bluuebunny/crossref_metadata_2025_split huggingface dataset:
P1096 The predictive value of intestinal ultrasound for treatment response in Inflammatory Bowel Disease: a systematic review and pooled data analysis
Authors: Vos H , Teichert C , de Voogd F , Pruijt M , D’Haens G , Benninga M , Koot B , Gecse K 
Published: January 2025

Abstract

Background
Intestinal ultrasound (IUS) is a promising tool in predicting treatment response in Inflammatory Bowel Disease (IBD). We aimed to systematically review current literature on the predictive value of IUS for treatment response.

Methods
A literature search was performed across multiple databases from inception to 17th of September 2024 (figure 1). We included articles in IBD patients where IUS was used for the assessment of treatment response. Data were analysed for Crohn’s disease (CD), ulcerative colitis (UC) and acute severe ulcerative colitis (ASUC), separately. Timing of IUS follow-up for CD and UC was categorized as baseline, rapid (0-3 weeks), short-term (4-8 weeks), intermediate (12-16 weeks) and long-term (&gt;16 weeks). For ASUC timing was categorized as ≤5 days or &gt;5 days. Treatment outcomes included endoscopic or clinical scores and therapeutic outcomes (e.g. surgery, treatment escalation). The quality of the included studies was evaluated using the QUIPS tool. For pooled data analysis, all authors analysing anti-TNF treatment of CD patients were contacted for raw data.

Results
In total, 28 articles were included with 17 in CD, 7 in UC and 4 in ASUC (figure 1). In general, quality of the included studies was adequate. In CD, IUS parameters at week 4-8 first differentiated between responders and non-responders with bowel wall thickness (BWT) as the most important parameter. Across 7 studies (335 individual patients) responders demonstrated a change in BWT of -43% to 0% vs -15.3% to 2% in non-responders. For UC, after 1 week a decrease of 1mm BWT in the rectum resulted in an OR of 1.9 (p=0.001) for predicting clinical remission at week 8 in one study (n=100). From 6 weeks onwards, there was a significant difference BWT decrease in the sigmoid colon for having future endoscopic response (-37% vs -20%; p=0.002) and remission (-49% vs -17%; p=0.002) in one study (n=50). In ASUC, BWT measured 1-3 days after starting iv. steroid treatment in two cohorts (n=66) significantly differed between responders and non-responders, with a change in BWT ranging from -34 to -13% vs -5 to 2% respectively. In the pooled data analysis, 6/13 authors shared data on BWT (n=187, table 1). At week 12-16, overall responders had a higher percentual decrease in BWT than non-responders (Δ-26% vs. Δ-2%, p&lt;0,001). When differentiating for outcome, there was a significant difference in BWT decrease between endoscopic responders and non-responders (Δ-35% vs Δ +2%, p&lt;0.001).

Conclusion
IUS predicts response in both CD, UC en ASUC in the early stages of treatment. Based on our pooled data analysis, a decrease in BWT of 26% (AUROC 0.813, sens 93%, spec 54%) after anti-TNF induction predicts future treatment outcomes.
P1097 Phase 1/2 study to assess safety, tolerability, and efficacy of XmAb942 (anti-TL1A) in healthy participants and participants with ulcerative colitis
Authors: Hung K , Aggarwal S , Gargosky S , Peterson C , Ramanujan S , Banfield C , Manukyan Z , Hassan-Zahraee M , Kanodia J , Woo J , Szymkowski D , Visonneau S , Burington B , Trout C , Leone D , Dahiyat B , Gujrathi S , Desjarlais J 
Published: January 2025

Abstract

Background
Tumour necrosis factor-like ligand 1A (TL1A) mediates a broad spectrum of pro-inflammatory and pro-fibrotic effects that have been linked to the pathogenesis of inflammatory bowel disease (IBD), as well as other autoimmune disorders. Recent clinical trials have demonstrated that antagonist antibodies that interfere with the interaction between TL1A and its cognate receptor, Death Receptor 3, can result in clinical remission in the two primary variants of IBD, ulcerative colitis and Crohn’s disease. XmAb942 is an anti-TL1A IgG1 antibody with ablated Fc-mediated effector function that incorporates the Xtend™ half-life extension technology. XmAb942 binds trimeric TL1A with high affinity and specificity and is highly potent across multiple preclinical assays. Allometric scaling of the non-human primate half-life of 23 days predicts a half-life of ≥ 70 days in humans. Quantitative systems pharmacology modelling supports the potential for superior drug exposure with less frequent dosing as compared to first-generation anti-TL1A antibodies. We now present details of the ongoing seamless Phase 1/2 study in healthy participants and participants with ulcerative colitis.

Methods
Phase 1 (Parts A and B) is a single ascending dose administered intravenously or subcutaneously followed by repeat dosing in healthy participants. Phase 2 (Part C) is in participants with ulcerative colitis with emerging Phase 1 data to determine dosing.

Results
The primary objectives of Parts A and B are to assess the safety and tolerability of single and repeat doses of XmAb942. Secondary objectives include assessment of pharmacokinetics (PK). Exploratory objectives include assessment of immunogenicity and pharmacodynamics. The primary objective of Part C is to evaluate the effect of repeat doses of XmAb942 on clinical remission in participants with moderately to severely active ulcerative colitis. Secondary objectives include evaluation of endoscopic improvement, endoscopic remission, clinical response, histologic-endoscopic improvement, histologic-endoscopic remission, as well as safety and PK assessments. Exploratory objectives include assessment of immunogenicity and pharmacodynamic effects.

Conclusion
The seamless Phase 1/2 study is designed to assess XmAb942 as a next-generation, potent, and long-acting anti-TL1A antibody therapeutic with potential best-in-class drug exposure and less frequent dosing. This study is currently enrolling in Australia, with Phase 2 to be expanded globally. Interim data are expected in the first half of 2025.

References
Clinical trials identification: NCT06619990
P1099 Simple magnetic resonance imaging markers are non-inferior measures of treatment response compared to complex disease activity scores in patients with active Crohn’s disease
Authors: Nejatbakhsh E , Rafaelsen S R , Brodersen J B , Knudsen T , Kjeldsen J , Juel M A , Jensen M D 
Published: January 2025

Abstract

Background
Minimally invasive modalities have shown significant potential for monitoring disease severity and treatment response in Crohn’s disease (CD). Several magnetic resonance imaging (MRI) scoring systems have been validated in research settings. However, these calculations are time-consuming, which limit their widespread adoption in clinical practice. This analysis evaluated treatment response in patients with active CD using simple imaging markers and compared them to complex multifactorial scores.

Methods
A post-hoc analysis was conducted using data from a prospective, blinded, multicenter study (ClinicalTrials.gov: NCT03435016). The study included patients with endoscopically active CD and a clinical indication for medical treatment. All patients completed ileocolonoscopy (IC) and MRI-enterocolonography with intravenous contrast and diffusion-weighted sequences before and after treatment. IC served as the gold standard. Response was defined as a ≥ 50% reduction of Simple Endoscopic Score for Crohn’s Disease (SES-CD). The simple markers evaluated were bowel wall thickness (BWT) and the apparent diffusion coefficient (ADC). Measurements were performed on the most severely affected ileocolonic segment and were compared to Magnetic Resonance Index of Activity (MaRIA), Simplified MaRIA (sMaRIA), and the Clermont score.

Results
Forty-two patients with known CD were included in the analysis. Patient characteristics are shown in Table 1. Endoscopic response was achieved in 19 patients (45.2%) with a median SES-CD of 11.5 (interquartile range [IQR] 9-17) and 7.0 (IQR 0-13) before and after medical treatment, both P &lt; 0.001. MaRIA, sMaRIA, Clermont score, BWT, and ADC all significantly improved in patients with endoscopic response compared to non-responders (P &lt; 0.05). Receiver operating characteristics are shown in Figure 1. The diagnostic accuracy for the absolute difference in BTW (AUC 0.735, 95% CI 0.583-0.886) and ADC (AUC 0.753, 95% CI 0.602-0.904) appeared to be higher than MaRIA (AUC 0.595, 95% CI 0.415-0.775), P = 0.12 and P = 0.13, respectively. The relative reduction of BTW (AUC 0.761, 95% CI 0.611-0.911) trended towards higher diagnostic accuracy compared to MaRIA (AUC 0.627, 95% CI 0.448-0.806, P = 0.098). A &gt; 17% relative reduction of BWT resulted in an optimal sensitivity and specificity of 73.7% (95% CI 48.8-90.9) and 82.6% (95% CI 61.2-95.0), respectively.

Conclusion
Repeated measurements of BWT or ADC in the most diseased ileocolonic segment appear to be non-inferior to validated scores like MaRIA and sMaRIA at determining response to medical treatment in patients with active CD. These measurements are simple to perform and do not require intravenous contrast.
P1104 Endo-histologic outcomes in patients with ulcerative colitis responding to tofacitinib
Authors: Singh D.M. A , Bhardwaj A , Jain D , Sharma R , Singh D , Mahajan R , Kaur K , Singh A , Narang V , Kaur H , Singh M , Gupta P , Sehgal T , Midha V , Sood A 
Published: January 2025

Abstract

Background
The therapeutic landscape for ulcerative colitis (UC) has shifted toward deeper disease control. The real-world data on efficacy of tofacitinib in inducing histologic remission (HR) remains limited. We evaluated the real-world efficacy of tofacitinib in achieving endoscopic remission (ER) and HR.

Methods
A prospective cohort study was conducted from January 2022 to June 2024. Adult patients with moderate-to-severe UC (Mayo score ≥6, endoscopic subscore ≥2), who responded to tofacitinib induction were included. Paired endoscopic and histologic assessments were performed at baseline and week 48. Endoscopic disease activity was graded using the Mayo endoscopic score (MES), while histologic activity was evaluated using the Nancy index. The primary outcome was combined endoscopic-histologic remission (EHR), defined as MES of 0 and a Nancy index of 0, at week 48. The secondary outcomes included ER, HR, histologic endoscopic mucosal improvement (HEMI) and endoscopic improvement histologic remission (EIHR).

Results
Seventy-seven patients were analyzed. Clinical response at week 8 was seen in 66 (85.7%) patients, with 43 (65.2%) of these patients maintaining clinical response through week 48. At week 48, combined EHR was achieved in 22 (28.6%) patients, while ER and HR were observed in 30 (38.9%) and 29 (37.6%) patients, respectively. HEMI was noted in 32 (41.6%) patients, while EIHR was seen in 27 (35.1%) patients. (Figure 1) The endoscopic and histological outcomes did not differ with concomitant administration of corticosteroids during induction, previous exposure to thiopurines and the time of achievement of symptomatic remission (8 weeks vs 16 weeks). (Figure 2) No significant predictors of ER, HR, or combined EHR were identified. No serious adverse effects were reported.

Conclusion
Tofacitinib is effective in achieving combined HER, ER, and HR. These findings support the potential for histologic healing as a therapeutic target for UC in real world.
P1106 Early surgical treatment after diagnosis of anal lesions of CD may reduce risk of and colostomy and rectal amputation
Authors: Sako M , Okamoto K 
Published: January 2025

Abstract

Background
Anal fistulas in Crohn’s disease (CD) are often indicated for surgical treatment. We examined the possibility of surgical treatment at early stage after the occurrence of anal lesions without extensive lesions or anal strictures, which can lead to earlier remission and longer maintenance.

Methods
113 CD patients (age 30.0 ± 9.0 years at the time of surgery, 86 males and 27 females) who continued to visit the hospital after surgery for anal fistula from 2003 to 2019 at the Department of Colorectal Surgery at Tokyo Yamate Medical Center were included. Surgery was performed for the purpose of drainage of abscess and removal of infected granulation tissue, and induction of biologics were decided by the physician and the anal surgeon in cases of postoperative wound healing was prolonged, except in cases which biologics had already been started for intestinal lesions. Remission of anal lesions was defined as the epithelialization and disappearance of drainage of the wound, and the rate of colostomy or rectal amputation due to continued activity of postoperative anal lesions was investigated in patients who underwent surgery within 1 year of diagnosis of anal lesions (31 cases, early group) and in cases that were performed after 1 year (82 patients, non-early group).

Results
Colostomy and rectal amputation were performed in 14.3% (4/28) in the early group and 37.8% (28/74) in the non-early group (p&lt;0.05). Biologics were used in 61.1% (69/113) in total, (IFX36, ADA24, UST9, VDZ1), 35.5% (11/31) in the early group and 70.7% (58/82) in the non-early group. The rate of colostomy and rectal amputation was 18.2% (2/11) in the early and bio group, 0% (0/20) in the early and non-bio group, 20.7% (12/58) in the non-early and bio group, and 29.2% (7/24) in the non-early and non-bio group. The rate of colostomy and rectal amputation was relatively low in early group and the risk was not reduced by biologics in non-early group.

Conclusion
In CD, early surgical treatment after diagnosis of anal lesions may contribute to reduced risk of and colostomy and rectal amputation.
P1115 Short- and Mid-term Effectiveness and Safety of Risankizumab in Refractory Crohn’s Disease: A Retrospective Study
Authors: Elosua Gonzalez A , Ramoneda G , Villalonga L , Pérez Ó , Zabalza L , Vicuña M , Nantes Ó , Rubio S , Rodriguez C 
Published: January 2025

Abstract

Background
Risankizumab (RSK) is the first anti-IL-23 drug approved in 2022 for moderate-to-severe Crohn’s disease (CD). Data on its real-world effectiveness and safety remain limited. This study assesses the short- and mid-term effectiveness of RSK and its safety profile in a clinical practice setting.

Methods
A retrospective analysis was conducted on patients with refractory luminal CD treated with RSK at our tertiary centre between March 2022 and July 2024 who completed induction therapy. The primary endpoint was clinical remission at weeks 12 and 24, assessed via the Physician Global Assessment (PGA) based on symptoms, laboratory data and endoscopy/imaging if available. Secondary endpoints included at least clinical response, steroid-free remission and response, adverse events, and drug persistence.

Results
Sixty-three patients were included (65% male, median age 31 years, median disease duration 9.8 years), with 95.2% previously exposed to anti-TNF, 82.5% to ustekinumab, and 52.4% to vedolizumab; 60% had prior exposure to three biologics, 25.4% to four, and 44% had undergone intestinal resection. Induction (600 mg) was administered intravenously in 88.9% of cases.
At week 12, remission and at least partial response rates were 25.4 % and 76.2%, respectively, while steroid-free remission and response rates were 22% and 65.1%. By week 24, 35 patients remained in the study, achieving remission/response rates of 25.7% and 62.8%, respectively, and steroid-free rates of 18.2% and 48.5%. No significant differences were found regarding prior ustekinumab exposure or response/remission outcomes between weeks 12 and 24. RSK persistence was 93%, with four patients discontinuing due to nonresponse. Additionally, by week 24, four patients had required reinduction with 1200 mg administered intravenously. Three adverse events (headache, insomnia, arthralgia) were mild and did not require treatment discontinuation.

Conclusion
Risankizumab demonstrated encouraging effectiveness in treating refractory Crohn’s disease, achieving clinical responses and steroid-free remission in the short- to mid-term. High drug persistence and a favorable safety profile highlight its potential as a valuable treatment option in real-world settings.
P1136 Mesenteric excision and endoscopic recurrence in ileocaecal Crohn’s Disease: a single centre experience
Authors: Jones T , Jayasooriya N , Thoua N , Ghanbari A 
Published: January 2025

Abstract

Background
Endoscopic recurrence of Crohn’s disease after ileocaecal resection is a major concern and has been linked to multiple factors. Endoscopic evidence of postoperative recurrence (ePOR) in the first 6 months ranging between 40-70%.1 Effects of mesenteric sparing versus extended resection in ileocaecal resection is thought to be one of the factors contributing to ePOR.2

Methods
All ileocacecal resections for Crohn’s Disease performed between March 2018 and December 2023 and with surveillance ileocolonoscopy were included in this retrospective analysis. Surgical procedure was standardised with ligation of the ileocolic pedicle at 2-3cm from the origin. Mesentery was excised from the point of vessel ligation directly to the limits of bowel resection. Extracorporeal ileocolonic anastomosis was performed in a stapled, side-to-side, antiperistaltic configuration with closure of the mesenteric defect. Principles of Enhanced Recovery After Surgery were adhered to. All specimens received histological analysis. Surveillance colonoscopy was performed with Modified Rutgeerts Score assigned by the endoscopist with retrospective review by a second endoscopist.

Results
Seventeen patients were eligible for inclusion. Median age was 36 years. Eleven patients (65%) received biologic therapy prior to surgery. Twelve patients (71%) received laparoscopic surgery. Median operative duration was 129 minutes. One patient (6%) had a Clavien-Dindo grade 3+ morbidity (radiological drainage of a collection) with no anastomotic leaks. Median length of stay was 7 days. Histological analysis demonstrated clear margins in all specimens. Six patients (35%) received biologic therapy after surgery. First endoscopic surveillance was performed at a median 18 months. Modified Rutgeerts Score was 0 in 2 (12%), 1 in 9 (53%), 2a in 1 (6%), 2b in 4 (24%) and 3 in 1 (6%) of patients. One patient underwent further surgery for proximal stricture &gt;5cm from the anastomosis. Median follow up was 98 months.

Conclusion
Mesenteric excision comparable to that of D2 lympadenectomy for colorectal cancer is safe. Furthermore, it may confer benefit with lower ePOR, compared to recent literature. Further research is needed to confirm the benefit of mesenteric excision in ileocaecal resection for Crohn’s Disease.

References
1.Nardone OM, Calabrese G, Barberio B, et al. Rates of Endoscopic Recurrence In Postoperative Crohn’s Disease Based on Anastomotic Techniques: A Systematic Review And Meta-Analysis. Inflamm Bowel Dis. 2024;30(10):1877–87.
2.Brown SR. How can the surgeon reduce recurrence after surgery for ileocolic Crohn’s disease? Semin Colon Rectal Surg. 2023;34(4):100985.
P1145 Comparison of Clinical Relapse between Tofacitinib and Filgotinib as Maintenance Therapy in Ulcerative Colitis Patients in Clinical Remission: A Retrospective Propensity Score-Matched Cohort Study
Authors: Yagi S , Fukui H , Ikenouchi M , Shiraishi T , Wakita M , Takagi Y , Sato T , Kawai M , Kamikozuru K , Yokoyama Y , Takagawa T , Shinzaki S 
Published: January 2025

Abstract

Background
Strategies to reduce relapse after induction therapy using JAK inhibitor are controversial in patients with ulcerative colitis (UC). In this study, we aimed to compare relapse rate between tofacitinib (TOF) treatment and filgotinib (FIL) treatment for UC patients in clinical remission.

Methods
We used the data of UC patients who received TOF 10mg/day or FIL 200mg/day as maintenance therapy between May 2018 and October 2024. We included UC patients in clinical remission at baseline. Clinical remission was defined as follows: partial Mayo score ≤2, each subscore ≤1 and a rectal bleeding subscore of 0. The primary outcome was the time to relapse, defined as the requirement of dose escalation or switching therapy for UC with the worsening of clinical symptoms. The secondary outcome was safety during the observation period. Kaplan-Meier analysis and log-rank test were used in order to assess difference in therapy duration between two groups. A propensity score-matched (PSM) analysis was performed to adjust for potential confounders.

Results
We enrolled patients with UC who received either TOF 10mg/day (n = 101) or FIL 200mg/day (n = 43) as maintenance therapy. The median age was 39 [IQR 28–50] and 44 [34–55] years, and the median disease duration was 4 [1–11] and 7 [5–16] years, respectively. The number of previous exposures to anti-TNF agent was 52 (51.5%) and 18 (41.9%), respectively. In the TOF group, cumulative relapse rates at 8, 16, 24, and 48 weeks were 0%, 8.8%, 12.7%, and 25.5%, respectively. On the other hand, in the FIL group, cumulative relapse rates at 8, 16, 24, and 48 weeks were 0%, 2.3%, 4.7%, and 7.0%, respectively. After PSM, forty-three patients in both the TOF and FIL groups were isolated. The cumulative clinical relapse rate was significantly higher in the TOF group than in the FIL group (p = 0.039). Adverse events that required treatment discontinuation were reported in 8 patients in the TOF group, but no adverse events leading to discontinuation were observed in the FIL group.

Conclusion
Our findings suggested that FIL could prevent relapse in UC patients who are in clinical remission more effectively than TOF.