bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

Abstract

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 &gt;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&lt;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

Abstract

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

Abstract

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 &lt;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 &lt;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&lt;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

Abstract

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

Abstract

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

Abstract

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 (&lt;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

Abstract

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.