bluuebunny/crossref_metadata_2025 huggingface dataset:
P882 A Phase I/II clinical trial of ex-vivo expanded human bone marrow derived allogeneic mesenchymal stromal cells in adult patients with perianal fistulizing Crohn’s Disease
Authors: Swaroop S , Vuyyuru S , Kante B , Kumar P , Mundhra S , Arora U , Goyal A , Kandasamy D , Sharma R , Kabilan K , Kedia S , Dash N , Ahuja V
Published: January 2024

Background

Perianal fistulas affect one-third patients with Crohn’s disease with limited therapeutic options. There is dearth of literature on safety and efficacy of bone marrow-derived mesenchymal stromal cells in this population.

Methods

An open-label, phase I/II, single-arm study was conducted involving local administration of human allogeneic bone marrow-derived mesenchymal stromal cells in perianal fistula of patients with Crohn’s disease refractory to standard therapies. Clinical severity and biomarkers were assessed at baseline and periodically till 104 weeks, and MRI at 24 and 104 weeks. Primary and secondary objectives were to assess safety and efficacy respectively. Fistula remission was complete closure of fistula openings with <2cm perianal collection on MRI, and fistula response was decrease in drainage by ≥50%. Change in perianal disease activity index, quality-of-life and Van Assche index on MRI over time was assessed using mixed-effect linear regression model.

Results

Ten patients (male:8, mean age:27.4±12.0years) were recruited. Self-resolving procedure-related adverse events occurred in three patients, with no follow-up adverse events. In intention to treat analysis at week 24, two patients (20%) achieved fistula remission and seven (70%) had fistula response. At week 52, two (20%) patients were in remission and seven (70%) maintained response. At 104 weeks, two (20%) patients maintained response and one (10%) was in remission. Statistically significant decrease in perianal disease activity index(P=0.008), Van Assche Index(P=0.008) and improvement in quality-of-life(P=0.001) were observed over time.

Conclusion

Allogeneic BMSCs are safe and effective for the treatment of PF in CD with significant improvement in clinical severity and radiological healing.
P907 Impact of preoperative use of biologics on 30-day surgical morbidity and mortality in patients with Crohn’s Disease undergoing ileocolectomy: National Surgical Quality Improvement Program database analysis
Authors: Daniel F , El Kouzi Z , Ibrahim M A , El Sheikh W , Khalife M , Tamim H
Published: January 2024

Background

Preoperative use of biologics has been inconsistently reported to be associated with increased frequency of infectious and surgical anastomotic complications in inflammatory bowel disease patients. We aimed to evaluate the rates of 30-day post operative morbidity and mortality in Crohn’s disease patients exposed preoperatively to biologics.

Methods

Data was collected from the NSQIP (National Surgical Quality Improvement Program) which is a nationally validated, risk adjusted program designed to measure and improve the quality of surgical care. Crohn’s disease patients undergoing open or laparoscopic ileocolectomy were identified using corresponding ICD 10 and CPT Codes from NSQIP PUF (Participant Use Data File) for the year 2021.Patients were divided based on the preoperative use of biologics (group 1) and (group 2) for whom no biologics were used. Univariate analysis was done on SPSS via Chi-squared and Fisher exact test for categorical variables, while independent sample T-test was used for continuous variables. Composite morbidity was defined as the association of any two morbidity events in the database. A multivariate regression analysis was done to predict post operative morbidity while controlling for the following variables: age, BMI, smoking, steroid use, diabetes, hypertension, sepsis, ASA classification, and preoperative transfusion.

Results

A total of 910 patients (female n=473; 52%, mean age of 42.3 ± 16.1) were included. The group1 patients were significantly younger (40.30 years ±15.33) than group 2 (43.58 years ±16.8 p=0.002) and had significantly slightly higher ASA III and IV scores (97.4% vs 97.2%, p=0.004). On the other hand, group 2 had a significantly higher prevalence of hypertension (20.2% vs 12.8%, p=0.003) and chronic obstructive pulmonary disease (2.6% vs 0, p=0.001). No significant difference in remaining preoperative variables, surgical approach (laparoscopic vs open) and comorbidities were found between the two groups. On univariate analysis of morbidity, only a significant prevalence of deep vein thrombosis and thromboembolism was found in patients exposed to biologics (1.1% vs 0 p=0.027). No significant difference was found in surgical site infections, sepsis, infectious complications, anastomotic failure, composite morbidity, or mortality. On multivariate analysis, no significant morbidity was noted between the two groups.

Conclusion

Crohn’s disease patients undergoing ileocolectomy and exposed preoperatively to biologics did not show a significant increase in 30-day postoperative morbidity and mortality.
P916 Off-label dose escalation of Ustekinumab in Inflammatory Bowel Disease patients. Incidence rate, timing, dosing patterns and outcomes
Authors: García-Morales N , Carmona A , Ayude M , Gayoso-Rey M , Agra-Blanco I , De Castro Parga M L , Rodriguez-Prada I
Published: January 2024

Background

In patients with inflammatory bowel disease (IBD), after intravenous induction,Ustekinumab (UST) is administered as maintenance 90 mg every 8 (Q8) or 12 weeks (Q12) subcutaneously. As with other biological drugs, dose intensification may be effective after inadequate response or loss of response. However, different dosing regimens have been used and the best strategy is unknown. Our aim was to evaluate the incidence and efficacy of UST off-label dose escalation in IBD.

Methods

We performed an observational cohort study in 2 hospitals in Vigo,Spain. All patients who started UST between 1 June 2017 and 31 December 2022 to control their active IBD were enrolled. The primary endpoints were incidence rate and outcomes of UST off-label dose intensification. Secondary endpoints were the timing of dose escalation and the patterns indicated.

Results

1

173 IBD patients received UST: females 53.8% (93), mean age 49.7(15.5) years, Crohn´s disease 82% (142), previous anti-TNF 93.6% (162) and vedolizumab 22.5% (39) (Table 1). Subcutaneous UST was maintained Q8 in 63.6% (110) and Q12 in 34.7% (60). Baseline activity data were higher in Q8 patients (p=0.001). At 16 week 23 patients (13.3%) had no response, but 9 (39.1%) became late responders at 6 months. Of the 173 IBD patients included, 38.2% and 30.6 % achieved clinical response and clinical remission at 1 year.

Dose escalation was performed in 32.4% (56) with different patterns: 54.5% Q4 (30), 21.8% reinduction plus Q4 (12), 12.7% Q6 (7) and 10.9% only intravenous reinduction (6). The timing of dose escalation was: before 6 months in 19.6% (11), at 12 months 42.8% (24) and at 2 years 73.2% (41). Response and remission were achieved in 28.6% (16) and 41.1% (23) after dose escalation respectively. In 6.4% of the patients (11) a second dose escalation was indicated. Neither previous anti-TNF or vedolizumab nor concomitant use of steroids at starting UST were associated to dose escalation. IBD patients that were initially scheduled to receive subcutaneous UST Q12 needed less dosing escalation (p<0.001).

Conclusion

Off-label UST dose escalation was frequent and effective in achieving response in IBD patients. The schemes of dose-escalation were heterogeneous between the participants. Patients initially scheduled Q12 due to lower inflammatory activity required less dose escalation.
P931 Burden of disease among Ulcerative Colitis patients with isolated proctitis in the United States and Europe
Authors: Armuzzi A , Danese S , Barreiro-de Acosta M , Hur P , Bartolome L , Wosik K , Knight H , Palace V , Peyrin-Biroulet L
Published: January 2024

Background

Isolated proctitis (IP), or ulcerative proctitis, a subtype of ulcerative colitis (UC), is associated with distressing symptoms such as abdominal pain and bowel urgency. As patients with IP not responding to conventional treatment are understudied and underrepresented in clinical trials, treatment guidance is limited. We aimed to understand disease burden among IP patients by describing patients delineated by disease extension and treatment experience.

Methods

Data were drawn from the Adelphi UC Disease Specific Programme™, a cross-sectional survey of gastroenterologists (GIs) and their consulting patients in France, Germany, Italy, Spain, the United Kingdom and the United States from October 2020 – March 2021. GIs reported patient demographics, disease extension, symptoms, components of the full Mayo score (allowing total scores to be calculated for patients), and treatment profile at time of consultation. Patients with a history of physician-assessed moderate-severe disease were included. Patients were categorised as IP (IP at diagnosis and consultation) or as more extensive UC (MEUC; where disease extended beyond IP at both diagnosis and consultation). According to ECCO consensus guidelines1, patients are considered refractory if they have failed oral steroids combined with oral and rectal 5-ASA therapy. In this analysis, non-refractory IP patients had only received 5-ASAs and/or steroids; refractory IP patients had received an immunomodulator (IM) and/or advanced therapy (AT; biologics, Janus kinase inhibitors). All analyses were descriptive.

Results

Overall, 221 IP patients (118 non-refractory, 103 refractory) and 1607 MEUC were analysed (Table 1). Among IP, non-refractory IP, refractory IP, and MEUC 49.3%, 55.1%, 42.7%, and 55.4% were male, respectively, and mean age ranged 39.0-40.2 years. Symptoms most reported by IP, non-refractory IP, refractory IP, and MEUC patients were abdominal pain (33.8%, 26.5%, 41.7%, 26.0%), fatigue/tiredness (22.7%, 20.4%, 25.2%, 23.8%) and bowel urgency (22.7%, 25.7%, 19.4%, 23.6%). According to Mayo scores at consultation, 40.3% of IP, 44.9% of non-refractory IP, 34.9% of refractory IP, and 50.4% of MEUC patients were in remission. Since diagnosis, 33.5% of IP, 71.8% of refractory IP, and 69.1% of MEUC cohorts had received AT.

Conclusion

Patients with IP experience a similar symptom burden to the MEUC population, despite currently available treatments for UC. The high AT use and low rate of remission indicates undertreatment of IP patients and a need for therapies with proven efficacy in this population, particularly after conventional therapy use.

1. Harbord et al. J Crohns Colitis. 2017 Jul 1;11(7):769-784.
P951 Efficacy and safety of tofacitinib for the treatment of moderate- severe ulcerative colitis in biologic naïve patients
Authors: Liatsos C , Michalopoulos G , Tzouvala M , Giouleme O , Kozompoli D , Mousourakis K , Kyriakos N , Giakoumis M , Striki A , Karoumpalis I , Bellou G , Zacharopoulou E , Katsoula A , Kalogirou M , Viazis N
Published: January 2024

Background

To assess the rates of clinical response at week 8, biochemical response, steroid-free clinical remission, endoscopic healing and safety data at week 26 of tofacitinib in biologic naive patients with moderate-severe ulcerative colitis (UC).

Methods

This was a retrospective analysis of prospectively collected data extracted from the notes of biologic naïve patients with moderate-severe UC who were treated with tofacitinib in the last 3 years in 5 Greek IBD centers and who had a follow up of at least 26 weeks after initiation of treatment. Tofacitinib was administered at a dose of 10 mg bid for 8 or 16 weeks followed by a maintenance dose of 5mg bid thereafter. Week-8 or -16 clinical response was defined as the reduction in the partial Mayo score of at least 2 points, without concomitant use of any steroid preparation [budesonide, prednis(ol)one, or methylprednisolone]. Steroid free clinical remission at week 26 was defined as a partial Mayo score of ≤1 points without concomitant use of any steroid preparation. Biochemical response at week 26 was defined as any reduction in fecal calprotectin or plasma C-reactive protein concentrations as compared to their baseline levels.Mucosal healing at week 26 was defined as Mayo endoscopic sub-score of ≤1. A safety list of all reported adverse events was completed. Treatment discontinuation due to adverse events was considered as treatment failure, whereas patients needing escalation of the maintenance dose were also considered as non-responders.

Results

Overall, 41 patients (26 males), aged (mean, SD) 35.2 (12.7) years and disease duration of mean (SD) 6.5 (4.8) years were included. UC was extensive in 22, left-sided in 17, and proctitis in 2 patients. Clinical response was seen in 31 (75.6%) and 34 (82.9%) patients at week 8 and 12 respectively.Biochemical response and steroid free clinical remission at week 26 were seen in 35 (85.4%) patients. Endoscopic healing was seen in 29 (70.7%) patients. Adverse events,which did not lead to treatment discontinuation, occurred in 5 patients (hyperlipidemia n=3, elevated liver enzymesn=1, herpes zoster n=1).

Conclusion

In this retrospective real-world ongoing cohort study, tofacitinib demonstrated clinical response at week 8 or 16 and steroid free clinical remission at week 26 in more than 75% of biologic naïve patients with moderate-severe UC with a good safety profile.
P968 Influences of Sequential Introduction of Thiopurine on Long-Term Efficacy of Infliximab in Patients with Inflammatory Bowel Disease
Authors: Zhang C , Zhang P , Mao R , Chen B , He Y , Zeng Z , Qiu Y , Chen M
Published: January 2024

Background

As one of the biological agents for the treatment of inflammatory bowel disease (IBD), infliximab (IFX) has gradually become a cornerstone drug over the past two decades. While there is still a non-negligible loss of response rate, which may be explained by immunogenicity. A coping method is adding immunomodulators, among which thiopurine (TP) is the most common choice. However, combination therapy may lead to an increased risk of infection and malignancy, and how to introduce immunosuppressive agents properly to maximize benefits remains a controversial dilemma. Therefore, this study aims to assess the impact of sequentially introducing TP on the long-term effectiveness of IBD patients receiving concurrent IFX treatment.

Methods

A retrospective analysis was conducted at a tertiary hospital between June 2013 and January 2022. Primary outcomes encompassed drug sustainability and biological switching. Multivariate analyses were employed to examine factors influencing these outcomes.

Results

Among 787 consecutive patients, 500 were included in the final analysis. Of these, 166 received IFX monotherapy and 334 were on IFX-TP cotherapy (173 were prior TP exposure, 59 initiating TP post 3 months of IFX treatment and 102 with de novo combination). A total of 152 (28.94%) patients discontinued the IFX regimen within 18.2 months. Additionally, 119 (22.67%) patients switched to alternative biologics within a median of 18.1 months, with higher switching rates in the monotherapy and early exposure groups (P = 0.027). Antibodies to infliximab (ATI) were detected in 36.7% patients within a median of 5 months. The monotherapy group exhibited higher cumulative rate of ATI development, ATI concentrations, and lower trough levels (TLs), while the de novo combination group demonstrated the lowest ATI development and highest TLs.

Only the order of introduction of TP therapy (HR 0.698, 95%CI 0.597-0.815, P <0.001) and ATI formation (HR 1.009, 95%CI 1.003-1.014, P =0.004) were associated with drug sustainability. Both the de novo (HR 0.367, 95%CI 0.263-0.512, P <0.001) and the late combination group (HR 0.53, 95%CI 0.359-0.782, P =0.001) had relatively higher drug retention when compared to the others.

In terms of biological switching, combination therapy (HR 0.41, 95%CI 0.19-0.88, P =0.023) and the order of introducing TPs had a significant effect (HR 0.391, 95%CI 0.183-0.836, P =0.015). Moreover, the de novo combination group demonstrated fewer clinical flares (P = 0.043).

Conclusion

Initiating TPs de novo may improve drug sustainability and offer better long-term efficacy for IBD patients receiving IFX therapy.
P972 Short and long-term outcomes after acute severe ulcerative colitis in children: A Canadian single centre experience
Authors: Vuyyuru S , Alphonsus L , De Silva T A , Archer M , Solitano V , Guizzetti L , Bax K , Ashok D , Watson M , Jairath V , Crowley E
Published: January 2024

Background

The short and long-term course of ulcerative colitis (UC) following an episode of acute severe UC (ASUC) in children is insufficiently characterized. We aimed to assess contemporary outcomes in children hospitalized with ASUC.

Methods

This was a retrospective cohort study of children aged 2-17 years hospitalized with ASUC between 2010 and 2022 at a tertiary center in London, Ontario, Canada. All data were recorded using standardised Case Report Forms, de-identified, and entered into a central database registry using Research Electronic Data Capture (REDCap) Steroid non-response was defined as requirement of medical rescue therapy or colectomy.

Results

A total of 58 children hospitalized with ASUC were included (male: 55.2% [n =32], mean age at admission: 12.2 ± 3.5 years). The majority had extensive colitis (82.4% [n = 42]) at the time of diagnosis. 74% (n = 43) presented within one year of symptom onset and 31% (n = 18) had ASUC as their index presentation with UC. 15.5% (n = 9) of patients had prior purine analogues and 20.7% (n = 12) had received biologics prior to ASUC presentation. Median Pediatric Ulcerative Colitis Activity Index (PUCAI) score on admission was 65.0 (IQR: 60.0 – 75.0). After intravenous corticosteroid therapy 68.9% (n = 40) responded to steroids. Of the patients with steroid non-response (31% [n = 18]), 3.4% (2/58) underwent colectomy and 27.6% (16/58) patients received infliximab rescue therapy. Median PUCAI score was significantly lower on day 3 between steroid responders and steroid non-responders (37.5 vs 60, p <0.01). The short term (3 months following discharge) and long-term (3-12 months following discharge) colectomy rates following discharge were 7.4% (4/54) and 8% (4/50) respectively. Short term and long-term hospitalization rates for UC exacerbation following discharge was 25.9% (14/54) and 16% (8/50) respectively. Similar rates of long-term colectomy and hospitalizations were observed between steroid responders and non-responders. On univariate analysis, no statistically significant factors associated with steroid non-response were identified.

Conclusion

17% of patients hospitalized for ASUC required colectomy within 12 months of presentation. Despite a high initial response to corticosteroids, long term colectomy rates and re-hospitalization rates are still high. Future research should focus on earlier identification and treatment of children at high risk of exacerbation to prevent complications.
P975 Monitoring Inflammatory Bowel Disease (IBD) by intestinal ultrasound decreases time to treatment change and time to remission in comparison to conventional management: Analysis of patients with IBD on multiple IBD therapies
Authors: Krugliak Cleveland N , Picker E A , Choi N K , Reddy N , Choi D , Rubin D T
Published: January 2024

Background

Intestinal ultrasound (IUS) is a non-invasive, repeatable, and accurate disease monitoring modality that can provide real-time assessment of inflammatory bowel disease (IBD). We previously demonstrated that IUS shortens time to treatment change and time to remission in patients receiving upadacitinib and monitored by IUS compared to conventional management (ACG 2023). Here, we aim to assess the impact of IUS on management and outcomes of our pts with IBD receiving any IBD therapy.

Methods

We performed a retrospective analysis of patients who completed induction therapy (per individual drug label) but have active disease as measured by SCCAI >2 or HBI >4 between October 2021 and October 2023. We assessed for the time to treatment change (time from a positive clinical index to the time of a medical decision made), and time to clinical remission (time from a positive clinical index to the time of normalization (SCCAI ≤2, HBI ≤4 of the clinical index) and compared those between patients monitored by IUS and those managed with a conventional approach. Patients were matched by their provider and disease type. Active disease by faecal calprotectin (FCP) (FCP >150 mcg/g) and endoscopy (Mayo endoscopic score (MES) >0) were assessed ± a month before a positive clinical index was collected. An abnormal IUS was considered bowel wall thickness (BWT) >3 mm in the colon or terminal ileum and any hyperemia by colour Doppler signal (CDS) (modified Limberg score >0). Chi square analysis was performed, with p<0.10 significance.

Results

54 patients (63 encounters) were included in this analysis (33 in the IUS cohort, 30 in the conventional management cohort) from 3 different providers. At inclusion, 9 (27%) pts in the IUS group and 10 (33.3%) in the conventional group had elevated FCP, and 5 (15.2%) pts in the IUS group and 29 (96%) had endoscopic disease. In the IUS group, the average time-to-treatment change was 2.2 (±1.2) days compared to conventional management 25.6 (±14.5), p=0.050. A total of 44 patients achieved clinical remission (22 IUS; 22 conventional management). The average time to remission in the IUS group was 128.1 days (±22.3) vs 230.6 (±38.2) days in the conventional management group, p=0.035). Drug class did not affect time to treatment change or time to remission (Table 1). The most significant reason for delay in the conventional group compared to the IUS group was awaiting endoscopy and FCP results.

Conclusion

Using IUS to assess disease activity in IBD is associated with earlier treatment changes and shorter time to remission compared to conventional approaches to disease monitoring, independent of therapy choice. Ongoing dissemination and incorporation of IUS in the management of IBD are warranted.
P981 Risankizumab, but not ustekinumab or vedolizumab, downregulates IL-23-induced mucosal pathogenic Th17 cells in patients with Crohn’s disease
Authors: Noviello D , Dusetti I , Pivorunas V , Lovati A E , Ciafardini C , Amoroso C , Conforti F , Piazza O Sed N , Vecchi M , Facciotti F , Paroni M , Caprioli F
Published: January 2024

Background

We recently described an interleukin(IL)-23-inducible pathogenic subset of CCR6+CXCR3-CCR5+ mucosal T helper (Th)17 cells (pTh17) infiltrating Crohn’s disease (CD) inflamed mucosa and specifically activated in response to Adherent-Invasive Escherichia Coli. pTh17 cells are functionally and phenotypically distinct from CCR6+CXCR3-CCR5- Th17 cells (cTh17) and from IL-12-induced CCR6+CXCR3+ Th1/17 subset. Here, we investigated pTh17 cells' recirculation into the bloodstream, localization into the intraepithelial lymphocyte (IEL) compartment, and in-vivo modulation by different biological therapies.

Methods

Adult patients with active CD initiating either vedolizumab as per clinical practice or ustekinumab and risankizumab during the SEQUENCE trial were prospectively recruited at Fondazione IRCCS Cà Granda, Ospedale Policlinico di Milano. In vedolizumab-treated patients, peripheral blood and intestinal biopsies were collected at baseline and at the end of induction. In ustekinumab- and risankizumab-treated patients, intestinal biopsies were collected outside study protocol assessments at baseline and week 24. Endoscopic response was defined as a greater than 50% decrease in the Simple Endoscopic Score from baseline. Peripheral blood mononuclear cells, lamina propria mononuclear cells (LPMC), and IEL were isolated and analyzed through flow cytometry.

Results

Overall, 34 CD patients were assessed. Demographic and baseline disease characteristics are summarized in Table 1. At baseline, as compared with cTh17, pTh17 cells: 1. are rarely found in the peripheral blood and express low levels of CCR9 and α4β7, 2. express high levels of tissue-resident markers CD69+CD103+ in the mucosa, and 3. infiltrate the IEL layer upon binding of CD103 with E-cadherin. Baseline pTh17 cells were upregulated in patients not achieving vedolizumab-induced endoscopic response. Upon vedolizumab treatment, a selective downregulation of mucosal cTh17 cells but not pTh17 was observed. Remarkably, risankizumab induced a specific downregulation of pTh17 cells, but not cTh17, in both LPMC and IEL layers. Conversely, ustekinumab reduced Th1/17 mucosal subsets, but not pTh17 cells (Figure 1).

Conclusion

pTh17 cells are largely unable to recirculate through the bloodstream, express markers of gut-tissue residency, and infiltrate the IEL compartment. IL-23 neutralization by risankizumab specifically downregulates mucosal pTh17 cells, as compared with vedolizumab and ustekinumab. Our immunologic results might provide mechanistic clues to vedolizumab latency effect in CD, and potentially explain early signs of risankizumab superiority over ustekinumab in the SEQUENCE study in terms of endoscopic response at 24 weeks.
P997 New Objective Assessment of perianal Crohn’s disease, Perianal Lesion Index; PLI
Authors: Yokoo T , Yoshikawa S , Masuda T , Terauchi S , Uchida H , Nakao T , Yamaoka K , Inagaki M , Tani T , Okamoto K , Inatsugi N
Published: January 2024

Background

In the previous survey, decisions of biological treatment (Bio) success for perianal Crohn’s disease (pCD) were made by the patient’s subjective improvement and physician’s assessment, so it lacks objectivity. Moreover, physicians, surgeons, and proctologists are related to treating pCD. This aspect is the difficulty of the treatment of pCD. We need a common assessment for each area’s doctor. We aimed to develop a new objective assessment of pCD, including endoscopic findings, and assess the efficacy of the newly launched Bio except anti-TNFα agents for pCD.

Methods

Usually, perianal abscesses and fistula are derived from ulcers in the lower rectum and anal canal, so we adapted SES-CD to the location and checked discharge and needs of setons, and finally scored it (Table 1). We named this assessment Perianal Lesion Index; PLI.

We retrospectively evaluated 20 pCD patients who received Ustekinumab (UST) and Vedolizumab (VDZ) from March 2017 to March 2023 at our institute. We checked each patient’s PLI, CRP, LRG, and CDAI and compared them before starting Bio and eight weeks after initiation of Bio using a paired T-test. Finally, we used the Pearson correlation coefficient to examine the correlation between PLI and conventional serum biomarkers and CDAI.

Results

The male-to-female ratio was 4.0, the average age at the treatment initiation was 35. Eighteen patient’s diseases were located in the small and large intestines, 10 patients were penetrating type, and 2 patients were stenotic type. We used UST for 16 patients and VDZ for 4 patients. Seven patients were naïve for Bio, 8 patients were treated by one Bio, and 5 patients were treated by two Bio.PLI was positively correlated with CRP (r=0.59, p<0.001) but not correlated with LRG (r=0.77, p=0.077) and CDAI (r=0.35, p=0.07). The pretreatment average PLI was 8.5 and significantly decreased to 3.9 (p<0.001) 8 weeks after Bio initiation. There was a significant change in CRP (3.1 to 0.9, p =0.03) but not CDAI (193 to 147, p=0.2). There were significant PLI changes in each treatment group; the UST group’s PLI change was 8.3 to 3.1 (p<0.001), and the VDZ group's PLI was 9.5 to 8.0 (p=0.02) (Figure 1).

Conclusion

PLI seems to be an objective assessment for pCD, and it was positively correlated to CRP. We could assess each drug’s efficacy for pCD. Further investigation is needed to establish PLI’s accuracy, and we hope this assessment will contribute to the choices of Bio for pCD and the evaluation of its efficacy
P1000 A meta-analysis and systematic review of 5-aminosalicylates withdrawal in Inflammatory Bowel Disease
Authors: Arzivian A , Kerkham A , Tran Y , Rubin D , Leong R
Published: January 2024

Background

5-aminosalicylic acids (5-ASA) are the first-line agents in mild-to-moderate ulcerative colitis (UC). They are not recommended for Crohn’s disease (CD) or moderate-to-severe UC. 5-ASAs are the most prescribed medication for all patients with inflammatory bowel diseases (IBD). Its continuous use is associated with significant cost, adverse effects, and delay in treatment escalation. Recent analyses suggest no benefit of 5-ASA use in patients escalated to more advanced therapies. Hence, 5-ASA withdrawal was suggested, but the outcomes remain unclear. We aimed to perform a meta-analysis of 5-ASA withdrawal in patients with IBD and compare the risk of disease relapse in different cohorts of patients.

Methods

A search for articles was conducted in five medical databases, studies were selected, and their quality was assessed. Studies were divided into six clinically relevant cohorts depending on the type of IBD and other treatments used; the relative risk of relapse for individual studies in each cohort was analysed.

Results

1714 studies were identified; 27 were included in the meta-analysis. Withdrawal of oral 5-ASA monotherapy was associated with a 60% increased risk of relapse. Similarly, withdrawal of rectal 5-ASA had a relative risk of relapse of 2.03. When combined with immunomodulators and/or biologics in UC or CD, oral 5-ASA withdrawal was not associated with an increased risk of relapse. Patients on combined oral 5-ASA and immunomodulators had a higher risk of relapse in the 5-ASA continuation group across three studies; this can be attributed to the persistence of oral 5-ASA use in patients with more severe disease, delaying the appropriate escalation to advanced therapies. Two studies reported no increased risk of colorectal cancer when 5-ASA was withdrawn either as monotherapy or when combined with other treatments.

Conclusion

Oral or rectal 5-ASA monotherapy in UC should not be discontinued. 5-ASA withdrawal does not increase relapse in patients with UC or CD escalated to immunomodulator and/or biological treatment. Oral 5-ASA continuation combined with immunomodulators delays escalation to advanced therapy. Available data suggest that 5-ASA withdrawal does not increase the risk of colorectal cancer; however, this must be considered carefully in patients with unmodifiable risk factors.
P1015 Subcutaneous infliximab effectively manages clinical outcomes of Inflammatory Bowel Disease independently of various confounding factors
Authors: Buisson A , Cummings F , Subramanian S , Rahmany S , Fumery M , Kwon B , Park S , Lee Y N , Smith P J
Published: January 2024

Background

Since its approval, many inflammatory bowel disease (IBD) patients have been treated with subcutaneous (SC) infliximab (IFX), but the association of various confounding factors with clinical outcomes is still elusive.

Methods

The ASSEMBLE project is an initiative to combine multi-national real-world cohort datasets and analyse the effectiveness and safety of SC IFX therapy. In the ASSEMBLE-1 database analysis, three studies from France and the United Kingdom1-3 were integrated to assess the clinical outcomes up to 6 months (6M) after switching from IV to SC IFX. Clinical remission was defined as Harvey-Bradshaw Index (HBI) or modified HBI (mHBI) <5 for Crohn’s disease (CD) and Simple Clinical Colitis Activity Index (SCCAI) or partial Mayo score (PMS) <3 for ulcerative colitis (UC). Treatment persistence was assessed by Kaplan-Meier survival analysis. After adjustment with inverse probability of treatment weights (IPTW), the association of various parameters on clinical outcomes was assessed with marginal structural models (MSMs), by comparing the estimated marginal means (EMMs) of remission rates at 6M between patients in each subgroup.

Results

The data of 428 patients were pooled from the three datasets (70.6% CD, 29.4% UC). 85.4% of patients were in clinical remission before switching to SC IFX with median HBI or mHBI of 1 (IQR 0,2) for CD and median SCCAI of 2 (IQR 1,3) or PMS of 0 (IQR 0,0) for UC. The overall clinical remission and persistence rates at 6M after switching were 84.7% and 94.5%, respectively. Pre-switch IV IFX regimens, immunomodulator (IMM) use, age, baseline fecal calprotectin (FC) level, or baseline C-reactive protein (CRP) level were not associated with persistence. Persistence rate was >90% regardless of body mass index (BMI), although it was higher for patients <25 kg/m2 BMI (98.1%). Assessment with MSMs indicated that the clinical remission rate of CD, but not UC, was expected to be significantly lower only if patients were treated with escalated IV IFX before switching rather than standard 5 mg/kg Q8W regimen (p=0.01; Table 1). No association with high BMI, IMM use, age, ≥150 μg/g FC, and ≥5 mg/L CRP was found in both CD and UC (Table 1). Perianal disease was not associated with CD remission either.

Conclusion

The ASSEMBLE-1 results confirm that switching from IV to SC IFX is well accepted and effectively manages the clinical outcomes of the disease regardless of various confounding factors in IBD patients. However, further studies are warranted to explore the association of pre-switch IV IFX regimens with clinical outcomes. [1] Smith et al. J Crohns Colitis 2022 [2] Buisson et al. Clin Gastroenterol Hepatol 2023 [3] Rahmany et al. Gastroenterology 2023.
P1017 Upadacitinib as rescue therapy for the treatment of Acute Severe Colitis in an acute care setting
Authors: Clinton J , Motwani K , Schwartz S , McCarthy P , Axelrad J , Cross R , George L
Published: January 2024

Background

Inflammatory bowel disease is a chronic, relapsing and remitting inflammatory disorder that despite advances in medical therapy often requires hospitalization for treatment of acute flares with intravenous corticosteroids. Many patients will not respond to corticosteroids and require infliximab or cyclosporine as rescue therapy. If medical therapy fails, definitive surgical management is required. Recently, Janus Kinase inhibitors, including upadacitinib, have been proposed as an alternative rescue therapy given their rapid onset of action. The aim of this study was to evaluate the efficacy of upadacitinib as an alternative rescue therapy for acute severe colitis.

Methods

We conducted a retrospective review of 12 inflammatory bowel disease patients admitted for acute severe colitis who received upadacitinib induction therapy. The rates of surgery, repeat or prolonged steroid use, and re-admission within 90 days of index hospitalization were measured. The need for re-induction with upadacitinib, change in medical therapy, rates of clinical remission, change in 6-point partial Mayo score, and laboratory markers of inflammation were measured as secondary outcomes. Statistical analysis of primary and secondary endpoints was performed with descriptive analysis.

Results

Five patients met the primary composite endpoint including four patients requiring surgery and one additional patient being unable to withdraw steroids within 90 days of hospital discharge. One patient required re-induction with upadacitinib within 90 days and no patients required change in medical therapy within 90 days. Of the patients who did not undergo surgery, 63% were in clinical remission within 90 days and showed clinical improvement with decreased 6-point partial Mayo scores at the post-discharge visit (4.75 during admission vs. 1.25 at post discharge visit, p<0.0001). There were no adverse reactions reported in relation to upadacitinib administration during the study period.

Conclusion

We found that two-thirds of patients treated with upadacitinib 45mg daily for acute severe colitis were able to avoid surgery during the index admission and within 90 days post-discharge. Of the patients who were able to avoid surgery, most were able to taper steroids, did not require readmission within 90 days of index hospitalization and were in clinical remission within 90 days. Upadacitinib may be effective salvage therapy for acute severe colitis, but larger controlled trials are required to validate these results.
P1035 CT-based radiomics signature of visceral adipose tissue and bowel lesions for identifying patients with Crohn’s disease resistant to infliximab
Authors: Wang Y , Zhou Z , Luo Z , Li X
Published: January 2024

Background

Data describing the effect of visceral adipose tissue (VAT) on infliximab treatment response in patients with Crohn’s disease (CD) remains scarce. We aimed to develop and validate a VAT-based radiomics model (RM) using computed tomography (CT) images to identify CD patients at high risk of primary nonresponse to infliximab, and explored whether it can improve the prediction efficacy of an established bowel lesions-based RM.

Methods

This retrospective study included 231 CD patients (training cohort, n=112; internal validation cohort, n=48; external validation cohort, n=71) from two tertiary centers. Machine-learning VAT model and bowel model were developed separately to identify CD patients with primary nonresponse to IFX. A comprehensive model incorporating VAT and bowel radiomics features was further established to verify whether CT features extracted from VAT would improve the predictive efficacy of bowel model. Area under the curve (AUC) and decision curve analysis were used to compare the prediction performance. Clinical utility was assessed by integrated differentiation improvement (IDI).

Results

VAT model and bowel model exhibited comparable performance for identifying patients with primary nonresponse in both internal [AUC: VAT model vs bowel model, 0.737(95% CI, 0.590-0.854) vs. 0.832 (95% CI, 0.750 - 0.896)] and external validation cohort [AUC: VAT model vs. bowel model, 0.714(95% CI, 0.595-0.815) vs. 0.799(95% CI, 0.687-0.885)], exhibiting a relatively good net benefit. The comprehensive model incorporating VAT into bowel model yielded a satisfactory predictive efficacy in both internal [AUC,0.840(95%CI, 0.706-0.930)] and external validation cohort [AUC,0.833(95%CI, 0.726-0.911)], significantly better than bowel alone (IDI=4.2% and 3.7% in internal and external validation cohorts, both P<0.05).

Conclusion

VAT has an effect on IFX treatment response. It improves the performance for identification of CD patients at high risk of primary nonresponse to IFX therapy with selected features from RM.
P1051 The role of Resection Margins in Crohn`s Disease – A potential risk factor for Disease Recurrence?
Authors: Kelm M , Buck V , Benatzky C , Schöttker K , Rosenfeldt M , Germer C T , Nusrat A , Meining A , Flemming S
Published: January 2024

Background

Postoperative disease recurrence after ileocecal resection for Crohn`s Disease is a major issue for all disciplines. While adequate therapeutic strategies are lacking, further criteria are necessary to improve the identification of patients at risk for disease recurrence. In line with that, the exact role of positive resection margins as a potential risk factor on disease recurrence remains unclear since current evidence is heterogenous.

Methods

All patients who received ileocecal resection due to localized terminal ileitis Crohn at the Department of Surgery at the University Hospital of Wuerzburg between 2014 and 2021 were evaluated. Primary endpoints were severe endoscopic (Rutgeerts-Score >2) and surgical recurrence (re-operation due to Crohn`s Disease) during follow up. Positive resection margins were identified by two independent pathologists and defined by the following criteria as international consensus: neutrophils localized in the epithelium, cryptitis, and/or plexitis.

Results

214 patients received ileocecal resection at the Department of Surgery. Of those, 159 patients were finally included for analysis with a median follow up of 35 months. Postoperative morbidity was not affected by inflammation at the resection margins. However, positive resection margins resulted in significantly increased rates of severe endoscopic recurrence at six months (2.0% versus 15.6%, p=0.02) and overall (4.2% versus 19.6%, p=0.001). Additionally, positive margins resulted in significantly increased rates of surgical recurrence (0% versus 4.5%, p=0.04).

Conclusion

Positive resection margins in Crohn`s Disease are associated with increased rates of severe endoscopic and surgical recurrence and should therefore be considered as risk factor for postoperative disease recurrence.
P1053 Ustekinumab trough concentration could predict the aggravation of endoscopic severity after de-escalation in the sub-analysis of CD-EXTEND study
Authors: Kato S , Tagawa K , Yamaga N , Yakabi K , Nagoshi S
Published: January 2024

Background

De-escalation was a useful strategy for improving patient’s QOL and reduction of medical expenses. However, endoscopic data after de-escalation of ustekinumab (UST) has not been reported. The aim of this study was to elucidate UST trough concentration for the prediction of endoscopic aggravation after de-escalation of UST.

Methods

This CD-EXTEND study was a single-centre prospective observational study approved by the institutional review board of our hospital. Thirty CD patients who selected de-escalate UST treatment after administration of intravenous UST 6 mg/kg and subcutaneous UST 90mg every 8 weeks until 54 weeks were enrolled in this cohort. Endoscopic evaluation was performed at baseline and at one year. Endoscopic aggravation was defied as the increase of SES-CD score. Cut-off values of prediction for endoscopic aggravation was calculated by receiver operating characteristic (ROC) curve.

Results

Endoscopic evaluation could be evaluated in 25 patients. Endoscopic aggravation was recognized in 9 patients. There was no significant differences of patient’s characteristics and biomarkers including CRP, fecal calprotectin (FC) and Leucin-rich alpha-2-glycoprotein (LRG) between aggravated and non-aggravated groups at the baseline. However, trough concentration was significantly higher in aggravated group than non-aggravated group at the base line (1.5 ± 0.7 vs 2.8 ± 1.3 μg/mL, p=0.02). CRP, FC and LRG significantly increased in aggravated group, not in non-aggravated group. However, trough concentration significantly decreased in both aggravated and non-aggravated groups. Trough at one year was significantly lower in aggravated group than non-aggravated group (0.44 ± 0.3 vs 1.0 ± 0.71 μg/mL, p=0.02). Cut-off values of trough concentration of prediction for endoscopic aggravation at base line and at one year were 2.15 and 0.4 μg/mL, respectively.

Conclusion

UST trough concentration was a good prediction marker for endoscopic aggravation.
P1084 Persistence and efficacy of Ustekinumab in Crohn's disease after antiTNF failure. May the response of the second biologic therapy be better than the first one?
Authors: Latrás Cortés I , Saéz Hortelano J C , Suárez Álvarez P , García Prada M , Cano Sanz N , Ortega Valin L , Sierra Ausín M
Published: January 2024

Background

After antiTNF failure, a second antiTNF in Crohn's disease (CD) is effective to achieve and maintain remission, but only50% remain with the drug after 12 months of treatment. Ustekinumab (UST) has a better persistence as second-line treatment and is effective to induce and maintain long-term remission.

Methods

Retrospective and observational study retrieved from a prospective database of Crohn's disease patients treated with UST, after approval of Research Ethics Committee. Data were collected at the beginning of treatment and after 4, 8, 16, 24 weeks, 12, 24, 36, 48, 60 months and at the end of follow-up (UST discontinuation or March 2023 if treatment continues).

Primary Objective

evaluate the persistence with UST and clinical (Harvey-Bradshaw index (HBI)<4) and biological remission (C-reactive protein (CRP)<5 mg/dl and/or fecal calprotectin (FC)<250 mg/kg) in each period of follow up.

Clinical remission in perianal disease was defined as absence of drainage both spontaneous and after soft pressure. Persistence of the first biologic therapy, reasons of treatment change, dose optimization, surgery, hospitalizations and adverse events were also evaluated.

Results

68 patients were included (Table 1).

Median survival of antiTNF is 1.65 years (IC95% 1.18-2.56). 72.06% patients receive antiTNF 1 year, 45.59% 2 years, 30.88% 3 years and only 8.82% are treated during 10 years.

Persistence with UST was longer than with antiTNF. 93.2% of patients receive UST 1 year, 89.4% 2 years and 86.1% 3 years.

There was a significant reduction of fecal calprotectin values during follow-up (p=0.0002).

7 patients with perianal disease achieved clinical remission (70.00%) and 4 complete fistula healing in magnetic resonance enterography (40.00%) at the end of follow-up.

60.29% patients received 90 mg every 8 weeks, but 36.76% required dose optimization (23.50% 90mg sq/4 weeks and 13.24%130mg/4 weeks ev).

86.76% continue UST at the end of follow-up, with a mean duration of treatment of 27.65 months (SD 18.27). 9 patients (13.24%) stopped treatment (1 primary non response, 5 loss of response, 3 adverse events).

11 patients (16.18%) needed surgery and hospitalization during follow up; 63.60% of them had stricturing disease.

Conclusion

Persistence with UST as a second line therapy was superior to antiTNF in first-line. 86.76% continued treatment with UST after 2 years. UST achieved early and long-term clinical remission in approximately two thirds of patients. 36.76% of patients required dose optimization. UST was effective in perianal disease after antiTNF failure.

Figure 1 shows clinical remission in patients with basal HBI>4.
P1112 Clinical features between familial versus sporadic inflammatory bowel disease: a retrospective single centre study
Authors: Dottor F , Marino M , Colombo A , Navarria L , Solito S , Berretti D
Published: January 2024

Background

Inflammatory bowel disease (IBD) is a group of chronic inflammatory conditions of the gastrointestinal tract. The two main types of IBD are Crohn's disease (CD) and ulcerative colitis (UC). Both conditions have a complex and multifactorial etiology, involving a combination of genetic, environmental, and immunological factors. If there is a family history of IBD, particularly in first-degree relatives (parents, siblings), there may be a higher risk for other family members to develop the disease. A retrospective cohort study was conducted between 2010 and 2022, to assess clinical features between familial versus sporadic inflammatory bowel disease

Methods

This observational monocentric retrospective study, includes 903 patients: 794 with IBD, with and without familiarity, referring to the Gastroenterology Service of the "Azienda Sanitaria Universitaria del Friuli Centrale". 10,6% of the patients have familiarity (54,2% with a first degree and 44,8% with a second degree relative). Table 1 provides data on patients and disease characteristics.

Results

The mean age of patients with familiarity for IBD was significantly lower compared to subjects without familiarity. Unexpectedly in our cohort familiarity in CD vs UC subjects were similar (respectively 10.7% vs 11.8%). A slight increase of women in the group with familiarity was detected although not statistically significant. EIMs occurred predominantly in the cohort with familiarity but the difference was not statistical significant. IBD subjects with familiarity need less surgery if compared with those with non familiarity (respectively 14,6% vs 18,2%), but the difference was no significant. Biological drugs have been used earlier and more frequently in patients with familiarity compared with those with not familiarity (29,3% vs 38,5%) although also in this case non significant. No differences on IBD phenotype have been noted between familial IBD vs sporadic IBD. Main data described in Table 2.

Conclusion

In this retrospective cohort study, family history of IBD was present in similar percentage between CD and UC. The only significant data in our cohort was the early age of onset of IBD in patients with familiarity. However IBD familiarity was associated with a trend of decreased risk of surgical procedures, increased use of biological medications and a trend for developing EIMs. While some data, for example the earlier and larger use of biologics could explain the less need of surgery in IBD patients, larger cohorts are essential to define the similarities and differences more robustly between familial and sporadic IBD.