bluuebunny/crossref_metadata_2025_split huggingface dataset:
P582 Combination of granulocyte–monocyte apheresis and ustekinumab: multicentre and retrospective study
Authors: Rodríguez-Lago I , Herrera-deGuise C , Boscá-Watts M , Rodríguez C , Leo E , Calvo M , Cañete F , Chacón S , Cuarán C , Elorza A , Guerra E , Iglesias E , Sánchez D , Barreiro-de Acosta M , Ginard D , Cabriada J L 
Published: January 2024

Abstract

Background
Granulocyte–monocyte apheresis (GMA) selectively removes activated leukocytes and immune mediators, and it has shown to be safe and effective in treating ulcerative colitis (UC). Previous reports have also described its combination with biologics, mainly with anti-TNF.

Methods
The aim of our study was to evaluate the clinical efficacy and safety of combining GMA after primary non-response (PNR) or loss of response (LOR) to ustekinumab (UST) in patients with UC. A retrospective, multicentric study was performed in 12 IBD Units, including all patients with refractory UC who received combined GMA plus UST. The number of GMA sessions, its frequency, filtered blood volume and time of each session were compiled, along with the clinical data. Efficacy was assessed 1 and 6 months after finishing the GMA by partial Mayo score, CRP and faecal calprotectin. Data regarding UST intensification, need for new immunomodulators/biologics and surgery were also compiled. Descriptive statistics and non-parametric tests were used in the statistical analysis.

Results
Nineteen patients were included (15 UC, 2 Crohn’s disease, 2 unclassified IBD; median age 48 years (IQR, 36-63); 68% male). At baseline, 78% were receiving steroids and 23% immunomodulators. Most patients (89%) had prior exposure to anti-TNF agents and 53% to vedolizumab. Baseline Mayo score was 6.5 (IQR, 5-7), with a median CRP of 9 mg/L (IQR, 4.8-20.8) and faecal calprotectin 1,612 mg/kg (IQR, 873-4,152). GMA was started mostly after PNR in 83%, the median number of GMA sessions was 16 (IQR, 11-27) and 50% of patients started maintenance GMA. Partial Mayo score significantly decreased 6 months after the last GMA session (p=0.019). During follow-up, 27% started a new biologic therapy and 13% required surgery. 64% of patients under steroids at baseline were able to stop them. Adverse events were reported in 5% of patients.

Conclusion
GMA can safely recapture the response to UST in refractory patients after PNR or LOR to this drug.
P585 Effectiveness of Switching to Subcutaneous Infliximab in Ulcerative Colitis Patients Experiencing Intravenous Infliximab Failure
Authors: Bae J H , Park J B , Baek J E , Hong S W , Park S H , Yang D H , Ye B D , Byeon J S , Myung S J , Yang S K , Hwang S W 
Published: January 2024

Abstract

Background
Studies on elective switching to the subcutaneous (SC) formulation of infliximab revealed comparable efficacy and safety and higher infliximab level than those exhibited by intravenous (IV) infliximab. However, no studies have reported on the effectiveness of SC switching in ulcerative colitis (UC) patients who experienced IV infliximab failure during maintenance treatment.

Methods
This retrospective study included UC patients who had been switched to SC infliximab because of IV infliximab failure, between January 2021 and January 2023. Group A was defined as having clinically and biochemically active UC (secondary loss of response), and group B consisted of patients with stable symptoms but biochemically active UC.

Results
Twenty-three patients met the inclusion criteria: 15 in group A and 8 in group B. The serum infliximab levels significantly increased after SC switching in both groups. Electively switched group also exhibited increased infliximab levels after SC switching. Group A showed improved partial Mayo score with a significant decrease in faecal calprotectin (FC) and C-reactive protein after switching. In group B, the FC level significantly decreased without clinical relapse after switching. A high proportion of patients (≥ 80%) in both groups achieved clinical and/or biochemical response at last follow-up. During the follow-up period, only two patients in group A discontinued SC infliximab, and only one complained of severe injection site reaction.

Conclusion
In UC patients who experience IV infliximab failure during maintenance treatment, switching to SC infliximab may be a promising option because of its efficacy and safety.
P595 Assessment of mucosal healing after exclusive elemental diet using small bowel capsule endoscopy in paediatric Crohn’s disease
Authors: Kim Y E , Choi H J , Jang J Y , Lee S H , Kim D Y , Oh S H , Kim K M 
Published: January 2024

Abstract

Background
Exclusive elemental nutrition (EEN) is an effective treatment for induction of remission and is recommended as first-line induction therapy in children with active luminal Crohn’s disease (CD). Evaluating treatment response is important because endoscopic or mucosal healing is associated with long-term outcomes, but it is difficult to perform repeated colonoscopies in children. Small bowel capsule endoscopy (SBCE) is used to diagnose small bowel lesions and is more convenient than colonoscopy. This study aimed to evaluate the improvement of small bowel mucosal lesions using SBCE in paediatric CD patients treated with EEN as induction therapy.

Methods
We retrospectively reviewed data from patients under 18 years of age who were newly diagnosed with CD and commenced EEN as induction therapy between May 2018 and April 2023. Among these patients, we included those who completed EEN for more than 6 weeks and underwent SBCE at both the time of diagnosis and within 2 weeks of completion of EEN. We analysed the proportion (%) of patients who achieved mucosal healing (defined as the Lewis score &lt; 135) and patients exhibiting improvement in ulcers on the follow-up SBCE after EEN. We also compared the Lewis score, laboratory tests, and BMI z-score before and after EEN using the paired t-test.

Results
A total of 71 patients (57 males, 14 females) were included with a mean age of 13.3 ± 2.27 years (range 7-17 years). After 6 to 8 weeks of EEN, 64 patients (90.1%) showed improvement in ulcers on follow-up SBCE, including 35 patients (49.3%) with complete disappearance of ulcers and 29 patients (40.8%) with partial disappearance of ulcers. Seven patients (9.9%) showed no improvement. The Lewis score was significantly decreased (p &lt; 0.001). In addition, mucosal healing, defined as the Lewis score &lt; 135, was achieved in 28 patients (38%). When comparing laboratory tests before and after EEN, haemoglobin and albumin increased (p &lt; 0.001), and ESR, CRP, and fecal calprotectin decreased significantly (p &lt; 0.001). However, BMI z-score was not improved after EEN (p = 0.46).

Conclusion
Most patients showed improvement in ulceration on SBCE after EEN. Additionally, improvements in blood test and fecal calprotectin levels were noted following EEN. It is suggested that SBCE is a useful tool to evaluate mucosal healing after EEN in paediatric Crohn's disease.
P615 Clinical efficacy of accelerated 4-weekly vs. Conventional 8-weekly ustekinumab dosing in Inflammatory Bowel Disease: A single centre experience
Authors: Lloyd A , Quarry S , Sugrue K , Gleeson S , O'Sullivan G , O'Sullivan C , Forde G , Doyle M , Moran C , Mcdonald C , Sheehan D , Buckley M , Iacucci M , McCarthy J 
Published: January 2024

Abstract

Background
8-weekly dosing regimen of ustekinumab in the treatment of moderate-to-severe Inflammatory Bowel Disease (IBD) is the current standard of care. Accelerated 4-weekly dosing has been suggested to be efficacious, however not licensed, in ‘non-responders’. The aim of this study is to determine how 4-weekly accelerated dosing regimen in ustekinumab drug levels correlate with response to treatment in patients with IBD.

Methods
Patients for inclusion were identified retrospectively utilising online prescription records at Mercy University Hospital, Cork. Inclusion criteria consisted of IBD patients commenced on ustekinumab with a treatment duration of at least 6 months. Participants were separated into 4-weekly and 8-weekly treatment groups. Faecal calprotectin (FCP) levels/ustekinumab drug levels were recorded from the 12-week check in post initiation and at the 2nd assessment. Symptoms were scored at these visits and further quantified using the Harvey Bradshaw index for Crohn’s Disease and the partial mayo score for Ulcerative Colitis.

Results
101 patients at the Mercy University Hospital Cork were identified utilising a database of prescriptions and physical charts (4-weekly: 27; 8-weekly: 74). A statistically significant decrease in FCP levels at 2nd assessment was noted in patients with 4-weekly dosing (p=0.028). There was no statistically significant relationship between dosing interval and symptoms (p=0.735). Individual patient factors including age, gender, type of IBD, and concurrent IBD medications did not have a statistically significant effect on faecal calprotectin levels or symptoms.

Conclusion
The greater percentage decrease in faecal calprotectin provides objective evidence supporting the escalated dosing interval at the Mercy University Hospital IBD centre. However, further study is necessary to justify increasing the dosing interval for all patients treated with ustekinumab for IBD.
P619 Sleep disruption is associated with reduced quality of life in inflammatory bowel disease through its interaction with pain
Authors: Barnes A , Mountifield R 
Published: January 2024

Abstract

Background
Quality of life is reduced in people with inflammatory bowel disease. Poor sleep is prevalent in people with inflammatory bowel disease. This study aimed to investigate the influence of sleep on quality of life in people with inflammatory bowel disease.

Methods
An online questionnaire was administered through three tertiary IBD centres, social media and through Crohn’s Colitis Australia. The questionnaire included the EQ-5D-5L measures of health-related quality of including EQ-5D utility score, EQVAS – visual analogue scale from 0-100 of quality of life and domains mobility, selfcare, activities, pain and depression and anxiety. Measures of sleep included the insomnia severity index (ISI), and the Pittsburgh sleep quality index (PSQI). IBD activity was assessed using validated patient reported scores. Demographic data and mental health scores were also obtained.

Results
Quality of life was lower in people IBD than the general South Australian population (utility score mean (SD) 0.79 (0.15) v 0.91(0.14)). Poor sleep and clinically significant insomnia were associated with lower quality of life (utility score 0.77 (0.15) and 0.71 (0.16) respectively, cohort 0.79 (0.15), p&lt;0.0001). Sleep quality scores moderately correlated with EQ-5D domains pain (Ro=0.35), usual activities (Ro=0.32), and depression-anxiety (Ro=0.37) but not domains self-care or mobility. After adjusting for demographic variables, IBD anxiety, depression, and anxiety the pain domain continued to be influenced by sleep quality, sleep disturbance and sleep duration, and the usual activities domain continued to be influenced by daytime dysfunction (see table 1).
Clinically significant insomnia was associated with a reduction of 13.6 (10.42-16.91) (univariate regression) in quality of life measured by EQVAS. Following introduction of demographic and IBD activity the reduction in EQVAS for clinically significant insomnia remained significant (10.11 (6.96-13.27)). Health related quality of life scores (EQVAS) were significantly worse in those with clinically significant insomnia and active IBD than with active IBD alone (see Figure 1).

Conclusion
Health related quality of life in IBD is influenced by aspects of sleep quality irrespective of IBD activity and mental health conditions. The presence of insomnia is associated with a significant decline health related quality of life. Consideration should be given to sleep targeting interventional studies in an IBD population.
P623 Network meta-analysis to evaluate the comparative efficacy of advanced therapies as first line for maintenance treatment of adult patients with moderate-to-severe Crohn’s disease
Authors: Schreiber S W , Danese S , Colombel J F , Hisamatsu T , Irving P M , Park H , Kim D H , Lee Y N , Hanauer S B 
Published: January 2024

Abstract

Background
Subcutaneous (SC) CT-P13 provides patients and physicians with a new opportunity for maintenance treatment of Crohn’s disease (CD).1 Given the rapidly expanding therapeutic armamentarium for CD and lack of direct comparative evidence,2 an updated network meta-analysis (NMA) of data from Phase 3 randomised controlled trials (RCTs) was performed to evaluate the comparative efficacy of advanced CD therapies licensed in Europe or the US.

Methods
Eligible studies, identified by systematic literature review (PROSPERO no.: CRD42023413752), evaluated the efficacy of maintenance therapy using intravenous (IV) or SC infliximab, SC adalimumab, IV or SC vedolizumab, SC ustekinumab, SC risankizumab or oral upadacitinib, in patients with moderate-to-severe CD who responded to induction therapy. Head-to-head studies (including with treat-through designs) comparing licensed advanced therapies were also eligible. Studies were placebo- (PBO) or active-controlled and included 52–64 weeks of follow-up. Patients had not received prior tumour necrosis factor inhibitors, other biologics or Janus kinase inhibitors, thus each drug was received as first-line advanced therapy. Clinical remission and endoscopic response rates achieved with maintenance treatment were synthesised and analysed in a frequentist NMA random-effects model.

Results
There were 9 eligible RCTs (ACCENT I, LIBERTY-CD, CHARM, SEAVUE, GEMINI 2, VISIBLE 2, IM-UNITI, FORTIFY, U-ENDURE). Among 14 compared treatment arms, SC infliximab 120 mg every 2 weeks (Q2W) showed the highest risk difference (RD) versus PBO for achieving clinical remission during the maintenance phase (0.38 [95% confidence interval (CI): 0.23, 0.53]), followed by SC adalimumab 40 mg QW (0.32 [0.17, 0.48]) and oral upadacitinib 30 mg once daily (0.30 [0.08, 0.53]) (Figure A). Endoscopic response data were available from LIBERTY-CD, FORTIFY and U-ENDURE: among 5 treatment arms, SC infliximab 120 mg Q2W showed the highest RD (95% CI) versus PBO for achieving endoscopic response (0.39 [0.29, 0.49]), followed by SC risankizumab 180 mg Q8W (0.37 [0.17, 0.56]) and SC risankizumab 360 mg Q8W (0.27 [0.06, 0.48]) (Figure B).

Conclusion
In this updated NMA, SC infliximab 120 mg Q2W demonstrated a favourable efficacy profile in terms of achieving clinical remission and endoscopic response, when administered as a first-line advanced therapy for maintenance treatment of patients with moderate-to-severe CD.
1Remsima summary of product characteristics (https://www.ema.europa.eu/en/documents/product-information/remsima-epar-product-information_en.pdf). Accessed 1 November 2023.
2Barberio B et al. Gut 2023;72:264–74.
P624 Development and Validation of a Clinical Decision Support Tool to Predict Outcomes of ustekinumab Treatment in Patients with Crohn’s Disease
Authors: Yao L , Cao Y , Cao Q 
Published: January 2024

Abstract

Background
Ustekinumab (UST) has been demonstrated for the treatment of Crohn's disease (CD) with a high efficacy and safety profile. There is limited data concerning disease progression after UST treatment. This study aims to establish a clinical decision support tool (CDST) to identify Chinese patients with CD who are less likely to experience disease progression under UST treatment.

Methods
A multicentre, retrospective observational study was conducted among Chinese patients with CD initiating UST between 1 May 2020 and 20 October 2022. Disease progression (including CD-related surgery, hospitalization and complications) was evaluated at week 24 (±4w). Logistic regression analysis was performed to identify factors associated with disease progression. The CDST, established based on these factors, was both internally and externally validated. The performance of this tool was tested using receiver operating characteristic (ROC) area under the curve (AUC) analyses.

Results
A total of 519 patients were enrolled in this study. In the derivation analysis, four factors including prior biologics usage, prior immunosuppressant usage, baseline faecal calprotectin, and baseline haemoglobin were identified to correlate with progression. A good predictive ability of this model was confirmed by AUC as high as 0.76 for the internal validation cohort and 0.72 for the external validation cohort, respectively. The CDST stratified patients into low, intermediate, or high risk of progression with cut-off values of 6 and 16.

Conclusion
We developed and validated a scoring system to identify CD patients less likely to experience progression at week 24 with UST therapy. This CDST will facilitate therapy decision-making and precision medicine.
P627 Real-world clinical effectiveness and safety of vedolizumab and ustekinumab in biologic-naïve patients with Crohn’s disease by disease location: Results from the EVOLVE Expansion study
Authors: Scharl M , Christensen B , Bressler B , Brett N R , Gianchetti L , Kamble P , Adsul S , Farhat Z , Ferrante M 
Published: January 2024

Abstract

Background
Crohn’s disease (CD) location may affect disease course and treatment (Tx) decisions. This analysis compared real-world clinical effectiveness and safety of vedolizumab (VDZ) and ustekinumab (UST) in biologic-naïve patients (pts) by CD location.

Methods
Medical charts of biologic-naïve pts with CD aged ≥18 years initiating VDZ or UST in Australia, Belgium or Switzerland from 2016 to 2021 were analysed in a multicentre, observational, retrospective EVOLVE Expansion study (NCT05056441). Subgroup analysis evaluated outcomes with VDZ vs UST in pts with baseline ileal, ileocolonic and colonic CD (Montreal classification). Data were collected from Tx initiation to the first of chart abstraction initiation, Tx discontinuation, loss to follow-up or death. Inverse probability of Tx weighting (IPTW) was used to balance baseline characteristics between cohorts. Clinical outcomes (clinical response, clinical remission, mucosal healing), as assessed using published algorithms,1 and Tx persistence during 36 Tx months were analysed in time-to-event analyses (Kaplan-Meier method). Risks of safety (serious adverse events [SAEs], serious infections [SIs]) and healthcare resource utilisation (HCRU; CD exacerbations, CD-related hospitalisations, CD-related surgeries) outcomes with VDZ vs UST during 36 months were also compared.

Results
This analysis included 293 pts with ileal (VDZ:158, UST:135), 185 with ileocolonic (VDZ:91, UST:94) and 121 with colonic (VDZ:84, UST:37) CD. Baseline characteristics after IPTW were similar between VDZ and UST cohorts in all 3 subgroups. Cumulative rates during 36 Tx months were similar between VDZ and UST cohorts in ileal, ileocolonic and colonic CD subgroups for clinical response (p=0.67, p=0.94, p=0.22, respectively), clinical remission (p=0.51, p=0.20, p=0.52), mucosal healing (p=0.29, p=0.60, p=0.71) and Tx persistence (p=0.37, p=0.29, p=0.50) (Figure). There were no differences in the risks of SAEs, SIs, CD exacerbations and CD-related hospitalisations between cohorts across disease location; risk of CD-related surgeries was similar in pts with ileocolonic and colonic CD, and higher in VDZ vs UST cohort (p=0.02) in pts with ileal CD (Table). However, in ileal CD subgroup, CD-related surgeries during 36 months were reported only in 12/158 (7.6%) pts in VDZ and 3/135 (2.2%) pts in UST cohort.

Conclusion
During 36 Tx months, effectiveness, safety and HCRU outcomes were similar between VDZ and UST cohorts regardless of baseline disease location; risk of CD-related surgeries was higher with VDZ vs UST in pts with ileal CD and similar between cohorts in other subgroups. However, the absolute number of pts requiring CD-related surgeries was low.
Reference:
1. Bressler B, et al. J Crohns Colitis. 2021;15(10):1694-1706.
P632 Isolation of a novel metalloproteinases transcriptional signature with robust anti-TNF therapy predictive power in patients with Ulcerative Colitis
Authors: Arosa García L , Camba-Gómez M , Calviño-Suárez C , Bastón-Rey I , Ferreiro-Iglesias R , Porto M , Nieto L , Domínguez-Muñoz J E , Barreiro-de Acosta M , Conde-Aranda J 
Published: January 2024

Abstract

Background
Anti-TNF agents were the only biologic for Inflammatory Bowel Disease (IBD) patients. However, new drugs targeting α4β7 integrin, IL-12/IL-23, and janus kinases were added to the IBD therapeutic armamentarium. Anti-TNFs are first-line biological agents in our country, and for that reason, the discrimination of patients who will be refractory of those therapies before treatment is relevant to prevent IBD patients from the exposition to multiple therapeutic failures. Therefore, we wanted to isolate robust and reproducible transcriptional markers able to specifically predict the response to anti-TNF therapy, which will contribute to targeted prevention, improve individual outcomes and decrease therapy expenditures.

Methods
We analysed publicly available microarray and RNAseq datasets of colon biopsies (GSE12251, GSE16879 and GSE73661) and whole blood cells from different cohorts of patients with Ulcerative Colitis (UC) (GSE191328). R package was used to perform the differential expression analyses and calculation of receiver operating characteristic (ROC). Cytoscape software and Morpheus (broadinstitute.org) was used to perform network data integration and visualization. Also, we used our local cohort of UC patients to further validate our results by RT-qPCR (n=21).

Results
We isolated a transcriptional signature composed of eight metalloproteases (MMPs) with high association with disease activity. Most of the transcripts of that signature were significantly upregulated in colon biopsies of non-responder patients to anti-TNFs before treatment in three different microarray datasets, but not in vedolizumab-treated patients. ROC curves of the different MMPs showed variability in the correlation to anti-TNF response among the different datasets analysed. Only three out of eight MMPs were still showing robust predictive power with an area under the curve around of 80% when all dataset were combined. Interestingly, PBMCs isolated from our local cohort of IBD patients presented increased expression of those MMPs in refractory patients to anti-TNF therapy, confirming that these three MMPs have the highest predictive power both in colon tissue and in peripheral mononuclear cells.

Conclusion
Overall, our study revealed a novel and robust MMP-transcriptional signature associated with anti-TNF but not vedolizumab therapy response. Nevertheless, our results should be corroborated in independent cohorts of patients with UC to test their efficacy and sensitivity in the clinical setting. Our data definitively contribute to the change from a reactive approach to predictive, preventive and personalised medicine.