab (2 x 8-week on-label maintenance dose interval) or >60 days for adalimumab (2 x days of supply mode) and (2) no dose change relative to the US label maintenance dose. It was assessed from index date until the earliest of discontinuation (event), dose change during maintenance phase (censoring), or last day of supply (censoring). Weighted Kaplan-Meier and Cox proportional hazards models adjusted for baseline classes of biologics were used to assess the outcome at 12 months post-index. RESULTS 903 bio-experienced patients with CD were included in the ustekinumab cohort (mean age 40.9 years old; 57.1% female) and 525 in the adalimumab cohort (mean age 41.3; 56.3% female). During the baseline period, 71.1% and 72.6% used corticosteroids, 41.2% and 40.8% used immunomodulators, and 11.1% and 12.6% had a prior CD-related surgery, in the ustekinumab and adalimumab cohorts, respectively. At 12 months post-index, the probability of persisting on the index biologic while on labeled maintenance dose was higher in the ustekinumab cohort versus adalimumab cohort (78.8% vs. 67.8%; Fig. 1). Patients in the ustekinumab versus adalimumab cohort had a 71% higher rate of persistence while on labeled maintenance dose (hazard ratio [HR] 1.71; 95% confidence interval: 1.31-2.23; P-value: <0.001*). CONCLUSIONS Bio-experienced patients with CD initiated on ustekinumab were significantly more persistent while on labeled maintenance dose compared to patients initiated on adalimumab. These results confirm results on persistence to biologics in bio-experienced patients with CD from a prior study.

INCORPORATION OF RISK ASSESSMENT TOOL IMPACTS PATIENT AND GASTROENTEROLOGIST CONFIDENCE AND TREATMENT DECISION MAKING IN BIONAIVE CROHN’S DISEASE

Abstract BACKGROUND Clinical guidelines recommend the incorporation of risk stratification assessments when making decisions about Crohn’s disease (CD) treatment. We aimed to evaluate if patient and gastroenterologist (GI) decision making and confidence about starting or changing therapy were impacted by reviewing a CD risk stratification assessment. METHODS We conducted a multicenter, prospective study evaluating the impact of a risk stratification tool on decision making by GIs and biologic naïve adult CD patients considering starting or changing therapy. Medical records were reviewed by a GI at the organizing site to determine risk according to the American Gastroenterological Association (AGA) Crohn’s Disease Care Pathway risk assessment tool. Patients with any risk factors for rapid disease progression (age<30 at diagnosis, deep ulcers, extensive anatomic involvement, perianal disease, prior CD surgery, and/or stricturing/penetrating behavior) were considered moderate-high risk. Patients and treating GIs were then provided a report with their risk assessment conveyed in both written and visual (“risk gauge”) format. Participants were surveyed at baseline and at 7 days after viewing the risk stratification assessment and were unaware which risk assessment tool was used to determine risk. The primary outcome was behavioral change defined as any modification in treatment plan or increase in patient or GI self-assessed confidence in need for treatment change (on 5-point Likert scale) from baseline to day 7. RESULTS 47 patient-GI pairs were enrolled across 14 sites. Among CD patients, mean age was 40.2 years, 59% were men, 70% were white, 80% had inflammatory (B1) disease behavior, 74% had no prior CD-related hospitalizations, and 82% no prior CD-related surgeries. 64% of patients were deemed moderate-high risk and 36% low risk by AGA criteria. In comparison, 40% of patients self-assessed their risk as moderate-high at baseline. The most common moderate-high risk factors were age<30 (45%) and stricturing/penetrating behavior (20%). At baseline, 49% of GI risk assessments of their patients were discordant with AGA risk stratification (e.g. moderate-high risk by AGA evaluated as low risk). Behavioral change was observed in 52% of participants at day 7 and was similar whether patient was low or moderate-high risk. At day 7, patient confidence increased in 21%, GI confidence increased in 23%, and treatment recommendation was changed in 36% of cases. Among patients assessed as low risk disease, confidence that patient would benefit from treatment change decreased in 47% of GIs and 59% of CD patients at day 7. CONCLUSION Incorporation of a simple risk stratification assessment when considering treatment change in CD can assist in patient and GI decision making. Low risk assessments are associated with lower confidence in decision making.

Preoperative Prognostic Nutritional Index and Nomogram for Predicting the Risk of Postoperative Complications in Patients With Crohn's Disease.

Patients with Crohn's disease (CD) are at a high risk of having postoperative complications. Preoperative prognostic nutritional index (PNI) has been extensively studied for postoperative complications in malignancies but seldom for CD. Patients who underwent CD-related bowel surgery for the first time in our hospital were retrospectively enrolled from January 2013 to October 2019. Differences in clinical features in low-PNI (≤34) and high-PNI (>34) groups were compared. A prognostic nomogram was then established to explore the risk factors and their assignments of postoperative complications. A total of 124 patients who underwent CD-related bowel surgery in our hospital from January 2013 to October 2019 were enrolled. Of these patients, 39 (31.5%) were categorized in the low-PNI group. The serum albumin levels (23.4 ± 4.8 vs 35.8 ± 5.2 g/L, P < 0.001), hemoglobin levels (98.0 ± 24.1 vs 115.8 ± 22.2 g/L, P < 0.001), and white blood cell counts (8.3 ± 5.4 × 10 9 vs 6.3 ± 3.0 × 10 9 , P = 0.009) of the patients in the low-PNI group were lower than those in the high-PNI group. Postoperative complications were observed in 35 cases of the total cohort, 20 of 39 (51.3%) in the low-PNI group, and 15 of 85 (17.6%) in the high-PNI group ( P < 0.001). A prognostic nomogram was built through least absolute shrinkage and selection operator regression. The nomogram revealed a significant difference in the length of postoperative stay between patients with high-risk postoperative complications and those with low-risk postoperative complications (17.07 ± 24.73 vs 10.36 ± 4.51, P = 0.02). PNI is closely associated with postoperative complications in patients with CD. Its inclusion in a prognostic nomogram provides a convenient mechanism to predict postoperative complications in patients with CD undergoing surgery.

Observational Burden of Illness Study in Patients With Crohn’s Disease With and Without Perianal Fistulas in the United States

This study compared disease burden, experiences, and health-related quality of life (HRQoL) between patients with Crohn's perianal fistulas (CPFs) and those with Crohn's disease (CD) without perianal fistulas (PFs; non-PF CD). This cross-sectional, observational study was conducted in 3 cohorts of US patients aged 18-89 years with self-reported, physician-diagnosed CD: (1) non-PF CD; (2) CPF without PF-related surgery; and (3) CPF with PF-related surgery. Data on medical and surgical interventions, CD-specific symptoms, HRQoL (assessed using the Short Inflammatory Bowel Disease and 5-dimension EuroQol questionnaires), and fecal incontinence (assessed using Revised Faecal Incontinence Scale and Fecal Incontinence Quality of Life questionnaires) were collected via a web-enabled questionnaire. In total, 403 patients with CD completed the questionnaire (non-PF CD, n= 300; CPF without surgery, n= 51; CPF with surgery, n= 52). A high symptom burden was seen across cohorts. More patients with CPF underwent ≥1 CD-related surgery and experienced ≥1 failure of CD-related surgery (79% and 20%) vs non-PF CD (53% and 9%; P < .001). Overall HRQoL outcomes were worse for patients with CPF vs non-PF CD, with significantly worse Short Inflammatory Bowel Disease and 5-dimension EuroQol questionnaire scores for those without PF-related surgery (P < .01). Across all cohorts, 58% of patients reported experiencing fecal incontinence, which had a greater negative impact (higher Revised Faecal Incontinence Scale scores; lower Fecal Incontinence Quality of Life scores) in patients with CPF vs non-PF CD. Patients with CPF experience substantial HRQoL burden, reflecting the impact of symptoms and medical/surgical interventions. These results may help to inform comprehensive care strategies to improve patient HRQoL.

CT-based radiomics signature of visceral adipose tissue for prediction of disease progression in patients with Crohn's disease: a multicentre cohort study

Visceral adipose tissue (VAT) is involved in the pathogenesis of Crohn's disease (CD). However, data describing its effects on CD progression remain scarce. We developed and validated a VAT-radiomics model (RM) using computed tomography (CT) images to predict disease progression in patients with CD and compared it with a subcutaneous adipose tissue (SAT)-RM. This retrospective study included 256 patients with CD (training, n=156; test, n=100) who underwent baseline CT examinations from June 19, 2015 to June 14, 2020at three tertiary referral centres (The First Affiliated Hospital of Sun Yat-Sen University, The First Affiliated Hospital of Shantou University Medical College, and The First People's Hospital of Foshan City) in China. Disease progression referred to the development of penetrating or stricturing diseases or the requirement for CD-related surgeries during follow-up. A total of 1130 radiomics features were extracted from VAT on CT in the training cohort, and a machine-learning-based VAT-RM was developed to predict disease progression using selected reproducible features and validated in an external test cohort. Using the same modeling methodology, a SAT-RM was developed and compared with the VAT-RM. The VAT-RM exhibited satisfactory performance for predicting disease progression in total test cohort (the area under the ROC curve [AUC]=0.850, 95% confidence Interval [CI] 0.764-0.913, P<0.001) and in test cohorts 1 (AUC=0.820, 95% CI 0.687-0.914, P<0.001) and 2 (AUC=0.871, 95% CI 0.744-0.949, P<0.001). No significant differences in AUC were observed between test cohorts 1 and 2 (P=0.673), suggesting considerable efficacy and robustness of the VAT-RM. In the total test cohort, the AUC of the VAT-RM for predicting disease progression was higher than that of SAT-RM (AUC=0.786, 95% CI 0.692-0.861, P<0.001). On multivariate Cox regression analysis, the VAT-RM (hazard ratio [HR]=9.285, P=0.005) was the most important independent predictor, followed by the SAT-RM (HR=3.280, P=0.060). Decision curve analysis further confirmed the better net benefit of the VAT-RM than the SAT-RM. Moreover, the SAT-RM failed to significantly improve predictive efficacy after it was added to the VAT-RM (integrated discrimination improvement=0.031, P=0.102). Our results suggest that VAT is an important determinant of disease progression in patients with CD. Our VAT-RM allows the accurate identification of high-risk patients prone to disease progression and offers notable advantages over SAT-RM. This study was supported by the National Natural Science Foundation of China, Guangdong Basic and Applied Basic Research Foundation, Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Nature Science Foundation of Shenzhen, and Young S&T Talent Training Program of Guangdong Provincial Association for S&T. For the Chinese translation of the abstract see Supplementary Materials section.

Serum Leucine-Rich α2 Glycoprotein: A Novel Biomarker for Transmural Inflammation in Crohn's Disease.

Leucine-rich alpha-2 glycoprotein (LRG) is a newly studied biomarker for inflammatory diseases. This study aimed to investigate whether LRG can be used for evaluating transmural activity in patients with Crohn's disease (CD). We performed magnetic resonance enterography (MRE) in 227 consecutive patients with CD from June 2020 to August 2021. We prospectively compared MRE findings with clinical and laboratory data including LRG. MRE was evaluated using 2 validated scoring systems, and transmural inflammation was defined as having a maximum simplified magnetic resonance index of activity (sMaRIA) score of ≥4 and a 5-point classification score of ≥9, respectively. The correlation between LRG and the total MRE score showed a positive correlation ( r = 0.576 for the sMaRIA score, P < 0.01, and r = 0.633 for the 5-point score, P < 0.01). Serum concentrations of LRG significantly increased as MRE scores increased ( P < 0.01). The area under the curve of LRG for a sMaRIA score of ≥4 and a 5-point score of ≥9 was 0.845 and 0.869, respectively, which was significantly higher than that of CDAI ( P < 0.01) or C-reactive protein ( P < 0.01). LRG levels of ≥14 μg/mL had a 67% sensitivity and 90% specificity for a sMaRIA score of ≥4 and a 73% sensitivity and 89% specificity for a 5-point score of ≥9. Patients with high LRG levels were also strongly associated with CD-related hospitalization, surgery, and clinical relapse compared with those with low LRG levels ( P < 0.01 for all). LRG is a highly accurate serum biomarker for detecting transmural activity in patients with CD. Results need to be validated in further multicenter studies.

How achievable are STRIDE-II treatment targets in real-world practice and do they predict long-term treatment outcomes?

ObjectiveThe second iteration of the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE-II) initiative recommends use of the Simple Endoscopic Score for Crohn’s disease (SES-CD) as a treatment target for...

USTEKINUMAB IN CROHN'S DISEASE MANAGEMENT: A BRAZILIAN OBSERVATIONAL STUDY.

Real-world data on the use of Ustekinumab (UST) in Brazilian and Latin American patients with Crohn's disease (CD) are scarce. The primary endpoint was assessment of clinical remission at weeks 8 and 52, and secondary endpoints were: assessment of clinical response at weeks 8 and 52, endoscopic remission, adverse events, and rates of CD-related abdominal surgery during follow-up. observational and retrospective study, including patients with CD treated at two centers, who received UST at any time during their treatment. Remission and clinical response were defined as a Harvey-Bradshaw index ≤4 and ≥3 points reduction, respectively. Seventy-four patients were included, 85.1% previously exposed to anti-TNFs. Clinical remission was observed in 45.8% and 59.4% of patients at weeks 8 and 52, respectively. The clinical response rates were 54.2% and 67.6% at weeks 8 and 52. Endoscopic remission was observed in 21.8% of patients. Seventeen patients had adverse events, mostly mild infections, with 22.9% of patients undergoing abdominal surgery (ileocolectomy being the most common procedure). UST therapy resulted in significant rates of remission and clinical response, as described in other real-world studies. Few patients had adverse events during treatment, showing its adequate safety profile.

S982 The Progression of Crohn’s Disease: Results From an Observational Study Using U.S. Claims Data

Introduction: Crohn’s disease (CD) is a chronic progressive inflammatory disease of the gastrointestinal tract. Disease progression is characterized by the occurrence of CD complications, including fistula, intestinal stenosis, and abscess. The aim of this study was to characterize progression among patients with CD without complications. Methods: This cohort study used data from the Optum claims database from 01/2016 to 06/2020. Patients without a previous CD diagnosis between 01/2017 and 06/2019 were considered as newly diagnosed cases; those with a previous CD diagnosis prior to the index date (CD diagnosis date) or 01/2017 were considered as existing cases. Patients with a history of CD progression were excluded. The primary objective was to estimate the risk of and time to progression from the time of CD diagnosis in patients newly diagnosed with CD without complications at baseline. Risk of progression (proportion of patients at risk who progressed) was estimated for both newly diagnosed and existing CD cases at 6 months and 1, 2, and 3 years. Kaplan–Meier estimates for time to progression (duration between index date and first progression event) were generated for newly diagnosed CD cases. Other outcomes e.g., demographic characteristics, were assessed over the follow-up period (between index date and 06/2020) using descriptive statistics. Results: In total, 23,241 patients (mean age 47.1 years [standard deviation 18.7]; 42.3% female) with CD were identified; 29.3% (n=6804) were newly diagnosed and 70.7% (n=16,437) were existing cases. The most common comorbidities in newly diagnosed and existing cases were obesity (25.4%; 18.4%), anxiety (24.5%; 21.9%), and depression (22.1%; 18.7%); extraintestinal manifestations (2.4%; 3.8%). The most common CD-related medication was antibiotics for newly diagnosed (25.2%; 18.3% existing) and acetylsalicylic acid for existing cases (27.5%; 13.1% newly diagnosed). Risk of CD progression over time ranged from 19.3% to 26.6% in newly diagnosed and 8.2% to 21.4% in existing cases (Table). A total of 6804 patients with newly diagnosed CD progressed with a median time to progression of 709 days (interquartile range: 415–987) (Figure). Conclusion: Over 20% of all patients with CD experienced progression during the follow-up period. Intestinal stenosis was a more common complication than fistula or abscess.Figure 1.: Time to Crohn’s disease progression events for newly diagnosed cases Time from CD diagnosis to progression event was assessed for the entire follow-up period for newly diagnosed cases only and was estimated as the time from the index date (date of the first CD diagnosis) to the progression date. If no such progression event was observed in the available follow-up period, the patient was censored. CD, Crohn’s disease; IQR, interquartile range. Table 1. - Risk of Crohn’s disease progression Period post-index date* Total follow-up period 6 months 1 year 2 years 3 years Newly diagnosed cases Existing cases Newly diagnosed cases Existing cases Newly diagnosed cases Existing cases Newly diagnosed cases Existing cases Newly diagnosed cases Existing cases Patients at risk of CD progression, n 6804 16,437 6117 15,182 5503 13,720 3875 11,238 1668 7856 Patients with CD progression†, n (%) 1714 (25.2) 3288 (20.0) 1183 (19.3) 1241 (8.2) 1188 (21.6) 1622 (11.8) 953 (24.6) 1879 (16.7) 444 (26.6) 1680 (21.4) CD fistula (diagnosis or surgery) 430 (6.3) 990 (6.0) 270 (4.4) 327 (2.2) 293 (5.3) 456 (3.3) 259 (6.7) 535 (4.8) 125 (7.5) 499 (6.4) Intestinal stenosis (stricture diagnosis or surgery) 1227 (18.0) 2211 (13.5) 843 (13.8) 798 (5.3) 845 (15.4) 1050 (7.7) 655 (16.9) 1224 (10.9) 320 (19.2) 1106 (14.1) Intestinal abscess (diagnosis or drainage procedure) 443 (6.5) 729 (4.4) 275 (4.5) 259 (1.7) 293 (5.3) 372 (2.7) 269 (6.9) 464 (4.1) 112 (6.7) 411 (5.2) Patients who underwent CD-related surgery, n (%) 354 (5.2) 684 (4.2) 198 (3.2) 214 (1.4) 217 (3.9) 305 (2.2) 206 (5.3) 417 (3.7) 95 (5.7) 384 (4.9) *Date of the first CD diagnosis. †A patient was considered to have CD progression if they had a diagnosis CD-related fistula, intestinal stenosis, or abscess, or underwent a CD-related surgery after the index date, whichever event occurred first. The date of the first of these progression events was considered the progression date. CD, Crohn’s disease.

S869 Real World Clinical Effectiveness and Safety of Vedolizumab and Adalimumab in Biologic-Naïve Patients With Crohn’s Disease: Results From the EVOLVE Study

Introduction: Vedolizumab (VDZ, a gut selective anti-α4β7-integrin) and adalimumab (ADA, anti-tumor necrosis factor) are approved biologic treatments for moderate to severe Crohn’s disease (CD). We aimed to evaluate the real-world clinical effectiveness and safety of VDZ versus ADA in biologic-naïve patients with CD. Methods: This was a retrospective cohort study in adult patients with CD who received first-line biologic treatment with VDZ or ADA at 37 sites in the US, Canada, and Greece. The index date was defined as the date of first-line biologic initiation between May 2014 and March 2018. Cumulative rates of treatment persistence and clinical outcomes over 12 months were estimated using the Kaplan-Meier method. Patients were censored at loss of follow up, death, end of chart abstraction, treatment discontinuation, or dose escalation, whichever came first. Clinical outcomes were assessed using pre-defined hierarchical algorithms of standard measures.1 Survival analyses were conducted for safety outcomes, CD-related exacerbations and CD surgeries. Adjusted analyses were performed using stabilized inverse probability weighting using baseline covariates. Results: 362 patients were included (VDZ: 218; ADA: 144). Baseline characteristics are shown in Table. Cumulative rates of clinical response (68.5% vs 61.1%; p=0.59) and mucosal healing (67.7% vs 56.0%; p=0.56) over 12 months were similar between treatment cohorts, whilst clinical remission rates (66.3% vs 46.4%; p< 0.01) were greater in VDZ- versus ADA-treated patients. Over 12 months, VDZ-treated patients were more likely to persist on treatment versus ADA-treated patients (89.3% vs 77.5%; p=0.02). VDZ-treated patients were significantly less likely to experience (incidence rates per 1000 person-years; HR [95%CI]) serious adverse events within 1 year (78.9 vs 166.2; 0.45 [0.22-0.93]), but there were no statistical differences in CD exacerbations (207.7 vs 261.8; 0.91 [0.56-1.47]), CD-related surgeries (10.3 vs 16.0; 1.55 [0.21-11.15]) or serious infections (20.5 vs 71.2; 0.27 [0.06-1.20]) versus ADA-treated patients. Conclusion: In a real-world setting in biologic-naïve patients with CD, VDZ-treated patients had equivalent rates of response and mucosal healing but a greater likelihood of persisting on treatment and achieving clinical remission versus ADA-treated patients. Studies assessing outcomes after dose optimization are needed. Table 1. - Baseline Characteristics of Biologic Naïve Patients with Crohn’s Disease Treated with Vedolizumab or Adalimumab Baseline Characteristics VedolizumabN=218 AdalimumabN=144 p-value Age, Mean (SD) 51.7 (16.8) 40.0 (14.9) < 0.001 Male, n (%) 114 (52.3) 75 (52.1 0.969 Disease duration, n with available data 176 111 0.016 < 2 years, n (%) 50 (28.4) 50 (45.0) 2- < 5 years, n (%) 32 (18.2) 16 (14.4) ≥ 5 years, n (%) 94 (53.4) 45 (40.5) Median (min-max) observation period, (months)* 15.7 (4.2-45.9) 19.3 (6.1-49.3) < 0.001 Crohn’s disease location at index, n with available data 196 121 0.047 Colonic with/without upper GI disease, n (%) 42 (21.4) 35 (28.9) Ileal with/without upper GI disease, n (%) 85 (43.4) 36 (29.8) Ileocolonic with/without upper GI disease, n (%) 69 (35.2) 50 (41.3) Disease severity at index, n with available data 180 116 0.161 Moderate, n (%) 84 (46.7) 58 (50.0) Severe, n (%) 17 (9.4) 17 (14.7) Abbreviations: GI = gastrointestinal; SD = standard deviation.*While all patients were required to have 6 months follow-up from time of treatment initiation to data abstraction, some patients were lost to follow-up and therefore minimum duration during the observation period was <6 months.

S771 Impact of Early Biologic Therapy in Real-World Cohort of Crohn’s Disease Patients

Introduction: Crohn’s disease (CD) is characterized by transmural inflammation and ongoing inflammatory activity, which over time results in the accumulation of bowel damage, which may lead to complications such as strictures, fistulas/fissures, and abscesses, as well as disability. Optimally controlling inflammation early in the disease course of CD, during the ‘window of opportunity,’ may be the best way to change disease course. Recent evidence and clinical practice guidelines suggest that early biologic therapy is preferred in treating moderate to severe CD. Early use of biologic therapy and achievement of mucosal healing can contribute to disease course modification. We hypothesize that significantly more CD patients treated within 2 years of diagnosis will achieve clinical remission and have less CD-related complications than those treated 2 or more years after diagnosis. Methods: We conducted a retrospective cohort study of CD patients treated within the Military Health System to assess the relationship of timing of initiation of biologic therapy with the control of CD. Data was collected from January 1, 2013 to December 30, 2020 to measure the course of patients’ disease as determined by clinical, biochemical, radiologic, and endoscopic/histologic findings, with an assessment of clinical outcomes and complications to include CD-related emergency room visits, steroid use, hospitalizations, and surgeries. Results: 343 patients with CD were identified, of which 184 were started on biologic therapy within 2 years of diagnosis, while 159 were started on biologic therapy 2 or more years after diagnosis. Patients who initiated biologic therapy within 2 years of diagnosis had significantly fewer CD-related complications (p< 0.0001) (Figure 1a). Evidence of perianal disease at diagnosis was predictive of an increased likelihood of CD-related complications (Figure 1b). Patients on monotherapy with thiopurines prior to biologic therapy were also more likely to experience CD-related complications (Figure 1c). Conclusion: These findings demonstrate that earlier initiation of biologics (within 2 years of diagnosis) results in a lower probability of CD-related complications, including emergency room visits, steroid use, hospitalizations, and surgeries. This real-world study is one of the first to confirm prior clinical trial data on decreased complications in early initiation of biologic therapy in CD patients.Figure 1.: Survival curves for complications with respect to timing of biologic start (1a), presence of perianal disease (1b) and thiopurine therapy prior to biologic stat (1c).

S862 Rates and Outcomes of Histologic Healing in Crohn's Disease

Introduction: Histologic healing (HH) has been associated with favorable outcomes in patients with ulcerative colitis but its clinical significance in Crohn’s disease (CD) remains unclear. We aimed to determine the prevalence, predictors, and outcomes of HH in patients with CD. Methods: This is a single center, retrospective review of CD patients age ≥18 from 1/1/2012-12/1/2021. Patients with and without endoscopic healing (defined as the absence of ulcers or erosions) were included. HH was defined as either normal or chronic inactive/quiescent inflammation on review of pathology reports. The primary outcomes were the prevalence and predictors of HH in both distal ileal and colonic CD. Secondary outcomes included rates of corticosteroid use, CD-related ED visits, surgeries, and hospitalizations analyzed individually and as a composite outcome. Continuous variables were analyzed using an unpaired student’s t-test. Categorical variables were analyzed using a chi-square test. Results: A total of 90 CD patients were included. The median age was 47 years (range 18-85), 52.0% were female, 63.3% had ileocolonic disease, and 72.2% had endoscopic healing. The overall rate of HH was 30.0%. Among patients with endoscopic healing (n=65), 41.5% (n=27) achieved HH. Ileal HH rate was 63.2% and colonic HH rate was 47.6%. There were no significant differences between the HH and non-HH groups in terms of baseline and disease characteristics (Table). The percentage of patients on biologic medications was 70.4% in the HH group vs. 50% in the non-HH group (p=0.1). In the HH group, the rate of corticosteroid initiation was 42.9% vs. 57.1%, (p=0.89) and the rates of ED visits, hospitalizations, and IBD-related surgeries were not significantly different between the two groups (Figure). The composite outcome was noted in 40.7% of patients with HH vs. 59.3% of patients without HH (p=0.91). Conclusion: In this pilot study, 30% of CD patients achieved HH, with a higher rate of ileal compared to colonic HH. Among patients with endoscopic healing, HH was not associated with any further decrease in adverse clinical outcomes. This study is limited by small sample size and potentially sampling error of endoscopic biopsies due to the patchy nature of CD inflammation. Larger studies are needed to identify predictors and significance of HH in CD.Figure 1.: Comparison of outcomes between histologic healing vs. no histologic healing (*Composite outcome is defined by either discontinuation of therapy/dose escalation, steroid use, ED visits and/or hospitalizations related to active CD). Table 1. - Comparison of Characteristics Between Histologic Healing vs. No Histologic Healing Patient characteristics Histologic Healing (n=27) No Histologic Healing (n=38) P-value Baseline characteristics Age (years), mean (SD) 52.6 (16.0) 48.7 (17.8) 0.36 Female sex, n (%) 13 (48.2) 26 (68.4) 0.10 Smoking, n (%) 5 (18.5) 4 (10.5) 0.36 Disease duration (years), median (IQR) 16 (7-21) 11.5 (4-21.8) 0.38 Disease characteristics Prior bowel resection, n (%) 6 (22.2) 9 (23.7) 0.89 Presence of extraintestinal manifestations, n (%) 7 (25.9) 11 (28.9) 0.79 Perianal disease, n (%) 8 (29.6) 11 (28.9) 0.95 Medication factors On biologic, n (%) 19 (70.4) 19 (50.0) 0.10 On immunomodulator, n(%) 6 (22.2) 7 (18.4) 0.71

S1050 Clinical Outcomes in Crohn’s Disease Patients With Acute Appendicitis Treated Operatively vs Non-Operatively

Introduction: The effects of surgical versus medical management of appendicitis in Crohn’s disease (CD) patients remain unknown. Our aim was to evaluate outcomes of CD patients who have undergone operative versus non-operative treatment of acute appendicitis. Methods: We performed a retrospective cohort study of adult CD patients presenting to the University of Minnesota with acute appendicitis between 1/1/2015 and 12/31/2020. Electronic health records were reviewed for demographics, CD classification, medications, disease activity, appendicitis course and subsequent complications and disease outcomes. A t-test was used to compare continuous variables and Fisher’s exact tests were used to compare categorical variables. Univariate logistic regression was used to compare outcomes for those treated with operative versus non-operative management of appendicitis. Results: We identified 24 patients with CD who underwent treatment for appendicitis. Eight patients (33%) received nonoperative management with antibiotics. Sixteen patients (66%) had surgical management. Of those managed with surgery, 4 (25%) were treated with concomitant antibiotics. Crohn’s disease activity, measured using the physician global assessment (PGA), was similar in both groups. Five patients (63%) in the medically managed group had a CD flare on admission compared to one (6%) in the surgically managed group (63% vs 6%, p< 0.01). Four patients (50%) treated with antibiotics eventually required an appendectomy. No differences in length of stay, rate of complications up to 6 months, time to subsequent CD-related surgery or time to CD flare were seen between the two groups. Conclusion: In CD, antibiotic therapy alone can be an effective and safe option for the treatment of acute appendicitis, especially in patients presenting with a concomitant flare. Non-operative management can also help avoid eventual surgery in half of patients. Further data are needed to better characterize individual risk factors and outcomes in this patient population and shared decision making should guide current management. Table 1. - Clinical characteristics of Crohn’s Disease patients presenting with acute appendicitis All Antibiotics (n=8) Surgery (n=16) P-value Sex >0.05 F 10 4 (50%) 6 (37%) M 14 4 (50%) 10 (63%) Physician global assessment score >0.05 Remission 8 1 (13%) 7 (44%) Mild 2 0 2 (12%) Moderate 6 3 (37%) 3 (19%) Severe 8 4 (50%) 4 (25%) Presence of flare during admission < 0.01 Yes 18 5 (63%) 1 (6%) No 6 3 (37%) 15 (94%) Age at appendicitis episode 31 (18-44) 40 (31-49) >0.05 Length of stay 2.5 (1.9-3.1) 2.3 (0.9-3.8) >0.05