bluuebunny/crossref_metadata_2025_split huggingface dataset:
P430 The influence of persistent organ damage on IFX pharmacokinetic modeling and disease progression assessment: findings from a prospective real-world study in inflammatory bowel disease patients
Authors: Magro F , Fernandes S , Patita M , Arroja B , Lago P , Rosa I , Tavares de Sousa H , Ministro P , Mocanu I , Vieira A , Castela J , Moleiro J , Roseira J , Cancela E , Sousa P , Portela F , Correia L , Moreira P , Afonso J , Dias S , Danese S , Peyrin-Biroulet L , Vucicevic K , Santiago M 
Published: January 2024

Abstract

Background
Effective management of inflammatory bowel disease (IBD) relies on a comprehensive understanding of infliximab (IFX) pharmacokinetics (PK). This study's primary goal was to develop a robust PK model, identifying key covariates influencing IFX clearance (CL), while concurrently evaluating the risk of disease progression during the maintenance phase of IBD treatment.

Methods
The multicenter, prospective, real-world DIRECT study was conducted in several care centers, which included 369 IBD patients in the maintenance phase of IFX therapy. A two-compartment population PK model was used to determine IFX CL and covariates. Logistic and Cox regressions were applied to elucidate the associations between disease progression and covariates embedded in the PK model.

Results
The PK model included the contributions of weight, albumin, antidrug antibody (ADA), and fecal calprotectin (FC). On average, higher ADA, FC concentration and weight, and lower albumin concentration resulted in higher IFX CL. In the multivariate regression analyses, FC levels influenced the odds of disease progression in all its different definitions, when adjusted for several confounding factors (Fig. 1). Additionally, alongside FC, both IFX and C-reactive protein demonstrated a significant impact on the temporal aspect of disease progression.

Conclusion
In this 2-year prospective real-world study, readily available clinical covariates, notably FC, significantly impacted IFX availability in IBD patients. We demonstrated that persistent gut damage, as mirrored by FC, substantially influenced IFX clearance. Importantly, FC emerged as a pivotal determinant, not only of IFX pharmacokinetics but also of the progression of the underlying disease. These findings underscore the imperative need to integrate FC into forthcoming IFX pharmacokinetic models, amplifying its clinical significance.
P462 The burden of mental health disease in people with inflammatory bowel disease - Crohn's Colitis Cure (CCC) Data Insights Program
Authors: Mcnamara J , Wilson W , Pipicella J L , Ghaly S , Gearry R , Williams A , Lynch K , Lawrance I , Schultz M , Walker G , Radford-Smith G , Connor S J , Andrews J M 
Published: January 2024

Abstract

Background
The impact of Inflammatory Bowel Disease (IBD) on individuals’ quality of life is well reported. Recent studies have shown that depression or anxiety affect almost 1 in 5 people with IBD and may be a predictor of active disease. We aimed to explore the burden of MHI in the Australasian IBD population and examine the real-world variation in screening and care across different sites and care settings

Methods
Crohn’s Colitis Care’s (CCCare) clinical quality registry (CQR) is created by deidentified data flowing across from routine care encounters. Data in the CQR for all individuals with a clinical encounter since August 2018 were interrogated in April 2023. Mental health data were collected from documentation during routine care or through patient consumer completion of embedded questionnaires, namely Depression Anxiety and Stress Scale 21 [DASS-21] and Kessler Psychological Distress Scale [K10]

Results
The CQR contained 6614 people with IBD with a mean age of 44.4 (SD +/- 22.09) and even gender distribution (50.9% female). 79.5% of people were from Australia and 20.5% from New Zealand. 57.1% of people had Crohn’s disease (CD), 40.4% ulcerative colitis (UC) and 2.5% IBDU with a mean disease duration of 13.3 years (SD +/-23.0). Anxiety was the 4th most listed comorbidity affecting 17.8% of individuals, depression 7th affecting 13.7% of people and both depression and anxiety 13th affecting 9.1% of people with IBD. In total 40.8% or 2 in 5 people with IBD in Australasia had received a formal diagnosis of a MHI.
2,928 consumers had been invited to complete the DASS-21 and 2,340 the K10 (44% & 35% respectively). Of the questionnaires sent, 32% of DASS-21s and 33% of K10s were completed. Rates of both invitation and completion varied significantly between centres. Invitation rates varied from 11% - 90% (p&lt;0.001) while questionnaire completion rates varied from 26% to 46.8% (p&lt;0.001).
The mean DASS-21 score for all people with IBD was 8.1 for depression (7-10 indicating moderate disease), 6.6 for anxiety (6-7 suggests moderate disease) and 11.2 for stress (10-12 indicates moderate disease). Individuals with current fistulising CD (representing severe IBD phenotype) mean DASS-21 scores were higher than the wider IBD population, averaging 9.9 for depression (p&lt;0.001), 7.4 for anxiety (p&lt;0.001) & 12.9 for stress (p&lt;0.001)

Conclusion
Individuals with IBD suffer from high rates of MHIs, with those suffering more severe disease phenotypes scoring worse on mental health assessment tools. Despite the availability of screening and monitoring tools, healthcare providers use these variably and insufficiently. This may result in unmet care needs. Standardisation of care addressing the psychosocial care needs of people with IBD is needed
P494 Efficacy and safety of Upadacitinib in moderate to severe paediatric Crohn’s disease and ulcerative colitis in a tertiary Paediatric IBD (PIBD) centre – A case series
Authors: Kontaki E , Merchant A , Gaynor E , Kiparissi F 
Published: January 2024

Abstract

Background
Upadacitinib is a selective Janus kinase 1 inhibitor approved for the treatment of patients 18 years and older with the diagnosis of Crohn’s disease and ulcerative colitis. Although there is promising data for its use in adult inflammatory bowel disease (IBD), limited data are currently available on its use in paediatric IBD. We present our experience in this case series of patients ≤ 18 years on Upadacitinib.

Methods
We identified patients under the age of ≤ 18 years, started on Upadacitinib for the indication of IBD. Data on demographics, disease subtype, duration on Upadacitinib, number of biologic failures, tofacitinib use, concomitant biologic use, adverse events and clinical remission were gathered.

Results
12 patients with paediatric IBD (median age at Upadacitinib start 15.5 years, range 13.9 to 17.8 years, 8 (67%) males, were identified. 7 patients had Crohn’s disease, 3 patients had ulcerative colitis and 2 patients had IBD unclassified. 4 patients (33%) were diagnosed under the age of 6 years with early onset IBD (EOIBD), 1 was 3.5 years old, 1 was 4 years old and 2 were 5 years old. 11/12 (92%) patients had failed 3 or more biologics. Upadacitinib was used as monotherapy in all patients and previous biologic treatments were stopped. 1 patient with a partial response to tofacitinib was switched to Upadacitinib. All patients had active disease at commencement of Upadacitinib. All 12 (100%) patients were started on 45 mg of Upadacitinib. 8/12 (67%) patients have been followed up for at least 8 weeks. Out of the 8 patients, 5/8 (63%) patients were in clinical remission between 8-16 weeks of therapy, 2/8 (25%) had partial response and 1/8 (13%) has been refractory to treatment. Relapse of symptoms was noted in 1 patient after dose was dropped to 30 mg; this patient had achieved remission on 45 mg. No serious adverse events occurred; 2 patients noted to have increased triglycerides (max 5.75mmol/L; range 0.38-1.58mmol/L). 1 of them had previous exposure to tofacitinib and the triglycerides were already raised prior to starting Upadacitinib. 1 patient developed headaches, as a result, Upadacitinib dose was decreased. There were no incidences of shingles or other serious infections.

Abbreviations
CD, Crohn's disease; UC, ulcerative colitis; IBD-U; inflammatory bowel disease unclassified; Upa, upadacitinib; AEs; adverse events

Conclusion
The patients in this case series, started on Upadacitinib, are a heterogeneous group with refractory disease. In these paediatric and adolescent patients Upadacitinib seemed safe and efficacious with a low side effect profile. Further national and international collaborative studies are needed to confirm our findings.
Table 1. Patient Characteristics
P515 Exclusive enteral nutrition downstages complicated Crohn’s disease prior to surgical resection: A feasibility study
Authors: Zuk D , Jaksic D , Andersson S , Soop M 
Published: January 2024

Abstract

Background
Exclusive enteral nutrition (EEN, oral or enteral liquid feeds only) is an established first-line therapy to induce remission in Crohn’s disease (CD) in children, but not in adults where low tolerance has been reported. Recently, smaller studies have suggested advantages of EEN in preoperative optimisation in adults. We hypothesise that in this setting, EEN is feasible and is associated with improved inflammatory and nutritional markers.

Methods
Consecutive patients with small bowel or ileocolic Crohns disease, who started preoperative EEN at two large IBD centres 2020-2023 were retrospectively studied. EEN was part of a 4-6week preoperative optimisation pathway. Outcomes were compliance and serum albumin, c-reactive protein and body weight, respectively. Medians (range) & Wilcoxon tests used.

Results
Thirty-two patients started EEN for stricturing (n=10) or penetrating disease (n=14). Six patients (19%) did not tolerate EEN and received parenteral nutrition (n=2) or reverted to normal diet (n=4), while 26 patients (81%) completed EEN until surgery. This group received EEN during 38 (17-70) days. C-reactive protein concentrations decreased from 8.5 (1-157) to 3 (1-96) mg/L (p = 0.0051), and albumin levels increased from 33.5 (27-44) to 38 (26-42) g/L (p&lt; 0.001), while body weight did not change, from 67 (48.5-107) to 66.6 (48.5-105.7) kg (p = 0.25). 21 (81%) EEN patients underwent minimally invasive surgery, 22 (85%) had a primary anastomosis and 4 a stoma. Median postoperative length of stay was 4 (2-11) days. One patient with a severe complication, no one with an anastomotic leakage.

Conclusion
EEN was well tolerated in this cohort of patients undergoing surgery for complicated CD. EEN was associated with improved systemic inflammation, a maintained nutritional status, and favourable postoperative outcomes despite the complexity of disease in this group of patients. These results align with previous studies that have shown the effectiveness of EEN in reducing disease activity and promoting mucosal healing in CD patients.By reducing inflammation and uphold nutritional status, EEN might help to create a more favourable surgical environment, potentially leading to better outcomes and decreased postoperative complications.
P548 Ustekinumab shows favourable safety profile and drug persistence rates in patients with Crohn’s Disease – results from a tertiary IBD centre
Authors: Snehali M , Ahmed A , Ghosh S , Iacucci M , Shivaji U N 
Published: January 2024

Abstract

Background
Patients with Crohn’s disease (CD) often require multiple biological therapies due to loss of response. Anti-TNF drugs are generally used as first-line biologic followed by a switch of class when patients lose response. Ustekinumab (UST), an IL12/23p40 antagonist is used in CD, often after anti-TNF failure. The aim of the study was to report on outcomes of UST therapy with a median follow-up period of nearly 24 months.

Methods
All CD patients who commenced UST therapy were identified from EMR at two tertiary referral centers between January 2017 and December 2021. All relevant demographic and clinical data were collected. Data on clinical response (defined as a downgrade in disease activity based on clinician assessment & biochemical parameters), steroid-free duration, and long-term response to UST at 52 and 104 weeks were recorded. The response was assessed clinically and supported by biomarkers, cross-sectional imaging, endoscopic data, and sustained maintenance of UST. Statistical analysis was carried out using the IBM® SPSS® Statistics software package Version: 28.0.0.0.

Results
A total of 249 CD patients (M=133 (53%); median age 41 years) were included, with a median follow-up period of nearly 24 months (5-79 months). 94 (38%) patients had stricturing (B2), penetrating (B3) and perianal phenotype at baseline and 104 (42%) had undergone previous resection/s. 207 (83%) had documented moderate to severe disease activity and 211 (85%) patients were exposed to at least one biologic prior to treatment with UST. 66 (27%) patients were on concomitant thiopurines at the start of treatment. 224 (90%) patients in our cohort showed clinical response to UST and all remained on treatment at the end of follow-up period. The distribution of patients as per disease activity at baseline, 52 and 104 weeks is illustrated in Figure 1. An improvement in haemoglobin levels was observed post-therapy with UST, which was statistically significant at 104 weeks (p&lt;0.001), with corresponding significant reduction in faecal calprotectin levels (median reduction: 506 mcg/g to 335 mcg at 104w; p&lt;0.001). Only 10 (4%) patients had side-effects which were directly attributed to UST therapy.

Conclusion
UST is an effective therapeutic option in CD for both bio-naïve and previous biologic failure patients. Although our cohort had a large proportion of patients with complicated and refractory disease, clinical response was observed, regardless of their previous exposure status to biologics, and disease phenotype. UST appears to be well tolerated with a reasonable safety profile. UST has good drug-persistence rates making it economically feasible in the long term. Clinicians could safely continue UST for longer durations to manage CD.
P568 Clinical relevance of baseline and change in Urgency Numeric Rating Scale score for mirikizumab treatment for Ulcerative Colitis
Authors: Clemow D , Dubinsky M C , Baygani S , Sands B E , Keohane A , Danese S , Travis S , Schreiber S , Walsh A , Hibi T , Hunter Gibble T , Moses R 
Published: January 2024

Abstract

Background
Mirikizumab (MIRI), an anti-IL-23p19 antibody, has demonstrated efficacy/safety in moderately-to-severely active ulcerative colitis (UC) Phase 3 trials (LUCENT-1 and -2; NCT03518086, NCT03524092). This analysis evaluated induction and maintenance efficacy of MIRI among patients with different baseline (BL) bowel urgency severity.

Methods
In LUCENT-1, patients were randomized to receive 3 intravenous doses of 300mg MIRI or placebo (PBO); 1 every 4 weeks (Q4W). In LUCENT-2, responders to MIRI induction at W12 were rerandomized to subcutaneous 200mg MIRI or PBO Q4W through W40 (52W continuous treatment). Endpoints: clinical response, clinical remission, endoscopic remission, symptomatic remission at W12 and W52 (definitions in figure legend), Urgency Numeric Rating Scale ([UNRS]: 11-point scale from 0 [no urgency] to 10 [worst possible urgency]). Analysis: Fisher's exact test with non-responder imputation by patient induction BL UNRS score: 0-3, 4-6, and 7-10; score cut-offs based on ≥3 being a clinically meaningful improvement (JPRO 2022;6:114).

Results
Number of patients by BL UNRS score of 0-3, 4-6, or 7-10: W12 – 149, 437, 576 patients, respectively; W52 – 70, 215, 259 MIRI responders. At W12 and W52, a significantly greater proportion of MIRI-treated patients achieved clinical response, clinical remission, endoscopic remission, and symptomatic remission, regardless of UNRS score group at induction BL, for all comparisons except W52 clinical remission score 0-3 (Figure 1). In general, across clinical endpoints and regardless of BL UNRS score, MIRI treatment improved UNRS scores at W12 and W52 for a majority of patients, regardless of achievement of the clinical endpoint, although to a lesser extent when not achieved. MIRI treatment improved UNRS scores at W12 and W52 to a greater extent than PBO treatment regardless of achievement of clinical endpoint (Table 1; clinical remission data shown). Regardless of BL UNRS score, individual-point score shift data (not shown) illustrated that score shifts generally were distributed across lower scores at W12 and W52 than BL. This is relevant since Dubinsky and colleagues (JPRO 2022;6:31) demonstrated that a UNRS 1-2-point change in score can be important to a patient.

Conclusion
Regardless of BL bowel urgency severity based on UNRS score, MIRI is efficacious in achieving symptomatic, endoscopic, and clinical endpoints in UC patients. MIRI improves bowel urgency severity vs PBO even if clinical endpoints are not achieved. Observing shifts in UNRS scores along the UNRS scale, regardless of starting point, may aid in understanding a patient’s efficacy outcomes. These results support MIRI’s efficacy in bowel urgency and the clinical relevance of bowel urgency severity assessment over time.
P571 The Effect of NLRX1 Activation on Eosinophils in Ulcerative Colitis and Inflammation: Translational Learnings Across Diseases and from Mouse to Human
Authors: Verstockt B , Dubinsky M , Peyrin-Biroulet L , Mosig R , Cataldi F , Vermeire S 
Published: January 2024

Abstract

Background
Although the precise role of eosinophils in IBD is debated, elevated eosinophils may influence response to therapy and clinical outcomes1. Thus, therapeutic agents which affect both neutrophil and eosinophil recruitment may provide more robust clinical improvement in patients with UC. NLRX1 is an immunometabolic protein which reduces oxidative stress, shifts cellular metabolism, and decreases inflammation in multiple cell types implicated in ulcerative colitis (UC). Studies of NLRX1 agonists (gut-selective NX-13 & systemic LABP-73) in diverse disease models identified novel cellular targets of NLRX1 activation. We compared NLRX1’s effect on eosinophils in 2 disease states, UC and the more prototypical eosinophilic disease, asthma, and evaluated the findings.

Methods
In the 4-week NX-13 Phase 1b, a double-blind trial of 36 patients with active UC (Total Mayo Score 4-10; Mayo endoscopic subscore 2-3) who were randomly assigned to NX-13 250mg Immediate Release (IR), 500mg IR, 500mg Delayed Release (DR) or Placebo QD for 4 weeks, histology was assessed using the Geboes score by a blinded pathologist2. For allergic asthma models, mice were immunized with ovalbumin or house dust mite followed by antigen challenge concurrent with LABP-73 or vehicle. Cells isolated from the lung were analyzed by flow cytometry using the BD FACS Celesta/Diva. Data are represented as means (standard error).

Results
In the 1b clinical trial, both the Geboes score and neutrophil subscores were reduced in the IR NX-13 group compared to placebo, consistent with the effects seen in preclinical IBD models. Upon examination, eosinophil infiltration was reduced in both the IR dose cohorts compared to placebo (Fig1A). In the subset of patients with active eosinophil infiltration at baseline (defined as Geboes subscore ≥2A.1), eosinophil reduction was seen in all NX-13 doses (Fig1B). Importantly, a numerically increased clinical response rate (decrease in total Mayo score of ≥3 or ≥30%) was seen in patients that demonstrated effective eosinophil reduction, compared to patients without improvement (75% versus 29%; Fisher’s Exact Test, p=0.08). In two allergic asthma models, NLRX1 activation by LABP-73 significantly reduced the fraction of eosinophils within the lung relative to vehicle control (n=7-8; p&lt; 0.05), confirming NLRX1 activation can regulate eosinophilic inflammation in Th2-mediated responses.

Conclusion
Neutrophil and eosinophil infiltration were reduced in UC patients treated with the gut selective NLRX1 agonist, NX-13, and was coupled with better clinical outcomes. The effect of NX-13 on eosinophils will be evaluated further in the ongoing phase 2 NEXUS trial in patients with UC.
1 A Mookhoek, et al. JCC (16).
2 L Peyrin-Biroulet, et al. JCC (17) Supp
P577 Histological Remission Leads to Less Endoscopic Flare-up in Moderate-to-Severe, Biologics Experienced Ulcerative Colitis Patients: A Comprehensive Retrospective Cohort Study
Authors: Wei Z H , Le P H , Chiu H Y , Yeh P J , Chiu C T , Chiu C H 
Published: January 2024

Abstract

Background
In the management of inflammatory bowel disease (IBD), adopting a treat-to-target strategy has proven beneficial. Current therapeutic targets primarily focus on achieving endoscopic remission. However, the significance of histological remission as a potential target. However, it remains underexplored in Asian populations. We aimed to investigate the role of histological remission in clinical outcomes among ulcerative colitis (UC) patients already in endoscopic remission.

Methods
In this retrospective cohort study, we enrolled moderate to severe, biologics experienced UC patients with endoscopic remission, defined as endoscopic Mayo subscore 0 point during June 2017 and September 2023 in Chang Gung Memorial Hospital, Linkou. Then the patients were divided into histological remission (HR) and non-histological remission (non-HR) groups according to histological Nancy index (NI). HR was defined as NI 0 point, and others belonged to non-HR group. Comparative analyses were performed between two groups regarding baseline characteristics, one year follow up and end of follow-up clinical outcomes. The location of biopsy was active inflammatory lesion, if no active lesion, we performed routine biopsy over rectum, 15cm level from anal verge. We took at least 4 pieces biopsy over each location.

Results
We enrolled 42 moderate-to-severe, biologics experienced UC patients (HR group, 23 patients and non-HR group, 19 patients) with endoscopic remission. The average follow-up duration was 17.6 months. In non-HR group, NI scores were categorized as follows: 1 point (42.1%), 2 points (31.6%), 3 points (21.1%), and 4 points (5.3%). Baseline characteristics showed no significant differences between the two groups. In terms of outcomes, the HR group demonstrated a significantly lower endoscopic relapse rate (26.1% vs. 68.4%, P=0.006) and better results in Kaplan-Meier survival analysis (log-rank P=0.015) at the end of the follow-up period. The HR group also exhibited a reduction in clinical relapses, emergency department visits, and hospital admissions. Although these differences did not attain statistical significance, this phenomenon is likely attributable to the study's constrained sample size.

Conclusion
In moderate-to-severe UC patients who are biologics-experienced and in endoscopic remission, achieving histological remission is associated with a reduced rate of endoscopic relapse.