bluuebunny/crossref_metadata_2025 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

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

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<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<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<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

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<5 mg/L and FC <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

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 <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 < 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

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

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

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

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<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.
P554 Assessment of corticosteroid prescribing trends and appropriateness for management of Inflammatory Bowel Disease in a secondary care centre in New Zealand
Authors: Hajelssedig O , Clark E , Edward P , Kenrick K , Inns S
Published: January 2024

Background

Corticosteroids are commonly used for inducing remission in Inflammatory Bowel Disease (IBD) but are considered ineffective for long-term maintenance1. Evaluating the appropriateness of corticosteroid usage is crucial in optimising IBD management given their common adverse effects.

Methods

This study aimed to assess the appropriateness of corticosteroid usage for patients with IBD in a secondary centre in New Zealand, using international standards2,3.

A retrospective records’ audit was conducted in 2020, encompassing all IBD patients encountered in Nelson Hospital from 2005 to 2020. Ethical approval was obtained beforehand. The primary outcome measure evaluated was the appropriateness of corticosteroid prescriptions, in accordance with established international standards (UK2 and ECCO3). Key criteria included dosage (strength and/or duration), patient counselling on side effects and alternatives.

Results

We studied a group of 613 IBD patients with an average age of 55, comprising 311 males and 302 females. Crohn's Disease was the predominant diagnosis (297 cases), followed by Ulcerative Colitis (252 cases) and Indeterminate Colitis (64 cases). Of the patients included in the audit, 51.4% (315 out of 613) were prescribed steroids during the 15-year study period. Of the 315 total prescriptions, 52.1% (163) were considered inappropriate. Among these, 28.6% (90) were excessively long courses, 23.5% (74) were due to under-dosing or multiple short courses, and 6.3% (20) were because of corticosteroid dependence. Out of a total of 315 prescriptions, Gastroenterologists issued 36.5% (115), while General Practitioners were responsible for 24.1% (76). The remaining prescriptions were divided among General Surgery (9%), General Medicine (6%), and the Emergency Department (5%).

Conclusion

Corticosteroid prescribing for IBD patients in this secondary centre in New Zealand deviated from international guidelines, primarily in terms of dose and duration. It’s vital to adopt accessible, customized guidelines and enhance quality measures to ensure IBD patients receive evidence-based corticosteroid treatment when needed.

References

1-Ford AC, Bernstein CN, Khan KJ, et al. Glucocorticosteroid therapy in inflammatory bowel disease: systematic review and meta-analysis. Am J Gastroenterol 2011;106:590-599; quiz 600.

2- Mowat C, Cole A, Windsor A, et al. Guidelines for the management of inflammatory bowel disease in adults. Gut. 2011;60:571-607.

3-Gomollon F, Dignass A, Annese V, et al. 3rd European evidencebased consensus on the diagnosis and management of Crohn’s disease 2016: part 1: diagnosis and medical management. J CrohnsColitis. 2017;11:3-25
P558 Clinical Effectiveness and Safety of Vedolizumab vs. Infliximab in Biologic-Naïve Ulcerative Colitis Patients: A Brazilian Real-World Multicentric Observational Study
Authors: Ferreira S , Chebli J M F , Parra R , Yukie Sassaki L , de Mello M K , Luporini R L , Chebli L A , Firmino Nóbrega F J , da Silva B C , Dutra R D M , de Oliveira Vasconcelos J R , Moraes Sales M P , Féres O , Parente J M L , Troncon L E D A
Published: January 2024

Background

Vedolizumab (VDZ) and infliximab (IFX), are considered first-line agents in the treatment of moderate to severe Ulcerative Colitis (UC). However, there are no head-to-head studies comparing the relative effectiveness of the two agents, and Real-world data on the effectiveness and safety of VDZ and IFX in UC are lacking in the Brazilian population. We aimed to compare effectiveness and safety of VDZ to IFX in Biologic-naïve UC patients.

Methods

We conducted a multicenter retrospective cohort study, including patients with moderate to severe UC (Total Mayo score 6-12, with an endoscopic subscore of 2 or 3) who treated with VDZ or IFX. The primary endpoints were: clinical remission, defined as a partial Mayo score (PMS) ≤2, endoscopic remission (endoscopic Mayo subscore of 1 or 0) and steroid-free clinical remission at week 52. Secondary endpoints included; clinical response at weeks 12 and 26, need for drug optimization, adverse events (AEs), need for hospitalization and colectomy, loss of response and biochemical remission (C-reactive protein [CRP] ≤ 0.5 mg/dl and/or fecal calprotectin [FC] ≤ 150 mcg/g) at week 52.

Results

A total of 174 UC (79 VDZ and 95 IFX) patients were included. Clinical remission and endoscopic remission at week 52 were achieved by 56 (70.8% vs 68.4%, p= 0.44) and 46 (58.2% vs 55.7%, p=0.18) of VDZ and IFX patients, respectively. Steroid-free clinical remission at week 52 was 84.2% and 54.1% in the VDZ and IFX group, respectively (p = 0.03). Clinical response at weeks 12 and 26 was reached in 80.0% vs 76.2%, p = 0.74 and in 71.4% vs 77.3%, p = 0.71 in the VDZ and IFX group, respectively. The need for drug optimization was higher for IFX than for VDZ (36.8% vs. 21.5%, p = 0.03). The incidence of AEs (26.3% vs 12.6%, p=0.03) and need for hospitalization (26.3% vs 11.4%, p=0.02) were higher for IFX than to VDZ patients. Secondary loss of response was similar in the two groups (16.4 % for VDZ and 16.8% for IFX, p = 1.00). Biochemical remission at week 52 was 75.0% for VDZ, and 63.9% for IFX, respectively (p=0,42).

Conclusion

In this real-world study VDZ and IFX had similar efficacy in inducing clinical remission, endoscopic remission, clinical response and biochemical remission at week 52. Compared to IFX, VDZ was superior in inducing steroid-free remission, in addition to having a better safety profile and less need for dose escalation. Both VDZ and IFX were effective treatment options in bio-naïve UC patients.
P559 Descriptive observational pilot study about the use of Virtual Reality (VR) in patients with Inflammatory Bowel Disease (IBD) and biological treatment
Authors: Díaz Molina R J , Comesaña Castellar C , Crespi Rigo J , Radu Tomsa C , Quesada Bauzá P , Porcel Corral I , Ginard Vicens D
Published: January 2024

Background

Virtual reality (VR) is a neurosensory experience in which simulated images and spaces are created where a person has the sensation of being and being able to function within them. A high percentage of patients with Inflammatory Bowel Disease (IBD) receive intravenous biological treatments in a day hospital (HDD) regime. VR has been used in some fields of medicine, such as Oncology, demonstrating its usefulness in reducing chronic symptoms such as pain or anxiety. However, we don’t have any literature demonstrating the applicability of VR in IBD.

Methods

Descriptive observational pilot study based on an initial cohort of 87 patients obtained from the HDD of the IBD Unit. Satisfaction and acceptance of VR through the use of 3D glasses and the reduction of negative symptoms during intravenous biological treatment in patients with IBD in HDD have been assessed.

Results

43 patients (52.4%) used VR and completed the study. The mean age was 45.3 years. The validated IBDQ-32 questionnaire on quality of life in IBD obtained a mean score of 169 points (range: 32-224). In the comparative analysis of the results of the questionnaires before and after the use of VR, a statistically significant improvement was observed in the patients' view of the ability of VR to achieve a reduction in stress (65% patients improve; p: 0.0021) and pain (VAS, 54% p. improve; p<0.05) during treatment. Likewise, with the applicability of VR in other areas of medicine (53%; p: 0.05) and with the possibility of improving well-being during the stay in the HDD (56%; p: 0.0014). No side effects were reported with the use of the 3D glasses.

Conclusion

The use of VR could be a useful complementary tool to improve the stay of patients with IBD on HDD during treatment with intravenous biologic drugs. To this end, we believe it is appropriate to complete our research and obtain more data through other studies along the same lines.
P560 The impact of reactive point-of-care drug level measurement on the medium-term course of inflammatory bowel disease
Authors: Ivány E , Farkas B , Resál T , Bacsur P , Bálint A , Farkas K , Molnár T
Published: January 2024

Background

First generation of biologicals (infliximab (IFX) and adalimumab (ADA)) has revolutionised the treatment of patients with Crohn’s disease (CD) and ulcerative colitis (UC), however, primary resistance or loss of efficacy are serious clinical challenges. Although there is currently insufficient evidence to recommend for or against the use of therapeutic drug monitoring to improve clinical outcomes, the determination of IFX and ADA levels with point-of-care tests (POCT) is fast, simple and can be a helpful tool to guide the therapy. Our aim was to evaluate the impact and duration of IFX and ADA level measurement with POCT on the medium-term course of the disease.

Methods

In our retrospective study we enrolled patients with UC and CD who were treated at our department with IFX or ADA and underwent a reactive drug level (DL) measurement which was carried out with POCT method between October 2021 and May 2023. We examined the types of therapeutical decision (dose intensification, switch or swap) were performed knowing DL and how the changes have affected the half-yearly outcome. Laboratory findings such as C-reactive protein (CRP), iron, albumin, haemoglobin, platelet, stool calprotectin level and calculated disease activity indices, Crohn’s disease activity index (CDAI), Harvey-Bradshaw Index (HBI), partial Mayo score and Simple clinical colitis activity index (SCCAI) were analysed at baseline and after 6 months.

Results

99 patients were enrolled; median age was 37 years (IQR 29-51 years). Baseline characteristics are shown in table 1. In 46 cases the drug level was subtherapeutical while in 53 cases was in normal range. At baseline patients with low drug level had significantly higher CRP (22.09 vs 10.7 mg/l, p=0.026), platelet count (344.6 vs 272.8 G/l, p=0.004) and significantly lower iron level (12.28 vs 15.6 umol/l, p=0.033) compared to patients with normal drug level while there was no difference between the activity indices (CDAI p=0.091; HBI p=0.187; SCCAI p=0.830; pMayo p=0.662) within the two groups. 70% of the patients in the low DL group had a therapeutic change: in 52% dose increase, in 13% switch, and swap in 15%. Changes in the therapy were significantly more frequent in the low DL group (p<0,0001). The difference in baseline CRP and iron level between the two groups was no longer detectable at month 6 (CRP 7.55 vs 8.7 mg/l, p=0.669, iron 14.1 vs 15.6 umol/l, p=0.325). All activity indices were significantly lower in low DL group at month 6 compared to baseline (CDAI p=0.022; HBI p=0.016; SCCAI p=0.047; pMayo p=0.046).

Conclusion

The drug level monitoring with POCT affected the decision-making process and presented beneficial effect for medium-term and helped to achieve stride therapy goals.
P563 Nutritional screening in patients with inflammatory bowel disease: a challenge in the timely diagnosis of malnutrition and sarcopenia
Authors: Parra Izquierdo L V , Orduz-Diaz G , Frías-Ordoñez J , Hoyos-Rondon S , Reatiga-Pedraza A , Sarmiento-Navarro J , Bohorquez L E , Cano D F , Pinto O , Duarte A , Florez-Sarmiento C , Cuadros C , Garces J , Acevedo J J , Barco A G , Flechas-Amaya S M
Published: January 2024

Background

Malnutrition is prevalent in inflammatory bowel disease (IBD) and has been reported in up to 70% in patients with active disease and 38% in patients in remission, being related to sarcopenia, so different tools have been proposed for the nutritional screening of these patients taking into account the importance of early intervention avoiding consequences related to altered body composition such as inadequate response to treatment and poor quality of life, but the evidence in IBD patients is still unclear and there are no studies in Colombian IBD patients. Therefore, the aim of this study is to describe the nutritional status of patients using multiple nutritional screening and assessment tools.

Methods

Descriptive observational cross-sectional study in patients diagnosed with IBD with clinical activity, by applying nutritional screening tools such as the Malnutrition Universal Screening Tool (MUST) and the Malnutrition Inflammation Risk Tool (MIRT) to determine their nutritional status and degree of sarcopenia.

Results

Nutritional screening was performed in 20 patients with Inflammatory Bowel Disease, with mild to moderate clinical activity of the disease; patients in clinical remission were excluded. Sixty percent were men and 40% women; with an average age of 44.5 years, 19 years as minimum age and 73 years as maximum age. Taking into account the Malnutrition Universal Screening Tool (MUST), 30% have a high risk of malnutrition, with a higher percentage in men. On the other hand, the MIRT (Malnutrition Inflammation Risk Tool), which evaluates BMI, showed that 25% have a score greater than or equal to 3, which indicates a risk. In addition, and 40% of the population underwent nutritional status assessment in order to rule out sarcopenia. Muscle strength, muscle mass and muscle function were assessed and 25% of this population were diagnosed with sarcopenia and another 25% with possible sarcopenia.

Conclusion

Patients with IBD are at increased risk of malnutrition, This is the first Colombian study to approach the nutritional assessment of IBD patients with mild to moderate disease activity using nutritional screening tools such as the Malnutrition Universal Screening Tool (MUST) and the Malnutrition Inflammation Risk Tool (MIRT), showing that up to one third of patients are at high risk of malnutrition and 50% have a diagnosis or possible diagnosis of sarcopenia, which is slightly lower than that described in the literature, However, it does raise awareness of the importance of nutritional screening in IBD patients as these alterations have been shown to be associated with increased hospitalisation requirements, number of disease flares and associated complications.
P566 Maintenance vedolizumab treatment in pediatric IBD: 54-week follow-up of the prospective multicenter VEDOKIDS study
Authors: Atia O , Shavit-Brunschwig Z , Focht G , Lev-Tzion R , Stein R , Broide E , Urlep D , Hyams J , Weiss B , Aloi M , Assa A , Russell R K , Turner D
Published: January 2024

Background

Prospective long-term data on vedolizumab (VDZ) in children with Crohn’s disease (CD) and ulcerative colitis (UC) are lacking. In this prospective, multicenter cohort study, we aimed to evaluate the effectiveness and safety of maintenance therapy with VDZ in pediatric CD and UC.

Methods

Children commenced on VDZ were followed at baseline and 2, 6, 14, 30 and 54 weeks thereafter. Serum for drug levels and stool for calprotectin were repeatedly obtained. The primary outcome was sustained steroid-free remission (SSFR), defined as clinical remission )PUCAI<10 or wPCDAI<12.5) without steroids/EEN at both 30 and 54 weeks, analyzed under the ITT principle.

Results

139 children were enrolled (77 [55%] UC, 62 [45%] CD; age 14.9 years (IQR 12.0-16.6). Of the 119 (86%) children >30kg, 110 (92%) received a dose of 300mg; 20 (14%) weighed<30 kg and received a dose of 8.3mg/kg (IQR 7–10.3). Week-54 remission rate was 52% in UC and 37% in CD; SSFR rates were 42% and 24%, respectively (OR 2.2 [95%CI 1.1-4.7] Figure). SSFR rate was numerically higher in isolated colonic CD than in ileal disease (5/11 [45%] vs 10/49 [20%], OR 3.3 [95%CI 0.8-12.9]; p=0.08). Infusion interval was shortened in 22 children (10 [13%] UC, 12 [19%] CD), of whom none achieved SSFR.

SSFR rate was higher in week-6 responders compared to non-responders in UC (51% vs 27%, OR 2.9 [1.1-7.7]) and CD (35% vs 14%, OR 3.4 [95%CI 0.95-12.4]), similar to the week-14 figures (UC: 50% vs 22%, OR 3.6 [1.2-11.1]; CD: 36% vs 8%, OR 6.2 [1.3-30.8]). SSFR was eventually achieved in 49% of UC children having mild disease at week-6 and 14% with moderate-severe disease (OR 5.8 [95%CI 1.2-28.2]); the corresponding rates in CD were 31% and 0% (p=0.02).

In multivariable models, the best predictors in CD were lower wPCDAI at baseline (AUROC 0.88 [95%CI 0.79-0.96]; optimal cutoff 25 (sens/spec 76%/80%)) and at week 6 (0.90 [0.82-0.98]; optimal cutoff 17.5 (80%/87%)). In UC, the best predictors were PUCAI at week 6 (0.70 [0.57-0.82]; optimal cutoff 10 (64%/57%)) and at week-14 (0.78 [0.67-0.89]; optimal cutoff 5 (76%/60%; Table).

In children <30kg, SSFR was associated with week 6 drug levels >30ug/mL, not reaching statistical significance (3/6 [50%] vs 1/8 [13%], OR 7.0 [95%CI 0.5-97]). By week 54, 197 adverse events were recorded, of which were VDZ-related in 8 (5.8%) children, and in 2 (1.4%) led to stopping VDZ; none were severe. There was 1 lymphoma case judged to be unrelated to VDZ.

Conclusion

VDZ was effective for maintaining remission, more so in UC and in colonic CD. The likelihood of eventually achieving SSFR was very low in children with moderate-severe disease or those not showing response at week-6, particularly in CD.
P583 Infliximab Monitoring in Crohn's Disease and Development of Neural Networks Using Clinical Variables to Predict Disease Activity and Immunogenicity
Authors: Gomes L E M , Genaro L M , Castro M M , Pascoal L B , Ricci R L , Silva F B C , Camargo M G , Bonfitto P H L , Ayrizono M L S , Azevedo A T , Leal R F
Published: January 2024

Background

Infliximab (IFX) is a biological drug that inhibits the action of tumor necrosis factor-alpha (TNFα), a pro-inflammatory cytokine enrolled in the pathogenesis of Crohn's disease (CD). Trough-level drug monitoring (TDM) has been increasingly used in clinical practice to optimize biological therapy and improve precision medicine. Therefore, this study aimed to analyze the serum level of IFX and antidrug antibodies (ADA) in active and in remission CD patients and develop prediction models via neural networks using a combination of clinical variables.

Methods

Seventy-five CD patients who underwent IFX therapy in the maintenance phase were included. Disease activity was defined by endoscopic and/or radiological criteria, comprising remission (CDR) and active (CDA) groups. Serum IFX levels were measured by ELISA (Promonitor ®) and rapid lateral flow test (Quantum-Blue®). ADA was measured using ELISA (Promonitor ®). For statistical analysis, a non-parametric test was used, with adopted p≤0.05. To create a prediction model, four sets of neural networks were constructed for the following output variables: remission/activity, presence or not of ADA, therapeutic level according to ELISA, and therapeutic level according to the lateral flow test. The neural networks and ROC curves were designed using the Keras package in Python software. The study was approved by the Research Ethics Committee.

Results

No differences were observed in the IFX level when comparing the CDA and CDR groups in both tests (p> 0.05). There was no statistical difference in IFX levels according to the use of immunosuppressants (IMS) (p>0.05). ADA levels > 5AU/mL were detected in only 11 (14.6%) patients. All patients with positive ADA had infratherapeutic IFX levels in both tests, and 72.7% were on combination therapy with IMS. Of the 4 neural networks developed, two, whose output variables were “remission/activity” and “presence or not of ADA,” showed excellent performance, with AUC ranging from 82% to 92% and 100%, respectively.

Conclusion

The introduction of IFX monitoring may allow more individualized and precise therapeutic management. Regarding the performance characteristics of the neural networks, an AUC >80% was evident in two of them. Through clinical and non-invasive laboratory variables, disease activity was determined. Furthermore, the finding of combinations of variables that determine the ADA level, and at the same time not having demonstrated good models for IFX serum level measurement, means that the latter continues to be necessary for clinical practice. Otherwise, ADA levels, which indicate immunogenicity, can be predicted by non-invasive clinical variables.
P584 Complication rates after two-stage vs three-stage restorative proctocolectomy with ileoanal pouch construction in the era of biologics
Authors: Doyon F , Saifi M , Doyon A , Kienle P
Published: January 2024

Background

Patients with proctocolectomy and ileoanal pouch construction typically undergo a two-stage or three-stage surgical procedure, depending on the general condition and recent immunosuppressive therapy. Our single center database prospectively records all surgeries performed since 2021 and retrospectively of patients before this year. Complications are registered by Clavien-Dindo classification.

Methods

All patients with two-stage or three-stage proctocolectomy and ileoanal pouch construction were identified from the database. The prevalence and severity of complications was analyzed according to Clavien-Dindo, with scores of 3 and above classified as severe complication. Patients were grouped by having either one or more severe complications or none at any surgical procedure.

Results

102 patients were identified from the database, of those 44 (43%) had a two-stage procedure and 58 (57%) a three-stage procedure.

In the three-stage group, 25 (43%) patients were on active systemic corticosteroid therapy at the time of the first surgery compared to 0 patients in the two-stage group (p<0.001). Biological therapy within the last 3 months before the first surgery was received by 35 (60%) of the patients in the three-stage group versus 16 (36%, p=0.016 ) in the two-stage group.

The three-stage procedure resulted in 11 out or 58 patients (19%) having at least one major complication compared to 3 out of 44 patients (7%) of the group with two-stage approach (p=0.077).

Conclusion

There is a trend towards a higher major complication rate in patients operated by a three- versus a two-stage approach in restorative proctocolectomy. This may be due to a selection bias as patients undergoing a three-stage procedure had significantly more often steroids at the time of first surgery and significantly more often biological therapy three months before the first surgery. Further data collection and then multivariate analysis including further risk factors, need to be done in order to better define the preferable individual surgical strategy.
P594 One-year success rates of targeted therapy in Ulcerative Colitis patients revisited
Authors: Creemers R , van Andel E , Wintjens D , van Bodegraven A
Published: January 2024

Background

Multiple new treatment options have been introduced in Ulcerative Colitis (UC) in recent years, leading peers to recommend a treat-to-target treatment approach, including mucosal or even histopathological healing. Patient-reported outcomes, and explicitly those validated on subjective patient-based values, are most commonly neglected in evaluating long-term treatment outcome while being of great importance in defining treatment success.

We re-examined registration and prospective trials with at least one year follow-up to estimate chance of beneficial outcome for patients using the most modern, though surely most expensive, medication. We compared endoscopic improvement and improvement on patient-reported outcomes in the long-term follow-up of new drug therapies in biological naïve patients as a marker for treatment success.

Methods

We assessed long-term endoscopic outcome measures and patient-reported outcomes measures in major registration trials of new biologicals and advanced small molecules in the period 2000-2023 by examination of PubMed. In these trials almost all UC patients had to be 5ASA-, corticosteroid- and/or immune suppressive refractory before inclusion in study.

Results

In figure 1, an overview is shown of long-term endoscopic and PROM improvement endpoints in major registration trials.

When focusing on endoscopic improvement or mucosal healing achieved by biologicals or advanced small-molecules in 5ASA-, corticosteroid- and/or immune suppressive refractory UC patients, most patients did not reach the pre-defined endpoint. In addition, although some registration trials report PROM data, improvement based on PROM’s is not consistently reported.

Conclusion

Reaching endoscopic improvement as definition of treatment success is unsuccessful in more than 60% of patients when accounted for placebo in all modern-era therapies for ulcerative colitis. As a consequence, when endoscopic treat-to-target treatment goals are strictly applied, surgery is warranted in more than 60% of UC patients within one year. Furthermore, lack of reporting of PROMs in registration trials complicate direct comparisons of alternative important endpoints.