bluuebunny/crossref_metadata_2025_split huggingface dataset:
P370 Correlation of the IBD Disk with intestinal ultrasound in patients with inflammatory bowel disease
Authors: Katsaros M , Kalogirou M , Katsoula A , Paschos P , Karabatsou S , Tsionis T , Soufleris K , Giouleme O 
Published: January 2023

Abstract

Background
The Inflammatory Bowel Disease (IBD) Disk represents a self-administered questionnaire that can facilitate, in real time, assessment of IBD related disability, and IBD-related daily life burden. Surrogate markers of IBD activity tend to associate with increased disability. Intestinal ultrasound (IUS) is a non-invasive tool that can objectively and accurately define disease activity and complications in IBD patients. We investigated the correlation between IBD-Disk and IUS in IBD patients.

Methods
We performed a cross-sectional study that included formally diagnosed IBD patients who underwent IUS and subsequently completed the IBD-Disk questionnaire. Active disease on IUS was defined as bowel wall thickness (BWT) &gt;3 mm at the most affected bowel segment. The overall IBD-Disk score was calculated as the sum of its 10 components, ranging from 0 to 100 (best score: 0, worst score: 100). We explored the correlation between IBD-Disk and its components with IUS. We additionally investigated the correlation of IBD-related daily life burden with IUS. (IBD-Disk total score &gt; 40: high IBD related daily life burden vs IBD-Disk total score ≤ 40: low IBD related daily life burden).

Results
We included 49 patients (table 1), who underwent IUS for disease monitoring (59.2%) and symptoms suggestive of disease flare (40.8%). Median IBD-Disk total score in our cohort was 48 (IQR 18-58). Median IBD-Disk total score was 52 (IQR 47.3-61.5) in IUS active vs 16 (IQR 5-25) in IUS inactive patients (p&lt;0.001). The area under the ROC curve of IBD-Disk total score in predicting IUS activity was 0.88 (95% C.I: 0.77-0.99, p&lt;0.001, Figure 1). IBD-Disk score &gt;31 predicted disease activity in IUS with 90.6% sensitivity and 88.2% specificity. We observed a moderate correlation between IBD-Disk score and BWT (ρ=0.61, p&lt;0.001) as well as between IBD-Disk score and C-reactive protein (ρ=0.66, p&lt;0.001). Among the components of the IBD-Disk, 8/10 manifested a moderate correlation with BWT (table 2). IBD-Disk score &gt; 40 was found in 27/32 (84.4%) of IUS active and 2/17 (11.8%) of IUS inactive patients, while IBD-Disk score ≤ 40 was found in 5/32 (15.6%) of IUS active and 15/17 (88.2%) of IUS inactive patients respectively (p&lt;0.001). Median BWT was 1.95 mm (IQR 1.53-4.40) in patients with IBD-Disk score ≤ 40 and 5.9 mm (IQR 4.8-6.8) in patients with IBD-Disk score &gt; 40 (p&lt;0.001).

Conclusion
IBD-Disk displayed a significant correlation with IUS evidence of disease activity in IBD patients. Active disease in IUS was significantly correlated with a high IBD-related daily life burden as expressed by IBD-Disk total score &gt; 40. IBD-Disk could be used in clinical practice to evaluate disease activity and severity in IBD patients.
P374 Therapeutic drug monitoring can guide the intravenous-to-subcutaneous switch of infliximab and vedolizumab: a pharmacokinetic simulation study
Authors: Wang Z , Verstockt B , Sabino J , Ferrante M , Vermeire S , Dreesen E 
Published: January 2023

Abstract

Background
Subcutaneous (SC) formulations of infliximab (IFX) and vedolizumab (VDZ) were recently approved for maintenance treatment of patients with inflammatory bowel disease. However, further investigation is required to identify the patients most likely to benefit from intravenous (IV)-to-SC switch. We hypothesise that therapeutic drug monitoring (TDM) can guide the IV-to-SC switch.

Methods
Population pharmacokinetic (popPK) simulations were performed with previously published popPK models to explore the exposure profiles following various label and off-label IV-to-SC dosing scenarios (NONMEM 7.5).1-3 All virtual patients received IV IFX or VDZ at treatment weeks 0, 2, 6, 14, 22, and 30, and then switched to every two weeks (Q2W) or Q1W SC dosing.

Results
Following IV-to-SC switch according to label, the serum trough concentrations (Ctrough) will gradually increase over eight weeks (for IFX) and 16 weeks (for VDZ) before reaching the new steady state (SS) (Figure 1A-B). A linear relationship was observed between IV and SC Ctrough,ss for both drugs, allowing the prediction of SC Ctrough,ss hnbased on previous IV Ctrough,ss (Figure 1C-D).
Administering the first SC dose four instead of eight weeks after the last IV dose will hit SS much faster (immediately for IFX and in two months for VDZ), thereby allowing earlier TDM and avoiding the risk of temporary underexposure (Figure 2). Patients on Q6W or Q8W IV infliximab can safely switch to Q2W SC infliximab without a meaningful decrease in Ctrough,ss, while patients on Q4W IV infliximab need Q1W SC infliximab (Figure 3A). Vedolizumab Ctrough,ss will always be maintained after switching to Q2W dosing (Figure 3B).
While the Ctrough,ss target is easily maintained, it is more challenging to guarantee a stable eight-week averaged area under the concentration-time curve at SS (AUC8w,ss) upon switch. Surprisingly, switching to Q2W SC infliximab resulted in a lower AUC8w,ss than all possible IV infliximab dosing regimens used in clinical practice (Figure 3C). Only patients on Q4W IV vedolizumab should switch to Q1W SC dosing (Figure 3D). Depending on the belief whether it is Ctrough,ss or AUC that drives therapeutic response, patients who were on escalated IV dosing regimens may need Q1W SC to guarantee similar exposure before versus after switch (Table 1).

Conclusion
We performed popPK simulations to inform clinicians how to integrate TDM of IFX and VDZ into their clinical practice as a tool to monitor patients and guide decision-making on the optimal dosing strategy.
REFERENCES:
1. EMA/CHMP/548703/2019. European Medicines Agency. 2019.
2. Rosario et al. Aliment Pharmacol Ther. 2015.
3. Rosario et al. J Crohns Colitis. 13, S357 (2019).
P379 Effect of upadacitinib on inflammatory markers and clinical outcomes in patients with Crohn’s disease in the phase 3, U-EXCEL, U-EXCEED, and U-ENDURE studies
Authors: Vermeire S , Danese S , Cohen B L , Magro F , Chen Y , Ha C , Dubcenco E , Lacerda A P , Marced E , Oomen J , Garrison A , Peyrin-Biroulet L 
Published: January 2023

Abstract

Background
Improvement in clinical outcomes and normalisation of objective markers of inflammation, high-sensitivity C-reactive protein (hs-CRP) and faecal calprotectin (FCP), are considered treatment targets per STRIDE-II guidelines.1 We evaluated the effect of the oral selective Janus kinase inhibitor upadacitinib (UPA) on changes in hs-CRP, FCP, and clinical outcomes in patients with Crohn’s disease (CD).

Methods
In 2 phase 3, randomized, double-blind, placebo-controlled induction studies (U-EXCEL, NCT03345849; U-EXCEED, NCT03345836), patients with moderate-to-severe CD received 12-week treatment with UPA 45 mg (UPA45) once daily (QD) or placebo (PBO). Patients with clinical response to UPA45 were rerandomised in U-ENDURE (NCT03345823) to receive 52-week maintenance treatment with UPA 30 mg QD (UPA30), UPA 15 mg QD (UPA15), or PBO. Endpoints included marker normalisation (hs-CRP ≤ 5 mg/L, FCP ≤ 250 µg/g) in patients with elevated baseline marker levels, normal marker and clinical remission by Crohn’s Disease Activity Index (CDAI &lt; 150) or very soft/liquid stool frequency (SF)/abdominal pain score (APS) (average daily SF ≤ 2.8 and average daily APS ≤ 1, neither greater than baseline), and ≥ 50% reduction from baseline in marker values with a decrease of at least 100 points in CDAI from baseline. Median changes from baseline in marker levels were also evaluated. Non-responder imputation with no special data handling for missing data due to COVID-19 was used.

Results
Of 1021 enrolled patients, 645 (63.2%) had elevated hs-CRP (&gt; 5 mg/L) and 750 (73.5%) had elevated FCP (&gt; 250 µg/g) levels at baseline. Significantly greater proportions of patients with elevated baseline marker levels achieved normalisation with UPA compared with PBO at week 12 (Fig 1A/B) and week 52 (Fig 2A/B; nominal P &lt; .001 for all). Decreases in marker levels from baseline with UPA were observed as early as week 2 and were significantly greater than with PBO through week 12 (Fig 1C) and week 52 (Fig 2C; nominal P &lt; .001 for all). Patients achieved clinical endpoints and improvements in markers at significantly higher rates with UPA45 vs PBO at week 12 (Fig 1D–F) and with UPA15 and UPA30 vs PBO at week 52 (Fig 2D–F; P &lt; .001 for all). The safety profile of UPA in CD was previously reported and no new safety concerns were identified.

Conclusion
Improvements in clinical endpoints and normalisation of objective markers of inflammation were achieved as early as week 2 with UPA45 induction and sustained with UPA15 and UPA30 maintenance therapy in patients with CD. Median changes in hs-CRP and FCP with UPA support continued improvement of inflammation up to week 52.
1. Turner D., et al. Gastroenterology. 2021;160(5):1570–1583.
P380 Changes in faecal microbiome and metabolome are more pronounced in Crohn’s disease patients who adhered to the CD-TREAT diet and responded by calprotectin.
Authors: Svolos V , Hansen R , Russell R K , Gaya D R , Seenan J P , Macdonald J , Wilson D , Henderson P , Din S , Ho G T , Quince C , Ijaz U Z , Milling S , Nichols B , Papadopoulou R , McKirdy S , Gervais L , Shields S , Gerasimidis K 
Published: January 2023

Abstract

Background
Treatment with the CD-TREAT solid food diet improves disease activity indices, faecal calprotectin (FCAL) levels and quality of life in adults and children with active Crohn’s disease (CD); particularly in patients who adhere to the diet. Here we describe changes in faecal microbiome parameters during therapy with CD-TREAT and explore these changes against adherence.

Methods
Children and adult patients with active CD completed an 8-week treatment with CD-TREAT. The levels of FCAL, pH, total sulphide (colorimetry), short chain fatty acids (SCFA), branched chain fatty acids (BCFA) (gas chromatography), total bacterial load (qPCR for total 16S rRNA gene copy number/g) were measured in baseline faecal samples and at four and eight weeks of CD-TREAT. Liquid chromatography mass spectrometry (LC-MS) faecal metabolomics and 16s rRNA sequencing of the faecal microbiome were performed at the same timepoints. Since CD-TREAT is gluten-free, detection of the gluten immunogenic peptide (GIP) in faeces was used as an objective biomarker of treatment adherence. Data are presented as median (IQR).

Results
Forty patients [17 children, age: 14.0 (11.3-15.1) years; 23 adults, age: 33.9 (27.8-45.9) years] participated. Eighteen (45%) patients had detectable GIP in at least one of the two follow-up timepoints, suggesting incomplete adherence; the remaining 22 (55%) patients had undetectable GIP throughout the treatment course. Baseline FCAL levels decreased significantly in the group of patients with undetectable GIP [mg/kg, baseline: 1,190 (3,611-129); 8 weeks: 534 (92-1,230), p&lt;0.05] but not in patients with detectable GIP [mg/kg, baseline: 599 (328-1,857); 8 weeks: 702 (278-1,496)]. During CD-TREAT, the concentration of faecal acetate, propionate, butyrate, total sulphide, total microbial load and faecal pH significantly changed in those with undetectable GIP but were less pronounced where GIP was detectable (Figure 1). Shannon diversity and richness significantly increased at both genus and OTU level, the abundance of several taxa changed, and LC-MS faecal metabolome shifted during CD-TREAT, but only in those with undetectable GIP (Figures 2 & 3).

Conclusion
We have identified that full adherence with CD-TREAT only occurs in ~55% of recipients, however a significant reduction in calprotectin is seen in those who adhere, and this is associated with microbial and metabolic changes which parallel those seen in successful exclusive enteral nutrition.
P387 Different rate of transmural remission between first and second line of biologic treatment in Crohn's disease
Authors: De Sire R , Rispo A , Caiazzo A , Testa A , Nardone O M , Guarino A D , Olmo O , Calabrese G , Fierro G , Toro B , Cantisani N M , Ferrante M , La Mantia A , D'Alessandro E , Castiglione F 
Published: January 2023

Abstract

Background
Transmural remission in Crohn’s disease (CD) has been associated with improved long-term clinical outcomes including reduced hospitalization, surgery, escalation of treatment, and a decrease in clinical relapse over endoscopic remission alone. Albeit transmural remission rate (TRR) in CD patients treated with anti-TNF drugs in first line has been well explored, data on TRR using vedolizumab (VDZ) or ustekinumab (UST) as second-line therapy for CD are still scarce. The aim of this study was to evaluate the TRR in CD patients in maintenance treatment, comparing adalimumab (ADA) in first line with VDZ/UST in second line.

Methods
From 2018 to 2021 we performed a real world observational longitudinal study evaluating the TRR in all consecutive CD patients in a 2-years maintenance treatment with ADA in first line compared with those treated by VDZ or UST in second line. HBI, fecal calprotectin (FC), SES-CD, and bowel wall thickness (BWT) at ultrasound were analyzed in all patients at the baseline (T0) and after 2 years of maintenance treatment (T1). Clinical remission was defined when HBI was &lt;4. Endoscopic remission was defined when SES-CD was &lt;2. Transmural remission was defined when BWT was &lt;3 mm at a “per-patient” analysis. In accordance with recent literature, laboratory remission was defined when FC was &lt;94 ug/gr.

Results
One hundred and forty-one CD patients (78 ADA, 31 VDZ, 32 UST) were included in the study. At T1, transmural remission rate was recorded in 39.7% of CD patients treated in first line with ADA, and in 22.5% and 18.7% for VDZ and UST, respectively, in second line (ADA vs VDZ/UST: p&lt;0.05; VDZ vs UST: p 0.7). Endoscopic remission rate was 50% for patients treated in first line with ADA, and 32.2% and 31.2% for second line VDZ and UST, respectively (ADA vs VDZ/UST: p&lt;0.05; VDZ vs UST: p 0.9). Laboratory remission rate was 53.8% for patients treated in first line with ADA, and 29% and 37.5% for VDZ and UST in second line, respectively (ADA vs VDZ/UST: p&lt;0.05; VDZ vs UST: p 0.4). Clinical remission rate was 58.9% for patients treated in first line with ADA, and 45.1% and 40.6% for second line VDZ and UST, respectively (ADA vs VDZ/UST: p=0.057; VDZ vs UST: p=0.7).

Conclusion
Our findings showed that in CD patients in maintenance treatment with biologics, ADA in first line showed a higher TRR compared with VDZ/UST in second line. Moreover, VDZ and UST showed similar TRR and other outcomes when used in second line.
P391 Relative association of bowel urgency clinically meaningful improvement or bowel urgency remission versus stool frequency remission and rectal bleeding remission with improvement in Inflammatory Bowel Disease Questionnaire scores in patients with moderately-to-severely active Ulcerative Colitis: An analysis from LUCENT-1 and LUCENT-2 phase 3 clinical trials
Authors: Sands B E , Feagan B , Gibble T H , Keohane A , Eastman W , Traxler K , Schreiber S , Jairath V , Armuzzi A 
Published: January 2023

Abstract

Background
Bowel urgency is increasingly being recognized as an impactful symptom in patients with ulcerative colitis (UC)1. However, limited information is available regarding its potential association with other patient reported outcomes. We assessed the association of bowel urgency clinically meaningful improvement (CMI) or bowel urgency remission with Inflammatory Bowel Disease Questionnaire (IBDQ) scores whilst adjusting for the potential confounding effects of stool frequency (SF) and rectal bleeding (RB) remission using data from LUCENT-1 (NCT03518086) and LUCENT-2 (NCT03524092) phase 3 trials.

Methods
Bowel urgency severity was assessed by the Urgency Numeric Rating Scale (UNRS) (0=no urgency to 10=worst possible urgency). Bowel urgency CMI was defined as ≥3-point decrease in UNRS compared to baseline and bowel urgency remission was defined as UNRS of 0 or 1.2 IBDQ scores (range: 32–224) were calculated; higher scores indicate better quality of life. Mediation analyses were performed to examine the relative association between direct effects of bowel urgency CMI and bowel urgency remission (separate predictors) and IBDQ scores while adjusting for the potential confounding effects of SF remission and RB remission (mediators). Analyses were treatment agnostic and combined patients from mirikizumab and placebo groups from LUCENT-1 (N=1162) and LUCENT-2 (N=544) trials at Week (W) 12 and 40 (W52 of continuous treatment).

Results
At W12 and W52, bowel urgency remission directly accounted for 44.8% and 32.5% improvement in IBDQ total score, respectively; 22.7% and 39.1% of improvement was mediated by RB remission and 32.5% and 28.4% by SF remission, respectively. At W12, bowel urgency remission resulted in the largest proportion of improvement in each of the IBDQ domain subscores, whereas at W52, RB remission had a greater confounding effect (Fig. 1A). At W12 and W52, bowel urgency CMI accounted for 70% and 57.3% improvement in IBDQ total score, respectively; 12.8% and 25.6% of effects were mediated by RB remission and 17.2% and 17.1% by SF remission, respectively (Fig. 1B). Bowel urgency CMI accounted for the largest proportion of association with improvement in each of the IBDQ domain subscores at both W12 and W52.

Conclusion
Improvements in IBDQ scores were primarily ascribed to bowel urgency remission and bowel urgency CMI relative to RB remission and SF remission, particularly at W12, in patients with moderately-to-severely active UC. These findings suggest that bowel urgency is a critical and independent symptom that considerably impacts patients’ quality of life.
References:
P401 Concomitant azathioprine treatment effects vedolizumab treatment persistence in Crohn’s Disease but not in Ulcerative Colitis
Authors: Toruner M , Guvenir T , Er R E , Soykan I 
Published: January 2023

Abstract

Background
Vedolizumab is a monoclonal antibody against integrin α4β7 that is being used for the treatment of moderate to severe Ulcerative Colitis (UC) and Crohn’s Disease (CD). Recent studies have shown conflicting results for the effect of concomitant azathioprine use with vedolizumab monotherapy. In this single center cohort study, we investigated the effect of concomitant azathioprine treatment on vedolizumab drug persistence in UC and CD treatment.

Methods
We performed a retrospective review of all adult (≥18 years) UC and CD patients started on VDZ at our infusion center. Data collection included baseline demographics, concomitant azathioprine therapy, VDZ therapy and disease activity scores using the partial Mayo score and Harvey Bradshaw Score. Data were obtained from the digital medical record. The primary outcome measure was VDZ persistence, represented in Kaplan-Meier analysis. This analysis assessed persistence on every 8 week dose regimen.

Results
This single center cohort included 142 VDZ treated UC (n=64) and CD (n=78) patients. All patients had a history of at least one anti-TNF treatment: Mean age 38.9±12.5 years and male gender 84 (59.2%). Median disease duration was 6±1.6 years. 6 Patients were excluded from the analysis since VDZ therapy has been stopped due to side effects. Mean duration of VDZ treatment in Crohn’s disease was 96.5±69.2 weeks and in UC was 72.1±60.5 weeks. Concomitant azathioprine therapy in CD increased VDZ persistence rate. However, in UC concomitant azathioprine therapy did not effect VDZ persistence rate.

Conclusion
The real-world data collected in this study demonstrate that concomitant azathioprine treatment increase the VDZ persistence rate in Crohn’s disease. However, concomitant azathioprine treatment does not effect the VDZ persistence rate in UC patients.
P428 Pharmacist led clinic in Inflammatory Bowel Disease
Authors: Kwok J , Smith J , Gashau W , Shuttleworth E 
Published: January 2023

Abstract

Background
Only 13% of IBD teams across the UK have a specialist pharmacist within the MDT (1). Pharmacists have a crucial role in safe and effective medication prescribing and monitoring (2). Studies have shown that pharmacist led clinics are acceptable to clinicians and patients (2). At our trust we set up a pharmacist led biologic switch clinic where a specialist pharmacist counselled regarding biologic therapy switch from intravenous (IV) to subcutaneous (SC) medication and assessed disease burden at baseline and follow up. We set up thiopurine clinic where the specialist pharmacist arranges monitoring and facilitates pre-emptive switch of stable patients to shared care prescribing with the GP, in line with the national commitment of providing convenient and easy access to services. We analysed patient feedback, biologic and shared care prescribing data to assess the impact of our pharmacist-led clinics.

Methods
Patients who had been scheduled in thiopurine and biologic switch clinic were sent with questionnaires either by post or email. Both paper and electronic data were collected and analysed using Microsoft ExCel. Biologic therapy and thiopurine prescribing and monitoring databases were setup and data were captured and analysed retrospectively.

Results
112 patients were switched from IV biologic therapy to SC therapy of which 8 patients needed to be switched back to IV due to either an adverse reaction or uncontrolled IBD. By reducing drug cost and increasing hospital CIU capacity, the biologic switch clinic has generated significant financial savings to the organisation (estimated £333,666 per annum).
In thiopurine clinic, 80 patients were identified as suitable candidates for shared care agreement with primary care. 88% patients have been successfully transferred to primary care and the remaining 12% remained under secondary care because the GP opted-out.
88% of patients who had been scheduled in pharmacist led clinic were happy with the service and the remainder had a neutral opinion regarding the service (see chart). Some patients fed-back that the telephone consultation did not happen at scheduled time or they preferred face to face clinic.

Conclusion
Pharmacist led clinic led to significant cost savings, increased accessibility to thiopurines and was acceptable to patients. In response to patient feedback we amended our appointment letters to clarify appointment time frames and give pharmacist contact details for further patient queries. We have also set up face to face clinics for patients preferring this option.
References:
1 Burns, Corrinne. Only 13% of IBD teams meet standards for pharmacist. London: Pharmaceutical journal, 2021
2 IBDUK. The hidden cost and a vision for change. London: Crohn's and Colitis care in the UK, 2021