bluuebunny/crossref_metadata_2025_split huggingface dataset:
OP23 Efficacy and safety of upadacitinib as induction therapy in patients with Moderately to Severely Active Ulcerative Colitis: Results from phase 3 U-ACCOMPLISH study
Authors: Vermeire S , Danese S , Zhou W , Pangan A , Greenbloom S , D’Haens G , Panes J , Juillerat P , Lindsay J O , Loftus Jr E V , Sandborn W J , Reinisch W , Sanchez Gonzalez Y , Huang B , Xie W , Liu J , Weinreich M A , Panaccione R 
Published: May 2021

Abstract

Background
Upadacitinib (UPA) is a selective and reversible Janus kinase inhibitor.U-ACCOMPLISH is one of two phase 3 induction trials that evaluated the safety and efficacy of UPA 45 mg once daily (QD) in adults with ulcerative colitis (UC).

Methods
U-ACCOMPLISH was a multicentre, randomized, double-blind, placebo-controlled trial (NCT03653026) that enrolled patients with moderate-to-severe UC (defined as adapted Mayo score 5–9 with centrally read endoscopic score 2–3) who had inadequate response, loss of response, or intolerance to aminosalicylates, immunosuppressants, corticosteroids and/or biologics. Patients were randomized 2:1 to UPA 45 mg QD or placebo (PBO) for 8 weeks. At week 8, responders entered the maintenance phase and non-responders entered the extended treatment period to receive open-label UPA 45 mg QD for additional 8 weeks.The primary endpoint (clinical remission per adapted Mayo Score) and ranked secondary endpoints including symptomatic, endoscopic– histologic evaluations from the 8-week PBO-controlled period are reported here. Non-responder imputation incorporating multiple imputation for missing data due to COVID-19 are reported.

Results
522 patients were randomized (UPA, n=345; PBO, n=177); the intent-to-treat population included 341 patients in UPA and 174 patients in PBO group. Baseline demographics and disease characteristics were similar between groups; 50.7% and 51.1% were biologic inadequate responders in UPA and PBO groups, respectively (Table 1). A significantly higher proportion of patients receiving UPA 45 mg QD (33.5%) versus PBO (4.1%) achieved the primary endpoint (adjusted treatment difference: 29.0% [23.2, 34.7]; P&lt;0.001). A significantly higher proportion of patients receiving UPA versus PBO also achieved all ranked secondary endpoints (all P&lt;0.001; Figure 1).Serious adverse events were reported by 3.2% and 4.5% of patients in UPA and PBO groups, respectively (Table 2). Similar rates of serious infection were observed in both groups (0.6%); 2 events each of herpes zoster and opportunistic infection were reported in UPA group. No active tuberculosis, malignancy, adjudicated major adverse cardiovascular events, or deaths were reported in the study. One patient with venous thromboembolism (deep vein thrombosis and pulmonary embolism) and 1 patient with gastrointestinal perforation were reported in the placebo group.

Conclusion
In U-ACCOMPLISH, 8-week UPA 45 mg QD induction treatment led to statistically significant improvements in clinical, endoscopic, and combined endoscopic-histologic endpoints. The treatment was well tolerated, and the safety profile and AE prevalence was comparable with previous studies of UPA with no new safety signals identified.
OP33 Oral ritlecitinib and brepocitinib in patients with Moderate to Severe Active Ulcerative Colitis: Data from the VIBRATO umbrella study
Authors: Sandborn W , Danese S , Leszczyszyn J , Romatowski J , Altintas E , Peeva E , Vincent M , Reddy P , Banfield C , Banerjee A , Gale J , Hung K 
Published: May 2021

Abstract

Background
The efficacy and safety of oral ritlecitinib (JAK3/TEC inhibitor) and brepocitinib (TYK2/JAK1 inhibitor) were assessed in a 32-week Phase 2b induction-maintenance umbrella study (VIBRATO) in participants with moderate to severe active ulcerative colitis who had inadequate or loss of response, or intolerance to corticosteroids, immunosuppressants, or biologic therapies. We report efficacy and safety results from the 8-week induction period of the VIBRATO study.

Methods
Adult participants with Total Mayo Score ≥6 and centrally-read Mayo endoscopic subscore ≥1 were randomised to receive oral ritlecitinib 20, 70, or 200 mg; brepocitinib 10, 30, or 60 mg; or placebo once-daily (QD) for 8 weeks. Participants then continued in their respective treatment cohorts to receive ritlecitinib 50 mg or brepocitinib 30 mg QD for 24 weeks. The proportions of patients who achieved remission (Total Mayo Score ≤2; no individual subscore &gt;1; rectal bleeding subscore 0), modified remission (Modified Mayo Score: Total Mayo without Physician’s Global Assessment; stool frequency subscore ≤1; rectal bleeding subscore 0; endoscopic subscore ≤1), or endoscopic improvement (Mayo endoscopic subscore ≤1) were analysed.

Results
319 participants were randomised: baseline mean (standard deviation [SD]) age 40.3 (13.8) years; mean (SD) Total Mayo Score 9.0 (1.5); and median (range) disease duration 4.8 (0.24, 36.5) years. Ritlecitinib and brepocitinib were generally safe and well tolerated. At Week 8, a dose–response relationship was observed across all efficacy endpoints for ritlecitinib and brepocitinib. The proportions of participants achieving remission were significantly higher (P&lt;0.05) with ritlecitinib 70 and 200 mg and brepocitinib 30 and 60 mg vs placebo (Figure 1). The proportions of participants achieving endoscopic improvement and modified remission were significantly higher in all ritlecitinib and brepocitinib groups vs placebo (Figures 2 and 3).

Conclusion
Ritlecitinib 70 and 200 mg QD and brepocitinib 30 and 60 mg QD demonstrated significant improvement in remission, modified remission, and endoscopic improvement in participants with moderate to severe active ulcerative colitis.
P035 Potential biomarkers for diagnosis through proteomics, in patients with Inflammatory Bowel Disease
Authors: Muñoz-Villafranca C , Aresti Goiriena U , Ispizua N , Irigoyen Muñoz M , Rivera Garcia N A , Ortiz de Zárate J , Arreba Gonzalez P , Calderón García Á J 
Published: May 2021

Abstract

Background
Currently,endoscopy,an invasive medical procedure, is the gold standard for diagnosis of inflammatory bowel disease (IBD) and to determine mucosal activity.Our main goal was to identify biomarkers in saliva samples that can be used as a screening tool for the diagnosis of ulcerative colitis(UC) and Crohn`s disease(CD).

Methods
100 saliva samples were collected from: healthy individuals(20), UC-active stage(10),UC-remission stage(31),CD-active stage(7) and CD-remission stage(32) patients. The samples were thawed on ice and centrifugated at 10,000g for 15 min at 4ºC.The supernatants were aliquoted and stored at -80ºC.
The protein extracts were digested with trypsin and peptides resulting from digestion were loaded onto a nano Acquity UPLC chromatograph and analysed in a nano Elute coupled on-line to a timsTOF Pro(Bruker).The data obtained was then processed and loaded onto the Progenesis LC-MS software (Nonlinear Dynamics) for Orbitrap data and PEAKS(Bioinformatics Solutions Inc.) for timsTOF Pro data. Finally, this information was converted to deregulation patterns at protein level and relative quantification was done.
Saliva protein levels were compared between healthy (always as control) and CD remission,UC remission,UC active and CD active stages respectively.The identification of potential biomarkers was carried out with classical statistic methods(p value&lt;0,05 and ratio&gt; 1,5) and data Mining mathematical model(p-value&lt;0,05, balanced accuracy ≥ 70, sensitivity ≥ 60 and specificity ≥ 60).

Results
We have chosen the most relevant classifiers according to statistical and biological criteria, based on their biological function and the pathogenesis of UC or CD(figure 1).
We have identified 152 classifiers(biomarkers),118 single and 34 dual, defined by one or two proteins of a list of 135 proteins(table 1).The classifiers are shown for each cohort compared to healthy control:42 biomarkers were found in Active UC,16 in Remission UC, 99 in Active CD and 13 in Remission CD,all of them compared to healthy controls.

Conclusion
Multiple potential biomarkers have been identified in saliva in relation to IBD.
Biomarkers with significant value have been found for identifying and classifying UC as well as CD, compared to controls.The number of biomarkers found in CD has been higher than in UC.
The simple biomarker option(versus dual) is recommended,since its application involves fewer errors.
P036 MicroRNA composition of colon crypt-top and crypt-bottom epithelial cells in Ulcerative Colitis
Authors: Inčiūraitė R , Juzėnas S , Ramonaitė R , Skiecevičienė J 
Published: May 2021

Abstract

Background
Ulcerative colitis (UC) is a chronic relapsing large intestine condition of inflammatory origin1. One of the most common features of UC is the injury of the intestinal barrier, which is composed primarily of colonic epithelial cells (CEpCs)2. The aim of this study was to identify UC-induced miRNA markers in CEpCs by determining the miRNA expression profile changes in crypt-top and crypt-bottom CEpC populations during active (aUC) and inactive (iUC) UC.

Methods
Crypt-top and crypt-bottom CEpCs were sorted from biopsies of healthy control (HC) individuals (n=19), patients with aUC (n=17) and iUC (n=15) using FACS technology. Total RNA was extracted, small RNA sequencing libraries were prepared and sequenced using Illumina platform. Sequencing data was processed with nextflow-core/smrnaseq pipeline. Differential expression, correlation, miRNA-target interactions, gene set enrichment analyses and data visualisation were performed using Rstudio software packages DESeq2, isomiRs, multimiR, SingleCellExperiment, clusterProfiler, ReactomePA, etc. The miRNAs with an adjusted p-value &lt; 0.05, and absolute value of log2 fold change &gt; 1 were considered to be significantly differentially expressed.

Results
432 unique miRNAs were identified in samples. Changes of expression profile during aUC were identified in crypt-bottom CEpCs (compared to: (i) HC - 23 miRNAs, (ii) iUC - 22 miRNAs), as well as in crypt-top CEpCs (compared to: (i) HC - 28 miRNAs, (ii) iUC - 9 miRNAs). Also, 7 miRNAs were differentially expressed in crypt-bottom CEpCs and 3 miRNAs in crypt-top CEpCs during iUC compared to HC. 5 miRNAs were identified to be differentially expressed during aUC, 2 miRNAs - during iUC, and 11 miRNAs in HC when comparing expression profiles of crypt-bottom and crypt-bottom CEpCs. We also identified 16 and 14 miRNAs which expression in crypt-bottom and crypt-top CEpCs moderately (0.5&lt;rho&lt;0.7) correlated with Mayo score, respectively. Finally, the gene sets of pathways revealed the involvement of several miRNAs in biological processes and molecular functions associated with UC pathogenesis.

Conclusion
The changes of expression profiles of miRNAs revealed that crypt-top and crypt-bottom CEpCs respond to inflammation differently, the expression of these miRNAs reflects disease activity and modulates the processes of UC pathogenesis.

References
P107 Monitoring inflammatory bowel disease in clinical practice using gut microbial markers in faecal samples. Prospective study in a clinical cohort
Authors: Miquel Cusachs J O , Bahí Saavedra A , Vila Currius M , Lliròs Dupre M , Leal Validivieso C , Aldeguer Manté X 
Published: May 2021

Abstract

Background
The gut microbiota(GM) plays a pivotal role in the pathogenesis of inflammatory bowel disease (IBD) which includes Crohn’s disease (CD) and ulcerative colitis(UC). The degree of IBD activity, and therefore of inflammation, modifies GM composition towards an altered pattern called dysbiosis This IBD-dysbiosis pattern is different from healthy individuals(HI). The degree of dysbiosis is a good indicator of IBD activity and could be useful in monitoring IBD. The AIM of this study is to quantify the degree of IBD dysbiosis of the GM, and determine the utility as a biomarker for monitoring IBD disease compared with HI.

Methods
80 IBD patients from 2 tertiary hospitals have been included. We included patients with clinical Remission (R), defined as Faecal Calprotectin (FC) levels &lt;250 µg/gr., and Activity (A) (FC &gt;250 µg/gr.) with mild to moderate disease. A blood sample (to determinate RCP, albumin and hemoglobin (Hb) levels) and stool sample (to determinate Faecal calprotectin (FC) and GM analysis) has been collected. DNA was extracted from fecal samples, using real-time qPCR techniques and 3 bacterial groups (Faecalibacterium prausnitzii (FP), Escherichia coli (EC), and total eubacteria (TE) that are highly representative of GM dysbiosis degree were analyzed. In regards to these bacteria, an index called FEI has been created to quantify GM dysbiosis. GM and FEI data has been collected in order to compare with standards analytical markers (Hb, Alb, RCP, FC). The duration of this study is 6 months with samples every three months (T0, T1 and T2).

Results
35 UC and 45 CD patients were included. Initial treatment in 76,25% of cases were biological drugs. 55 % of patients were in remission at first sample. The analysis of clinical data showed that only PCR and CP had significantly differences between R and A (p=0,0037) and type of disease (p=0,018) and temporal evolution (p=0,004). Higher levels of FP are been observed in UC (p=0,0013) and higher levels of EC in CD (p=0,003) in all 3 samples. FEI values are higher in UC (p=0,001) and different between CD and UC and HI (p=0,015) indicating FEI ability to differentiate between 2 disease subtypes and HI. FEI cut-off point has been set at 1,869 (S 0,44 and E0,82; AUC 0,658) in T0. The IBD-GM compared with HI-GM showed lower FP abundance (p=0,002) and higher TE abundance (p=0,0001) with increased non-significant EC abundance. The A and R abundances for FP,FEI and TE showed significant differences between CD, UC and HI, indicating capacity to differentiate between activity and remission in T0.

Conclusion
Microbiological markers and FEI allow to differentiate between IBD subtypes and HI, and between A and R. The combination if RCP, FC and FEI can become a potential biomarker of IBD activity.
P138 Platelet-to-lymphocyte ratio index: a reliable tool for non-invasive assessment of endoscopic activity in small bowel Crohn’s Disease
Authors: Macedo Silva V , Freitas M , Xavier S , Cúrdia Gonçalves T , Boal Carvalho P , Dias de Castro F , Rosa B , Moreira M J , Cotter J 
Published: May 2021

Abstract

Background
The platelet-to-lymphocyte ratio (PLR) index has been a recent focus of investigation as a reliable marker of inflammation. This score was recently shown to have a good accuracy upon predicting endoscopic remission in patients with colonic Crohn’s Disease (CD). We aimed to assess the discriminative power of PLR index in patients with isolated small bowel CD.

Methods
Single center study of consecutive patients with isolated small bowel CD (L1 ± L4 disease according to Montreal classification) who underwent small bowel capsule endoscopy (SBCE) for assessment of endoscopic activity between January 2019 and December 2020. Only complete SBCEs were considered. CD endoscopic activity was classified according to the Lewis score (LS) value. Complete blood count, C-reactive protein and fecal calprotectin values were collected within 1 month of SBCE.

Results
Final sample included 49 patients, 35 (71.4%) of them females, with a mean age of 35.1±11.8 years. SBCE reported mucosal healing (LS&lt;135) in 30.6% of the patients; mild activity (135≤LS&lt;790) in 42.9% and moderate-to-severe activity (LS≥790) in 26.5% of the patients.
PLR index positive correlation with LS was significant and moderate (k=0.597; p&lt;0.001). This correlation was stronger than the one seen between fecal calprotectin (k=0.525; p=0.001) or C-reactive protein (k=0.321; p=0.029) and the LS score.
In particular, PLR index presented an excellent accuracy for predicting patients with a moderate-to-severe endoscopic activity (AUC=0.908; 95%CI=0.816–0.999; p&lt;0.001), with an optimal cut-off of PLR above 157 (sensitivity 92.3%; specificity 82.9%). The accuracy for prediction of mucosal healing was good (AUC=0.743; 95%CI=0.600–0.887; p=0.007), with an optimal cut-off of PLR below 126 (sensitivity 66.7%; specificity 80.0%).

Conclusion
PLR index demonstrated an excellent acuity for predicting patients with moderate to severe disease in small bowel CD. Moreover, it also demonstrated good acuity for predicting mucosal healing on this set of patients. These results come from a significant correlation of PLR index with endoscopic activity in small bowel CD. Our findings establish this index as a promising and easy-to-apply tool for non-invasive and regular follow-up of patients with small bowel CD.
P166 Impact of consultation frequency and time to diagnosis on subsequent Inflammatory Bowel Disease outcomes
Authors: Jayasooriya N , Saxena S , Blackwell J , Petersen I , Bottle A , Creese H , Pollok R 
Published: May 2021

Abstract

Background
The impact of length of time between the point of initial contact, at symptom onset, with a health-care provider and diagnosis of inflammatory bowel disease (IBD) on subsequent disease outcomes, is unclear. Diagnosis can be challenging and delay common, with an excess of gastrointestinal (GI) symptoms reported 3 years before the diagnosis of IBD compared to the background population.1
We describe the impact of time to diagnosis and frequency of consultation amongst individuals with GI symptoms who later go on to develop ulcerative colitis (UC) and Crohn’s disease (CD).

Methods
Using the Clinical Practice Research Datalink, a nationally representative research database, incident cases of IBD were identified between 2003 and 2016. GI symptoms were defined as abdominal pain, diarrhoea, or rectal bleeding. The proportion of individuals consulting for incident GI symptoms within 3 years prior to IBD diagnosis was identified. Using a multivariable regression model we evaluated the association between time to diagnosis from incident consultation and consultation frequency for GI symptoms on disease outcomes (corticosteroid (CS) and thiopurine (TP) use, hospitalisation and major abdominal surgery) 5 years after IBD diagnosis.

Results
Six thousand nine hundred and sixty-seven incident cases of IBD were identified during the study period. Within 3 years prior to IBD diagnosis, 2,645 (38%) patients had an incident presentation with GI symptoms in primary care (782 CD, 1,863 UC). Presentation with GI symptoms occurred &gt;3 years before IBD diagnosis in 2,842 (41%) of patients. There was no recorded primary care consultation for 1,480 (21%) patients.
Time to diagnosis from initial consultation was not associated with worse subsequent disease outcomes. However, amongst patients later diagnosed with UC, ≥3 prior consultations for GI symptoms was associated with an increased subsequent risk of CS use (HR 1.19, 95% CI 1.05 -1.36), CS dependency (HR 1.50, 95% CI 1.10 -2.05), TP use (HR 1.60, 95% CI 1.22 – 2.11) and colectomy (HR 1.91, 95% CI 1.21 – 3.04). Amongst patients with CD, ≥3 prior consultations were associated with an increased subsequent risk of major abdominal surgery (HR 1.75, 95% CI 1.22 -2.5) and hospitalisation (HR 1.58, 95% CI 1.18 -2.11)

Conclusion
Frequent primary care consultation with GI symptoms, but not symptom duration prior to IBD diagnosis, was associated with worse subsequent disease outcomes. Steps are needed to expedite IBD diagnosis to reduce the risk of adverse disease outcomes.

Reference
P226 Does faecal Calprotectin help differentiate inflammatory from fibrous stenosis in Crohn’s disease?
Authors: Ben Farhat F , Sabbah M , Ben Abid M , Bibani N , Bellil N , Aoun K , Bouratbine A , Gargouri D 
Published: May 2021

Abstract

Background
Digestive stenosis is the most common complication of Crohn’s disease. It can be either inflammatory or fibrous. The clinical, biological and especially morphological characteristics of the stenosis can help differentiate inflammatory stenosis from fibrous stenosis. The aim of our study was to evaluate the performance of fecal calprotectin (FC), a marker of intestinal inflammation, in identifying the type of stenosis.

Methods
A prospective study including all patients followed for Crohn’s disease in the Gastroenterology Department of Habib Thameur Hospital over a 6-month period from July 2020 to December 2020 was performed. Clinical, biological, endoscopic and radiological data were collected. The inflammatory nature of the stenosis was mainly retained according to radiological activity signs objectified by cross-sectional imaging. All patients were given a FC assay at the time of inclusion. FC was dosed by using the Bulhmann® FCAL ELISA technique. The statistical study was carried out using the SPSS software version 22.0 (p value significant if lower than 0.05).

Results
Fifty patients were included in our study (mean age 40.54 years [18–67] and sex ratio (M/F) = 1.77). The average evolution time of the disease was 8 years [6 months- 27 years]. The disease was ileal in 16 patients, colic in 4 patients and ileocolic in 30. Twenty patients (40%) had an intestinal stenosis whose location was: ileocaecal anastomosis (n=9), ileal (n=8) and colic (n=3). Multiple stenoses (colic and ileal) were noted in 3 patients. Fifteen patients were on medical treatment at the time of inclusion: 7 patients were on Infliximab, 5 were on azathioprine and 3 were on 5ASA. Digestive symptoms such as diarrhoea or subocclusive syndromes were noted in 7 patients. A biological inflammatory syndrome (CRP &gt;10mg/L) was noted in 8 patients. Of the 20 stenoses included, 8 were of the inflammatory type (40%). In the presence of stenosis, the mean level of FC was 224.9 μg/g. A high level of FC was associated with the inflammatory type of stenosis (p&lt;0.001). A cut-off of 135 µg/g had a sensitivity 100% and a specificity of 90%. CRP did not differentiate between inflammatory stenosis and fibrous stenosis (p=0.4).

Conclusion
According to our study, FC is a good marker of intestinal inflammation allowing to differentiate an inflammatory from a fibrous stenosis during Crohn’s disease better than the usual biological markers. These results should be confirmed by larger studies.