bluuebunny/crossref_metadata_2025_split huggingface dataset:
P0967 The role of bound anti-drug antibodies to infliximab in predicting future immunogenic failure when de-escalating from combination therapy with an immunomodulator to anti-TNF monotherapy (RAPID-IM Study)
Authors: Cameron K , Sam M , Theena N , Gu B , Arzivian A , Skinner T , Shelton E , Connor S J , Toong C , Gibson P R , Gibson D J , Sparrow M P , Ward M G 
Published: January 2025

Abstract

Background
Withdrawing immunomodulators (IM) from combination therapy with infliximab (IFX) can lead to immunogenic failure due to development of antibodies to IFX (ATI). Conventional drug sensitive ELISAs detect ATI only when IFX drug levels are undetectable. We investigated whether bound ATIs detected using a novel drug tolerant ELISA taken at time of de-escalation to IFX monotherapy, predicted subsequent loss of response and unfavourable IFX pharmacokinetics in IBD patients on combination therapy.

Methods
Multicentre case-control retrospective study of IBD patients treated with combination IV IFX and IM. Patients had &gt; 6 months steroid-free clinical (Harvey Bradshaw Index ≤ 4 / Partial Mayo Score ≤ 2) and biochemical remission (C-reactive protein (CRP) &lt;5 mg/L or faecal calprotectin (FCP) &lt;150 µg/g). Cases (withdrew IM and continued IFX monotherapy) were compared to controls (continued combination therapy). The primary endpoint was relapse (clinically active disease with elevated FCP or CRP) over 24 months follow-up; secondary endpoints included changes in therapy and IFX drug levels. Therapeutic drug monitoring with a drug-tolerant ELISA was collected within 3 months of IM withdrawal.

Results
Bound-ATI were detected in 7/45 (15.6%) cases and 5/37 (13.5%) of controls, none of which tested positive for ATI using drug sensitive ELISA. The groups were well matched, although median duration of combination therapy was longer in cases than controls (41 vs. 20 months, p=0.045) (Table 1). Median duration of follow-up was 17 months. No patients with bound ATI at baseline met the primary endpoint of disease relapse. Higher rates of biochemical disease activity and treatment escalation in the withdrawal group were noted, however ATI status was not associated with these outcomes. When considering changes in IFX levels over subsequent 12 months, there was no significant difference between cases and controls (-0.99 and -0.84 mg/L respectively, p = 0.20). However, in all IM withdrawal patients with ATI, IFX levels reduced from baseline, with greater decreases in IFX drug levels observed in this cohort.

Conclusion
Drug tolerant ELISA can detect bound-ATI that were previously not measureable using drug sensitive ELISA. However, presence of bound-ATI did not predict subsequent disease relapse suggesting conventional assays are suitable in this setting. In IM withdrawal, ATI positivity is associated with greater risk of reduction in IFX levels, and ultimately, potential immunogenic failure. Higher rates of disease activity were observed in IM withdrawal, suggesting that IM might be important in maintaining disease control.
P0971 Effectiveness of Vedolizumab in Bio-Naïve Chinese Patients with Crohn’s Disease: A Subgroup Analysis of Second Interim Analysis of the VALUE Study
Authors: Guo H , Shen H , Jiang Q , Xu X , Qian X , Zhou F , Chen M 
Published: January 2025

Abstract

Background
Vedolizumab (VDZ) is a humanized monoclonal antibody, that selectively targets α4β7 integrin and is approved for Crohn’s disease (CD) and Ulcerative colitis (UC). Previous studies demonstrated better efficacy of VDZ in bio-naïve pts with CD, however, there is lack of sufficient data in Chinese pts. VALUE study (NCT04872491) is a prospective, multicenter, single-armed observational study evaluating the safety and effectiveness of VDZ in UC and CD patients (pts).

Methods
This subgroup of bio-naïve pts with CD in second interim analysis of VALUE trial was assessed for clinical effectiveness (clinical response: ≥3 point-reduction in Harvey-Bradshaw index (HBI) score; clinical remission: HBI score ≤4; endoscopic remission: absence of any ulcers excluding aphthous ulcers.) on treatment of Vedolizumab, at week 14, 30, and 54. (Data cutoff: 21 Oct 23).

Results
Of the 91 pts with CD, 57 pts (62.64%) were bio-naïve, with a mean HBI score of 6.0±3.51 with the median duration of CD of 2.693 (4.1384) years. The majority of disease locations were Ileocolonic (49.12%) with 2 (3.51%) pts had history of Fistulas (Table 1).
After treatment with VDZ, 44.44% (16/36), 52% (13/25) and 53.85% (7/13) achieved clinical response at week 14, 30 and 54, respectively. Overall, 83.33% (30/36), 96.15% (25/26) and 92.31% (12/13) pts achieved clinical remission at week 14, 30 and 54, respectively. Additionally, 100% of pts (13/13) achieved clinical response or remission, by 54 weeks (Figure 1). Further, 66.67% (4/6), 33.33% (2/6) and 0/1 pts achieved endoscopic remission at week 14 ,30 and 54, respectively.

Conclusion
This study demonstrated good effectiveness of VDZ in bio-naïve patients with CD in China.
P0976 Guselkumab efficacy and safety in East Asian participants with moderate to severely active Crohn’s disease: Subgroup analysis of the GALAXI 2 & 3 Phase 3 studies
Authors: Nakase H , Chen B , Cao Q , Matsuoka K , Hisamatsu T , Park D I , Wahking B , Yiu W C , Zhuo J , Chen M 
Published: January 2025

Abstract

Background
Guselkumab (GUS), a dual-acting interleukin-23p19 subunit inhibitor, demonstrated efficacy and safety in participants (pts) with moderately to severely active Crohn’s disease (CD) in the global Phase 3 GALAXI 2 & 3 (G2 & G3) studies.1 We report a subgroup analysis of GUS efficacy and safety in East Asian pts from G2 & G3.

Methods
G2 & G3 (NCT03466411) are identical 48-week, randomised, double-blind, double-dummy, placebo (PBO)- and active comparator- (ustekinumab; UST) controlled treat-through trials assessing the efficacy and safety of GUS in pts with CD (Figure 1).1 Pts with moderately to severely active CD (Crohn’s Disease Activity Index [CDAI] 220–450 and either mean daily stool frequency [SF]&gt;3 or abdominal pain [AP]&gt;1), Simple Endoscopic Score for Crohn’s Disease (SES-CD) ≥6 (≥4 for isolated ileal disease), and inadequate response or intolerance to conventional or biologic therapy were randomised 2:2:2:1 to the following induction→maintenance regimens: GUS 200 mg intravenous (IV) every 4 weeks (q4w) (x3)→100 mg subcutaneous (SC) every 8 weeks (q8w), GUS 200 mg IV q4w (x3)→200 mg SC q4w, UST ~6 mg/kg IV→90 mg SC q8w, or PBO. PBO pts not in clinical response at Week (W)12 switched to UST. Composite co-primary endpoints for both studies were (1) clinical response at W12 + clinical remission at W48 and (2) clinical response at W12 + endoscopic response at W48, comparing each GUS regimen to PBO. This subgroup analysis included G2 and G3 pts from study sites located in East Asia (China, Japan, Korea, and Taiwan).

Results
The East Asian subgroups included 98 G2 and 94 G3 pts. Greater proportions of G2 & G3 pts in both GUS SC maintenance dose cohorts achieved the composite co-primary efficacy endpoints relative to PBO (Figure 2).
In pooled analysis of G2 & G3 in 192 pts, proportions of pts with ≥1 treatment-emergent adverse event (TEAE)/serious TEAE through W48 were 87.3%/11.1% in the GUS 200 mg IV→100 mg SC q8w cohort, 90.2%/7.8% in the GUS 200 mg IV→200 mg SC q4w cohort, 71.9%/15.6% for PBO pts, and 89.1%/13.0% among UST pts. Corresponding rates of infections/serious infections were 57.1%/0 in the GUS 100 mg SC q8w cohort, 54.9%/0 in the GUS 200 mg SC q4w cohort, 25.0%/6.3% for PBO, and 52.2%/4.3% for UST.

Conclusion
Efficacy of GUS in the subgroup of East Asian pts from G2 & G3 was consistent with that observed in the global study population. The safety profile of GUS was also favourable and consistent with previous reports.
This study was supported by Janssen Scientific Affairs, LLC.

References
1.Panaccione R, Danese S, Feagan B, et al. Gastroenterology. 2024;166(5 Suppl):1057b.
P0978 Effectiveness of risankizumab in moderate-to-severe Crohn’s Disease: A Canadian multicentric real-world study
Authors: Zoughlami A , Abbas A , Almushir S , Zeghal M , Khan N S , Milgrom R , Daher S , McCurdy J D , Narula N , Rosenfeld G , Silverberg M S , Lakatos P L , Bessissow T 
Published: January 2025

Abstract

Background
Risankizumab is an interleukin-23 (IL-23) targeting monoclonal antibody, and has recently been approved for the treatment of moderate-to-severe Crohn’s Disease (CD). To this date, there is limited effectiveness and safety real-world data.

Methods
We performed a retrospective chart review at 5 inflammatory bowel disease centers in Canada between January 2023 and November 2023 to evaluate the safety and effectiveness of risankizumab in moderate-to-severe Crohn’s Disease. Adult patients with confirmed CD diagnosis on risankizumab for active clinical or endoscopic disease were included. Patients with indeterminate colitis, and patients treated for post-operative recurrence prophylaxis were excluded. Clinical, biochemical and endoscopic data was collected at 3, 6, and 12 months.We evaluated the rates of clinical remission (defined as Harvey-Bradshaw Index (HBI) &lt;5) and response (decrease in HBI of &gt;50%), biochemical remission (CRP&lt;5mg/L and/or fecal calprotectin (FCAL) &lt; 250ug/g), as well as endoscopic remission (SES-CD &lt;4) and response (SES-CD decrease &gt;50%) at each time point. If HBI or SES-CD scores were not available, treating physicians’ assessments of response and remission were used. Requirement for steroids, drug discontinuation, and drug-associated adverse events were also collected.

Results
A total of 335 patients were included in the study. Baseline data is presented in Table 1. Median age was 39, and 172 (51.3) of patients were female. Most patients (304, 90.7%) had previous biologic exposure, and 112 (33.4%) patients had been exposed to three or more biologics.
Overall, 131/235 (55.7%) patients clinically responded at 3 months, and 121/233 (51.9%) were in clinical remission. At 12 months, rates of clinical response and remission were similar (73/129, 56.6% and 74/132, 56.1% respectively). Endoscopic remission was noted in 6/17 (35.3%), 13/41 (31.7%), and 29/72 (40.3%) at 3, 6 and 12 months respectively. Normalization of biochemical parameters at 12 months was found in 73/99 (73.7%) of patients for CRP, and 21/49 (42.9%) for FCAL. Patients were less likely to require steroids over time, with respectively 49 (14.6%), 25 (7.5%) and 15 (4.5%) of them with active steroid use at 3, 6 and 12 months. Forty-seven (16.1%) patients had discontinued risankizumab prior to 12 months of use. By 12 months, 28 (8.4%) had to undergo surgery for active disease, and 41 (12.2%) required hospitalization.

Conclusion
In this real-world, multicentric, Canadian study, risankizumab was an effective therapy in the management of Crohn’s Disease in a population with significant number of patients with refractory disease.
P0981 Comparative efficacy of standard vs enhanced dose treatment with infliximab in the management of acute severe ulcerative colitis: a single centre retrospective cohort study
Authors: Saeed M H , Ismail A , Thiruselvan K , Umar N , Slater J , King D , De Silva S 
Published: January 2025

Abstract

Background
Acute severe ulcerative colitis (ASUC) often requires rescue therapy with infliximab, typically administered at an initial dose of 5mg/kg or 10mg/kg. There is some uncertainty regarding the optimal dose of infliximab for rescue therapy and current guidance leaves this to the discretion of the treating clinician. A previous multicentre randomised controlled trial (PREDICT-UC) did not find a significant difference in clinical response or colectomy rates between 5mg/kg and 10mg/kg of infliximab in steroid-refractory ASUC 1. This study aimed to compare the clinical outcomes of patients receiving either 5mg/kg or 10mg/kg infliximab in the management of ASUC.

Methods
This retrospective cohort study examined patients with ASUC who were treated with rescue infliximab between 2019 and 2022. Patients were categorised into two groups based on the dose received; 5mg/kg and 10mg/kg. Demographic and clinical variables, including age, sex, disease extent (Montreal classification), and prior treatments (no prior treatment, 5-ASA, biologics), were recorded. The outcomes measured included remission (defined as sustained remission at 1 year), the need for surgery, the requirement for additional doses of infliximab, or change in biological agent. Outcomes at 1 month, 6 months, and 1 year were also recorded. Chi-square tests were used to analyse differences between the two treatment groups.

Results
Of the 50 UC patients, 60% received 5 mg/kg, and 40% received 10 mg/kg. No significant differences were found between the 5 mg/kg and 10 mg/kg infliximab treatment groups for outcomes including surgery (p = 1.00), remission (p = 0.22), and biologic switch (p = 0.22). Additionally, no significant differences were observed when categorising patients by pre-existing treatment (p = 0.06) or disease severity subgroups (E1, E2, E3). When assessing the effect of severe disease markers on treatment outcomes, no significant difference in colectomy rates was found between the two groups for CRP &gt; 50 mg/L (p = 0.34) and albumin &lt; 25 g/L (p = 0.13).

Conclusion
This study showed no significant difference in the clinical outcomes between patients receiving 5mg/kg and 10mg/kg infliximab for the management of ASUC. These findings suggest that escalating the dose to 10mg/kg does not provide a clear clinical advantage in reducing the need for surgery or achieving sustained remission. Larger, multicentre studies with more diverse patient populations are needed to further investigate the potential benefits of higher infliximab dosing in this clinical context.

References
1.Intensified versus standard dose infliximab induction therapy for steroid-refractory acute severe ulcerative colitis (PREDICT-UC): an open-label, multicentre, randomised controlled trial. Choy, Matthew C et al. The Lancet Gastroenterology & Hepatology, Volume 9, Issue 11, 981 - 996
P0983 Addition of fibre to exclusive enteral nutrition (EEN) improves colonic effects and symptoms without compromising the benefits on small bowel paracellular permeability in healthy humans
Authors: Melton S , Gibson P , Taylor K , Halmos E 
Published: January 2025

Abstract

Background
How EEN works in Crohn’s disease is uncertain, but a unique compositional feature compared with whole-food diet is the absence of fibre. We aimed to determine the effects of EEN with and without fibre in healthy adults (to minimise confounders) on 1) intestinal barrier function, in the basal/fasting state and in response to acute stress; 2) inflammatory markers; 3) regional gut transit and fermentation; and 4) symptoms.

Methods
In a single-centre pilot study, 20 participants (age 33 [range 21-49] y, 10 female) were evaluated on their habitual diet and after 3 weeks of either ‘no-fibre EEN’ (n=10) or ‘fibre-EEN’ (22 g/d, 6 fibres) (n=10). Measures were: 1) small bowel permeability via 2-h lactulose:rhamnose ratio (LRR) in basal state and after 100 mg IV corticotrophin-releasing hormone (CRH) to simulate acute stress, and serum markers of lipopolysaccharide translocation; 2) intestinal and systemic inflammation via faecal calprotectin and serum C-reactive protein (CRP); 3) regional gut transit times and colonic H2 concentrations (carbohydrate fermentation) via a gas-sensing capsule; and 4) reported symptoms.

Results
There were no fibre-associated differences in barrier markers. EEN did not change basal barrier function overall, but normalised LRR when elevated (&gt;0.05) on habitual diet (n=7; Fig 1). CRH-induced changes in LRR during the habitual diet were minimised by no-fibre EEN with a similar trend for fibre-EEN (Fig 2). CRP did not change. Calprotectin increased from median 11 (range: 0.5-44) to 41 (2-247) μg/g (p=0.006) with no-fibre-EEN and 13 (4-99) to 27 (4-167) μg/g (p=0.037) with fibre. Gastric emptying and small intestinal transit times on EEN ±fibre were not different to those on habitual diet, but colonic transit time was prolonged (36 [5-69] h) on no-fibre EEN compared with habitual diet (16 [6-24] h; p=0.04), but not on fibre-EEN (24 [16-44] vs 25 [0.4-89] h; p=0.32). Median colonic H2 concentrations were 11.2 [0.4-20.9]% with fibre vs (0.2 [0-7]%;) without fibre (p&lt;0.001) The decreasing proximal-distal gradient in normalised H2 concentrations (1.7 [0-2.5] to 0 [0-1.3]%.h) with no-fibre were not seen for fibre-EEN (6.5 [0.7-12.6] to 10.6 [0.6-20.6]%.h) or habitual diet (3.2 [0-10.1] to 7.1 [0-13]%.h). Headaches in 6/10 within first week of no-fibre EEN and nausea in 9/10 were not reported with fibre-EEN, which induced abdominal pain in 2.

Conclusion
EEN ±fibre normalises basal small intestinal permeability and minimises stress-induced changes. The addition of fibre prevented marked prolongation of colonic transit, reduced carbohydrate fermentation and common symptoms with no-fibre EEN. Addition of fibre improves outcomes without compromising small intestinal action of EEN.
P0986 Sequencing of biological therapies and impact on persistence: Report from a tertiary referral center
Authors: Amato L M , Antoci C , Melatti P , Di Giorgio F , Salerno I A , Ajovalasit R , Di Prima L , Bracciamà E , Scalia S , Celsa C , Cappello M ,   University of Palermo
Published: January 2025

Abstract

Background
Biologics and small molecules are increasingly used in inflammatory bowel diseases (IBD). However, real-world data on sequence choices are still limited as well as the impact of treatment sequence on outcomes. The aim of this study was to evaluate the treatment persistence for different lines of biological drugs in two samples of patients, one suffering from Crohn’s disease (CD) and the other from ulcerative colitis (UC), refractory to conventional therapy.

Methods
This retrospective-prospective real world study included consecutive IBD patients followed in our IBD tertiary referral center. Sankey diagrams were used to describe sequencies. Treatment persistence was assessed using Kaplan-Meier curves and Hazard Ratios (HR) were calculated to compare persistence across treatment lines. Patients discontinued for non-efficacy/safety reasons or treated with non-IBD doses or indications were excluded.

Results
228 IBD patients; 122 CD (Mean age 51,5, range 21-84) and 106 UC (Mean age 54,9, range 18-86) were enrolled. In CD (Picture 1) the third and fourth lines of treatment compared to the first line have the highest level of persistence, 96 (HR 2,6759; IC 95% 1,7803-4,0221) and 64 (HR 4,0229;IC 95% 2,0228-8,0006) months respectively. Vedolizumab had the highest persistence in the first and third line, 40 (IC 95% 15,750-61,000) and 39 (IC 95% 14,000-90,750) months respectively. In UC (Picture 2) the lines with a higher median of persistence are the second and third lines. The medians of persistence are greater for vedolizumab in all lines. Data on ustekinumab and tofacitinib need further observation.

Conclusion
Our study suggests that second-line biologics may offer benefits in terms of therapeutic continuity, likely due to improved efficacy and tolerability. These results encourage the use of second-line drugs earlier, to ensure sustained remission and potentially change the disease course.
P0990 Real-world effectiveness of upadacitinib induction therapy in Crohn’s disease, with a focus on patients with concomitant IMIDs
Authors: Elosua Gonzalez A , Zabalza L , Vicuña M , Rubio S , Nantes Ó , Rodriguez C 
Published: January 2025

Abstract

Background
Upadacitinib (UPA), a selective JAK1 inhibitor, has demonstrated efficacy across immune-mediated inflammatory diseases (IMIDs) and is approved or in development for conditions beyond Crohn’s disease (CD). Effective therapies are essential for managing CD, especially in complex cases involving multiple IMIDs. This study evaluates UPA as induction therapy in CD patients, focusing on outcomes for both CD and associated IMIDs.

Methods
This retrospective study at a Spanish tertiary care centre included adults with moderate-to-severe CD who initiated UPA in routine practice. Data on baseline characteristics, prior therapies, disease duration, and IMIDs were collected. The primary outcome was CD remission at week 12, assessed by Physician Global Assessment (PGA). Secondary outcomes included IMID remission by PGA, adverse events, and discontinuation.

Results
Thirty-four patients were included (mean age 45.5 years, 55.8% female, median CD duration 6 years). All had prior advanced therapy exposure, with 26.5% treated with at least three therapy lines. Ileal involvement was seen in 62%, with 30% showing upper GI involvement,24% stricturing disease and 56% had non-stricturing, non-penetrating disease. IMIDs were present in 35%, including psoriasis, juvenile idiopathic arthritis, uveitis, atopic dermatitis, spondyloarthritis, rheumatoid arthritis, and giant cell arteritis.
At week 12, 30.4% of CD patients achieved clinical remission, and 84.8% had at least a partial response. Among those with IMIDs, 33.3% achieved remission, with at least a partial response in 83.3%. In patients with both CD and IMIDs, 41.7% achieved remission in both conditions, and 75% showed at least a partial response in both.
Most patients (88%) began with a 45 mg/d dose, with 9% requiring extended induction (&gt;12 weeks) at the same dose. Maintenance dosing was 30 mg in most cases, except for 6% who received a lower dose (15 mg). Discontinuation occurred in 32% of patients, primarily due to lack of response (54%) and adverse events (13%).

Conclusion
Upadacitinib (UPA) shows potential in improving both CD and associated IMIDs, with a notable proportion achieving remission or partial response in both conditions at 12 weeks. These findings suggest UPA may be a valuable option for managing complex cases with multiple IMIDs, though further research is needed to confirm efficacy and optimise treatment.
P0991 Laparoscopic ileocecal resection in pediatric Crohn’s disease: effect of anastomotic configuration on postoperative outcomes in the era of biologic therapy
Authors: Dotlacil V , Lerchova T , Kucerova B , Schwarz J , Hradsky O , Skaba R , Rygl M 
Published: January 2025

Abstract

Background
Postoperative complications and recurrence (POR) frequently follow Ileocecal resection (ICR) in pediatric Crohn’s disease (pCD) patients. Evidence addressing the effect of anastomosis type on complications and POR in children remains limited. We aimed to compare laparoscopic-assisted end-to-end (ETE), side-to-side (STS), and Kono-S anastomoses and evaluate their outcomes based on the followed parameters.

Methods
From April 2018 to December 2023, we prospectively collected data on anastomosis configuration, colonoscopy at 6 months post-surgery, perioperative and demographic parameters from all pediatric patients referred to ICR for pCD. Complications were classified according to the Clavien–Dindo classification (CDc). Logistic regression estimated odds ratios (OR) and 95% confidence intervals (CI) for endoscopic recurrence (ER), defined as Rutgeerts score &gt;1. The ETE was set as the reference. Artificial Intelligence (AI) were not used in the production of this abstract.

Results
Thirty-eight patients (18 females, 47.4%) were included, 14 in ETE, 10 in STS, 14 in Kono-S. No preoperative differences were observed. Median surgery durations were 151 minutes for ETE, 142 for STS (p=0.78), and 169 for Kono-S (p=0.09). Complication rate did not significantly differ. Median hospitalisations were 6.5 days for ETE, 6 for STS (p=0.85), and 6 for Kono-S (p=0.70). Neither Kono-S nor STS showed a higher risk of ER compared to ETE, with OR=1.13 (95%CI=0.21-6.16) for STS and OR=0.41 (95%CI=0.09-1.87) for Kono-S.

Conclusion
Kono-S and STS anastomoses demonstrated comparable complication rates to ETE, without significantly prolonging hospitalization or operation duration. Neither type of anastomosis was associated with an increased risk of ER.