bluuebunny/crossref_metadata_2025_split huggingface dataset:
OP10 Comparative efficacy of biologics for endoscopic healing of the ileum and colon in Crohn’s Disease
Authors: Narula N , Wong E , Dulai P , Marshall J , Jairath V , Reinisch W 
Published: January 2022

Abstract

Background
We compared the efficacy of adalimumab, infliximab, ustekinumab, and vedolizumab for achieving endoscopic healing (EH) in the ileum and colon after one-year of therapy in Crohn’s disease (CD).

Methods
A pooled analysis of patient-level data from 344 patients with CD from four clinical trial programs was performed. Patients who received continuous adalimumab, infliximab, ustekinumab, or vedolizumab throughout the trial and had at least one ileocolonic segment with a Simple Endoscopic Score for CD (SES-CD) ≥ 3 at enrolment were included. Proportions of patients achieving one-year endoscopic healing (EH), defined as SES-CD of 0, using each of four biologics were compared. Multivariate logistic regression was used to model the relationship between individual biologics and one-year outcomes, adjusted for potential confounders of EH, including disease duration, concomitant corticosteroid use, and prior anti-TNF failure.

Results
Compared to vedolizumab [10/77 (13%)], both infliximab [29/79 (36.7%), aOR: 3.27 (95% CI: 1.34–8.01), p&lt;0.001] and adalimumab [12/40 (30%), aOR: 3.01 (95% CI: 1.10–8.21), p=0.032] were superior for achieving one-year EH of the ileum among patients with ileal involvement at baseline. No difference was observed between ustekinumab [5/22 (22.7%)] and vedolizumab [aOR: 2.75 (95% CI: 0.76–9.91), p=0.123]. In biologic-naïve patients, ustekinumab, adalimumab, and infliximab were superior to vedolizumab for achieving one-year EH of the ileum. For colonic disease, in comparison to ustekinumab [9/31 (29.0%), adalimumab [30/48 (62.5%), aOR: 4.04 (95% CI: 1.88–8.71), p&lt;0.001] and infliximab (55/105 (52.4%), aOR: 2.02 (95% CI: 1.03–3.99), p=0.041] were superior for one-year EH in the colon among patients with colonic involvements at baseline. No difference was seen between vedolizumab [26/87 (29.9%)] and ustekinumab [aOR: 1.01 (95% CI: 0.39–2.59), p=0.987]. Similar differences were noted among biologic-naïve patients.

Conclusion
In this post-hoc analysis of pivotal clinical trials, TNFα antagonists were generally superior to vedolizumab and ustekinumab for achieving EH of the ileum and colon in patients with CD. However, among biologic-naïve patients, ustekinumab, adalimumab, and infliximab were superior to vedolizumab for attaining one-year EH of the ileum.
DOP03 The use and efficacy of biological therapies 2010–2020 for Inflammatory Bowel Disease in a Danish tertiary centre
Authors: Wewer M D , Arp L , Melek S , Oluf Krautwald F , Vind I , Pedersen G , Nielsen A M , Kiszka-Kanowitz M , Boysen T , Theede K , Nordgaard-Lassen I , Bendtsen F , Burisch J 
Published: January 2022

Abstract

Background
Direct health care costs have shifted towards drug-related expenditures in patients with inflammatory bowel disease (IBD). Frequently, patients will have to switch to a second- or third-line biological therapy due to no response or loss of response. The aim of this study was to describe the use and efficacy of biological therapy in a tertiary centre during a 10-year period and investigate the need for surgery.

Methods
The study population consisted of all bio-naïve IBD patients who initiated biological therapy between January 1, 2010 and February 19, 2020 at the Gastro unit, Hvidovre Hospital, Denmark. The electronic medical records were reviewed, and data were systematically registered. Failure of the biological therapy as no response and loss of response was defined by the need for surgery, steroid or shift in biological therapy.

Results
The study population consisted of 291 (46.9%) patients with ulcerative colitis (UC), 327 (52.7%) with Crohn’s disease (CD) and 3 with (0.5%) IBD Unclassified (IBDU), who initiated biological therapy with a median follow-up of 3 (IQR=2–5) years from initiation of therapy. The annual number of patients who initiated biological therapy was increasing throughout the study period.
Most patients (457, 73.6%) received one biological drug, 126 (20.3%) received two, and 38 (6.1%) received three or more different types of biological drugs during the study period. Systemic steroid was required in 99 patients (15.9%) and the 5-year surgery-free survival was 76.5% (120 patients with surgery). 302 patients (54.3%) had effect of the first biological therapy at one year follow-up.
In multivariate Cox-regression analyses, concurrent treatment with thiopurines decreased the risk of failure of the first biological therapy in UC patients (hazard ratio (HR) 0.745, 95% CI: 0.559–0.992) but not in CD patients (HR 0.969, 95% CI: 0.722–1.300). Male gender decreased the risk of failure (HR: 0.677, 95% CI: 0.505–0.908) while higher age at initiation of biological therapy increased the risk (HR: 1.0152, 95% CI: 1.004–1.027) in CD patients. These factors had no impact in UC patients. Prior surgery, disease duration and location were not associated with increased risk of failure of first biological therapy.

Conclusion
In conclusion, an increasing number of IBD patients received biological therapy during the 10-year period at our tertiary centre. A considerable part of IBD patients in biological therapy will require surgery, additional steroids, or second line biological therapy. Our findings suggest a beneficial role of thiopurine in combination with biological therapy. Improved identification of patients not responding to first line biological therapy is of great importance.
DOP11 Early intestinal ultrasound predicts endoscopic response to anti-inflammatory treatment and shows drug-specific response to biologicals and tofacitinib in Ulcerative Colitis
Authors: de Voogd F , Bots S , Van Wassenaer E , De Jong M , Pruijt M , Löwenberg M , D’Haens G , Gecse K 
Published: January 2022

Abstract

Background
Objective evaluation of treatment response is the gold standard in ulcerative colitis (UC). In this setting, intestinal ultrasound (IUS) is a non-invasive alternative to endoscopy. Recent studies showed change in IUS parameters after treatment initiation but studies with an endoscopic reference standard are scarce. The aim of this study was to evaluate early change of IUS parameters and determine cut-off values for endoscopic endpoints in UC patients starting anti-inflammatory treatment.

Methods
In this longitudinal prospective study consecutive patients with moderate-severe UC (baseline endoscopic Mayo score (EMS)≥2) starting an anti-inflammatory treatment were included. Clinical scores, biochemical parameters and IUS parameters were collected at baseline, after 2 (T1), 6 (T2) and 8–26 weeks (T3) around time of the second sigmoidoscopy/colonoscopy. IUS parameters were measured as previously established1. Endoscopic remission (ER) and mucosal healing (MH) were evaluated in the sigmoid and defined as EMS=0 and EMS≤1, respectively. The ultrasonographist and endoscopist were blinded for the outcomes of endoscopy and IUS, respectively.

Results
51 consecutive patients were included (Table 1) of whom 31 underwent a second endoscopy (MH: n=15 (45%), ER: n=9 (27%)). Two additional patients underwent colectomy and were considered non-responders. 18 patients did not undergo second endoscopy due to the COVID-19 pandemic (n=2), refusal (n=5), loss to follow-up (n=1) or treatment escalation because of clinical deterioration confirmed by IUS and biomarkers before second endoscopy was performed (n=10). Bowel wall thickness (BWT) was significantly lower from T2 onwards in patients reaching MH (p=0.026) and ER (p=0.002) at T3 (Fig 1). A significant decrease in BWT was already visible at T1 in patients receiving infliximab (p=0.001) or tofacitinib (p=0.007), but not in patients treated with vedolizumab (p=0.11) (Fig 2). Most accurate BWT cut-off values at T3 to determine MH and ER were 3.52 mm (AUROC: 0.95, 95% CI: 0.86–1.00, p&lt;0.0001, sens: 91%, spec: 91%) and 2.98 mm (AUROC: 0.94, 95% CI: 0.85–1.00, p=0.001, sens: 87%, spec: 100%), respectively. Other IUS parameters at T3 did not improve association with MH or ER. IUS parameters at T2 that predict MH and ER are demonstrated in Table 2.
Table 1

Fig 1

Fig 2

Table 2

Conclusion
BWT and Colour Doppler Signal 6 weeks after start of treatment are associated with and could predict MH and ER. In addition, treatment response patterns at IUS are drug-specific. Furthermore, we have provided accurate BWT cut-off values for endoscopic outcomes. In a point-of-care setting, (early) treatment evaluation with IUS could guide treatment decision in UC in order to optimize treatment response.

Reference
1. Bots et al, JCC, 2021
DOP18 Advanced optical diagnosis technology for assessment of endoscopic and histological remission in Ulcerative Colitis: A systematic review and meta-analysis
Authors: Nardone O M , Snir Y , Hodson J , Cannatelli R , Labarile N , Siau K , Hassan C , Yanai H , Dotan I , Ghosh S , Iacucci M 
Published: January 2022

Abstract

Background
Advanced endoscopic technologies led to significant progress in the definition of endoscopic remission of ulcerative colitis (UC), and correlate better with histological changes, compared to standard endoscopy. However, whilst studies have assessed the diagnostic accuracy of endoscope technologies individually, there is current limited data comparing between technologies. As such, we aimed to compare the correlations between endoscopy and histology disease activity scores across endoscope technologies

Methods
We searched PubMed and Embase in January 2021 for eligible studies reporting the correlation between endoscopy and histology activity scores in UC. Studies were grouped by endoscope technology as standard-definition white light (SD-WLE), high-definition white light (HD-WLE), or electronic virtual chromoendoscopy (VCE), and comparisons made between these groups

Results
A total of N=27 studies were identified, of which N=12 were included in a meta-analysis of correlations between endoscopic and histological activity scores. Combining these returned a pooled correlation coefficient (rho) for the SD-WLE group of 0.61, which did not differ significantly from HD-WLE (rho: 0.79, p=0.140) or VCE (rho: 0.70, p=0.471) [Fig 1a]. In addition, N=4 studies reported the accuracy of endoscopic activity scores on WLE and VCE to diagnose histological remission. Pooling these found significantly higher accuracy for VCE, compared to WLE (risk ratio: 1.13, 95% CI: 1.07–1.19, p&lt;0.001).[Fig 1b]

Conclusion
Activity scores assessed using endoscopy are strongly correlated with activity on histology. VCE appears to have better accuracy for the diagnosis of histological remission in UC, compared to WLE.
DOP28 Venous thromboembolism following discharge from hospital in patients admitted for Inflammatory Bowel Disease
Authors: Harvey P , Coupland B , Mytton J , Trudgill N , De Silva S 
Published: January 2022

Abstract

Background
Patients admitted to hospital with active Inflammatory bowel disease(IBD) are at increased risk of thromboembolism. Surgical specialties have demonstrated benefits of thromboembolism prophylaxis after hospital discharge in high risk groups.
This study aims to identify IBD patients at increased risk and develop a scoring system to recognise them.

Methods
Hospital episode statistics data was used to identify all patients admitted for IBD emergently or electively for surgery. All Patients with a thromboembolism within 90 days of hospital discharge were identified. A multilevel logistic regression model was used to identify patient and admission level factors associated with increased risk of thromboembolism. A scoring system to identify higher risk patients was constructed based on this model. Score performance was assessed using bootstrapped data.

Results
201,779 admissions in 101,966 patients were included. The rate of thromboembolism within 90 days was 17.24 per 1000 patient years at risk. This was highest in patients admitted as an emergency undergoing surgery (36.91) followed by emergency admission without surgery (15.63) and elective admission for surgery (15.60). The rate of thromboembolism between 180 and 270 days following discharge was 0.84, 1.59 and 1.70 per 1000 patient years at risk respectively.
Regression analysis demonstrated that female gender (OR 0.65(95%CI 0.53–0.80),p&lt;0.001), increasing age (49–60 years,(4.73(3.40–6.58),p&lt;0.001), increasing length of stay; 5–7 days (1.77(1.27–2.46),p=0.001), 7–10 days (1.91(1.40–2.60),p&lt;0.001), &gt;10 days (4.04(2.98–5.46),p&lt;0.001), increasing number of prior admissions for IBD in preceding 3 months; 1 (1.36(1.11–1.68),p=0.004), 2 (1.66(1.23–2.22),p=0.001), &gt;2 (2.32(1.67–3.21),p&lt;0.001), Ulcerative Colitis (1.46(1.19–1.79),p&lt;0.001) and admission type compared to Elective surgery (Emergency admission including surgery (1.64(1.15–2.33),p=0.006)), (Emergency admission not including surgery(1.57(1.07–2.32), p=0.023)) were statistically significant associations.
In the scoring system, a score &gt;=9 gave a positive predictive value of 1%. The AUC was 0.71(95%CI 0.69–0.72)

Conclusion
Patients admitted to hospital have ongoing increased risk of thromboembolism in the 90 day period following discharge. Risk was increased in patients with prolonged length of stay, increasing age, male gender or admitted as an emergency requiring surgery. Higher risk patients were identifiable by a scoring system.
DOP37 Efficacy and safety of filgotinib in patients with Ulcerative Colitis stratified by age: Post hoc analysis of the phase 2b/3 SELECTION and SELECTIONLTE studies
Authors: Schreiber S , Loftus E V , Maaser C , Danese S , Rudolph C , Jongen R , De Haas A , Oortwijn A , Vermeire S 
Published: January 2022

Abstract

Background
With a growing prevalence of inflammatory bowel disease (IBD) in elderly patients, there is a clinical requirement to understand the impact of treatment in this population.1 Filgotinib (FIL) is an oral Janus kinase 1 preferential inhibitor. This post hoc analysis of data collected in the phase 2b/3 SELECTION programme evaluated the efficacy and safety of FIL in patients with ulcerative colitis (UC) stratified by age.

Methods
The SELECTION programme includes two Induction Studies, a Maintenance Study (NCT02914522) and a long-term extension (LTE) study (NCT02914535). Adults aged 18–75 years with moderately to severely active UC were randomized 2:2:1 to receive FIL 200 mg or 100 mg or placebo once daily for 11 weeks. Responders at week 10 were re-randomized 2:1 to continue assigned FIL treatment or placebo from week 11–58. In LTE, patients with disease worsening and those completing week 58 continued assigned treatment before receiving open-label FIL. We assessed the efficacy and safety of FIL at any dose in the overall cohort of SELECTION and LTE, stratified into five age groups: &lt;30, ≥30–&lt;40, ≥40–&lt;50, ≥50–&lt;60 and ≥60 years. Clinical remission was evaluated at week 10 and pMCS remission was assessed at week 10, 58 and LTE weeks 2, 4, 12 and 24. Exposure-adjusted incidence rates (EAIRs) were calculated for adverse events (AEs). A data cut-off of 28 February 2020 was used.

Results
Baseline disease activity and previous and concomitant treatments were comparable across age groups in each treatment arm. While there were fewer patients in the ≥60 years group, patient distribution was similar in all other age groups. FIL induced clinical (~16%) and pMCS (~36%) remission in similar proportions of patients across all age groups at week 10 (Figure 1). At week 58, pMCS remission was achieved in ~53% of FIL-treated patients across age groups (Figure 2). In LTE, the proportion of FIL-treated patients in pMCS remission generally increased with time and remained similar across all age groups (Figure 3). FIL-treated patients aged ≥60 years had higher EAIRs of any AE, infections, herpes zoster, malignancies, NMSC and MACE than younger patients (Table). One thromboembolic event occurred in a FIL-treated patient aged &lt;30 years. Three deaths related to cardiovascular disease occurred in FIL-treated patients aged ≥50 years.

Conclusion
These findings suggest FIL is efficacious in inducing and maintaining symptomatic remission and could have an acceptable safety profile in adults with UC of all ages, including ≥60 years old. Age-related increases in incidences of certain AEs might be expected in patients with IBD; however, the number of patients ≥60 years limits comparison of these data with reported rates.

Reference
1Zammarchi et al. BMC Gastroenterol 2020;20;147
DOP44 Long-term use of ozanimod in patients with moderately to severely active Ulcerative Colitis
Authors: Danese S , Colombel J F , Ponich T , Jovanovic I , Bossuyt P , Longman R , Alekseeva O , Petersen A , Chitkara D , Marta C , Charles L , Rubin D T , Afzali A , Loftus E V , Wolf D C 
Published: January 2022

Abstract

Background
Ozanimod was approved by the FDA to treat patients (pts) with moderately to severely active Ulcerative Colitis (UC) based on the results from the 52-week (wk) phase 3 True North (TN) study. We sought to evaluate long-term efficacy and safety of ozanimod.

Methods
We examined data from an interim analysis of pts in the TN parent study who entered the ongoing TN open-label extension (OLE). Pts entered the TN OLE from the phase 3 TN study if they were non-responders at the end of induction, lost response during maintenance, or completed maintenance treatment, or from the phase 2 Touchstone OLE if they remained at study closure and received once-daily oral ozanimod 0.92 mg (equivalent to ozanimod HCl 1 mg). Clinical remission, clinical response, endoscopic improvement, and corticosteroid (CS)-free remission were evaluated at Wks 46, 94, and 142 in the TN OLE for all pts who entered the OLE from the TN parent study, and in the subset of pts in clinical response at the OLE entry. The data were analysed in the intent-to-treat population using observed cases (OC), which used the number of pts remaining in the study at the corresponding time point, and non-responder imputation (NRI), which used the number of pts remaining in the study at the corresponding time point and those who withdrew before the time point but would have reached the time point if they had stayed. Treatment-emergent adverse events were evaluated from the pooled phase 2 and phase 3 UC studies.

Results
A total of 823 pts from TN entered the TN OLE; as of the cut-off date (Sept 30, 2020), 64% completed Wk 46, 34% completed Wk 94, and 14% completed Wk 142 of the OLE. The most common reason for discontinuation was lack of efficacy (21%). Baseline demographics were similar as in the TN study. A total of 261 pts were in clinical response at the time of OLE entry. OC analyses showed that the percentage of pts achieving clinical remission, clinical response, endoscopic improvement, and CS-free remission was maintained over time (Table). Efficacy in the responders was higher compared to the total population and was comparable within the endpoints at Wks 46 and 94. Using the more conservative NRI analysis, the proportion of pts achieving each endpoint was lower than in the OC; however, after 94 wks of OLE treatment, 34% of all pts and 55% of the responders still maintained clinical response. No new safety signals were seen with longer-term ozanimod use in the 1158 pts in the pooled population.

Conclusion
UC pts from the phase 3 TN study demonstrated maintenance of response with long-term ozanimod treatment. These data reflect approximately 2 years of additional ozanimod treatment, with no new safety signals identified.
DOP58 An artificial intelligence–driven scoring system to measure histological disease activity in Ulcerative Colitis
Authors: Peyrin-Biroulet L , Adsul S , Dehmeshki J , Kubassova O 
Published: January 2022

Abstract

Background
Histological remission is increasingly regarded as an important and deep therapeutic target for ulcerative colitis (UC). Assessment and scoring of histological images is a tedious procedure, that can be imprecise and prone to inter- and intra-observer variability. Therefore, a need exists for an automated method that is accurate, reproducible and reliable. This study aimed to investigate whether an artificial intelligence (AI) system developed using image processing and machine learning algorithms could measure histological disease activity based on the Nancy index.

Methods
A total of 200 histological images of patients with UC from a database at University Hospital, Vandoeuvre-lès-Nancy, France were used for this study. The novel AI system was used to fully characterise histological images and automatically measure Nancy index. The in-house AI algorithm was developed using state-of-the-art image processing and machine learning algorithms based on deep learning and feature extraction. The cell regions of each image, followed by Nancy index, were manually annotated and measured independently by 3 histopathologists. Manual and AI-automated measurements of Nancy index score were done and assessed using the intraclass correlation coefficient (ICC).

Results
The 200-image dataset was divided into 2 groups (80% was used for training and 20% for testing). ICC statistical analyses were performed to evaluate AI tool and used as a reference to calculate the accuracy (Table 1). The average ICC amongst the histopathologists was 89.33 and average ICC between histopathologists and AI tool was 87.20. Despite the small number of image data, the AI tool was found to be highly correlated with histopathologists.

Conclusion
The high correlation of performance of the AI method suggested promising potential for IBD clinical applications. A standardised and validated histological AI-driven scoring system can potentially be used in daily IBD practice to eliminate the subjectivity of the pathologists and assess the disease severity for treatment decision.