bluuebunny/crossref_metadata_2025 huggingface dataset:
P421 The faecal biomarker LDN-051 is a novel tool for monitoring disease activity and therapeutic response in Inflammatory Bowel Diseases
Authors: Jójárt B , Resál T , Diána K , Molnár T , Bacsur P , Szabó V , Varga Á , Szántó K J , Pallagi P , Földesi I , Molnár T , Maléth J , Farkas K ,   HCEMM-USz Molecular Gastroenterology Research Group
Published: January 2024

Background

Crohn’s disease and ulcerative colitis, two forms of inflammatory bowel disease (IBD) require lifelong treatment and patient monitoring. Current predictors of relapse and therapeutic success have limitations, therefore there is high unmet need to identify novel biomarkers in IBD. Monitoring approaches for IBD are mostly invasive, time-consuming, and expensive. Therefore, a simple, rapid, and non-invasive test, with ability to differentiate IBD from other gastrointestinal conditions and to monitor disease activity, will have important clinical implications. Our previous mucosal cytokine profiling identified that Plasminogen activator inhibitor type 1 (PAI-1) is expressed in IBD patients with active disease, but not in control. Therefore, our aim was to assess the utility of PAI-1 in monitoring disease activity and therapeutic response of IBD patients in different biological samples.

Methods

Serum, biopsy and faecal samples were collected from 132 IBD patients and 30 controls without IBD. ELISA method was used to define the level of PAI-1 in the mucosa, serum, and faecal samples and the serum CRP levels were also determined. For the mucosal gene expression analysis qRT-PCR was used. The correlation and ROC analyses were applied to observe the relationship between the disease activity and PAI-1 level.

Results

The applied screening approach detected significant higher expression of PAI-1 in active IBD. We demonstrated that the serum, mucosal and faecal PAI-1 concentration was significantly elevated in IBD patients showing clinical and endoscopic activity. Additionally, in responder patients the initial PAI-1 level decreased significantly upon successful therapy, whereas it remained unchanged in non-responders. We also showed that faecal PAI-1 selectively increases in active IBD patients, but not in other organic gastrointestinal diseases. In addition, the stability analysis of faecal PAI-1 showed that the protein was detectable up to one week at room temperature and 4ºC. The serum, mucosal and faecal PAI-1 level showed positive correlation to the endoscopic activity. ROC curves demonstrated that faecal PAI-1 showed a relatively high power to distinguish between active and control patients. However, the serum CRP level no reflected to the therapeutic response.

Conclusion

Our results suggest that serum, mucosal and faecal PAI-1 expression reflects to the disease activity in IBD, which could be used to disease monitoring and possibly therapeutic response. The correlation between the faecal PAI-1 level and the endoscopic activity promotes that it could be used as a novel non-invasive disease specific faecal biomarker in the IBD diagnosis.
P447 Anti-αvβ6 integrin antibody as a novel serum biomarker for diagnosis of ulcerative colitis; a nation-wide multicenter validation study in Japan
Authors: Okabe M , Yamamoto S , Kitamoto H , Kuwada T , Shiokawa M , Yamazaki H , Seno H ,   UCV6 Dx Study Group
Published: January 2024

Background

There is no established diagnostic biomarker for ulcerative colitis (UC). Although we recently reported an anti-αvβ6 integrin antibody to diagnose UC, there is no large-scale validation study on this antibody to diagnose UC. This study aimed to validate the diagnostic value of anti-αvβ6 integrin antibody for UC in a nation-wide, multicenter cohort (UCV6-Dx Study).

Methods

We enrolled 1241 UC patients, 798 Crohn’s disease (CD) patients, and 207 other gastrointestinal disease patients from 28 Japanese high-volume referral centers. Anti-Integrin αvβ6 ELISA Kit (MEDICAL & BIOLOGICAL LABORATORIES CO., LTD., Tokyo, Japan) was used to measure the titer of anti-αvβ6 integrin antibody. The cut-off value was 1.64 U/mL (the mean +3SD of 83 serum samples from healthy volunteers determined by the manufacturer). The primary outcome was the diagnostic value of the anti-αvβ6 integrin antibody. Secondary outcomes were factors associated with false negative results in UC patients, factors associated with false positive results in non-UC patients, and the optimal cut-off values using receiver operating characteristic (ROC) analysis.

Results

The diagnostic sensitivity of the anti-αvβ6 integrin antibody in UC was 87.7% and the specificities were 82.0% in CD and 87.4% in other gastrointestinal diseases. Multivariate logistic regression analysis showed that false negative results in UC patients were associated with age at the time of sample collection [odds ratio (OR) 1.0242, p=0.034, 95% confidence interval (CI) 1.0018-1.0470], smoker (OR 2.5504, p=0.002, 95% CI 1.4216-4.5755), partial Mayo score (OR 0.8623, p=0.038, 95% CI 0.7495-0.9921), and advanced therapies (OR 0.5875, p=0.019, 95% CI 0.3765-0.9167) and false positive results in CD patients with disease location L2 (OR 2.6858, p=0.013, 95% CI 1.2323-5.8533). No factor was associated with false positive results in patients with other intestinal diseases. ROC analysis revealed that the optimal cut-off values estimated by the Youden method were 2.07 U/mL [area under the curve (AUC) 0.9003, sensitivity 85%, specificity 87%], and 1.78 U/mL (AUC 0.9206, sensitivity 87%, specificity 89%) for discriminating UC from CD and other gastrointestinal diseases, respectively.

Conclusion

The usefulness of anti-αvβ6 integrin antibody for diagnosing UC was validated in the Japanese large-scale, nation-wide multicenter study.
P456 Pragmatic trial design to compare real-world effectiveness of different treatments for inflammatory bowel diseases: the PRACTICE-IBD international consensus
Authors: Fantini M C , Fiorino G , Colli A , Laharie D , Armuzzi A , Caprioli F A , Gisbert J P , Kirchgesner J , Macaluso F S , Magro F , Ghosh S ,   The PRACTICE-IBD study group: Matthieu Allez Aurelien Amiot Raja Atreya Manuel Barreiro-de Acosta Livia Biancone Fabiana Castiglione María Chaparro Axel Dignass Glen Doherty Eugeni Domènech Walter Fries Jonas Halfvarson Uri Kopylov Sara Onali Daniela Pugliese Davide Giuseppe Ribaldone Simone Saibeni Edoardo Vincenzo Savarino
Published: January 2024

Background

Pragmatic studies designed to test interventions in everyday clinical settings can successfully complement the evidence from registration and explanatory clinical trials. The international consensus project PRACTICE-IBD was developed to identify essential criteria and address key methodological issues needed to design valid comparative pragmatic studies in inflammatory bowel diseases (IBDs).

Methods

Statements were issued by a panel of 11 European experts in IBD management and trial methodology on four main topics: (I) study design; (II) eligibility, recruitment and organization, flexibility; (III) outcomes; (IV) analysis. The consensus process followed a modified Delphi approach, involving two rounds of assessment and rating of the level of agreement (1 to 9; cut-off ≥7 for approval) with the statements by 18 additional European experts in IBD (Fig.1)

Results

At the first voting round, 25 out of the 26 statements reached a mean score ≥7. Following the discussion that preceded the second round of voting, it was decided to eliminate two statements and to split one into two. At the second voting round, 25 final statements were approved: 7 for study design, 6 for eligibility, recruitment and organization, flexibility, 8 for outcomes, and 4 for analysis (Table 1).

Conclusion

Pragmatic randomized clinical trials can address important questions in IBD clinical practice, and may provide complementary high-level evidence, as long as they follow a methodologically rigorous approach. These 25 statements intend to offer practical guidance in the design of high-quality pragmatic clinical trials that can aid decision making in choosing a management strategy for IBDs.
P472 A Real World Practice of Intestinal Ultrasound in the Monitoring of Disease Activity in Ulcerative Colitis
Authors: Kim K W , Lee C H , Lee T , Kim S , Han Y M , Lee H J , Yoon H , Kang H W , Im J P , Kim J W , Park Y S , Kim J S , Koh S J ,   Seoul National University Inflammatory Bowel Disease Research Network (SIRN)
Published: January 2024

Background

Intestinal ultrasound (IUS) has emerged as an important monitoring tool in the clinical course of ulcerative colitis (UC). Previously known factors about UC have been considered in terms of the associations with IUS. However, a few studies reported about the associations between the findings of IUS and clinical factors.

Methods

We performed a multi-center, cross-sectional study of patients with UC who received IUS and clinical exams including endoscopy simultaneously. The primary endpoint was the association between endoscopic disease activity as Mayo endoscopic score (MES) and IUS finding as Milan ultrasound criteria (MUC). The secondary endpoint comprised the various clinical factors associated with MUC. Patients with MUC<6.2 were defined as low MUC group and others as high MUC group.

Results

A total of 35 patients were enrolled in this study. The numbers of Low- and high-MUC groups were 23 and 12, respectively. The median age in each group was 41 and 53 years old. The portion of male sex in each group was 57% and 75%. There were no significant differences in terms of body mass index, onset age, disease duration, current medication such as 5-aminosalicylic acid, steroid, immunomodulator, and biologics and small molecules between both groups.

Compared with low and high MUC groups, endoscopic remission was more significantly associated with the low MUC group than the high MUC group (35% vs. 0, p = 0.032). In addition, the rate of disease activity ranged from remission to mild, as tolerable clinical activity, was also significantly higher in the low MUC group than the high MUC group (91% vs. 58%, p = 0.033). Other outcomes such as symptomatic remission, histologic remission, and biochemical response revealed similar rates between the two groups.

Conclusion

Low MUC of IUS in the patients with UC showed significant clinical association such as endoscopic remission and tolerable clinical activity. This study is now ongoing prospective research and further investigation into the relationship between IUS and clinical outcomes of UC will elicit robust results.
P502 Multimodal profiling of peripheral blood identifies proliferating circulating effector CD4 T cells as predictors for response to integrin alpha4 beta7-blocking therapy in patients with Inflammatory Bowel Disease
Authors: Horn V , Cancino C , Steinheuer L , Obermayer B , Fritz K , Siegmund B , Thurley K , Hegazy A N ,   TRR241 IBDome Consortium
Published: January 2024

Background

Despite the success of biological therapies in inflammatory bowel disease (IBD), patient management remains challenging due to a lack of therapy response predictors.

Methods

Here we prospectively sampled two cohorts of IBD patient cohorts receiving the anti-integrin α4β7 antibody vedolizumab. Samples were subjected to mass cytometry, single-cell RNA sequencing, single-cell V(D)J sequencing, serum proteomics, and multidimensional flow cytometry to comprehensively assess vedolizumab-induced immunological changes in the peripheral blood and their potential associations with treatment response.

Results

Vedolizumab induced changes in the abundance of both circulating innate and adaptive immune cell compartments and modified the T cell receptor diversity of circulating gut-homing CD4+ memory T cells. Through integration of multimodal parameters and machine learning, we identify that pretreatment activated proliferating CD4+ memory T cell abundance is associated with treatment failure, independent of clinical variables, thereby providing a reliable predictive classifier with significant implications for the personalized management of IBD patients.

Conclusion

Our study provides a comprehensive framework for assessing therapy response and understanding the mechanisms underlying resistance in chronic immune-mediated inflammatory diseases such as IBD. Identifying personalized treatment strategies based on individual patient characteristics, as exemplified by our "stratify to target" approach, can significantly improve IBD management.
P538 Platelet-rich stroma during surgery for treatment-refractory perianal fistulizing Crohn’s disease: long-term outcomes of a pilot study
Authors: Bak M , Witjes C , Arkenbosch J , Dwarkasing R , van Dongen J , Fuhler G , Schouten R , van der Woude J , de Vries A , van Ruler O
Published: January 2024

Background

Platelet-rich stroma (PRS), a combination of stromal vascular fraction and platelet-rich plasma, proved to be safe and feasible for the treatment of treatment-refractory perianal fistulizing Crohn’s disease (pCD). This study aimed to assess the long-term outcomes in patients with pCD treated with PRS.

Methods

Long term results from adult patients with pCD, who underwent fistula curettage, closure of the internal fistula opening and PRS injection, included in an earlier conducted pilot study (n=25) were assessed up to October 2023. The primary outcome was complete clinical closure at long-term follow-up (closure of all treated external opening[s]). Secondary outcomes comprised complete radiologic closure (absence of fluid-containing tracts on MRI), partial clinical closure (closure of ≥ 1 treated external opening[s]), recurrence (reopening of the external opening after complete clinical and/or radiological closure) and the need for unplanned re-intervention(s).

Results

The majority of the patients was female (56.0%)(mean age 34.4 years [SD: 0.9], and mean follow-up 3.7 years [SD: 0.6])(Table 1). 68% of the patients were concomitantly treated with a biological. During follow-up, ≥1 unplanned re-intervention(s) were necessary in 44% of the patients which were minor (e.g. incision and drainage) in the vast majority (83%)(Table 2). Complete clinical closure at long-term follow-up was reached in 88%. Complete radiologic closure was reached in 75% of patients. Partial clinical closure was reached in all patients (100%). Recurrence was reported in 8% of patients, all whom reached (partial/complete) clinical closure, whereas no recurrence was experienced in patients with complete closure on MRI. All patients with complete radiologic closure achieved clinical closure. Vice versa, patients with clinical closure achieved complete radiologic closure in 82% of the cases.

Conclusion

In this pilot study with treatment-refractory pCD patients treated in a tertiary referral center, all patients had benefit from surgical treatment and an additional injection of PRS. At long-term follow-up, treatment with PRS injection during surgery is promising as complete clinical and radiological closure is achieved in the majority of these patients. In addition, complete radiologic closure seems a valuable prognostic parameter for long-term success for fistula closure. Future (randomized) research is warranted to further assess the effectiveness of PRS in patients with pCD.
P612 Switching from intravenous to subcutaneous VEDOlizumab formulation in ulcerative colitis patients in clinical remission: the SVEDO Study, a multicenter IG-IBD study
Authors: Ribaldone D G , Parisio L , Variola A , Bossa F , Castiglione F , Marzo M , Piazza N , Aratari A , Savarino E V , Bodini G , Mastronardi M , Micheli F , Mazzuoli S , Ascolani M , Viganò C , Cappello M , Bezzio C , Ciccocioppo R , Scardino G , Sarli E , Pugliese D , Scaldaferri F , Napolitano D , Todeschini A , Geccherle A , Colaci N , Guerra M , Annese M , Testa A , Caiazzo A , Conforti F S , Festa S , Lorenzon G , Marra A , Magiotta A , Baccini F , Amato A , Vernero M , Caprioli F , Caviglia G P ,   Italian Group for the study of Inflammatory Bowel Disease (IG-IBD)
Published: January 2024

Background

The administration of biologic drugs in inflammatory bowel diseases (IBD) is increasingly moving from intravenous to subcutaneous formulations. Limited data is available on the effectiveness of subcutaneous vedolizumab in patients switching from long-term intravenous therapy. The aim of the study was to evaluate the efficacy and safety of vedolizumab subcutaneous administration after switching from intravenous administration in ulcerative colitis patients in corticosteroid-free clinical remission.

Methods

An observational, multicentre, prospective study was conducted by the Italian Group for the study of IBD in Italy (IG-IBD). Ulcerative colitis patients in clinical remission (pMAYO < 2) not receiving steroids for > 8 months before the switch, and with at least 6 months of follow-up were included. Switch from intravenous to subcutaneous vedolizumab was defined as successful in patients not experiencing a disease flare (pMAYO ≥ 2) or needing oral steroids or stopping vedolizumab during the 6 months of follow-up after the switch.

Results

One hundred sixty-eight patients were included. The switch was a complete success in 134 out of 168 patients (79.8%). In particular, vedolizumab retention rate was 88.7% at month six. No predictor of complete switch success was found at multivariate analysis. C-reactive protein and faecal calprotectin values did not significantly change after the switch (p = 0.07 and p = 0.28, respectively). Ten of the 19 patients who stopped subcutaneous formulation switched back to intravenous formulation, with a success in recapturing clinical remission in 80%. Twenty-two out of 168 patients (13.1%) experienced side effects while on subcutaneous formulation, including 4 cases of rheumatological side effects, 4 cases of injection site reactions, 3 allergic reactions, 3 cases of cancers.

Conclusion

Effectiveness of switching from intravenous to subcutaneous vedolizumab formulation in UC patients in steroid-free clinical remission is confirmed in a real-world setting.
P613 Dietary intervention as a novel tool to improve diagnostic accuracy of patency capsule in Crohn’s Disease patients
Authors: Talan Asher A , Lahat A , Ukashi O , Yablecovitch D , Engel T , Shachar E , Selinger L , Ungar B , Kopylov U , Eliakim R , Ben- Horin S ,   for the Israeli IBD Research Nucleus (IIRN)
Published: January 2024

Background

Patency capsule (PC) is recommended to confirm the patency of the small bowel before ingestion of video capsule endoscopy (VCE). However, in some patients non-expelled PC could be due to slow transit time and not due to small bowel stricture. We examined if dietary intervention during the PC could improve passed PC rate and reduce false positive results.

Methods

A retrospective study of patients who received diet-modified protocol of PC test, introduced into routine clinical practice on February 2023, compared with standard protocol. Dietary-modification comprised individualized dietary advice on the consumption of personally-conceived laxative foods after PC ingestion. Abdominal X-ray at 30 hours post-ingestion was performed to ascertain passage of PC in patients who did not see an intact PC in stool, followed by low-dose limited computed tomography (CT) in patients with evident PC on X-ray to assure passage to colon.

Results

A total of 52 Crohn's patients who ingested PC were included (median age 32.4, 28.8% with previous intestinal resection). 26 of the patients followed the dietary-modified personalized protocol and 26 followed the standard protocol. In total, 38/52 PC passed and 14/52 (26.9%) failed. Patients on dietary modification had significantly reduced rate of a failed PC compared to patients receiving standard protocol (7.7% versus 46.1%, respectively, odds ratio 0.1, 95% confidence interval 0.02-0.49, P=0.005). 12/14 patients with a failed PC underwent low-dose CT, which showed PC was in the colon (false positive PC) in 11/12 patients (92%, 9/11 in standard group, 2/11 in dietary group). All 11 patients with a passed PC in colon subsequently ingested a VCE without complications.

Conclusion

Majority of failed PC are falsely positive, stemming from slow-transit of PC in the colon. Personalized dietary intervention to promote colonic transit may serve as a novel practical tool to reduce false positive tests and improve the diagnostic accuracy of patency capsule.
P620 A cost-effective Inflammatory Bowel Disease flare management pathway utilising rapid access intestinal ultrasound and nurse-led triage to achieve hospital avoidance with increased patient satisfaction
Authors: Fernandes R , Khoo E , Harris H , Gilmore R , Khaing M , Begun J , An Y K ,   Mater IBD Research Group
Published: January 2024

Background

Timely inflammatory bowel disease (IBD) flare treatment improves outcomes, but quick differentiation from other symptom causes is challenging. We aimed to reduce unplanned hospital presentations with a novel IBD clinical care pathway (CCP) allowing appropriate early flare management, utilising nurse-led triage and objective assessment with rapid access intestinal ultrasound (RAIUS).

Methods

Prospective data collection from 15 November 2022 until 14 June 2023, including clinical outcomes, pre-specified criteria for healthcare utilisation impact, clinical coding data, and patient satisfaction surveys. A senior IBD nurse assessed patients using a symptom severity-based algorithm, utilising a modified partial Mayo score and Harvey-Bradshaw Index. Standardised blood and stool tests were collected. Based on clinical urgency, patients were discussed with their specialist, referred for RAIUS, or considered for planned hospitalisation if severe symptoms (bypassing emergency department (ED)).

Results

There were 211 episodes of care (EOCs), with 407 initial and follow up encounters. The median patient age was 34 (IQR 25-44), a majority female (66%), 54% with Crohn’s disease, and 61% bio-exposed. Most (78%, n=165) EOCs were for flare symptoms (mild 41% (n=69), moderate 49% (n=80), severe 10% (n=16)) and the remainder for non-flare concerns (n=46). Of those with flare symptoms, 36% (n=59) had medication optimisation for active disease (5% (n=11) started steroids), 41% (n=67) reassured of remission, 12% (n=19) aperients for faecal loading, 5% (n=8) referred for further investigations, 2% (n=4) seen urgently in colorectal clinic for perianal flare, 2% (n=3) electively admitted, and 3% (n=5) seen urgently in IBD clinic. RAIUS was performed in 56 EOCs (27%), showing active disease in 32% (n=18), response/remission in 43% (n=24), and faecal loading in 23% (n=13). After RAIUS, 52% (n=29) had IBD medication optimisation. Based on pre-specified criteria, unplanned hospitalisation was avoided in 10% (n=20) of EOCs, urgent clinic review avoided in 58% (n=123), and no direct impact in 32% (n=68), with a net saving of AUD$146418 (Figure 1). Clinical coding data showed lower hospital presentations (Figure 2). Only 7 patients (3%) had an unplanned hospital presentation within 30 days of CCP engagement (most after-hours) and 5 (2%) were seen urgently in IBD clinic. With the CCP, more survey respondents (n=60) were "satisfied" or "very satisfied" with the IBD service, increasing from 53% (n=32) to 85% (n=51).

Conclusion

Our novel CCP improved IBD care through timely assessment, with high patient satisfaction and cost savings. Better integration of nursing and intestinal ultrasound resources can improve IBD care.
P626 JNJ-77242113, an oral peptide selectively targeting the IL-23 receptor, demonstrates pharmacodynamic activity in rat and human colon tissue explants following oral dosing
Authors: de Leon-Tabaldo A , Strawn D , Chang L , Cheng X , Greving C , Knight B , Sendecki J , Sherlock J , Modi N B , Kannan A , Fourie A
Published: January 2024

Background

The interleukin (IL)-23 pathway is a pathogenic driver in psoriasis, psoriatic arthritis, and inflammatory bowel disease (IBD). There are currently no approved oral therapies selectively targeting the IL-23 pathway. JNJ-77242113 (JNJ-2113) is a targeted oral peptide that binds the IL-23 receptor with high affinity, and potently and selectively inhibits IL-23 proximal signaling and downstream cytokine production. Oral JNJ-2113 showed dose-dependent inhibition of IL-23–induced IL-17A production in rat blood and attenuated signs of disease in a rat colitis model. A Phase 1 study showed inhibition of IL-23–induced IFN-γ production in blood from participants dosed with JNJ-2113 (Fourie et al. ISID. 2023).

Methods

We evaluated IL-23–induced IL-22 expression in colon tissue after exposure to JNJ-2113 or JNJ-2100 (a tool molecule with similar affinity and potency). IL-22 mRNA was measured after IL-23 stimulation in rat colon biopsies treated with JNJ-2100 in vitro or in colon tissue from rats 6 h after oral JNJ-2100 dosing. Human colon explants from donors were treated in vitro with JNJ-2100 or JNJ-2113, stimulated with IL-23, and IL-22 mRNA was measured. Colon and rectum biopsies from healthy participants dosed for 10 days with oral JNJ-2113 or placebo in a Phase 1 study were obtained, stimulated with IL-23 ex vivo, and IL-22 mRNA was evaluated.

Results

Overall, inhibition of IL-23–induced IL-22 expression was observed in colon tissue exposed to JNJ-2100 or JNJ-2113. Dose-dependent inhibition of IL-22 expression was observed in rat colon biopsies exposed to JNJ-2100 in vitro. Colon explants from rats dosed with 0.3, 3, and 30 mg/kg oral JNJ-2100 showed dose-dependent inhibition of IL-22 expression (52%, 88% and 96%, respectively) compared with explants from rats treated with vehicle. Human colon explants exposed to JNJ-2100 or JNJ-2113 in vitro also showed dose-dependent inhibition of IL-23–induced IL-22 expression, with >90% inhibition at the highest doses. Importantly, in colon biopsies from Phase 1 participants dosed with oral JNJ-2113 versus placebo, significant inhibition of IL-23–induced IL-22 expression was seen (P<0.05), with an average of 65% and 66% inhibition observed in sigmoid colon and rectum biopsies, respectively.

Conclusion

These results demonstrate pharmacodynamic activity of JNJ-2100 in vitro and ex vivo in rat colon tissue, of JNJ-2100 and JNJ-2113 in vitro in human colon explants, and of JNJ-2113 in colon biopsies from healthy human volunteers. These data support development of JNJ-2113 for the treatment of IBD. Of note, a Phase 2b dose-ranging study has demonstrated clinical activity of JNJ-2113 in moderate-to-severe plaque psoriasis (NCT05223868).
P680 Comparative risk of serious infection with vedolizumab vs anti-TNF in Inflammatory Bowel Disease: Results from nationwide Swedish registers
Authors: Karlqvist S , Sachs M , Eriksson C , Cao Y , Montgomery S , Ludvigsson J F , Olén O , Halfvarson J ,   The SWIBREG Study Group
Published: January 2024

Background

The real-world comparative safety of vedolizumab in inflammatory bowel disease (IBD) remains uncertain. We aimed to assess the risk of serious infection in IBD patients treated with vedolizumab, compared to (i) those treated with anti-tumour necrosis factor (TNF) treatment and (ii) the general population.

Methods

In this nationwide cohort study, treatment episodes were identified from Swedish health registers (from 1 May 2014 – 31 December 2020). Patients were considered exposed from initiation of treatment until 90 days after discontinuation of treatment. We used Cox regression with propensity score-matched cohorts to estimate hazard ratios (HRs) for incident serious infection, defined as infection requiring hospital admission.

Results

After propensity score matching, the cohorts were not materially different at baseline with regard to demographic, disease and treatment characteristics (Table 1). During 1376 treatment-episodes in patients with Crohn’s disease, there were 5.18 (95%CI: 3.98-6.63) serious infections per 100 person-years (PY) with vedolizumab vs 3.54 (95%CI: 2.50-4.85) per 100 PY with anti-TNF; HR 1.72 (95%CI: 1.12-2.65; Figure 1A). When examining site-specific infections in Crohn’s disease, vedolizumab was associated with an HR of 2.47 (95% CI: 0.96-6.39) for serious gastrointestinal infections. Compared to the rate of 0.75 (95%CI: 0.59-0.92) serious infections per 100 PY in the general population, vedolizumab demonstrated an increased HR of 7.00 (95%CI: 5.04-9.72).

Across 1294 episodes among patients with ulcerative colitis there were 3.74 (95%CI: 2.66-5.11) serious infections per 100 PY with vedolizumab vs 3.42 (95%CI: 2.31-4.89) per 100 PY with anti-TNF, corresponding to HRs of 0.80 (95%CI: 0.47-1.36, Figure 1B) within the initial 1.1 years of treatment and 2.03 (95%CI: 0.65-6.32) after 1.1 years (follow-up truncated due to non-proportional hazards). In ulcerative colitis, there was no statistically significant association between vedolizumab treatment and any of the site-specific serious infections. Compared to the rate of 0.69 (95%CI: 0.53-0.87) serious infections per 100 PY in the general population, vedolizumab showed an increased HR of 5.45 (95%CI: 3.67-8.11).

Conclusion

Vedolizumab was associated with higher hazard ratios of serious infections compared to anti-TNF in Crohn’s disease, but not in ulcerative colitis. Nonetheless, in both IBD subtypes vedolizumab exhibited increased hazard ratios compared to the general population. These results underscore the importance of heightened clinical awareness of infections in vedolizumab-treated patients and may help clinicians understanding the optimal positioning of vedolizumab.
P681 Preliminary data from the Biologic and Partial Enteral Nutrition in Crohn’s Disease Study (BIOPIC)
Authors: White B , Jatkowska A , Campbell I , Brownson E , Short B , Clowe J , Seenan J P , Gaya D , Din S , Ho G T , Robertson E , Mowat C , Milling S , Macdonald J , Gerasimidis K
Published: January 2024

Background

Biologics such as adalimumab (ADA) are used to induce clinical remission (CR) in individuals with active Crohn’s disease (CD) but around 50% of patients actually achieve clinical remission. Exclusive enteral nutrition is also an effective induction treatment, but tolerability limits its use, especially in adults. This study aimed to assess the efficacy and tolerability of partial enteral nutrition (PEN) in combination with ADA compared to ADA monotherapy.

Methods

In this multi-centre (n=8) RCT (NCT04859088), adults with active CD (Crohn’s Disease Activity Index, CDAI ≥ 150) due to start ADA as their first-line biologic were randomised to either continue their habitual unrestricted diet (UD) or to replace half of it with PEN during their first 6 weeks of induction treatment Primary outcome clinical efficacy (i.e., clinical response, CDAI baseline decrease of ≥ 70 or CR, CDAI score <150) was assessed after 12 weeks of ADA initiation. Secondary outcomes included changes in inflammatory markers (faecal calprotectin, (FCAL), CRP) and quality of life (SIBDQ), at 3 (only FCAL), 6 and 12 weeks. To calculate adherence to PEN, used/unused tins were returned and compared to number provided. Analysis was performed using intention-to-treat analysis.

Results

32 participants (13 UD, 19 PEN) have completed the study; 29 (13 UD, 16 PEN) of whom completed the full 12 weeks of the study. Adherence rate to PEN was high (~96%). Clinical efficacy (response & remission) was UD: 92% vs PEN: 84%, p=0.490 at 6 weeks and UD: 85% vs PEN: 58%, p=0.11 at week 12. FCAL data was available for 22 participants (9 UD, 13 PEN). FCAL (g/g) significantly decreased after 12 weeks in patients receiving PEN (mean difference 189, p=0.009) but this effect did not quite reach statistical significance (p=0.052) in the UD group (Fig 1). Proportionally more patients from the PEN group had FCAL <100 mg/kg compared to the UD group (3, 6, 12 weeks, PEN: 62%, 69%, 69% vs UD: 33%, 33%, 56%) during the study course. CRP (mg/L) significantly decreased at week 6 and 12 in patients receiving PEN (week 6 & week 12, p<0.0001) and in patients continuing their UD (week 6, p=0.001, week 12, p=0.007). SIBDQ score increased in both groups (PEN, p=0.023 vs UD, p=0.008).

Conclusion

Preliminary data from the BIOPIC study suggests equivalence in clinical efficacy between the two groups but better responses to blood and gut inflammatory markers when ADA is combined with PEN. High tolerability of PEN suggests it can be a viable option for adult patients with active luminal CD.
P720 Exit interviews exploring Crohn’s disease patients’ experience of changes in their bowel urgency during the mirikizumab Phase 3 clinical trial in adult patients with moderate to severe Crohn disease
Authors: Gibble T H , Macey J , Makin H , Rosu R , Mellor K , Kitchen H , Carlier H , Dubinsky M C
Published: January 2024

Background

The objective of this study was to explore the clinical trial experience of patients with Crohn’s disease (CD), including perceptions of the Urgency Numeric Rating Scale (Urgency NRS) and meaningful within-patient change (MWPC).

Methods

Qualitative, 90-minute exit interviews were conducted with patients who had moderate to severe CD and completed the VIVID-1 phase 3, multicentre, randomized, double-blind, placebo and active-controlled, mirikizumab clinical trial in the past 3 weeks. The semi-structured interview guide included cognitive debriefing to explore the content validity of the 11-point Urgency NRS (0=No urgency to 10=Worst possible urgency in the past 24 hours). Interview transcripts were analysed using qualitative directed content analysis and framework analysis.

Results

Interviewed participants (N=62) were from the US (n=29), Czech Republic (n=10), Poland (n=8), Germany (n=7), Canada (n=4), Australia (n=3) and the UK (n=1). Participants (age 22–75 years, 55% female, 53% high school education or lower) were diagnosed with CD for 1–54 years. Most participants understood the Urgency NRS as assessing the severity of feeling an immediate need to go to the bathroom and used it accurately and without difficulty. Participants interpreted the Urgency NRS as ranging from “no urgency” [0] to an “immediate, sudden need or loss of bowel control” [10]. Participants reported that a ‘good day’ or ‘remission’ would feature reduced or no or minimal bowel urgency and permit adequate time to find a bathroom, feature no accidents and allow participation in daily/leisure/social activities and work away from home. Participants considered Urgency NRS scores ≤3 as a ‘good day’ (n=45/59) and ≤2 as ‘remission’ (n=41/57). Most reported that the bowel urgency improvement they experienced was meaningful (n=51/55; Table 1) because it improved their quality of life. A 3-point Urgency NRS improvement was identified as the smallest meaningful change (n=40/54; Table 1). Most participants associated bowel urgency with CD severity when responding to a Patient Global Rating of Severity (PGRS; n=42) and a Patient Global Impression of Change (PGIC; n=32). Most participants related Urgency NRS scores of 0 to None, 2 to Very Mild, 4 to Mild, 6 to Moderate, 8 to Severe and 10 to Very Severe on the PGRS (Figure 1). Urgency NRS improvements of 3-10 points were considered Much better or Very much better on the PGIC (Figure 1).

Conclusion

The Urgency NRS was well understood and a ≥3-point improvement in Urgency NRS score was considered a MWPC. Participants with CD who had completed the mirikizumab clinical trial perceived a meaningful change in bowel urgency to feature reduced or minimal bowel urgency enabling improved daily functioning.
P742 The efficacy of comprehensive multivitamin and mineral supplement to treat symptoms of fatigue in patients with Inflammatory Bowel Disease in remission with immunomodulators and or biological agents
Authors: Laheij R , Bierens-Peters D , Bruin K , Lutgens M , Sikkema M , de Wit U , Laheij R
Published: January 2024

Background

Patients with inflammatory bowel disease(IBD) very often report feeling tired for no reason. Malnutrition and vitamin or mineral deficiencies are also very common among patients with IBD. The aim of this study was to evaluate the efficacy of a multivitamin and mineral supplement for the treatment of fatigue in patients with IBD.

Methods

Single-centre, randomized placebo-controlled clinical trial to compare a comprehensive over-the-counter multivitamin and mineral supplement (supplemented group) with an identical presented placebo (placebo group) for the treatment of fatigue. Non-vitamin deficient patients with IBD in remission with immunomodulators and/or biological therapy were asked to report score their fatigue on a Visual Analog Scale (0-10) and the validated Chalder fatigue questionnaire (CFQ) at baseline, week 12 and 24. The validated CFQ has a scoring range from 0-33 and 2 subscales physical and psychological fatigue. Patients were considered to be fatigued by the CFQ with a score of 12 or above.

Results

A total of 214 patients reported fatigue at the start of the study. Of these patients 115 and 99 were assigned to the supplement and placebo groups, respectively. In the supplemented and placebo group, 32 (34%) and 18 (21%) patients, respectively, experienced no fatigue according to the CFQ definition at 24 weeks (Unadjusted Odds Ratio (OR): 2.0 (95% Confidence Interval (CI):1 - 3.8). In particular patients with Ulcerative Colitis (UC) and supplement use experienced less fatigue at 24 weeks (OR 5.7 (95% CI:1.3 - 24.1). Improvement of fatigue experienced between baseline and 24 weeks was not statistical different for either the supplemented and placebo group.

Conclusion

Although improvement in fatigue score was limited, a significant number of patients with IBD in remission with immunomodulators, and/or biological therapy using a very comprehensive vitamin and mineral supplement reported improvement of fatigue after 24 weeks of use.
P763 Rare and severe adverse events in pediatric inflammatory bowel disease: identification of safety signals through the international prospective PIBD-SETQuality Safety Registry
Authors: Klomberg R , Hellendoorn A , Kemos C , Rizopoulos D , Ruemmele F , Croft N , de Ridder L ,   PIBD-SETQuality Safety Registry collaborative group
Published: January 2024

Background

Rare but severe adverse events (AEs) can occur in pediatric inflammatory bowel disease (PIBD) due to ongoing inflammation, secondary to immunosuppressive drugs or as coincidental finding. These events can lead to significant disability or even death. Limited prospective research hampers the understanding of the incidences, risk factors, and outcomes associated with these events.

Methods

As part of the ongoing international PIBD-SETQuality Safety Registry, participating pediatric gastroenterologists prospectively reported the occurrence of any of 10 listed rare and severe AEs in their PIBD patient population (<19 years) via monthly electronic surveys since October 2016. Additionally, physicians could report ‘other rare and severe AEs’. Participants received an annual denominator survey, to report the number of PIBD patients under their care. Incidence rates (IRs) were calculated for each AE using Poisson regression models and were compared between countries. Upon reporting AEs, participants received specific follow-up forms to collect patient and IBD characteristics, as well as complication details (diagnosis, risk factors, management, outcome).

Results

Over a 77-month study period (October 2016 to April 2023), 222 pediatric gastroenterologists from 167 centers across 36 countries actively contributed to the registry, completing 7,975 monthly surveys with a median response rate of 86% [IQR 82%-88%]. On average, participants contributed for 53 months [IQR 25-72]. They covered 30,192 PIBD patients, with 114,528 patient-years (PY) of follow-up. In total, 285 listed complications were reported, alongside 117 uncategorized ‘other rare and severe AEs’. The highest IRs (95%CI) per 10,000 PY were found for VTE (IR 5.50 [2.74-4.99]), renal failure (IR 3.67 [2.67-4.89]), opportunistic infections (IR 2.88 [2.01-3.98]), and cancer (IR 2.71 [1.86-3.77]) (Figure 1). The lowest IRs (95%CI) per 10,000 PY were found for liver failure (IR 0.35 [0.11-0.81]) and HLH (IR 0.52 [0.21-1.06]). Combined IRs of the listed AEs did not differ among the five countries with the highest contribution of PY (p=0.18).

Conclusion

Through international collaboration among a large network of PIBD specialists, the Safety Registry has confirmed the increased incidence of several AEs in PIBD, including VTE, cancer and renal failure. Clinical characterization of these events may lead to a better understanding of their underlying etiologies and outcomes. This improves patient care by providing guidance for management development, facilitating well informed clinical decision making and may lead to prevention of these rare and severe events.
P822 Therapeutic Management And Risk Of Colectomy In Patients With Acute Severe Ulcerative Colitis And Previous Exposure To Anti-Tnf Drugs. A Cohort Study Of Geteccu
Authors: Mesonero Gismero F , López-García A , Miranda-Bautista J , Rubín de Célix C , Marín-Jiménez I , Suárez C , Martin-Cardona A , Fuentes E , Mínguez A , Castaño A , Roig C , Fernández-Clotet A , Gargallo-Puyuelo C J , Álvarez Herrero B , García M J , Segarra-Ortega J X , Rodríguez-Grau M C , López Romero-Salazar F , Olmella I , Martín-Rodríguez D , González Vivo M , Ponferrada Á , Baston-Rey I , Benítez J M , Reygosa C , Lastiri González E A , Delgado-Guillena P G , Torrealba L , Hernández-Camba A , Bernal L , Pinero G , Brunet E , Irabien M , Marquès-Camí M , Zabana Y , Gutiérrez A ,   On behalf of Young Group of GETECCU
Published: January 2024

Background

There are few data regarding the management on acute severe ulcerative colitis (ASUC) flare in patients with previous anti-TNF exposure. We evaluated the medical management, the risk of colectomy and factors associated comparing with a bionaive cohort.

Methods

A retrospective and multicentric study of GETECCU. Patients with ASUC episode between 2010-2020 were included in two cohorts: bio-exposed (cohort 1) and bio-naive (cohort 2). Patients with previous other biologics or JAK inhibitors exposure were excluded. Steroid response was defined as reduction of bowel movements and C Reactive Protein (CRP). Rescue therapy was used after steroid failure and maintenance therapy after steroid or rescue therapy response/remission. Clinical effectiveness of rescue and maintenance therapy was analyzed using partial mayo score (clinical response with decreased of 2-3 points, clinical remission ≤2). Colectomy rate was evaluated at short and long-term using survival analysis and was compared using cox logistic regression.

Results

Finally, 461 patients were included from 33 centres. Basal characteristics and medical management are shown in Table 1. Bioexposed patients received steroid therapy less frequently (82 vs 97%, p 0.001). Comparing with bionaive cohort, there were differences between medical management although steroid response and the use of rescue therapy were similar. However, clinical remission at one year was lower (44 vs 59%, p 0.03). Colectomy rates at 1 and 12 months were of 15 and 17% in Cohort 1, respectively. Comparing with bionaive cohort, there were a higher risk of colectomy at short and long-term, HR 2.46 (1.57-3.87, p 0.001) (Figure 1). There were no factors associated with colectomy at one year. Response to steroids was the only protective factor of colectomy at one year (RR 0.17, 0.07-0.45, p 0.001).

Conclusion

Management of ASUC in bio-exposed patients is heterogeneus and differs from bionaive patients. The risk of colectomy is increased. Although the response to medical treatment is not negligible, special efforts in standardizing therapies are warranted in order to improve prognosis.
P840 Structural evaluation of Inflammatory Bowel Disease Comprehensive Care Units in Brazil
Authors: Quaresma A , Guedes L , Barros J , Baima J , Imbrizi M , Zeroncio M , Kotze P , Flores C ,   GEDIIB
Published: January 2024

Background

In Brazil there is no methodology for evaluating health services recognized as Comprehensive Care Units (CCU), making it difficult to assess the quality of care provided for IBD patients. Aims: Map the distribution of this units and identify strengths and weaknesses, considering local and regional characteristics with a view to proposing a ranking system for Brazilian centers.

Methods

The study was carried out in three phases. First, GEDIIB developed 22 questions to characterize CCU in Brazil. The questionary was constructed based on GETECCU criteria. All GEDIIB members were invited to respond to the survey with the 11 questions considered most relevant. In the last phase, an analysis of the results obtained in the CCU was carried out, using the IBM SPSS Statistics v 29.0.1.0 software. Descriptive statistics were used to characterize the unit´s profile. The chi-square test was used to compare categorical variables

Results

There were 109 responses, 53 from public centers. Of these, 11 were excluded. Most units were concentrated in the Southeastern region 22 (52.4%) and only one (2.4%) in the Northern region of Brazil. Thirty-nine centers (92.9%) perform endoscopic procedures, but only 9 (21.4%) have access to enteroscopy and/or capsule endoscopy. Thirty-three centers (78.6%) offer infusion therapy locally, 26 (61.9%) maintain IBD patient records, 13 (31.0%) reported having an IBD nurse, 34 (81.0%) have specific evidence-based protocols and only 7 (16.7%) have a patient satisfaction methodology. In the private scenario there were 56 responses, of which 10 were excluded. There is also a concentration in the Southeastern and Southern regions. Thirty-nine centers (84.8%) have access to endoscopic procedures and 19 perform enteroscopy and/or capsule endoscopy. Infusion therapy is available in 24 centers (52.2%). Thirty-nine (84.8%) maintain a specific database of IBD patients, 17 (37%) have an IBD nurse, 36 (78.3%) have specific evidence-based protocols, and 22 (47.8%) apply a patient satisfaction methodology. Multidisciplinary teams (p< 0.002) and infusion centers (p< 0.01) predominate in public centers as compared to private ones. Telemedicine (p< 0.027), capsule endoscopy (p< 0.001), exclusive registration of patients with IBD (p< 0.015) and patient satisfaction methodologies (p< 0.002) are predominant in private centers as compared to public centers.

Conclusion

IBD CCU in Brazil were mainly located in the southeastern and southern regions of the country. Most centers have dedicated multidisciplinary teams and specialists involved in IBD treatment. There is still a current need to improve the proportion of nurses' involvement in IBD care in Brazil.