bluuebunny/crossref_metadata_2025_split huggingface dataset:
P482 Diagnostic accuracy of contrast-enhanced ultrasound for fibrotic strictures of Crohn’s disease: a systematic review and meta-analysis of individual participant data
Authors: Sagami S , Miyatani Y , Nylund K , Wilkens R , Quaia E , Kataoka Y , Hibi T , Kobayashi T 
Published: January 2024

Abstract

Background
Crohn's disease (CD) often leads to the development of intestinal strictures, requiring effective differentiation between inflammatory and fibrotic for the optimal treatment strategies. Despite recent advances in drug development targeting fibrosis, current evaluation methods remain insufficient. Contrast-enhanced ultrasound (CEUS) is a promising modality for assessing vascularity and inflammation, yet its accuracy in fibrosis detection needs more validation.

Methods
A systematic review and meta-analysis were conducted using IPD to determine the diagnostic accuracy of CEUS in identifying intestinal fibrosis in CD. Our search included databases such as MEDLINE, EMBASE, and Web of Science up until March 23, 2023. Inclusion criteria required a confirmed diagnosis of CD and studies that evaluated the accuracy of CEUS parameters, including total area under the curve (AUC), wash-in AUC, wash-out AUC, peak enhancement, wash-in perfusion index, wash-in rate, wash-out rate, rise time, fall time, and mean transit time related to fibrosis in CD (Figure 1 (A)). The quality of included studies was assessed using the QUADAS-2 tool, with each study mandatorily using surgical specimen pathology as a reference standard in at least one instance.

Results
Our qualitative synthesis included eight studies encompassing 306 patients. These studies were generally assessed to have a high risk of bias. It is important to note that while peak enhancement and AUC were frequently examined across studies, neither parameter had established absolute cutoff values for the diagnosis of fibrosis. From the three studies where IPD was available, detailed data from 80 patients were included in the meta-analysis (colon n=11 and small bowel n= 69). Among them, 54 underwent surgical intervention with fibrosis being confirmed in 31. The highest diagnostic accuracy was observed for total AUC and wash-in AUC, with pooled sensitivity and specificity for predicting fibrosis at 0.86 (95% CI, 0.59–0.97) and 0.25 (95% CI, 0.03–0.76), respectively (Figure 1 (B)).

Conclusion
This meta-analysis with IPD pioneers the exclusive evaluation of CEUS for fibrotic strictures in CD. It reveals a significant risk of bias in the primary research and a notable absence of consensus on the CEUS parameters' threshold values for distinguishing fibrosis from inflammation. The observed low specificity highlights the need for innovative strategies in future research, such as integrating CEUS with techniques like elastography, to enhance the precision of fibrosis detection in CD. PROSPERO 2020 CRD42020214472. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020214472
P497 Malnutrition in inflammatory bowel disease: a correlation between clinical and nutritional parameters
Authors: Bezzio C , Brinch D , Vernero M , Ribaldone D , Scalvini D , Ciminnisi S , Sferruzza G , Cappello M , Saibeni S 
Published: January 2024

Abstract

Background
In recent years there has been a growing focus on malnutrition affecting patients with inflammatory bowel disease (IBD) due to its consequences, including increased risk of complications, reduced quality of life and response to treatment. Several screening tools are available to assess malnutrition, but none are specific to IBD. We assessed the accuracy of MUST and Saskatchewan IBD-Nutrition Risk tool (SaskIBD-NR) compared to malnutrition according to ESPEN criteria and the association between the mediterranean diet, clinical, biochemical, and anthropometric parameters and malnutrition.

Methods
This cross-sectional study was conducted at the tertiary IBD centres of Rho Hospital and Policlinico of Palermo between October 2022 and July 2023. Consecutive outpatients with an established diagnosis of IBD participated at the study. All patients completed the MUST and SaskIBD-NR tool. IBD type, age, smoking habit, disease features (location, behaviour,), steroid therapy, previous surgery, clinical and endoscopic disease activity and anthropometric data (BMI, waist and calf circumference, handgrip strength) were analysed. Mediterranean diet score was also administered to assess adherence to the Mediterranean diet.

Results
The study sample consisted of 158 IBD patients, 96/168 (60.7%) with Crohn’s disease and 62/168 (42.28%) with ulcerative colitis (UC) were enrolled. Median age was 46.5 (32-58). The handgrip strength mean values were 31.96±10.73 Kg and the calf circumference median values were 34 cm (32-37). The prevalence of malnutrition was 13.3 %; 16/96 (16.7%) were affected by CD and 5/62 (8.1%) by UC. A moderate correlation was found between the MUST and the SaskIBD-NR tool (P&lt;0.0001, r:0.581, Spearman). MUST have good performance in detecting malnutrition in terms of sensitivity (89%) and specificity (90%) and large area under the ROC curve (AUC 0.924, p&lt;0.001). SaskIBD-NR had lower accuracy (AUC 0.731;p=0.0002) and sensibility (695) but high NPV (94%). Calf circumferences had a strong accuracy in predicting malnutrition with AUC of 0.887 (p&lt;0.0001) and sensibility of 84%. At the multivariate logistic regression, waist circumference (OR 0,69 95% CI: 0,54-0,89; p=0,004) and albumin (OR 0,03, 95% CI 0,01-0,85; p=0.04) were independently associated with malnutrition.

Conclusion
Malnutrition is frequent in IBD patients. SaskIBD NR tool is less sensitive than MUST but could be useful to exclude non-malnourished patients. Anthropometric parameters such as calf and waist circumference and bioumoral parameters such as albumin should be assessed because they can predict malnutrition. Further studies are needed to validate this finding.
P516 Subcutaneous infliximab cut-off points in a large cohort of Spanish patients with inflammatory bowel disease and factors associated with long-term outcomes
Authors: Iborra M , Caballol B , Garrido A , Huguet J M , Mesonero F , Ponferrada A , Arias-García L , Boscá-Watts M M , Fernández-Prada S J , Brunet-Mas E , Gutierrez-Casbas A , Ordás I , Ruiz L , García de la Filia I , Escobar Ortiz J , Sicilia B , Ricart E , Nos P 
Published: January 2024

Abstract

Background
Evidence suggests that subcutaneous formulation of biosimilar infliximab (CT-P13) (SC-IFX) is capable to maintain clinical remission safely and to increase drug levels with a good acceptance in patients with Crohn’s disease (CD) and ulcerative colitis (UC) patients. The aims of this study were to evaluate which are the adequate drug concentration thresholds to maintain remission, and the factors involved in the long-term outcomes.

Methods
Multicentre, descriptive, and observational study including CD and UC patients who were going to be switched from IV-IFX to SC-IFX on the ENEIDA registry (a large, prospectively maintained database of the Spanish Working Group in IBD–GETECCU). All patients were on clinical remission at least 24 weeks before changing. Clinical activity, C reactive protein (CRP) and fecal calprotectin (FC), as well as trough levels were collected at baseline, at 12, 24 and 56 weeks.

Results
Two hundred and twenty patients were included 74 UC (34%) and 146 (66%) CD. IV-IFX was mainly administered due to active disease (73%) and perianal disease (12%) and for 52.5 months [range 25-89]. Pre-switch, 106 (49%) were with intensified IV-IFX dose and 97 (44%) were on concomitant immunomodulatory therapy (IMM). Many patients (172, 78%) remained with standard dose. While that SC-IFX levels significantly increased following the switch from IV to SC-IFX, clinical indices, CRP levels and FC remained unchanged during the 52 weeks of follow-up (figure).
SC-IFX levels were significantly higher between patients receiving the standard IV-IFX dose than those receiving the intensified IV-IFX dose, but CRP and CF were significantly lower at all observed points. IMM at baseline and perianal disease had no effect on IFX trough levels. However, the higher body mass index was associated with a decrease in IFX trough levels. Low levels before switching and high levels at week 24 were associated with better outcomes. SC-IFX levels of 16.6 μg/dl (11.4-21.6) at week 12 were significantly associated with deep remission (CRP&lt;5 mg/L and FC &lt;250 μg/g) (p=0.017). The suggested optimal SC-IFX cut-off concentration in all patients and in both UC and CD is shown in the table.
During 1 year of follow-up, 29 (13%) patients discontinued IMM, 19 (8.6%) had adverse events, 5 (2.3%) were hospitalised, 12 (23.2%) required surgery and 14 (6%) withdrawn SC-IFX. Global drug persistence was high (92% at week 52), but outcomes were worse in CD than in UC.

Conclusion
Switching from IV IFX to SC IFX has been shown to safely maintain long-term remission in patients with CD and UC. Our cut-off point for deep remission was 12.22 μg/g at week 12 and 13.23 μg/g at week 56.
P522 Post hoc analysis reveals limited efficacy of induction therapy in ileum only Crohn´s disease
Authors: Lundin P , Bock D , Harper A R , Strömbeck A , Beaton A , Marks D J B 
Published: January 2024

Abstract

Background
Crohn´s disease (CD) can affect any part of the GI tract, although has a predilection for the terminal ileum and colon. Approximately 30% of patients have inflammation restricted to the small intestine, another 30% have disease limited to the colon, and the remainder have a combination of small and large bowel involvement. Despite studies suggesting that ileal and colonic CD may be distinct disease phenotypes and might therefore respond differently to treatment, CD patients are typically enrolled into clinical trials irrespective of the site of gastrointestinal involvement. The aim of this systematic review and meta-analysis was to assess treatment efficacy in patients with small bowel disease.

Methods
Embase and PubMed databases were searched until October 2023 for randomised, placebo-controlled, clinical trials that reported induction efficacy, based on clinical remission (CDAI &lt;150), in ileal-only Crohn’s disease between 2010 and 2023. The following search criteria were employed: Crohn´s disease AND [2010-2023] AND (small bowel OR ileum OR ileal OR L1) AND (CDAI OR clinical remission AND induction AND placebo). Additional studies, not identified through this search strategy were also considered. Resultant studies were systematically reviewed before a random-effects meta-analysis was undertaken to assess induction efficacy, based on clinical remission, in ileal only CD.

Results
A total of 9 studies, involving 709 adult patients, were identified: two via Embase and PubMed; six from supplementary search materials; and one post-hoc analysis of brazikumab data (not published). The studies provided CDAI remission results by disease location subset. The induction treatment times ranged from 6-12 weeks, and both bio-naïve and bio-failure patients were included. The studies were relatively homogenous (I2 = 38.5%, Q = 13.0 (p-value = 0.112)) with a random effect meta-analytic estimate of difference versus placebo in CDAI remission of 2.1% (95% CI -6% to 11%). Two studies used clinical response (defined as ≥ 100 point decrease or score &lt; 150) as indicated in the figure.

Conclusion
This is the first systematic meta-analysis of treatment effects in ileal-only CD. The available evidence suggests treatment effect heterogeneity, with inferior outcomes in ileal disease versus a broader patient population with ileocolonic or colonic involvement. Previous systematic review1 on clinical remission after induction treatment demonstrate placebo adjusted values in the range of 12-20% in a no defined disease site population. This indicates the need for novel therapies with a mechanism of action directly tailored to heal the small intestine in patients with CD.
P527 Factors associated with choice of treatment regimen after the induction period in patients with Ulcerative Colitis treated with vedolizumab
Authors: Vuksanovic S , Spiric J , Toplicanin A , Nikolic A , Jovicic I , Djuranovic S , Popovic D , Dragasevic S , Sokic Milutinovic A 
Published: January 2024

Abstract

Background
Vedolizumab (VDZ) is a selective, alpha4-beta7 anti-integrin antibody used for treatment of inflammatory bowel diseases. The aim of our study was to investigate factors that influence the decision making and determine further therapeutic regimen after the induction period in patients with ulcerative colitis treated with VDZ and to identify predictors for early response to VDZ.

Methods
A retrospective study conducted at the Clinic for gastroenterohepatology, University Clinical Center Serbia included 89 patients with ulcerative colitis (mean age 47±15; 45 males) treated with VDZ (69 bio-naïve and 20 previously exposed to anti-TNF). Localization of disease, endoscopic score at the beginning of therapy, together with CRP and fecal calprotectin levels before the initiation of therapy and at week 14, and prior exposure to anti-TNF in relation to the treatment regimen at the end of the induction period were analyzed.

Results
After induction therapy total of 55 patients (61.8%) continued with standard dosing regimen, while in 34 patients (38.2%) shortening the interval to 4 weeks as optimization of VDZ treatment was prescribed. Patients whose treatment regimen was optimized at week 14 had had statistically significantly higher baseline CRP levels (p=0.025), as well as CRP levels at week 14 (p=0.002) and fecal calprotectin at week 14 (p=0.000), while there was no difference in the baseline fecal calprotectin between patients in standard and optimized regimen (p=1.000). There was no statistical difference in localization of disease and prior anti-TNF exposure between these two groups of patients (p=0.732 and p=0.449, respectively).

Conclusion
Higher CRP and fecal calprotectin levels at week 14 were determining factors for optimization of VDZ treatment. Higher levels of CRP before biologic therapy was started was associated with the increased need for optimized regiment at week 14. Extensive disease and prior anti-TNF exposure did not correlate with need for optimization of treatment after the induction period.
P541 Long-term follow-up results of darvadstrocel for complex perianal fistulas in patients with Crohn's disease: 3-year outcomes from a Japanese phase 3 study
Authors: Uchino M , Ikeuchi H , Ito T , Sakakibara Y , Nakaya R , Yamaguchi T 
Published: January 2024

Abstract

Background
Darvadstrocel (DVS), a suspension of expanded human allogeneic mesenchymal stem cells extracted from adipose tissue, is for the treatment of complex perianal fistulas in patients with Crohn's disease (CD). In Japan, DVS was approved in 2021 based on the Japanese phase 3 study Week 52 data combined with the pivotal study ADMIRE-CD data. Patients who participated in the Japanese study were monitored for 3 years, and we report the results at Week (W) 156.

Methods
This was an open-label, uncontrolled, phase 3 study (converted to a post-marketing clinical study after approval) conducted from March 2019 to February 2023 in Japan. Subjects had complex Crohn’s perianal fistulas (CPF) refractory to conventional treatments with a maximum of 2 internal openings (IO) and 3 external openings (EO). The fistula tract was curetted approximately 2-3 weeks before DVS administration, and a drainage seton was placed. On the day of administration, seton was removed, fistula tracts were curetted again, and IO was sutured. A total of 24 mL of DVS (including 120x106 cells) was administered around the IO and into the wall of fistula tracts. During the 2-year follow-up period after W52, medical and surgical treatment for CD and CPF was given as needed, and subjects were assessed every 6 months.

Results
22 Japanese patients were enrolled from 9 sites. The mean (SD) age was 36.4 (10.4) years, 63.6% were male, and the mean (SD) duration of CD was 11.3 (6.6) years. By W156, most frequently reported adverse events (AE) were anal fistula (7/22), proctalgia (7/22), and nasopharyngitis (6/22). New serious AE occurred after W52 were found in 9 subjects: COVID-19 (4), CD (2), perianal fistula, small bowel obstruction, premature labour (1 each). None of these were considered DVS-related. At W156, the combined remission rate (clinical and MRI assessment) was 15/22 (68.2%, 95% CI [48.7%, 87.6%]), clinical remission rate (clinical assessment) was 15/22 (68.2%, 95% CI [48.7%, 87.6%]), response rate (no drainage from ≥50% of treated EOs) was 20/22 (90.9%, 95% CI [78.9%, 100.0%]), and relapse rate (at least 1 relapse by W156 after achieving remission at W52) was 3/15 (20.0%, 95% CI [0.0%, 40.2%]). Mean Perianal Disease Activity Index (PDAI) total score (SD) was 4.8 (2.2) at baseline, which was decreased to 2.1 (2.1) at W52, and 1.7 (2.0) at W156. Mean Crohn's Disease Activity Index (CDAI) total score (SD) was 94.3 (60.1) on the day of administration, which was decreased to 73.7 (73.6) at W52, and 71.4 (51.2) at W156.

Conclusion
This is the first prospectively observed clinical outcomes in CPF for 3 years after DVS administration. There were no new safety findings, and fistula remission observed at W52 was maintained until W156.
P545 Long-term efficacy of ozanimod up to 3 years in patient response subgroups identified using group-based trajectory modelling
Authors: Schreiber S W , Feagan B G , Sands B E , Rieder F , Torres J , Liu Z , Jain A , Poehler A M , Wu H , Osterman M T , Abreu M T , Dulai P S 
Published: January 2024

Abstract

Background
Ozanimod is approved in multiple countries for the treatment of adults with moderately to severely active ulcerative colitis (UC). A previous post hoc analysis of individual outcomes in the phase 3 True North trial (NCT02435992) identified 5 groups of patient-response trajectories to ozanimod using group-based trajectory modeling (GBTM) and found that populations with fast response had higher rates of disease control, including patient-reported intestinal symptoms and objective measures of disease activity. This analysis of the True North open-label extension study (OLE; NCT02531126) evaluated the durability of ozanimod in the 5 groups for up to 3 years in the OLE (Week [W] 142).

Methods
In patients who entered the OLE from the 5 patient groups (Group 1 [super-response], Group 2 [sustained improvement], Group 3 [partial improvement], Group 4 [fast rebound], and Group 5 [slow rebound]), symptomatic endpoints were evaluated throughout the OLE until W142. Clinical and mucosal endpoints were evaluated at OLE W46, W94 and W142. Efficacy endpoints were evaluated using nonresponder imputation analysis.

Results
The percentage of patients who continued into the OLE was similar among the 5 trajectory groups, but higher proportions of patients in Groups 1–3 completed W52 before entering the OLE (Group 1 [84.2%], Group 2 [85.9%], Group 3 [86.7%], Group 4 [32.0%], and Group 5 [28.6%]). Notably, more patients from Groups 1 (60.6%), 2 (62.3%), and 3 (60.0%) completed OLE W142 than those in Groups 4 (20.0%) and 5 (26.3%). More patients in Groups 1–3, with the highest rates in Group 1, retained symptomatic response and remission through OLE W142 with continuous ozanimod treatment compared with those in Groups 4 and 5 (Figure). Higher proportions of patients in Groups 1–3 achieved and sustained response in all clinical and mucosal outcomes at OLE W46, W94, and W142 compared with Groups 4 and 5 (Table).

Conclusion
This analysis showed that personalized patient trajectory response-based modeling distinguished patients in terms of long-term outcomes. Specifically, patients with more robust patterns of response (Groups 1–3, especially Group 1) had higher sustained rates of symptomatic, clinical, and mucosal efficacy for up to 3 years of ozanimod treatment in the OLE than patients with less robust response patterns (Groups 4 and 5).
P550 Short and long-term outcomes after acute severe ulcerative colitis in adults: A 12 year Canadian experience in the post biologic era
Authors: Vuyyuru S , Alphonsus L , De Silva T A , Archer M , Solitano V , Guizzetti L , Crowley E , Ponich T , Beaton M , Gregor J , Yan B , Sey M , Jairath V 
Published: January 2024

Abstract

Background
Patients with acute severe ulcerative colitis (ASUC) are at increased risk of colectomy following an episode of acute severe exacerbation. Medical rescue therapy in steroid non-responders has reduced the need for emergency colectomy. However, impact of biologics on longer-term colectomy risk is unclear.

Methods
A retrospective cohort study of adult patients aged ≥18 years hospitalized with acute exacerbation of UC requiring hospitalization and managed with intravenous corticosteroids between 2010 and 2022 at two regional hospitals in London, Ontario, Canada. Steroid non-response was defined as requirement of medical rescue therapy or colectomy.

Results
A total of 264 adults hospitalized with ASUC were included in the analysis (male: 51.1% [n=136], mean age at admission: 40.8±17.8 years). The majority had extensive colitis (71.3% [n=169]) at the time of diagnosis. 46.3% (n=118/255) presented within one year of disease onset and 23% (n=61) had ASUC as their first presentation with UC. 25.7% (n=66/257) of patients had prior purine analogues and 23.3% (60/257) had previous biologics prior to ASUC presentation. After admission, 55.7% (n=147) responded to intravenous corticosteroids. Of the steroid non-responders, 37.5% (n=99) patients were managed with infliximab rescue therapy and only one patient received tofacitinib rescue therapy. Median CRP, stool frequency and Lindgren index score were statistically significant between steroid responders and non-responders (Table 1). A higher proportion of steroid non-responders had prior exposure to biologics or tofacitinib compared to steroid responders (31.9% vs 16.3%, p&lt;0.01). On multivariate analysis for various factors predicting steroid non-response, assessment by Oxford criteria on day 3 was the only factor that was statistically significant (odds ratio 4.70 (95% CI 1.06-20.8), p = 0.04). Oxford criteria on day 3 had a sensitivity, specificity of 58.6% and70.8%, respectively for predicting steroid non-response. 8% (n=21) required colectomy during index admission. An additional 13% (n = 32) underwent colectomy within 12 months of discharge, for which there was no difference between steroid responders and non-responders (12.2% vs 14.7%). The short term (3 months following discharge) and long-term (3-12 months following discharge) colectomy rates following discharge were 8% (20/245) and 5.4% (12/223) respectively. Hospitalization with UC exacerbation rate following discharge was 17% (38/223).

Conclusion
8% of patients admitted for ASUC require colectomy during the same admission and additional 13% required colectomy within 12 months of discharge. Despite a high initial response to corticosteroids, long term colectomy rates and re-hospitalization rates remain high.