bluuebunny/crossref_metadata_2025_split 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

Abstract

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 &lt;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

Abstract

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

Abstract

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&lt;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

Abstract

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

Abstract

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

Abstract

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 &lt;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 &lt;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

Abstract

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 &lt;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

Abstract

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 &gt;2 or HBI &gt;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 &gt;150 mcg/g) and endoscopy (Mayo endoscopic score (MES) &gt;0) were assessed ± a month before a positive clinical index was collected. An abnormal IUS was considered bowel wall thickness (BWT) &gt;3 mm in the colon or terminal ileum and any hyperemia by colour Doppler signal (CDS) (modified Limberg score &gt;0). Chi square analysis was performed, with p&lt;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.