bluuebunny/crossref_metadata_2025_split huggingface dataset:
P551 Platelet-to-lymphocyte ratio index for non-invasive assessment of endoscopic activity in small bowel Crohn’s disease: application and prospective validation.
Authors: Macedo Silva V , Ferreira A I , Lima Capela T , Arieira C , Cúrdia Gonçalves T , Boal Carvalho P , Dias de Castro F , Moreira M J , Cotter J 
Published: January 2023

Abstract

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

Methods
Single center study including patients with isolated small bowel CD (L1 ± L4 disease according to Montreal classification) undergoing small bowel capsule endoscopy (SBCE) for assessment of endoscopic activity. 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.
A retrospective sample was used for initial assessment of PLR index performance, followed by a prospective 2-years application on a distinct sample.

Results
The initial sample included 49 and the validation sample 48 patients, both groups being age- and gender-matched.
On the initial cohort, PLR index presented a positive moderate correlation with LS (k=0.597; p&lt;0.001), which was stronger than the one found with fecal calprotectin (k=0.525; p=0.001) or C-reactive protein (k=0.321; p=0.029). PLR index presented an excellent accuracy for predicting patients with a moderate-to-severe endoscopic activity (AUC=0.91; 95%CI=0.82-0.99; p&lt;0.001), and a good accuracy for prediction of mucosal healing (AUC=0.74; 95%CI=0.60-0.89; p=0.007).
These results were confirmed on the prospective validation cohort, as the correlation of LS with PLR index (k=0.631; p&lt;0.001) was further stronger than with fecal calprotectin (k=0.355; p=0.040) and C-reactive protein (k=0.183; p=0.219). The accuracy of PLR index was confirmed to be excellent for moderate-to-severe endoscopic activity (AUC=0.87; 95%CI=0.76-0.98; p&lt;0.001) and good for mucosal healing (AUC=0.74; 95%CI=0.59-0.87; p&lt;0.001).

Conclusion
PLR index demonstrated an excellent acuity in predicting moderate-to-severe disease and good acuity in predicting mucosal healing in patients with small bowel CD, with both associations confirmed on a prospective validation cohort. 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.
P556 Surgery in high-risk paediatric Crohn’s Disease treated with up-front anti-TNF agents and long-standing biologic therapy
Authors: Musto F , Distante M , Dei Rossi E , Calicchia A , Veraldi S , Mondi’ F , Tarani F , D’Arcangelo G , Aloi M 
Published: January 2023

Abstract

Background
High-risk (HR) Crohn’s Disease (CD) is associated with high surgical and progression rates. Therefore, recent ESPGHAN guidelines (GL) suggest starting an early anti-TNFα treatment to modify the natural history of the disease. The aim of our study was to evaluate the surgical rate in a population of HR-CD paediatric patients treated with up-front anti-TNFα agents and long-standing biologic therapy

Methods
This is a retrospective, observational, single-center study conducted at the Paediatric Gastroenterology, Hepatology, and Endoscopy Unit at Policlinico Umberto I Hospital – Sapienza University of Rome. We collected data from all patients diagnosed with CD under 18 years, with a minimum follow-up of 12 months. between June 2008 to July 2022. Patients were then stratified at the diagnosis into HR and LR, based on ESPGHAN GL criteria. Demographic, clinical, laboratory, endoscopic, and imaging data were collected at 6, 12, 24, 36, 48, and 60 months

Results
130 patients were enrolled, 76 HR (58%) and 54 LR (42%) [median age 12.5 (IQR) yrs, female 45 (35%), medium follow-up 54±24 months]. The HR group included 39 patients (51%) with panenteric disease, 15 (20%) with a structuring behavior (B2), 3 (4%) with structuring/penetrating disease (B2-B3), and 26 (34%) with perianal involvement (p). Early anti-TNFα agents were started in 80% of patients &lt;6 months from the diagnosis, while 15 (20%) started biological therapy between 6 and 12 months from the diagnosis. All patients continued biologic therapy throughout the study follow-up: 20 (26%) optimized anti-TNF, 25% switched biologic, 11% added an immunomodulator, and 4% combined 2 biological drugs. The surgical rate at 5 years was 29% (n=22) and 29% n=16) in HR and LR groups respectively (p-value 1,0). Eleven % (n=8) of HR patients needed surgical resection, while perianal surgery (seton drainage, fistulotomy, fistulectomy) was performed in 18% (n=14), with no significant difference with LR group [(intestinal resection 18% (10/55), perianal surgery 11% (6/55), p &gt; 0.05]. Perianal disease resulted positively associated with surgical risk (p 0.002, OR 5.62 CI 1.84-17.15) while small bowel imaging at the diagnosis was a protective factor for surgery (p 0.017, OR 0.23 CI 0.07-0.77). No significant difference was found in the interval free from surgery between HR and LR, although HR children mainly needed surgery in the first 12 months after the diagnosis.

Conclusion
Our data suggest that paediatric patients with HR-CD treated with early anti-TNF agents and long-standing biologic therapy have a similar disease course and surgical risk to those with LR disease. At a 5-year follow-up, one-third of patients needed surgery, mainly in the first year after the diagnosis
P557 Analysis of colectomy rates and advanced therapy prescribing for ulcerative colitis in Lothian; Scotland an updated population based cohort study
Authors: Jenkinson P , Plevris N , Gros Alcalde B , Lyons M , Derikx L , Constantine-Cooke N , Arnott I , Jones G , Lees C 
Published: January 2023

Abstract

Background
The impact of advanced therapies on colectomy rates in UC remains unclear. We have published a population-based cohort reporting patterns of advanced therapy prescribing and the impact on colectomy rates complete to 2018 The aim of this study was to describe recent trends by extending the study period to 2021.

Methods
The Lothian IBD registry (LIBDR) is a manually validated, comprehensive, population dataset of the Edinburgh area . The LIBDR contains measured point prevalence between 2008-2018 and estimated prevalence from 2018-2028 (derived from AARIMA modelling). All patients with a diagnosis of UC who commenced advanced therapy or underwent a colectomy in Lothian, Scotland between 01/01/2005 and 31/12/2021 were included interrogating multiple clinical and administrative databases. Linear and segmental regression analyses were used to identify the annual percentage change (APC) and temporal trends (statistical joinpoints) in colectomy rates and drug initiation. Kaplin Meier curves were created for drug ersistence and compared with the log rank test.

Results
484 patients underwent colectomy for UC between 2005 and 2021. Colectomy rates per 100 UC patients fell from 1.47 colectomies in 2005 to 0.25 in 2021 (p=0.009). Temporal trend analysis (2005-2021) identified a significant joinpoint in colectomy rates in 2014 (p=0.009) (Figure 2).

Figure 1, Colectomy rates per 100 UC patients from 2005-2021. Joinpoint regression separated at inflection point at 2014 (dashed line).
383 patients were treated with their first advanced therapy for UC between 2005 and 2021, of whom 165 progressed to second line therapy. The annual percentage change in first line therapy was 34.7%, with joinpoints at 2013 and 2015 (p&lt;0.001).

Figure 2, First line advanced therapy prescription rate per 100 UC patients per year between 2005-2021 stratified by agent used.

Figure 3, Second line advanced therapy prescription rate per 100 UC patients per year between 2005-2021 stratified by agent used.
The 1 and 2 year persistence on first line advanced therapy was; 44.8% and 24.1% for adalimumab, 60.7% and 54.4% for infliximab and 79.8% and 67% for vedolizumab (p=0.001) (Fig 3).

Fig 4, Persistence on first line advanced therapy.

Conclusion
This population based cohort study has shown a significant increase in advanced therapy prescription for UC. Whilst we cannot ascribe causality this has been paralleled by a significant reduction in the rate of colectomy that has been maintained in recent years.
P565 Comparison of the efficacy of adalimumab and ustekinumab for prevention of intestinal fibrosis in bio-naive Crohn's Disease patients
Authors: Biscanin A , Tomašić V , Babic F , Ćaćić P , Ogresta Kordej D , Hrabar D , Kralj D , Dorosulić Z 
Published: January 2023

Abstract

Background
Adalimumab (ADA) and ustekinumab (UST) are effective and efficient therapeutic options for patients with luminal Crohn's disease (CD). However, data evaluating treatment efficacy in stricturing CD are lacking. The aim of this study was to compare real-life efficacy of ADA and UST in prevention of development and/or progression of preexisting bowel stenosis in bio-naive CD patients. Secondary aim was to identify potential factors affecting treatment success.

Methods
A single-center, non interventional, retrospective chart review (January 2015 – April 2022) ofadult bio-naive CD patients treated with ADA or UST for a minimum of 6 months was performed.
Fibrotic intestinal stricture was defined as stenosis with a prestenotic small bowel or colon dilatation seen on magnetic resonance enterography or intestinal ultrasound or as a small bowel or colon obstruction impassable for an endoscope.
Continuous variables were compared using Mann-Whitney test, and categorical variables using X2 Fisher exact test when appropriate. Categorical variables were presented as numbers and valid percentages. Logistic regression was performed to determine potential predictors for stenosis development or progression.

Results
Total of 63 CD patients were included, with in ADA group (69.8%). Patients characteristics were similar in both observed groups regarding median disease duration prior to induction of biologic (57 (20-132) months on ADA, 57 (20-161) months on UST) and median treatment persistence (21 (10-38) months on ADA, 20 (14-53) on UST). Patients on UST were significantly older (ADA mean 37 y vs UST mean 51 y; p&lt;0.05). Combotherapy was used in 35.1% of patients in ADA group.
After average of 20 months of treatment duration 9.1% people in ADA group and 5.3% in UST group developed new symptomatic bowel stenosis. At the time of biologic introduction, 4 people in ADA (9.1%) and 1 in UST group (5.3%) had preexisting bowel stenosis - out of those patients, 3 in ADA group (6.8%), had a worsening of stenosis which required treatment discontinuation. Surgery was performed in 2 patients, both in ADA group (4.5%).
Statistically significant difference wasn’t observed between ADA and UST group in stenosis development or progression (p=0.52). Combotherapy had no influence on primary aim in ADA group (p=0.59)Age, gender, biologic therapy, combotherapy as well as disease and therapy duration don't seem to be connected with stenosis development or progression

Conclusion
These real world data suggest that longterm treatment with both ADA and/or UST provide comparable efficiency for prevention of intestinal bowel fibrostenosis occurrence or progression. Larger, prospective studies should be conducted
P566 Colitis due to immunotherapy with anti-PD-1: a case series
Authors: De Ruvo M , Barberio B , Zingone F , Bonanno L , Dal Maso A , Stefano F , Chiarion Sileni V , Savarino E V 
Published: January 2023

Abstract

Background
Anti-programmed death-1 (PD-1) drugs have been associated with immune-mediated gastrointestinal adverse events in 0.5-9% of the cases. The aim of this study was to investigate the characteristics of colitis occurring in oncological patients treated with anti-PD-1 drugs.

Methods
This is a prospective cohort study including patients referred for new onset colitis at Azienda Ospedaliera of Padua between 2020 and 2022.
All patients were treated with anti-PD-1 drugs at Istituto Oncologico Veneto due to oncological disease [n=2 melanoma, n=1 colorectal cancer, n=1 pleural mesothelioma, n=14 non-small-cell lung cancer (NSCLC)].
Median duration of follow up was 10 months.

Results
Eighteen patients who developed diarrhea (≥G2, CTCAE) following treatment with anti-PD-1 were included (n=12 males, median age 70 years).
The diarrhea began after a mean of seven months of therapy and after two to six months its discontinuation in 3/18 patients.
The mean fecal calprotectin values at diarrhea onset was 1063 ug/g.
Most of the patients (14/18) had their immunotherapy suspended, among them four required hospitalization. All patients were initially treated with systemic steroids (1 mg/kg). Seven patients had ulcerative colitis (UC)-like colitis (n=5 pancolitis, n=2 left colitis) while the others (60%) had microscopic colitis (MC, n=9 collagenous, n=1 lymphocytic) with unspecific inflammatory mucosal abnormalities in half of the cases.
Among patients with UC-like colitis, two were hospitalized and treated with anti-TNFα because of steroid refractoriness; all remaining patients with UC-like colitis are maintaining remission with oral mesalamine or with budesonide non-MMX or low-dose systemic steroid (0.1 mg/kg). Two patients restarted anti-PD-1 drugs with no colitis relapse in the following three months, with mesalamine as maintenance therapy.
Among patients who developed a MC, one required Vedolizumab as maintenance therapy, while 8/10 achieved partial or complete remission with oral budesonide non-MMX or low-dose systemic steroid. Three patients restarted anti-PD-1 drugs with no colitis relapse in the following three months, taking budesonide non-MMX as maintenance therapy.
In our cohort of study all patients with MC were previously treated with anti-PD-1 drugs for NSCLC, while those with UC-like colitis were treated for NSCLC (n=4), melanoma (n=2) and colorectal cancer (n=1).

Conclusion
We observed a significant proportion of microscopic colitis in patients with NSCLC, while UC-like colitis was equally distributed in the other forms of neoplasia.
Men are at higher risk to develop anti-PD-1 induced MC in NSCLC, rather than women.
Anti-PD-1 induced microscopic colitis presents more frequently endoscopic signs of inflammation.
P569 Can thiopurines prevent crohn’s disease endoscopic postoperative recurrence in at risk patients?
Authors: Chehaider A , Serghini M , Labidy A , Ben Mustapha N , Fekih M , Boubaker J 
Published: January 2023

Abstract

Background
Postoperative relapse (POR) of Crohn’s disease (CD) is frequent in the absence of prophylactic treatment. Screening for known risk factors allows to stratify patients and consider appropriate therapy. In Tunisia, the cost-effectiveness of thiopurines makes it prescribed even when moderate or high risk of POR. The aim was to describe the efficacy of thiopurines in preventing endoscopic POR in patients at risk.

Methods
We conducted a retrospective study enrolling CD patients who underwent curative ileo-caecal resection and received thiopurines to prevent POR. They all had at least one risk factor for POR knowing: smoking, fistulizing phenotype, extensive ileal resection (≥ 50 cm), previous bowel resection. The risk was moderate in the presence of one risk factor and high if at least two factors. Patients with a follow-up less than 6 months were excluded. All patients had undergone ileocoloscopy to screen for endoscopic POR wich was stratified according to the Rutgeerts score. Endoscopic POR was defined by a score ≥ i2 and was severe if score ≥i3.

Results
Thirty nine patients were included with a sex ratio M/F =1.8 and a mean age of 31 years. CD was ileal and ileocolic in 92.3% and 7.7% respectively, with perineal involvement in 7.2%. The mean extent of ileal resection was 39.7±4 cm. The ileal and colonic histological margins were pathologic in 17.9% and 7.7% respectively. Risk factors for POR were distributed as follow: Active smoking (28.2%), previous bowel resection (17.9%), fistulizing phenotype (84.6%) extensive resection (35.9%).
The risk was high in 51.3% and moderate in 48.7% of cases. The delay of introduction of thiopurines was on average 31.8±53 days from the restoration of digestive continuity at a mean dose of 2.3 mg/kg and ileocoloscopy was performed at a mean delay of 19.3 months. Rutgeerts' score was as follows: i0, i1, i2, i3 and i4 in 34.7%, 8.2%, 16.3%, 6.1% and 10.2% respectively. Endoscopic POR was noted in 43.6% and was severe in 21.6% of cases.
The cumulative POR rate was 16% at 6 months, 52% at 12 months and 67.5% at 24 months. In univariate analysis, factors associated with endoscopic POR on thiopurines were male gender (p=0.012), laparotomy (p=0.02), the extent of ileal resection and extensive ileal resection (p=0.003). In multivariate analysis, the factors retained were male gender with an OR=11 (p= 0.024) and the extent of ileal resection with an OR=1.05 (p=0.02). Time to introduction of thiopurines, fistulising phenotype and smoking did not significantly influence the risk of POR.

Conclusion
Thiopurines would be able to prevent endoscopic POR in more than half of the patients at risk. However, anti-TNF therapy should be indicated immediately in males and in cases of extended ileal resection.
P572 Coexisting Inflammatory bowel disease and Ankylosing spondylitis: Management and clinical outcomes
Authors: Savin E , Levartovsky A , Gendelman O , Lidar M , Ben-Horin S , Kopylov U 
Published: January 2023

Abstract

Background
Ankylosing spondylitis (AS), which occurs in about 10% of inflammatory bowel disease (IBD) patients, is more common in Crohn's disease and does not correlate with bowel activity. The occurrence of IBD in patients with AS is 5-10%. We aimed to investigate the patterns of treatment modifications following newly diagnosed AS in patients with IBD or a new IBD diagnosis in patients with AS.

Methods
This is a retrospective observational study that included patients with coexisting IBD and AS that were followed simultaneously by the gastroenterology and the rheumatology departments of the Sheba Medical Center. Patients with a follow-up duration of at least 3 months since the second diagnosis were included.

Results
The cohort consisted of 68 patients, 41 with a first diagnosis of IBD (fIBD-group) and 27 with a first diagnosis of AS (fAS-group). Patients in the fAS-group were younger (median age of 36 years, inter quartile range (IQR) 25-48 vs. 43 years IQR 35-56, p=0.043), had more Crohn's disease (92.6% vs. 68.3%, p=0.016), had a shorter interval up to the second diagnosis (median of 3 years, IQR 1-6 vs. 6 years, IQR 2-11.5, p=0.03), and had an increased rate of past/current biologic treatment (81% vs. 51%, p=0.019) compared with the fIBD-group. Therapy modifications rates were 78% in the fIBD-group and 96% in the fAS-group as presented in Figure 1. The most common modification for the fIBD-group was initiation of biologic therapy in 18/32 patients (Adalimumab 44%, Infliximab 33%, Golimumab 5.75%, Etanercept 5.75%, Certolizumab pegol 5.75%, Ustekinumab 5.75%). In the fAS-group, switching biologic agent to Adalimumab or Infliximab (42%) and ceasing NSAIDs (27%) were the most common.
At 1-year follow-up there were no significant differences in clinical outcomes (treatment failure, surgery/hospitalization, clinical remission) between fIBD and fAS groups. However, patients in both groups with treatment modifications, had a trend for higher rate of IBD clinical remission than patients without (72% vs. 40%, p=0.066). No difference was found in AS clinical outcome.

Conclusion
Treatment modifications are common among newly coexisting IBD and AS patients, preferably biologic drug modifications. These modifications may contribute to IBD clinical remission.
P574 Characterization of plasma inflammatory protein abundance in patients with ulcerative colitis treated with etrasimod: an exploratory analysis of the phase 3 ELEVATE UC 52 and ELEVATE UC 12 trials
Authors: Siegmund B , Ryan R , Abreu M T , Vermeire S , Dotan I , Goetsch M , Crosby C , Woolcott J , Komori H K , Danese S 
Published: January 2023

Abstract

Background
Etrasimod is an investigational, once-daily, oral, selective sphingosine 1-phosphate receptor 1,4,5 modulator (S1P1,4,5) in development for the treatment of moderately to severely active ulcerative colitis (UC). To better understand how etrasimod reduces inflammation and induces clinical remission, the phase 3 ELEVATE UC 52 and ELEVATE UC 12 trials included a per protocol exploratory analysis of peripheral blood inflammatory proteomics, the results of which are presented here.

Methods
In ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369), patients (16-80 years) with moderately to severely active UC were randomised 2:1 to once-daily etrasimod 2 mg or placebo (PBO). Plasma was collected at baseline and week 12 for both trials and week 52 for ELEVATE UC 52. Characterization of plasma inflammatory protein abundance and changes in abundance over time were assessed by proximity extension assay using the Olink Target 96 Inflammation panel. Normalized protein expression and change from baseline by visit were summarized by descriptive statistics; fold changes in Olink measurements were expressed as log2.

Results
Plasma samples were collected and analysed from 238 patients in ELEVATE UC 52 (162 etrasimod, 76 PBO) and 163 patients in ELEVATE UC 12 (108 etrasimod, 55 PBO). While no meaningful changes in protein biomarkers were observed over time in PBO-treated patients, factors modulated by etrasimod included those associated with tissue remodelling (MMP-1, MMP-10), T-cell response (CD5, CD6, CD8A, TNFRSF9), chemotaxis (CCL11, CCL19, CCL28, CX3CL1), and pleiotropic cytokine response (IL-7, IL-17A, IL-10, OSM), with a high degree of overlap and consistency in trends between the two trials (Figure 1). Etrasimod induced statistically significant reductions in circulating inflammatory proteins including IL-17A and OSM at week 12, and these remained decreased at week 52. Decreases in IL-17A and OSM at weeks 12 and 52 correlated with efficacy outcome measures across various clinical subgroups in responders vs nonresponders (Table 1).

Conclusion
In this per protocol exploratory analysis of two independent phase 3 randomised controlled trials, etrasimod induced consistent, statistically significant changes in circulating inflammatory proteins involved in tissue remodelling, T-cell response, chemotaxis, and cytokine response, including IL-17A and OSM. The reduction in activated immune cells in the peripheral blood of responders suggests etrasimod induces a reduction in inflammation that could contribute to remission.