bluuebunny/crossref_metadata_2025_split huggingface dataset:
P487 Automated Scoring of Patient Endoscopy Videos Using Deep Learning Techniques: A Promising Approach for Clinical Trials in Inflammatory Bowel Disease
Authors: Badalamenti S , Sarker H , Zhao W , Bozhao Q , Pochet E , Trullo R , Tang Q , Zhang J , Kruger A , Wiekowski M 
Published: January 2024

Abstract

Background
Accurate assessment of patient endoscopy videos is crucial for various clinical trials, including those related to inflammatory bowel diseases (IBD). However, manual scoring by trained local and central readers can lead to discrepancies, inconsistencies, and logistical challenges. To address these issues, we devised a novel approach utilizing deep learning techniques to automate the analysis, parsing, and scoring of patient endoscopy videos. Our objectives were to reduce human error/variability, accelerate endoscopic scoring by enhancing read accuracy, and lower clinical trial cost.

Methods
We developed and trained deep learning models using a large dataset of labeled patient endoscopy images. The models were designed to predict the Mayo endoscopic score (MES), which serves as a standardized measure of disease severity in IBD. Our approach developed convolutional neural networks (CNNs) to extract features from raw video data and processed them into meaningful patterns. The models were optimized using transfer learning and validated on external endoscopy video datasets through rigorous testing protocols.

Results
Using an iterative process, we developed two sets (total 4) of proof-of-concept (POC) Artificial Intelligence (AI) models using frame level datasets from endoscopy videos. First, quality was assessed by the blur detection model, currently performing at &gt; 90% accuracy, and the bowel preparation model, performing at &gt; 95% accuracy compared to the labels provided by human annotators. Second, MES sub-score prediction currently performs with &gt;75% accuracy for 4-level Mayo sub-score prediction and &gt;90% accuracy in predicting advanced MES scores (2 or higher compared with consensus score derived from 3 annotators).

Conclusion
The presented study highlights the potential of deep learning techniques in revolutionizing the assessment of patient endoscopy videos in clinical trials for IBD. Automating the endoscopic scoring process enables faster, more accurate, and cost-efficient evaluations, ultimately leading to better detection of patient outcomes. Future research directions involve further refining the models to enhance their performance and expand their application to other gastrointestinal diseases.
P509 Upadacitinib improves symptomatic responses in patients with moderately to severely active Crohn’s disease
Authors: Blumenstein I , Torres J , Ma C , Lindsay J O , Ungaro R , Thin L , Lacerda A P , Anyanwu S I , Garrison A , Ford S , Louis E 
Published: January 2024

Abstract

Background
Upadacitinib (UPA), an oral Janus kinase inhibitor approved for the treatment of moderately to severely active Crohn’s disease (CD), has demonstrated the ability to provide rapid symptom relief within the first week of induction treatment in patients with CD.1 As symptomatic remission is critical for patients, this phase 3 post hoc analysis evaluated the impact of UPA on patient-reported outcomes (PROs) of abdominal pain score (APS) and stool frequency (SF) over the full induction and maintenance time periods.

Methods
Data were pooled from the U-EXCEL (NCT03345849) and U-EXCEED (NCT03345836) induction studies evaluating patients with moderately to severely active CD with an average daily APS ≥ 2 and/or SF ≥ 4 and received UPA 45 mg (UPA45) once daily (QD) or PBO for 12 weeks. Patients who achieved clinical response to 12 weeks of UPA45 induction were re-randomised in a maintenance study (U-ENDURE, NCT03345823) to receive UPA 15 mg (UPA15) QD, UPA 30 mg (UPA30) QD, or PBO for 52 weeks. APS and SF were recorded in a daily diary and evaluated over time.

Results
The average daily APS (mean: PBO 1.9, UPA45 1.9) and SF (mean: PBO 5.6, UPA45 5.4), were similar between the treatment groups at induction baseline (BL). Of patients reporting BL APS ≥ 1 (PBO 91.6%, UPA45 92.4%) or BL SF ≥ 2.8 (PBO 85.6%, UPA45 85.2%), higher proportions of patients receiving UPA vs PBO achieved APS = 0 or SF ≤ 1, or complete resolution of symptoms (APS = 0 and SF ≤ 1) at week 12 of induction, as well as at week 52 of maintenance (all P ≤ .001; Figure 1A). During induction, the mean change from BL in APS and SF was improved with UPA45 vs PBO starting at week 2 through to week 12 (all P &lt; .001; Figure 1B-C). Throughout the 52-week maintenance period, a higher proportion of patients receiving UPA15 or UPA30 achieved APS ≤ 1 or SF ≤2.8 vs PBO (Figure 1B-C). Patients treated with UPA30 demonstrated a numerically higher rate of symptomatic response vs UPA15. In patients who met the Crohn's Disease Activity Index (CDAI) criteria per US labeling (CDAI ≥ 220 at induction BL; clinical response [CR-100] at week 12 with UPA45),2 comparable symptom improvements were observed over time compared to the overall study population.

Conclusion
Patients with moderately to severely active CD demonstrated improvements in APS and SF as early as 2 weeks after UPA induction treatment. A greater proportion of patients achieved PRO-defined remission within 12 weeks of UPA induction treatment compared with PBO, which were sustained through week 52 of UPA maintenance treatment.
References:
1. Colombel, J. F. et al. J. Crohn’s Colitis. 2023;17;i102–3
2. AbbVie Inc. RINVOQ® (upadacitinib) [Package Insert]. N. Chicago, Ill.: AbbVie Inc., 2023
P512 Early proactive therapeutic drug monitoring with ustekinumab therapy in paediatric Crohn's Disease
Authors: Ricciuto A , McKay H , deBruyn J , Crowley E , Church P , Huynh H , Otley A , Shaikh A , El-Matary W , Wine E , Walters T , Griffiths A 
Published: January 2024

Abstract

Background
In the treatment of paediatric Crohn’s disease (CD), the youngest (lightest) children have historically been underdosed by standard weight-based dosing. Paediatric data on optimal dosing and drug levels are sparse. We aimed to examine real-world post-induction pharmacokinetic and effectiveness in a prospective multicentre paediatric CD cohort.

Methods
Luminal CD patients 2-17 years old in the Canadian Children IBD Network were eligible if they received UST IV and had a serum UST level measured proactively at week (wk) 8. Wk8 and subsequent UST levels were compared between children &lt;40 and ≥40 kg (Mann-Whitney-U), dosed in accordance with an ongoing phase 3 paediatric trial. We calculated a “dose to exposure ratio” by dividing induction dose by wk8 level. Clinical remission was defined as wPCDAI &lt;12.5 while still on UST. We used ROC curves to define optimal (Youden index) wk8 levels associated with wk16 remission and subsequent UST continuation. Continuous measures are reported as median (IQR).

Results
44 children were eligible from April 2017-April 2023 (70% M; age 13.1 (10.8-15.5) y; disease duration 0.3 (0.08-1.3) y; weight 44.7 (30.4-55.0) kg, 12 &lt;40kg; 75% bio-naïve; L1 18%, L2 23%, L3 52%; SES-CD at diagnosis 17 (11-21)). At UST start, wPCDAI was 27.5 (10-52.5) and albumin was similar between weight groups (p=0.3). Median follow-up was 10 (7-13) months. 68% received 260 mg IV loading dose, 16% 390 mg. All received 90 mg SC q8 weekly maintenance. Induction doses in mg/kg and mg/m2 were significantly higher in children &lt;40 kg (Table 1). Despite this, wk8 levels were similar between weight groups, with the same pattern at other times. The dose (mg/kg) to exposure ratio was 1.45x higher in children &lt;40kg, indicating they received more drug per unit increase in serum UST level relative to heavier children. Interval shortening to q4wk occurred in 7 prior to wk16, and in 16 (36%) by 6 months. By wk16, 56% of patients with available wPCDAI were in clinical remission and 60% at 1 year. Overall, 7 (16%) ceased UST. Wk8 UST levels were numerically higher in those who achieved wk16 clinical remission (7.4 (6.2-10.2) vs. 5.5 (2.6-7.1), p=0.094), and numerically lower in those who ceased UST (4.9 (2.6-6.9) vs. 7.3 (5.4-10.7), p=0.087). Based on ROC, the optimal wk8 UST level associated with wk16 clinical remission was 5.8 (AUC 0.68, sensitivity 78%, specificity 57%). The optimal level associated with UST continuation was 7.9 (AUC 0.73, sensitivity 43%, specificity 100%, Figure 1).

Conclusion
Paediatric CD patients weighing &lt;40kg required higher UST doses to achieve comparable drug exposure to those ≥40kg. Positive clinical outcomes were associated with higher UST levels (with optimal cut-offs 6-8).

Figure 1
P513 Clinical efficacy and durability of subcutaneous infliximab in patients with inflammatory bowel disease after switching from intravenous in a Korean multicenter prospective cohort study
Authors: Kim K , Hong S N , Kang S B , Lee K M , Koo J S , Jung Y , Lee B J , Yoon H , Kim H W , Lim Y J , Lee H S , Lee Y J , Lee J , Lee C K , Shin S Y , Moon J M , Seo J , Choi C H 
Published: January 2024

Abstract

Background
Subcutaneous infliximab (IFX-SC) has shown comparable efficacy and safety with IV infliximab (IFX-IV) in inflammatory bowel disease (IBD), such as ulcerative colitis (UC) or Crohn's disease (CD), since its launching in 2021. We aimed to investigate the real-life efficacy and durability of IFX-SC after IFX-IV in Korea.

Methods
This multicenter, prospective cohort study included IBD patients who administered IFX-IV maintenance therapy from September 2021 to November 2023. Patients received IFX-SC 120mg after the last IFX-IV administration (Week [W] 0), and every 2 weeks thereafter. Patients who administered IFX-SC less than W8 were excluded. Clinical relapse (CREL) at W26, W50, and one-year drug survival were assessed. Among IBD patients with W0 clinical remission, CREL was partial Mayo score ≥2 points among UC patients, and Crohn’s disease activity index ≥150 points among CD patients. Drug survival was evaluated based on the time of drug persistence from W0 to the last date of IFX-SC administration among drug-off cases. Rate of drug re-switch (from IFX-SC to IFX-IV) was also investigated.

Results
A total of 447 patients (UC with 154, and CD with 287) were enrolled. Enrolled patients included young adults with a male predominance (Table 1). At W0, 77 patients with UC and 185 patients with CD showed clinical remission. Patients with UC showed 15.7% (11 out of 70 patients) of W26 CREL, and 12.1% (seven out of 58 patients) of W50 CREL (Figure 1A). Among patients with CD, rates of W26 CREL and W50 CREL were 5.9% (nine out of 153 patients) and 10% (11 out of 110 patients), respectively. On the other hands, one-year drug survival was also investigated (Figure 1B). Among patients with UC, W26 drug survival rate was 89.8% (95% confidence interval [CI], 0.836–0.937), and W50 drug survival rate was 89.0% (95% CI, 0.827–0.931). Among patients with CD, it showed higher drug survival rate, showing W26 drug survival rate of 97.8% (95% CI, 0.951–0.990) and W50 of 94.9% (95% CI, 0.911–0.971). During the study, 3.4% (15 patients) of serious adverse events were reported. Drug re-switch rate was 5.4%, mainly due to injection site discomfort.

Conclusion
In real-world settings, IFX-SC seems to be a feasible option for the maintenance therapy, following IFX-IV administration. Considering favorable drug survival rate, low relapse rate, and tolerable safety profile, it may facilitate individualized treatment.
P520 Preferences towards treatment attributes among patients with Crohn’s disease and ulcerative colitis in Argentina, Australia, Brazil, Saudi Arabia and Taiwan: a discrete choice experiment
Authors: Argollo M , An Y K , Balderramo D , Nahla A , Kuo C J , Fadeeva O , Uy E 
Published: January 2024

Abstract

Background
Advanced therapies (ATs) with different mechanisms of action and routes of administration (RoA) are used for inflammatory bowel disease (IBD: Crohn’s disease [CD] and ulcerative colitis [UC]), and patients (pts) play an increasing role in the decision-making process.Pts’ preferences for treatment attributes from 7 European countries have been reported previously; however, evidence from non-European countries is lacking.

Methods
Adult pts with CD or UC on treatment for ≥6 months from Argentina, Australia, Brazil, Saudi Arabia and Taiwan were enrolled in this cross-sectional, self-administered online survey (Oct 2022 to May 2023). Pts’ preferences for IBD treatment attributes are described. In a discrete choice experiment, the relative importance of treatment attributes was estimated using conditional logit models.

Results
Overall, 706 pts with CD and UC (n=353 each) completed the survey. Mean (standard deviation [SD]) ages (years [y]) were 36.8 (9.9) and 37.7 (10.2), 47.9% and 47.6% were female, and mean (SD) disease durations (y) were 4.5 (6.0) and 4.6 (6.7) for CD and UC, respectively; 58.1% (CD) and 56.1% (UC) were exposed to ATs. For pts with CD, the rate of long-term remission on maintenance therapy (MT) was the most important attribute for treatment choice (32.5%), followed by the rate of 1-y remission (25.7%), RoA (24.6%) and risk of serious adverse events (AEs, 11.5%) and mild AEs (5.8%). For pts with UC, the rate of corticosteroid-free remission after 1 y was the most important attribute (30.8%), followed by RoA (27.4%), rate of mucosal healing after 1 y (16.1%), long-term remission on MT (14.9%) and risk of serious AEs (10.0%) and mild AEs (0.8%). Country-specific results are shown in the Table. Compared with intravenous administration every 4–8 weeks, pts with CD preferred subcutaneous (SC) administration every 1–2 weeks (odds ratio [95% confidence interval]: 1.41 [1.27–1.56] P&lt;0.001) or every 4–12 weeks (1.22 [1.08–1.39, P=0.002]), and pts with UC preferred taking a tablet (1.41 [1.25–1.59], P&lt;0.001) or SC administration every 4–12 weeks (1.30 [1.14–1.48], P&lt;0.001) or every 1–2 weeks (1.20 [1.07–1.35], P=0.002). Pts exposed to ATs ranked the importance of RoA lower than that of effectiveness compared with AT-naïve pts, and 49.3% of pts with CD and 50.5% with UC indicated that they wanted ATs to start earlier.

Conclusion
This study highlights the importance of treatment effectiveness, RoA and safety for pts with IBD. Personalised care is crucial given that preferences for treatment attributes may vary across countries and among pts. Patient–physician shared decision-making discussions regarding therapy choice and timing should happen throughout the treatment journey.
P531 Long-Term Evaluation of Intensified Ustekinumab in Crohn's Disease: Real-Life Results
Authors: Molina Arriero G , González Furelos T , Mauriz Barreiro V , Echarri Piudo A 
Published: January 2024

Abstract

Background
Dose intensification of ustekinumab (UST) is implemented in clinical practice to rescue patients with loss of response or suboptimal clinical response to the drug. Observational studies, with contradictory results, associate higher UST trough concentration and clinical outcomes in Crohn's disease (CD). The primary outcome was to evaluate the long-term effectiveness of dose intensification of UST in terms of clinical and biochemical remission and its relationship with serum trough concentrations.

Methods
A retrospective, single-center observational study was conducted, including patients with CD treated with intensified UST, analyzed from January 2023 to the present. Demographic data, smoking status, disease pattern and duration, extraintestinal manifestations, perianal disease, and prior exposure to biologics were collected.
Laboratory markers (fecal calprotectin (FCP) and C-reactive protein (CRP)), disease activity scores (Harvey-Bradshaw Index (HBI)), and drug serum levels at the time of intensification, at 6 and 12 months, were analyzed to evaluate response. Clinical remission was defined as HBI &lt; 5, clinical response was defined as reduction in the HBI by ≥3 points and biochemical remission as FCP &lt; 150 µg/g. Data were collected from the electronic medical record. Quantitative variables were expressed as median (interquartile range). To analyze the results, a logistic regression was performed.

Results
A total of 35 patients were included. Patients' clinical and demographic characteristics are summarized in Table 1. All were intensified with subcutaneous dose of 90 mg every 4 weeks (31.4% underwent intravenous re-induction).
At 6 months after UST intensification, 82.86% (n=29) of the patients presented clinical remission, with a statistically significant decrease in FCP levels (247.78 µg/g vs. 133.55 µg/g (p = 0.0026)). At 12 months, 85.71% had achieved clinical remission, also presenting a statistically significant decrease in FCP levels (370.41 µg/g vs. 200.94 µg/g (p = 0.0200)). Drug levels, classified as &gt;2.2 µg/ml and &lt;=2.2 µg/ml, were not related to remission at 6 months (OR 0.94, 95%CI 0.05-16.35. p=0.97) or at 12 months (OR 0.87, 95%CI 0.13-6.03. p=0.89).

Conclusion
UST intensification proves to be an effective long-term optimization strategy in CD, without an apparent correlation with higher serum drug levels in our series.
P537 Analysis of immunological VAriables in ex vivo Tofacitinib-treated human biopsies from Active ulcerative colitis patients to predict clinical Response (the AVATAR study)
Authors: Onali S , Di Petrillo A , Soddu P , Ibba I , Demurtas M , Raho N , Morrocchi E , Amodio D , Palma P , Milenkovic S , Ceccarelli M , Fantini M C 
Published: January 2024

Abstract

Background
Ulcerative colitis (UC) is characterized by chronically relapsing inflammation of the colonic mucosa. Tofacitinib (TOFA) is a paninhibitor of the JAK kinases, a family of intracellular kinases in volved in the signal transduction pathway of multiple inflammatory signals. Despite the efficacy shown by TOFA in inducing and maintaining remission in moderately-to-severely active UC, rates of primary non response remains high. We propose a new method to identify predictors of responsiveness to TOFA based on "ex-vivo" challenge of organ cultures from biopsies collected from candidate patients.

Methods
Baseline biopsies from inflamed areas of UC patients with active disease and candidate to receive TOFA 10mg b.i.d. for 8 weeks, were used for "ex-vivo" organ culture and stimulated with TOFA 20μM and 200nM or left untreated. After 24 hours, proteomic analysis was performed and quantitative expression of 92 inflammation-related human proteins (Olink® Human Inflammation panel) was correlated with week 8 clinical response defined by Modified Mayo Score (MMS). Intestinal biopsies were also collected at baseline and at 8 weeks for proteomic analysis. To decipher the nature of TOFA's effects, both unsupervised and supervised machine learning (ML) methods were employed (sklearn module, Python). The K-means method was used for unsupervised learning followed by a supervised ML approach to classify week 8 responders and non-responders. Data were transformed in into a second-order polynomial format and logistic regression was used for modelling.

Results
Between Jannuary 2022 and January 2023, 17 UC patients were enrolled (Table 1). At week 8, 13/17 (76.5%) patients treated with TOFA showed clinical response. Unsupervised ML, utilizing proteomic data from organ cultures stimulated with TOFA 200nM, achieved a 90% success rate in predicting a positive clinical response. This prediction was based on forming two distinct clusters, with significant contributions from key variables such as CASP-8, CCL19, CCL20, CD5, CXCL9, EN-RAGE, GDNF, HGF, IL-18R1, MCP-1, MCP-2, MCP-4, MMP-10, OPG, PD-L1, STAMBP, TNFRSF9, TRANCE, TWEAK, and VEGFA. In our supervised ML approach, logistic regression was employed with 30 shuffle splits to refine the predictive model. We discovered that transforming the dataset into a second-order polynomial format significantly enhanced the model's performance. The most effective logistic regression model achieved a mean precision score of 0.82 (Fig.1).

Conclusion
Our predictive model demonstrates a high level of precision in identifying positive treatment responses, emphasizing the potential of further dataset expansion and the use of advanced machine-learning to predict response in TOFA-treated UC patients.
P589 Real-world data on upadacitinib in the treatment of inflammatory bowel disease: safe and highly effective with extremely positive patient feedback
Authors: Harris C , Gee T , Barcan A , Yanagisawa Y , Brown M , Gordon J N 
Published: January 2024

Abstract

Background
Upadacitinib is a selective Janus kinase inhibitor that has recently been approved in England for the treatment of ulcerative colitis (UC) and Crohn’s disease (CD) though real-world data is lacking. Furthermore, there is very limited information available on patient reported experiences of treatment with a small molecule compared with biological therapies. The object of this study was to provide real-world data on the efficacy of upadacitinib in the treatment of IBD in conjugation with collecting specific patient-reported feedback on acceptability and experience of treatment with upadacitinib.

Methods
We prospectively collected data on all IBD patients treated with upadacitinib between November 2022 and November 2023 in a large NHS Trust serving approximately 1% of the population of England. The primary objective was to assess patient response to induction at 8 weeks (UC) and 12 weeks (CD). Demographic details, biochemical markers (faecal calprotectin and CRP) and disease activity scores were recorded. We also undertook a bespoke anonymised electronic survey to assess the patient experience and views on treatment with upadacitinib in comparison to previous treatments.

Results
Forty-two patients were included in the study (34 UC/8 CD). The average age was 41 (range 18-76) and 27 (64%) were male. 11/34 UC patients were biologic naïve. All CD patients were biologic experienced with the majority exposed to an anti-TNF, vedolizumab and ustekinumab. Overall, 34/40 (85%) patients responded to induction treatment based on disease activity scores (27 UC, 7CD), with 68% (22 UC, 5 CD) in remission. Data was missing for two patients. Response rates were similar between biologic naïve and biologic exposed patients (82% and 86% respectively). In the UC cohort, mean calprotectin at baseline improved from 1718ug/g (range 8-6000ug/g) to 311ug/g (4-3014ug/g). In the CD cohort, mean calprotectin improved from 1719ug/g (115-5874ug/g) to 314ug/g (4-917ug/g). 3/42 (7%) of patients discontinued upadacitinib due to disease progression with the remaining 93% continuing treatment. Our patient survey results revealed very high satisfaction with treatment (85%), with the vast majority preferring treatment with upadacitinib to their previous biological therapy.

Conclusion
In this real-world study, induction therapy with upadacitinib was well tolerated and demonstrated good efficacy with excellent response and remission rates in a mixed patient cohort that included many with highly refractory disease. No unexpected safety signals were seen. The patient experience was overwhelmingly positive. If this data is replicated in larger studies there is an increasingly strong rationale for introducing upadacitinib earlier in the sequencing of advanced therapies.