CD-related Hospitalization Research Articles

Dual Biologic Therapy Induces Remission in Refractory Crohn’s Disease with Vedolizumab and Ustekinumab

Abstract Background Despite advancements in the therapeutic armamentarium for Crohn’s disease (CD), biologic and small molecule monotherapies are associated with sub-optimal response and remission rates. Utilizing dual biologic therapy (DBT) holds the potential of increasing efficacy in treatment refractory or partially responsive CD. Evidence pertaining to this strategy remains limited. Methods We retrospectively examined refractory CD patients treated with combination ustekinumab and vedolizumab. Outcomes to DBT at week 52 were compared to monotherapy. The primary outcome constituted corticosteroid-free remission. Secondary outcomes included adverse events, infections, hospitalizations, surgeries, treatment persistence and disease clearance. Results Sixteen of 21 active refractory CD patients (76%) on DBT achieved disease remission at week 52. Mucosal healing was observed in 38% (n=6), biochemical remission in 25% (n=4), and both clinical and biochemical remission in 38% (n=6). Of these patients, 50% (n=8) achieved corticosteroid free remission. Three patients (37.5%) with corticosteroid free remission achieved complete disease clearance. Paired median FC decreased from 508 µg/g to 118 µg/g (p < 0.0001). Paired CRP median decreased from 1.04 mg/dL to 0.50 mg/dL (p < 0.0001). Median HBI score reduced from 7 to 2 (p=0.003). Endoscopic healing was achieved with a paired SES-CD decrease from 6 to 3 (p=0.013). Corticosteroid dependency reduced from 17 to 8 patients discontinuing altogether. Patients still requiring corticosteroids experienced a decrease in average daily dose from 9 mg to 6 mg (p=0.045). At week 52, five patients (24%) did not meet criteria for remission with 4 requiring CD related surgical intervention. Mean CD-related hospitalizations reduced from 2.95 ± 2.33 to 0.52 ± 1.12 (p<0.001) and surgeries from 1.76 ± 1.3 to 0.14 ± 0.4 (p<0.001). Three infections with 1 requiring hospitalization and 1 report of headache were noted. Two patients discontinued DBT. Conclusion DBT with ustekinumab and vedolizumab is a safe and effective strategy to induce disease remission in refractory CD. Large scale studies are necessary to validate findings in a prospective setting.

Inadequate Efficacy of Biologics for Treating Proximal Ileal Lesions in Crohn's Disease; a prospective multicenter study.

While biologic therapy has revolutionized the treatment of Crohn's disease (CD), surgery remains unavoidable in cases involving ileal complications. We aimed to evaluate the efficacy of biologics on proximal ileal lesions using balloon-assisted enteroscopy (BAE). This open-label multicenter prospective study was conducted at tertiary referral centers in Japan. We enrolled 253 patients with active ileal CD who were treated with biologics (infliximab/adalimumab/ustekinumab/vedolizumab). BAE was performed at week 0 and week 26, and endoscopic findings were centrally assessed. We evaluated the rate of endoscopic remission (defined as having a maximum mSES-CD <4) at week 26 and patient prognosis (CD-related hospitalization and surgery). At baseline, 74 (29.2%) patients had proximal ileal ulcerations without terminal ileal ulcerations. The second BAE showed that endoscopic remission was achieved in 91 (36.0%) patients. Of the patients with complete ulcer healing of the terminal ileum, 28.6% (22/77) had residual ulcers in the proximal ileum. The rate of endoscopic remission in the proximal ileum (50.9%) was relatively lower compared to the colon (63.4%) and terminal ileum (56.7%), a trend consistently observed across all treatment agents. After a median follow-up of 134 weeks, residual ulcerations in the proximal ileum were associated with a poorer prognosis (P=0.0126 for hospitalization and P=0.0014 for surgery). A substantial proportion of patients with CD exhibited ulcerations in the proximal ileum which correlated with a poorer prognosis. These lesions proved challenging to heal, regardless of the type of biologic used.

Progression of Crohn’s Disease in Newly Diagnosed Patients: Results from an Observational Study Using US Claims Data

BackgroundPatients with Crohn’s disease (CD) experience disease progression over time, including strictures/stenoses, penetrating fistulae, and abscesses.AimsThis retrospective US population-based study aimed to characterize CD progression in newly diagnosed patients.MethodsPatient-level data from the Optum® Market Clarity database from January 1, 2016, to June 30, 2020, were used. The study comprised a 12-month baseline period (pre-diagnosis), an index date (diagnosis date), and a follow-up period. The risk of, and time to, CD progression since CD diagnosis, dispensed treatment changes following CD progression, and healthcare resource utilization before and after CD progression were assessed.ResultsOverall, 6804 newly diagnosed patients were included. Of these, 1714 (25.2%) experienced CD progression as follows: 19.3% (1183/6117) in the first 6 months, 21.6% (1188/5503) by 1 year, 24.6% (953/3875) by 2 years, and 26.6% (444/1668) by 3 years. Intestinal obstruction/stenosis was more common than fistula or abscess. Among patients with CD progression, the median (interquartile range) estimated time to progression was 2 (0–140) days; the shortest time to progression was seen with a first intestinal obstruction/stenosis (0 [0–137] days). The frequency of several dispensed treatments increased following CD progression. Among patients who experienced progression, CD-related inpatient hospital admissions/visits increased from 436 of 1714 patients (25.4%) in the month before progression to 965 (56.3%) in the month after progression.ConclusionsOver one quarter of patients with newly diagnosed CD experienced CD progression and complications within 3 years of diagnosis, highlighting the importance of monitoring for progression and early intervention to limit progression.

Optimal timeframe for achieving biochemical remission in Crohn's disease patients treated with first-line biologics: A retrospective multicenter study.

Predicting treatment response in Crohn's disease (CD) patients initiating biological therapy is crucial. The first step involves considering symptom control and normalization of C-reactive protein (CRP). However, data on the actual rates of achieving CRP normalization and the appropriate timeframe are lacking. Therefore, we aim to investigate the rate of attaining CRP normalization and identify its optimal timeframe in CD patients initiating biological therapy. In this retrospective multi-center study, we analyzed moderate to severe CD patients initiating biological therapy from January 2012 to July 2023. The primary outcome was the rate and timeframe for achieving CRP normalization. Secondary outcomes included clinical outcomes in patients who achieved CRP normalization and factors associated with early CRP normalization. Of 183 patients, 123 (67.2%) achieved CRP normalization, with a median duration of 3.8 months (interquartile range 1.4 to 7.4 months). The duration and value difference for CRP normalization between anti-tumor necrosis factor agents, ustekinumab, and vedolizumab were statistically insignificant. Cumulative rates of CD-related hospitalization, intestinal resection, and drug discontinuation over 8 years were 11.4%, 2.4%, and 12.2%, respectively. The duration of CRP normalization correlates with drug discontinuation (area under the curve: 0.64). Treatment with 5-aminosalicylic acid (HR 2.77; 95% confidence interval [CI] 1.26-6.11) and high albumin level (HR 1.64, 95% CI 1.04-2.61) favored early CRP normalization, whereas structuring behavior less likely than inflammatory behavior (HR 0.43, 95% CI 0.19-0.96). We have provided the actual rate of achieving CRP normalization and its appropriate timeframe as an initial target in CD treatment.

Comparative real-world outcomes between ustekinumab, infliximab, and adalimumab in bio-naïve and bio-experienced Crohn’s disease patients: a retrospective multicenter study

BackgroundNumerous studies have compared the efficacy of ustekinumab (UST) and anti-TNF agents [infliximab (IFX) or adalimumab(ADA)] in moderate to severe Crohn’s disease (CD) patients. This study aims to compare the efficacy of UST, IFX, and ADA while differentiating between bio-naïve and bio-experienced patients, which is an underexplored aspect, particularly in Asia.MethodsWe conducted a retrospective multi-center study from 2012 to 2023, categorizing patients into bio-naïve and bio-experienced groups. We evaluated clinical remission rates after induction therapy and clinical outcomes, including CD-related hospitalization, intestinal resection, and drug discontinuation during maintenance therapy.ResultsAmong the 214 bio-naïve CD patients, 60 received UST, 108 received IFX, and 46 received ADA. After 1:1 propensity score matching between UST and anti-TNF agents groups, 59 patients were analyzed in each group (45 in the IFX group and 14 in the ADA group). We found no significant differences in clinical remission rates (P = 0.071), CD-related hospitalization (P = 0.800), intestinal resection (P = 0.390), or drug discontinuation (P = 0.052) between the UST, IFX, and ADA groups in bio-naïve CD patients. In bio-experienced CD patients, with 35 in the UST group and 13 in the anti-TNF agents group, the UST group showed a lower risk of drug discontinuation (P = 0.004) than the anti-TNF agents group.ConclusionsThis study suggests that UST, IFX, and ADA are equally effective in bio-naïve CD patients, while in bio-experienced patients, mostly with previous exposure to anti-TNF agents, UST may offer superior drug durability.

Associations between prior healthcare use, time to diagnosis, and clinical outcomes in inflammatory bowel disease: a nationally representative population-based cohort study

BackgroundTimely diagnosis and treatment of inflammatory bowel disease (IBD) may improve clinical outcomes.ObjectiveExamine associations between time to diagnosis, patterns of prior healthcare use, and clinical outcomes in IBD.DesignUsing the Clinical...

Prior Appendectomy Is Associated With a Milder Clinical Course in Crohn's Disease: A Nationwide Population-based Cohort Study.

Appendectomy may affect the clinical course of Crohn's disease (CD), but rigorous evidence is sparse and contradicting. The aim of this study was to examine the association between appendectomy and the clinical course of CD. All patients diagnosed with CD in Denmark in the period from 1977 to 2017 were identified from the Danish National Patient Registry. Patients with appendectomy were matched with up to 10 comparators with CD and no appendectomy; and rates of CD-related hospital admissions were compared between CD patients with and without appendectomy using incidence rate ratios (IRRs). We used stratified Cox regression analysis to calculate adjusted hazard ratios (aHRs) of initiating treatment with biologics or undergoing intestinal resections. In all, 21 189 CD patients (1936 with appendectomy and 19 253 without) were identified and followed for a median of 13.6 years. Crohn'sdisease patients who had undergone appendectomy experienced a lower rate of CD-related hospital admissions (appendectomy before CD: IRR = 0.83; 95% confidence interval [CI], 0.81-0.85; appendectomy after CD:IRR = 0.85; 95% CI, 0.81-0.88) compared with CD patients without appendectomy. For patients with appendectomy before CD diagnosis, the rate of initiating biologics was lower compared with CD patients with no appendectomy (aHR1-<5 years = 0.61; 95% CI, 0.46-0.81; aHR5-<10 years 0.47; 95% CI, 0.33-0.66; aHR10-20 years = 0.61; 95% CI, 0.47-0.79), as was the risk of undergoing colorectal resections (aHR1-<5 years = 0.94; 95% CI, 0.77-1.15; aHR5-<10 years 0.63; 95% CI, 0.47-0.85; aHR10-20 years = 0.75; 95% CI, 0.54-1.04). Rates of small bowel resections were comparable for CD patients with or without appendectomy prior to CD. Appendectomy performed after CD did not influence the rate of initiating treatment with biologics or undergoing intestinal resections. The clinical course of CD is milder for those who have previously undergone appendectomy.

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

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

Prevalence and Impact of Obesity in a Population-Based Cohort of Patients With Crohn's Disease.

Obesity is on the rise within the inflammatory bowel disease population. The impact obesity has on the natural history of Crohn's disease (CD) is not well-understood. We aimed to describe the prevalence of obesity in a population-based cohort of newly diagnosed patients with CD, and the impact obesity had on disease phenotype and outcomes of corticosteroid use, hospitalization, intestinal resection, and development of fistulizing or penetrating disease. A chart review was performed on Olmsted County, Minnesota residents diagnosed with CD between 1970 and 2010. Data were collected on demographics, body mass index, CD location and behavior, CD-related hospitalizations, corticosteroid use, and intestinal resection. The proportion of individuals considered obese at the time of CD diagnosis was evaluated over time, and CD-associated complications were assessed with Kaplan-Meier survival analysis. We identified 334 individuals diagnosed with CD between 1970 and 2010, of whom 156 (46.7%) were either overweight (27.8%) or obese (18.9%) at the time of diagnosis. The proportion of patients considered obese at the time of their diagnosis of CD increased 2-3 fold over the course of the study period. However, obesity did not have a significant impact on the future risk of corticosteroid use, hospitalization, intestinal resection, or development of penetrating and stricturing complications. Obesity is on the rise in patients with CD, although in this cohort, there did not appear to be any negative association with future CD-related outcomes. Further prospective studies, ideally including obesity measures such as visceral adipose tissue assessment, are warranted to understand the implications of the rising prevalence of obesity on CD outcomes.

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

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

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

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

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

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

P115 Ustekinumab in DEVELOP: A safety analysis from an Inflammatory Bowel Disease multicenter, prospective, long-term registry of paediatric patients

Abstract Background DEVELOP is a multi-center, global, prospective, observational, longitudinal registry of long-term safety of infliximab (and other treatments) in paediatric patients (pts) with inflammatory bowel disease (IBD) &amp;lt;18 years (yrs) at diagnosis. Over the course of follow-up, many pts required changes in therapy. Ustekinumab (UST) is approved for treatment of Crohn’s disease (CD) in adults and is currently being evaluated for safety/efficacy in paediatric pts. This report focuses on assessment of safety of UST in paediatric pts with CD from DEVELOP. Methods Data included paediatric pts treated with UST from 31 May 2007 through 30 June 2022; data are collected every 6 months. The analyzed population included: all paediatric pts (all pts), pts weighing &amp;lt;40kg (&amp;lt;40kg group), and pts weighing ≥40kg (≥40kg group). Assessments included medical and treatment history, UST exposure, adverse events (AEs), serious AEs (SAEs), CD-related SAEs leading to hospitalization, IBD surgeries, serious and opportunistic infections, malignancies, and deaths. Results A total of 150 pts received UST (49.3% females); 31 in the &amp;lt;40kg group and 119 in the ≥40kg group (Table 1). Most treated pts (92.0%) were 12-17yrs. The majority (91%) of pts were initially dosed with UST every 8 weeks (q8w); at the last known dose, 64% received UST q8w and 22% q4w. Mean (SD) age of initial UST exposure was 15yrs (2.19). Prior IBD surgery was reported in 65.3% pts. The majority of pts (98%) had prior biologic therapy and 72% received ≥2 biologics prior to UST. Overall, 37/150 (24.7%) of pts discontinued UST during follow-up, with a mean (SD) time to discontinuation of 16.7 (17.00) months; 84/150 (56.0%) were exposed to UST for ≥24 months. Rates (events/100 pt-yrs) of AEs were higher in the ≥40kg group (177.62) than in the &amp;lt;40kg group (101.27). Rates of SAEs were slightly lower among the ≥40kg group (25.42) vs &amp;lt;40kg (32.67). There were no SAEs related to infusion or injection site reactions. Rates of serious infections and CD-related hospitalizations were low and similar between groups, and rates of IBD-related surgeries were similar between groups (Figure 1). One malignancy (malignant carcinoid tumor) was reported in a female (18yrs) in the ≥40kg group with a history of prior therapy with vedolizumab, methotrexate, and 6-MP. No deaths or opportunistic infections were reported. Conclusion The safety profile observed for this off-label use of UST in paediatric CD pts in DEVELOP was similar to that of the treated adult population, despite most paediatric pts having prior biologic exposure. No new safety signals are identified in this paediatric population.

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

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

P075 Early intestinal ultrasound non-response is a prediction tool of complicated disease outcome in Crohn’s disease patients treated with infliximab

Abstract Background The ultimate goal of Crohn’s disease (CD) treatment is to modify the natural course of disease and prevent complications. We aim to assess the role of intestinal ultrasound (IUS) as predictor tool for complicated disease. Methods Prospective longitudinal study including patients with active CD starting infliximab. Clinical, laboratorial and IUS parameters were assessed at week(W) 0, 14, 30, and 54. The IBUS-SAS score was used to assess ultrasonographic disease activity and includes, among others, bowel wall thickness (BWT) measurement. IUS response was defined as reduction in 25% in BWT and IUS remission as the normalization of BWT (≤3mm), doppler sign (≤1), stratification (BWS), and inflammatory fat in the most affected segment. Ileocolonoscopy was done at W0 and 54. Endoscopic healing (EH) was defined as SES-CD &amp;lt;3. We defined a composite outcome(CO) for complicated disease including development of stricturing or penetrating disease, need for bowel surgery, CD-related hospitalization, or the need to switching due to loss of response to therapy. Results We included 48 patients (48% male; median age 31 years, IQR 26-44). The median follow-up time was 23.5 months(M) (IQR11-38.25). The median time until the development of the outcome was 12M, IQR 9.75-15.25. During follow-up, 37.5% developed the CO (27.1% with stricturing or penetrating disease, 12,5% needed bowel surgery, 18,8% needed hospitalization and 6% switched therapy). Baseline disease behavior (B1:21,2% vs B2/B3:73.3% p&amp;lt;0.001) and a higher IBUS-SAS score (70.34 vs 58.80 p=0.042) were associated with development of CO during follow-up. Patients who developed the CO had a numerically higher BWT throughout the first year of therapy (W14: 5.00mm vs 3.65mm, p=0.007; W30: 4.78mm vs 3.43mm, p=0.007); a higher IBUS-SAS score was also seen at W14, W30 and W54 (57.00 vs 40.35, p= 0.03; 54.74 vs 31.00, p=0.004 and 29.84 vs 23.39, p=0.026, respectively). On survival analysis, IUS remission at W30 (HR 0.27 95% CI (0.76-0.94), p=0.04) and IUS response at W30 (HR 0.27 95% CI (0.09-0.94), p =0.015) were protective for the development of the CO. In multivariate Cox regression, the absence of IUS response at W30 (HR 4.80, 95% CI 1.03-22.45, p=0.046), and EH at W54 (HR 5.70, 95% CI 1.33-24.45, p=0.02) were independent predictors of worse outcome. The best cut-off at W30 to predict the CO was IBUS-SAS &amp;gt;52 (AUC 0.74) and BWT &amp;gt; 4.11 mm (AUC 0.75). Conclusion Early assessment of ultrasonographic response at W30 of therapy can help to predict prognosis in CD. Our results highlight that in the absence of significant IUS response after 6 months of therapy, we should consider treatment intensification and close monitoring to prevent complications.

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

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

P624 Development and Validation of a Clinical Decision Support Tool to Predict Outcomes of ustekinumab Treatment in Patients with Crohn’s Disease

Abstract Background Ustekinumab (UST) has been demonstrated for the treatment of Crohn's disease (CD) with a high efficacy and safety profile. There is limited data concerning disease progression after UST treatment. This study aims to establish a clinical decision support tool (CDST) to identify Chinese patients with CD who are less likely to experience disease progression under UST treatment. Methods A multicentre, retrospective observational study was conducted among Chinese patients with CD initiating UST between 1 May 2020 and 20 October 2022. Disease progression (including CD-related surgery, hospitalization and complications) was evaluated at week 24 (±4w). Logistic regression analysis was performed to identify factors associated with disease progression. The CDST, established based on these factors, was both internally and externally validated. The performance of this tool was tested using receiver operating characteristic (ROC) area under the curve (AUC) analyses. Results A total of 519 patients were enrolled in this study. In the derivation analysis, four factors including prior biologics usage, prior immunosuppressant usage, baseline faecal calprotectin, and baseline haemoglobin were identified to correlate with progression. A good predictive ability of this model was confirmed by AUC as high as 0.76 for the internal validation cohort and 0.72 for the external validation cohort, respectively. The CDST stratified patients into low, intermediate, or high risk of progression with cut-off values of 6 and 16. Conclusion We developed and validated a scoring system to identify CD patients less likely to experience progression at week 24 with UST therapy. This CDST will facilitate therapy decision-making and precision medicine.

HOSPITALIZATION, USE OF BIOLOGICS AND SURGERY RATES IN INFLAMMATORY BOWEL DISEASES: A SINGLE-CENTRE COMPARATIVE ANALYSIS BETWEEN PUBLIC AND PRIVATE HEALTHCARE SYSTEMS IN A TERTIARY UNIT FROM LATIN AMERICA.

Inflammatory bowel diseases (IBD) have rising incidence and prevalence rates globally. In IBD, there are scarce stu-dies comparing differences between patients according to socioeconomic status. Our aim was to comparatively evaluate hospitalizations, use of biologics and rates of surgery in patients with IBD between public and private healthcare systems. Single-center retrospective cohort study in patients with IBD from a tertiary referral unit from Latin America, between 2015 and 2021. CD and UC patients were classified into two subgroups: public and private systems. Demographic characteristics, hospitalizations, need for surgery and biologics were compared. A total of 500 patients were included, 322 with CD and 178 with UC. CD-related hospitalizations were frequently observed in both healthcare systems (76.28% in private and 67.46% in public). More than half of the patients had been submitted to one or more CD-related abdominal surgery, with no significant difference between the subgroups. Although there was no difference in the rates of use of biological therapy in CD subgroups, infliximab was more used in the public setting (57.69% vs 43.97%). There was no difference in UC-related hospitalizations between the subgroups (public 30.69% and private 37.66%) as well as the rates of colectomy (public: 16.83%, private: 19.48%). Biologics were prescribed almost twice as often in private as compared to public (45.45 vs 22.77%). There were no differences in the rates of hospitalization and abdominal surgery between the systems. In patients with UC, there was greater use of biological therapy in the private healthcare setting. • In a tertiary IBD center in Latin America. • More than half of the patients had been submitted to one or more CD-related abdominal surgical procedure. • Between the two healthcare systems, there was no difference in the rates of use of biological therapy in patients with CD, and in UC-related hospitalizations. • Biologics were prescribed almost twice as often in the private system as compared to the public in patients with UC.

Early Ileocecal Resection for Crohn’s Disease Is Associated With Improved Long-term Outcomes Compared With Anti-Tumor Necrosis Factor Therapy: A Population-Based Cohort Study

Early Crohn's disease (CD) treatment involves anti-tumor necrosis factor (TNF) agents, whereas ileocecal resection (ICR) is reserved for complicated CD or treatment failure. We compared long-term outcomes of primary ICR and anti-TNF therapy for ileocecal CD. Using cross-linked nationwide registers, we identified all individuals diagnosed with ileal or ileocecal CD between 2003 and 2018 and treated with ICR or anti-TNF agents within 1 year of diagnosis. The primary outcome was a composite of ≥1 of the following: CD-related hospitalization, systemic corticosteroid exposure, CD-related surgery, and perianal CD. We conducted adjusted Cox's proportional hazards regression analyses and determined the cumulative risk of different treatments after primary ICR or anti-TNF therapy. Of 16,443 individuals diagnosed with CD, 1279 individuals fulfilled the inclusion criteria. Of these, 45.4% underwent ICR and 54.6% received anti-TNF. The composite outcome occurred in 273 individuals (incidence rate, 110/1000 person-years) in the ICR group and in 318 individuals (incidence rate, 202/1000 person-years) in the anti-TNF group. The risk of the composite outcome was 33% lower with ICR compared with anti-TNF (adjusted hazard ratio, 0.67; 95% confidence interval, 0.54-0.83). ICR was associated with reduced risk of systemic corticosteroid exposure and CD-related surgery, but not other secondary outcomes. The proportion of individuals on immunomodulator, anti-TNF, who underwent subsequent resection, or were on no therapy 5 years post-ICR was 46.3%, 16.8%, 1.8%, and 49.7%, respectively. These data suggest that ICR may have a role as first-line therapy in CD management and challenge the current paradigm of reserving surgery for complicated CD refractory or intolerant to medications. Yet, given inherent biases associated with observational data, our findings should be interpreted and applied cautiously in clinical decision making.

Comparison of infliximab with adalimumab in biologic-naïve patients with Crohn's disease: a single-center 13-year experience.

Long-term comparison studies between infliximab (IFX) and adalimumab (ADA) with or without immunomodulator therapy are still needed in Crohn's disease (CD). In this study, we evaluated IFX and ADA for long-term clinical effectiveness and safety in CD patients who had not previously received a biologic treatment. The data of adult CD patients were collected retrospectively between December 2007 and February 2021. We compared CD-related hospitalization, CD-related abdominal surgery, steroid use, and serious infections. Out of 224 CD patients, 101 started IFX first (median age: 38.12 years, 61.4% male), while 123 started ADA first (median age: 30.2 years, 64.2% male). The disease durations were 7.01 years and 6.91 years for IFX and ADA, respectively. There were no significant differences between the two groups with respect to age, gender, smoking, immunomodulator usage, and disease activity score at the onset of anti-TNF therapy (p>0.05). Overall, the median follow-up time was 2.36 and 1.86 years after starting anti-tumor necrosis factor-alpha (anti-TNF) therapy in the IFX and ADA groups, respectively. Steroid use (4.0% vs. 10.6%, p=0.109), hospitalization for CD (13.9% vs. 22.8%, p=0.127), abdominal surgery for CD (9.9% vs. 13.0%, p=0.608), and major infections (1.0% vs. 0.8%, p>0.999) did not differ significantly from one another. There were also no significant differences in the rates of these outcomes between concomitant immunomodulator therapy and monotherapy (p>0.05). In this study, we observed no significant differences in the long-term effectiveness and safety of IFX and ADA in biologic-naïve patients with CD.