bluuebunny/crossref_metadata_2025_split huggingface dataset:
P0583 The Effects of a Dual-Strain Probiotic Versus Placebo on Cytokine Levels in Patients with Ulcerative Colitis
Authors: Carroll A , Meagher S , Walker C , Magdeldin H , McNamara D , Ryan B , O'Donnell S , Breslin N , Corr S , O'Connor A 
Published: January 2025

Abstract

Background
Ulcerative colitis (UC) is a form of Inflammatory Bowel Disease (IBD) characterised by chronic mucosal inflammation of the colon. It has been shown that fatigue in patients with ulcerative colitis is a particularly burdensome symptom[1]. Studies have shown that patients with IBD have higher fatigue scores than non-IBD control groups[1]. In UC, activation and dysregulation of the adaptive immune response at the epithelial level results in the abnormal response to antigens leading to an inflammatory cascade resulting in a production of multiple different pro-inflammatory cytokines including IL10, IL23 and TNF-α amongst others[2]. The aim of this study therefore is to evaluate the effects of a dual-strain probiotic versus placebo on cytokines in relation to UC and fatigue.

Methods
This is a single centre double-blind randomised placebo-controlled trial in Tallaght University Hospital, Dublin. Participants are between the ages of 18 to 65 and have a confirmed diagnosis of ulcerative colitis. After randomisation, participants were enrolled on either a 3 month probiotic or placebo arm. Participants had blood tests and a faecal calprotectin at baseline and at conclusion of the study. The probiotic is a dual strain Bifidobacterium longum 35624® combined with B. longum 1714®.

Results
10 controls and 59 participants meeting eligibility criteria were successfully recruited. After double-blind randomisation, 30 participants were on the active dual-probiotic arm with 29 participants on the placebo arm (table 1). In our cytokine analysis the mean concentrations for IFN-α, IFN-γ, IL-10, IL-12p70, IL-6, IL-8, IP-10 and MCP-1 increased post the probiotic. SAA and IL-17A remained relatively unchanged post the probiotic, and an improvement was seen in IL-1β and TNF-α. Contrasted with the placebo arm of the study where mean concentrations in IFN-γ, IL-17A, IL-6, IP-10 and MCP-1 increased post the placebo. SAA and IL-8 remained relatively unchanged post the placebo. There was an improvement seen in IFN-α, IL-10, IL-12p70, IL-1β and TNF-α (table 2). Results could be due to low detection rates.

Conclusion
This study found probiotics may not always be beneficial for patients with UC and may worsen some pro-inflammatory cytokine levels.

References
1.Römkens TEH, van Vugt-van Pinxteren MWJ, Nagengast FM, van Oijen MGH, de Jong DJ. High prevalence of fatigue in inflammatory bowel disease: A case control study. Journal of Crohn's and Colitis. 2011;5(4):332-7.
2.Ordás I, Eckmann L, Talamini M, Baumgart DC, Sandborn WJ. Ulcerative colitis. Lancet. 2012 Nov 3;380(9853):1606-19.
P0585 A treat to target approach in IBD: contemporary real-world perspectives from an international survey
Authors: Sharip M T , Brezina B , La Revilla Negro J , Subramanian S , Parkes M , Raine T , Noor N M 
Published: January 2025

Abstract

Background
The management of Inflammatory Bowel Disease (IBD) varies due to differences in healthcare systems, treatment costs, access to diagnostics, and diverse clinical practices between specialists. Despite the frequent advocacy of a treat-to-target (T2T) approach, there is insufficient clarity on how clinicians implement T2T in real-world settings. We aimed to conduct a large, global survey among IBD experts to identify current practices in management.

Methods
A prospective, cross-sectional study was conducted using a 16-item survey divided into two sections — for Ulcerative Colitis (UC) and Crohn’s Disease (CD) — and distributed to practicing IBD clinicians. A hyperlink to the survey was widely circulated among attendees to the ECCO annual congress 2024 as well as ECCO members using the ECCO online platform, ECCO newsletter, and the ECCO electronic app. The survey was active from 17/01/2024 until 31/03/2024. Completion of the anonymous survey was deemed to imply consent for data analysis.

Results
A total of 261 respondents from 88 countries participated in the survey, with the majority (253/261) being physicians and 8 IBD nurse specialists. Despite global guidance, only a quarter of respondents routinely performed an endoscopy to assess response after starting an advanced therapy (28.4% in UC vs 23.5% in CD). Moreover, despite an increasing academic focus on intestinal ultrasound (IUS), 171 (66%) of respondents in UC and 132 (51%) in CD reported that they did not routinely undertake IUS to guide treatment decisions. Faecal calprotectin for monitoring treatment response was routinely used by 87% (90% in UC and 84% in CD) of respondents. Forty-five percent reported use of therapeutic drug monitoring (TDM) both proactively and reactively and 35% reported only using TDM reactively.

Conclusion
Our study shows considerable variation in IBD management across different countries, and interpretation of the T2T approach. This highlights the need for standardised and pragmatic guidelines to help improve outcomes for patients with IBD globally.
P0589 High treatment persistence following infliximab dose escalation in Inflammatory Bowel Disease: A real world study
Authors: Salehi O , Gondal F , Terlato M , Pillay L , Macrae F , Rentsch C , Dimkovski S , Segal J P 
Published: January 2025

Abstract

Background
Biologic dose escalation is frequently employed in inflammatory bowel disease (IBD) patients who lose response to standard dosing regimens. Infliximab (IFX), the most commonly used biologic in IBD, has a well-established role in inducing and maintaining remission in IBD, particularly in fistulising Crohn's disease (CD).¹ Secondary loss of response to IFX can occur due to low serum drug levels, primarily from immunogenicity.² We investigated the effectiveness and treatment persistence of IFX dose escalation in IBD patients with inadequate response to standard dosing after initial clinical response.

Methods
We conducted a retrospective analysis of IBD patients who underwent IFX dose escalation between 2020-2024 at a tertiary IBD centre. Dose escalation was defined as increase in dose (&gt;5mg/kg) and/or frequency [&gt;every 8 weekly (Q8W)]. Primary outcomes included clinical disease activity scores (Simple Clinical Colitis Activity/SCCAI Index for UC, Harvey-Bradshaw Index/HBI for CD), biochemical markers (CRP, faecal calprotectin) and treatment persistence, evaluated at 3-12 months, 12 months, and annually up to 36 months post-escalation.

Results
The cohort included 47 patients (mean age 29 years, 52% female), comprising 33 CD (70%) and 14 UC (30%) patients. Primary indication for dose escalation was low drug levels (76%), followed by loss of response despite adequate levels (24%). Dose escalation led to significant improvements in disease activity scores (HBI: p=0.01; SCCAI: p=0.04) and CRP (p=0.02) at 3-12 months. These improvements were sustained at 12 months for CRP (p=0.04) but not for clinical scores. Treatment persistence at 36 months was notably high at 100% for biologic-naïve patients and 92% for biologic-exposed patients. Mild adverse events occurred in 5 patients (11%) including psoriasiform rash (n=3), transient liver enzyme derangement (n=1) and shingles (n=1). No serious adverse events occurred.

Conclusion
IFX dose escalation demonstrates significant improvements in clinical and biochemical parameters in the short term, with high treatment persistence up to 36 months. While both groups showed excellent outcomes, biologic-naïve patients achieved superior persistence (100% vs 92%). These findings support dose escalation as a viable therapeutic option for maintaining response in IBD patients, with an acceptable safety profile. Prospective studies are needed to identify predictive factors for successful dose escalation and optimal timing of intervention.

References
1.Hanauer SB, Feagan BG, Lichtenstein GR, et al. Maintenance infliximab for Crohn's disease: the ACCENT I randomised trial. Lancet. 2002;359(9317):1541-1549.2. Rahman MU, Strusberg I, Geusens P, et al. Double-blinded infliximab dose escalation in patients with rheumatoid arthritis. Ann Rheum Dis. 2007;66(9):1233-1238.
P0597 Clinical and biochemical correlates of infliximab pharmacokinetics in adult patients with Inflammatory Bowel Disease
Authors: Pool I A , Volkerink I , Stavast M , Kosterink J G W , Dijkstra G , Mian P , Bourgonje A R 
Published: January 2025

Abstract

Background
Antibodies against tumor necrosis factor-alpha (TNF-α) such as infliximab (IFX) are important in the treatment of patients with inflammatory bowel disease (IBD), but many patients lose drug response over time or do not respond at all. Loss-of-response and non-response can at least be partially attributed to suboptimal dosing due to individual differences in pharmacokinetics (PK)1. In this real-world study, we aimed to identify clinical, biochemical and endoscopic variables influencing IFX PK in patients with IBD.

Methods
Patients diagnosed with IBD aged ≥18 years who were treated with IFX were included based on available IFX trough levels from a hospital-based pharmacy registry. Information on endoscopic, clinical, and biochemical parameters was collected. Univariable and multivariable linear mixed-effects models were used to model associations between individual IFX trough level trajectories and identified factors to examine their relative contributions to IFX PK. In addition, a systematic literature study on IFX PK in adults with IBD and other immune-mediated inflammatory diseases was performed to better contextualize the obtained findings.

Results
A total of 200 patients were included (Crohn’s disease [CD] (n=163) and ulcerative colitis [UC] (n=37)) with 452 IFX trough levels available for analysis (Figure 1). Patients with antibodies (ATI) to IFX (unstandardized β=4.35, p&lt;0.001) and those treated with longer dosing intervals (β=-1.89, p=&lt;0.001) exhibited lower trough levels (Figure 2). Higher levels of aspartate aminotransferase (AST) (β=0.04, p=0.027), hemoglobin (β=0.76, p=0.022) and albumin (β=0.15, p=0.029) were positively associated with IFX trough levels. Among clinical factors, Simple Clinical Colitis Activity Index (SCCAI) scores in patients with UC, both as continuous (β=3.31, p=0.03) and as categorical variable (β=13.25, p=0.033), were positively associated with higher IFX trough levels. The presence of endoscopic inflammation, regardless of its severity, was also positively correlated with IFX trough levels (β=2.60, p=0.045).

Conclusion
This data demonstrates a role of AST, albumin, hemoglobin, SCCAI, and endoscopic inflammation as covariates potentially relevant to IFX PK in IBD. Findings of albumin, endoscopic inflammation, dosage interval and ATI were supported by our systematic review confirming them as previously identified covariates. AST, hemoglobin, and SCCAI were newly identified covariates. These covariates could optimize treatment strategies and should therefore be considered for integration in population-PK/PD models and PK dashboards in order to make patient-specific prediction models for IFX treatment.

References
1.Hemperly, A & Vande Casteele, N. Clin Pharmacokinet. 2018 doi: 10.1007/s40262-017-0627-0.

Figure 1. Snippets of tables 1 and 2.

Figure 2.
P0601 Is advanced combination therapy effective in patients with refractory Inflammatory Bowel Disease?
Authors: Rodríguez Gallardo M , Valdés Delgado T , Maldonado Pérez B , Belvis Jiménez M , Aguado Paredes A , Castro Laria L , Argüelles Arias F 
Published: January 2025

Abstract

Background
Advanced combination therapy (ACT) involves combining two biological therapies or a biological drug with a small molecule, in order to complement their mechanisms of action inhibiting multiple inflammatory cascades. The primary aim of our study was to evaluate the effectiveness of combination therapies in Inflammatory Bowel Disease (IBD)

Methods
A prospective, single-centre observational study was conducted, including all patients diagnosed with ulcerative colitis (UC) or Crohn´s disease (CD) starting treatment with ACT from March to August 2024. Clinical and biological response and remission were assessed at week 16 and the last available visit. Clinical response was defined as a decrease ≥3 points from baseline Harvey-Bradshaw Index (HBI) in CD or baseline Partial Mayo Score (pMS) in UC. Clinical remission was considered as a HBI score ≤4 or pMs of 0-1. Biological response was determined as a ≥50% decrease from baseline C-reactive protein (CRP) and faecal calprotectin (FC) and remission as a CRP&lt;5 and FC&lt;250

Results
A total of 20 patients were included, 70% (14/20) diagnosed with UC (Figure 1A). The most frequent combination was vedolizumab (VEDO) with upadactitinib (UPA) (Figure 1B)
The median baseline HBI was 10.5 [IQR 6-15] decreasing to 6.5 at week 16 [IQR 3-11] and to 5.5 [IQR 2-10] at the last follow-up (p&lt;0.001)(Figure 2A). The median baseline pMS was 7 [IQR 5-8] decreasing to 4 [IQR 2-4] at week 16 and to 2 [IQR 1-3] at the last visit (p&lt;0.005) (Figure 2B)
The median baseline FC was 1994 [IQR 805-3238], decreasing to 635 [IQR 183-222] at week 16 and to 387 [IQR 93-1115] at the last follow-up (p=0.047) (Figure 2C). Regarding CRP, the median baseline was 5.3 [IQR 1-31], decreasing to 2.4 [IQR 1-5] at week 16 and to 1.2 [IQR 1-4] at the end of follow-up (p=0.014) (Figure 2D)
65% of patients achieved clinical response and 20% reached clinical remission at week 16. At the end of follow-up, 80% achieved clinical response and 65% clinical remission (Figure 2E)
At week 16, 45% and 20% of patients achieved biological response and remission, respectively. At the end of follow-up, 65% were in biological response and 45% in biological remission (Figure 2F)
Treatment was discontinued in 3 patients, in 2 of them due to improvement and in the reimaining one due to lack of response. Treatment intensification was required in 7 patients. A total of 8 mild adverse effects were recorded, none of which led to discontinuation of the ACT

Conclusion
These results demonstrate adequate clinical and biological response in patients treated with ACT. Clinical and biological remission was achieved in 65% and 45% of patients at the end of follow-up, with good safety profile. Nevertheless, to confirm this results futher large prospective studies are needed
P0602 Long-term effectiveness and safety of ustekinumab dose escalation in patients with refractory ulcerative colitis: a multicenter retrospective cohort study
Authors: Van Lierop L , Albino L , Rosentreter R , Thomas P W A , Lu C , Siffledeen J , Kroeker K I , Ma C , Peerani F , Halloran B P , Baumgart D C , Dieleman L A , Du L , Hoentjen F , Wong K 
Published: January 2025

Abstract

Background
Ustekinumab dose escalation (DE) may be an effective strategy to recapture clinical response in patients with ulcerative colitis (UC). The aim of this study was to assess the real-world long-term effectiveness and safety of ustekinumab DE in patients with refractory UC.

Methods
This multicenter retrospective cohort study included patients with refractory UC who received at least one IV induction ustekinumab dose between January 2016 and November 2021. We compared ustekinumab DE to no DE, examining clinical, biochemical, and endoscopic disease outcomes. The primary endpoint was corticosteroid-free clinical remission (partial Mayo score ≤ 2 without systemic corticosteroids) at the end of follow-up. Cox-proportional hazards regression analysis was performed for factors associated with time to DE, and a Kaplan-Meier plot was created for visualizing drug persistence probabilities.

Results
We enrolled 121 patients. Eighty-one patients (67%) underwent DE during a median follow-up of 141 weeks. Corticosteroid-free clinical remission at the end of follow-up was achieved for 53.2% (DE group) and 59.0% (non-DE group). In the DE group, 53% discontinued ustekinumab, mainly due to a lack of effectiveness. At the end of follow-up, 47% of DE patients remained on ustekinumab, compared to 55% in the non-DE group. Ustekinumab persistence probability after 2 years was 40% (DE group) versus 79% (non-DE group). Only 2 patients discontinued ustekinumab for adverse events.

Conclusion
Our results indicate that DE is a common method for optimizing ustekinumab treatment in refractory UC. While DE appears safe, effectiveness and drug persistence of DE beyond 2 years are limited.
P0603 The real-world use of intravenous and subcutaneous Vedolizumab in IBD across Australia and New Zealand, Crohn’s Colitis Cure Data Insight’s Program
Authors: Su W K , Wilson W , Wark G , Ghaly S , Lynch K , Lawrance I , Walker G , Forbes A , Brett L , An Y K , Connor S J , Andrews J M 
Published: January 2025

Abstract

Background
Vedolizumab, an established therapy for inflammatory bowel disease (IBD), has been proven to be effective in both intravenous (IV) and subcutaneous (SC) formulations. This study aims to understand the patterns of use of both formulations in real world clinical care.

Methods
Crohn’s Colitis Care (CCCare) is a cloud-based IBD-specific electronic medical record used in Australia (AUS) and New Zealand (NZ). Data feed into a de-identified clinical quality registry (CQR), which was interrogated in August 2024. We examined the real-world use of Vedolizumab in people with IBD under usual ambulatory care. People with Crohn’s Disease (CD) or Ulcerative colitis (UC) with a clinical assessment ever recorded were included.

Results
Of 8,724 eligible people with IBD, 13.6% (n=1,187) have ever received Vedolizumab, 734 (61.8%) of whom have UC and 453 (38.2%) have CD. The median age was 42 years (IQR 31 – 56), and the median disease duration was 11.1 years (IQR 5.6 – 19.1). There was an even gender distribution with 50.0% (n=593) male. The majority of people resided in AUS (n=1,117, 94.1%) with 5.9% (n=70) in NZ.
A higher proportion of people with UC have received vedolizumab compared to those with CD (19.5% vs 9.1%, p&lt;0.001). In those where residential location was documented, Vedolizumab was more frequently used in people residing in a metropolitan compared to a non-metropolitan area (n=875, 15.2% vs n=177, 10.7%, p&lt;0.001). In those currently receiving Vedolizumab (n=541), there was no difference in the formulation used across metropolitan and non-metropolitan areas (72.9% IV vs 71.3% IV, p=0.75).
Of those who ever received maintenance IV Vedolizumab (n=1,015), only 59 people (5.8%) have switched to SC Vedolizumab. The median duration on IV before switching was 97 weeks (IQR 59.5 – 217.8). There was no difference in the rate of IV to SC switching in CD compared to UC (4.9% vs 6.4%, p=0.34). Of those who ever received maintenance IV Vedolizumab, 161 (15.9%) were on dose escalated (DE) therapy. The proportion of people on DE Vedolizumab did not differ between CD and UC (13.2% vs 17.5%, p=0.07).

Conclusion
In this large, real-world data of people with IBD, Vedolizumab has been used in 13.6% of the cohort, more often in people with UC compared to CD. The majority of people receiving Vedolizumab remain on IV formulation with only a small subset of people changing to, or established on, SC route. SC formulations have the potential to reduce the patient’s burden of disease by reducing travel costs and time out of role, promoting autonomy and empowering people living with IBD. However, in the absence of economic incentive or policy change, there will remain inertia to change to SC formulation.
P0608 Safety of guselkumab in Inflammatory Bowel Disease up to 1 year: Integrated safety analysis of phase 2 and 3 studies in Crohn’s Disease and Ulcerative Colitis
Authors: Sands B E , Panaccione R , Danese S , Panés J , Hisamatsu T , D’Haens G , Van Rampelbergh R , Olurinde M , Yee J , Baker T , Yarandi S , Germinaro M , Vetter M L , Li H , Rosas Ballina M , Allegretti J , Afzali A , Rubin D T 
Published: January 2025

Abstract

Background
Guselkumab (GUS), a dual-acting IL-23 inhibitor that potently neutralizes IL-23 and binds to CD64 (a receptor on cells that produce IL-23), is currently approved in the United States for treatment of ulcerative colitis (UC) and worldwide for the treatment of plaque psoriasis and psoriatic arthritis. While GUS has been shown to be safe in Crohn’s disease (CD) and UC, safety results have only been reported in individual trials to date. To characterize the overall safety profile of GUS in inflammatory bowel disease (IBD), we evaluated pooled safety data from Phase 2/3 clinical trials of GUS in CD and UC.

Methods
Participants (pts) with moderately to severely active CD (n=1492; GALAXI 1, 2, and 3, and GRAVITI) or UC (n=1514; QUASAR Induction Study 1, Induction Study 2, and Maintenance Study and VEGA-GUS monotherapy arm only) were assigned to GUS 200 mg intravenous (IV) or 400 mg subcutaneous (SC) induction (GRAVITI only) at Weeks 0, 4, and 8, followed by GUS 100 mg SC every 8 weeks or 200 mg SC every 4 weeks; or placebo (PBO). SC maintenance treatment continued through approximately 1 year. GUS studies were pooled for the induction period (GALAXI, GRAVITI, and QUASAR; IV and SC, Weeks 0-12 [VEGA excluded due to no PBO control]) and through 1 year (GALAXI, GRAVITI, QUASAR, and VEGA). In this pooled analysis, safety events were normalized to 100 pt-years (PY) of follow-up with corresponding confidence intervals.

Results
Through Week 12, 1703 pts were treated with GUS with 399.9 PY of follow-up. Rates of adverse events (AEs) were similar between pts treated with GUS (200 mg IV or 400 mg SC) and PBO (Figure 1A). AEs occurred at a rate of 202.82/100 PYs and 223.26/100 PY, serious AEs at 11.75/100 PY and 28.56/100 PY, AEs leading to study agent discontinuation at 5.50/100 PY and 16.32/100 PY, and serious infections at 1.50/100 PY and 1.17/100 PY, for GUS and PBO, respectively.
Through 1 year, 2057 pts were treated with GUS, with 1752.1 PY of follow-up. Rates of AEs, SAEs, AEs leading to discontinuation, and serious infections, were no higher in GUS-treated than PBO-treated pts (Figure 1B). Through 1 year, no anaphylactic or serum sickness reactions were reported, and rates of malignancy, opportunistic infection, major adverse cardiovascular events, and clinically important hepatic disorders were low (Table 1). In GUS-treated pts, one pt (from an endemic region) reported active tuberculosis, and 2 deaths (acute myocardial infarction in a pt with pre-existing cardiovascular risk factors and non-suicidal gunshot wound, respectively) occurred.

Conclusion
Through 1 year of treatment, GUS demonstrated a favorable safety profile comparable to placebo in patients with CD and UC. No new safety concerns were identified.