bluuebunny/crossref_metadata_2025_split huggingface dataset:
P995 Development and validation of a deep learning model based on histological characteristics to predict primary non-response of infliximab in Crohn's disease
Authors: Liu Z , Mao R , Wang Y , Huang B , Ye Z 
Published: January 2024

Abstract

Background
Predicting primary non-response to infliximab (IFX) is important to select the optimal therapy and utilize personalized management in patients of Crohn’s disease (CD). This study aimed to develop and validate a deep learning (DL) model based on histological characteristics for predicting primary non-response to IFX in CD.

Methods
A training cohort and a validation cohort were recruited from the First Affiliated Hospital of Sun Yat-sen University. Clinical features, serological biomarkers, imaging features and histological characteristics of colonoscopy biopsy at baseline of IFX therapy were obtained as candidate predictors. Primary non-response was assessed at week 14. We developed a model using a multi-instance learning framework. This model combines patch-level features from whole slide images (WSI) with multi-modal information, together with pre-treatment image features and clinical features, to predict the response to infliximab (IFX) therapy. Finally, the model was validated for area under the curve (AUC) in a reference validation cohort.

Results
A total of 131 patients were included in the derivation cohort. The DL model based on pathologic features only had an under-the-curve receiver operating characteristic (AUROC) value of 0.87 in the 10-fold cross-validation cohort. The mean AUROC for the model combining pathologic and radiographic features was 0.88. The DL model achieved the highest AUROC value of 0.91 when combining pathological, radiomics and clinical features (Figure 1). When the pathological film was visualized by attention thermography, it was found that the ulcerated tissue was focused on, especially in areas dominated by neutrophils, lymphocyte aggregation and abnormal crypt structure.

Conclusion
The study developed several accurate DL models for predicting primary non-response to IFX by WSI. The DL model combining pathological, radiomics and clinical features achieving best performance. This model may help clinicians select appropriate therapeutic strategy and avoid unnecessary exposure to IFX in CD patients.
P1002 De novo and drug-induced skin manifestations in Inflammatory Bowel Disease patients: The impact of anti-tumour necrosis factor therapy
Authors: Zhao H , Whitehead E , Fitzgerald A , Robertson H , Turnbull J , Sebastian S 
Published: January 2024

Abstract

Background
Skin disorders in inflammatory bowel disease (IBD) consist of extra-intestinal manifestations (EIM) or drug-induced lesions. This study explores de novo skin lesions and the emergence of immune-mediated skin disorders induced by anti-tumour necrosis factor (anti-TNF) agents.

Methods
Patients with EIMs, de novo skin lesions, and drug-induced skin eruptions were identified from an IBD patient database on advanced therapies. Data on time intervals from the initiation of IBD treatment to the development of skin disorders, causative agents, and subsequent management were collected.

Results
In a cohort of 1,773 patients (993 with ulcerative colitis, 746 with Crohn’s disease, and 31 with IBD unclassified), 30% (549) exhibited skin manifestations, with 28% (491 cases) showing de novo skin conditions. Identified skin manifestations included psoriasis/psoriasiform rash (18.3%), eczema (16.3%), seborrheic dermatosis (13.8%), acne (9.8%), actinic keratosis (5.3%), rosacea (4.7%), erythema nodosum (EN, 3.5%), cutaneous Crohn's disease (CCD, 2.6%), folliculitis (1.8%), pyoderma gangrenosum (PG, 1.5%), and others. Of the skin lesions, 31.8% (175) occurred before the IBD diagnosis, with a median duration of 8 years, while 51.9% (286) developed post-diagnosis unrelated to therapies.
Biologic therapies improved extraintestinal skin lesions in 19 patients (3.4%). Notably, all 3 EN cases and 4 out of 5 PG cases achieved full resolution with biological treatments, leading to improved IBD activity. Similarly, 9 out of 10 Crohn’s disease patients with CCD showed improved skin conditions following biological treatments
Fifty-eight patients (3.3%) experienced drug-induced skin lesions, with a median age at IBD diagnosis of 35 years (ranging from 17 to 67). The majority (91.3%) of cases were attributed to anti-TNF agents, and psoriasiform lesions were the most prevalent (60.3%). The median duration from treatment initiation to the onset of drug-induced skin lesions was 23 months (ranging from 0 to 115 months). Among the affected individuals, 19 using originator anti-TNF agents developed skin lesions, with 13 having psoriatic lesions. In comparison, 34 patients on biosimilar anti-TNF agents developed skin lesions, and 23 of them had psoriatic lesions. The progression of skin lesions led to anti-TNF discontinuation in 33 patients, of whom 25 transitioned to Vedolizumab or Ustekinumab. Resolution occurred in 22 patients.

Conclusion
Anti-TNF-induced skin lesions, notably psoriasiform lesions, appear to be more prevalent in the biosimilar era among IBD patients, often leading to discontinuation. Nevertheless, resolution is possible through strategic switches to alternative biologic agents.
P1024 The current role of Tofacitinib in acute severe ulcerative colitis in adult patients: A systematic review and pooled analysis
Authors: Fousekis F , Mpakogiannis K , Christodoulou D , Katsanos K 
Published: January 2024

Abstract

Background
Despite rescue therapy, acute severe ulcerative colitis (ASUC) is associated with high colectomy rates, while treatment options remain limited. Tofacitinib, a rapidly acting Janus Kinase (JAK) inhibitor, could be an effective treatment option for managing acute severe ulcerative colitis, contributing in parallel to avoiding colectomy.

Methods
A systematic in-depth literature search in the PubMed and Scopus databases until 20 October 2023 was undertaken for all available studies of adult patients with ASUC treated with tofacitinib. Finally, we included 18 articles from a total of 705 articles resulting from our initial search. The primary outcomes were the pooled colectomy rate and the 90-day and 6-month colectomy-free rate.

Results
Overall, one retrospective study, three observational studies, nine case series and five case reports incorporating 264 patients who received tofacitinib in ASUC (preferably defined according to the Truelove ad Witts criteria) identified with a follow-up period ranging from 30 days to 14 months. In total, the pooled colectomy rate was 20.4% (95% CI 15.7-25.1). The pooled 90-day and 6-month colectomy-free rates were 85.6% (95% CI 81.1-90.1) and 82.1% (95% CI 77.6-86.6), respectively (Figure). The most common side effect was infections, with C. difficile infection being the most frequent adverse event among them.

Conclusion
Tofacitinib may be an alternative promising option for the treatment of ASUC. Furthermore, it should be mentioned that tofacitinib could be considered a safe treatment option, taking into account that adverse effects occurred in a small amount of the patients studied. Nevertheless, randomized clinical trials are required to estimate the efficacy and safety of tofacitinib in cases of ASUC.
P1025 Analysis of the Clinical Characteristics of Elderly-onset Crohn's Disease
Authors: Lin J 
Published: January 2024

Abstract

Background
The prevalence of Crohn's disease in the elderly is increasing today. The purpose of this study was to analyze the clinical characteristics of elderly-onset patients with Crohn's disease and compare with non-elderly-onset adult patients.

Methods
All Crohn's disease patients with onset aged 60 years and older at our Inflammatory Bowel Disease Center in recently ten years were retrospectively included. The elderly were compared with adult patients aged 18-59 at the time of onset, who were matched according to diagnosis time and gender by a 1:3 ratio of propensity score matching. After matching, the clinical data were recorded and analyzed to compared between the two groups of patients.

Results
A total of 68 patients were included, including 17 patients in the elderly-onset group and 51 patients in the non-elderly-onset adult group. The mean age of diagnosis in the two groups was 30.3±8.7 years and 63.9±4.24 years, and the mean course of disease was 30.3 months and 63.9 months, respectively. According to the Montreal classification, most elderly patients presented with L3 (70.6%) and B1 (58.8%), no cases involving the upper digestive tract or multiple lesion sites, showed mild disease activity (76.5%). The elderly group had fewer intestinal complications and parenteral manifestations. The medication types of elderly are 5-aminosalicylates (52.9%), traditional immunosuppressive agents (45.6%) and enteral nutrition preparations (29.4%) being the more frequent types of medications used, and glucocorticoids and biologics being used less frequently. Exposure to two or more IBD medications was 31.4% and 52.9% in the non-elderly onset adult group versus the elderly onset group, respectively (p=0.110). During follow-up, symptoms such as diarrhea (11.8 vs 5.9%), abdominal pain (35.3% vs 17.6%) and weight loss (11.8% vs 3.9%) were more common in the elderly-onset group. Elderly patients had more hospitalizations on average (0.22 vs. 1.12). 40.7% of elderly patients underwent CD-related surgery during the duration of their disease, with 50.0% of patients undergoing reoperation.

Conclusion
Compared with non-elderly-onset adult patients, elderly-onset patients with Crohn's disease are more common in women, and the lesion mainly in the ileum and ilecolon; the disease behavior is mainly B1; nearly half of the patients have intestinal complications The elderly have atypical clinical manifestations, basically haven’t family history of IBD, take longer to diagnose, have more underlying diseases, more hospitalizations on average, and are more likely to have complications. They are more likely to receive conservative treatment, but with more frequent medication adjustments and a higher likelihood of undergoing CD-related surgery.
P1028 Clinical decision support tool for vedolizumab can predict treatment persistence in Crohn's disease but not in ulcerative colitis
Authors: Ocepek A , Molinari N , Maček P 
Published: January 2024

Abstract

Background
Vedolizumab (VDZ) has displayed up to 82.9% treatment persistence as a first-line biologic for ulcerative colitis (UC) and ranked third in the second line. It ranked fourth in treatment persistence as the first or second-line biological therapy in Crohn's disease (CD). Factors most commonly associated with treatment outcomes have been indicators of more aggressive disease, like refractoriness to corticosteroids and tumour necrosis factor (TNF) alpha inhibitors, elevated baseline patient-related outcomes (PROs), comorbidities in CD and faecal calprotectin. Pre-treatment prediction of response and long-term persistence could help optimise treatment in an individual patient.

Methods
We performed a retrospective single-centre cohort study based on the UR-CARE registry. Data for 129 patients treated with VDZ from July 2016 until April 2023 were analysed. A validated clinical decision support tool (CDST) for CD and UC was used to stratify patients according to the probability of response to VDZ. We used Kaplan-Meier survival curves to analyse treatment persistence at week 52, depending on the CDST group for CD and UC. The association between the CDST group and the optimisation of VDZ therapy was evaluated using the chi2 test.

Results
The study included 57 CD patients, median age 34 years, 38.6% male, and 72 UC patients, median age 32.1 years, 59.7% male. Patients with CD had longer disease duration (4.1 years) than UC patients (2.6 years). 33.3% of CD patients had ileo-colonic disease, 24.6% had upper GI involvement, 33.3% had fistulising disease, and 56.1% had prior surgery. 63.9% of patients with UC had pancolitis, and 34.7% had concomitant corticosteroids at baseline. Before VDZ, more than half of patients were exposed to TNF alpha inhibitors in both CD and UC (57.9% and 52.8%, respectively). We found significantly higher treatment persistence in CD patients stratified into groups with intermediate (group 1) and high (group 2) probability of response, according to CDST compared to the group with low (group 0) probability of response. The VDZ therapy was discontinued in 76.9%, 28.6% and 6.3% of patients within CDST groups 0, 1, and 2, respectively. The association was statistically significant (p &lt; 0.001). In UC, however, we could not confirm any significant difference in treatment persistence between CDST groups. The VDZ therapy was discontinued in 50.0%, 34.9%, and 21.9% in groups 0, 1, and 2, respectively. While the trend between discontinuation of the VDZ and CDST groups can be observed, the association was not statistically significant (p = 0.165).

Conclusion
In our study, treatment persistence for VDZ could be predicted using CDST for CD, but not for UC.
P1031 Intestinal ultrasound for monitoring therapeutic response in patients with ulcerative colitis treated with upadacytynib
Authors: Kaniewska M , Krogulecki M , Lewandowski K , Filipiuk A , Gonciarz M , Rydzewska G 
Published: January 2024

Abstract

Background
Intestinal ultrasound (IUS) is a noninvasive method to assess disease activity in inflammatory bowel disease (IBD) although there are still limited data of usefulness of IUS in ulcerative colitis (UC) compared to Crohn’s disease (CD). The aim of the study was to evaluate usefulness of intestinal ultrasound in comparison to endoscopy in assessment of the efficacy of upadacytynib (UPA) in induction of remission in patients with UC.

Methods
This was a prospective, two-centers study in which we enrolled 27 patients with a flare of UC (total Mayo score&gt;7) treated with UPA (8 weeks of induction period). IUS, calprotectin level and laboratory tests were conducted in week 0, 4 and 8. Milano ultrasound criteria (MUC) were used to assess the IUS disease activity.

Results
Among 27 patients 34% achieved clinical remission and 40,6% endoscopic remission already in week 4. After 8 weeks of treatment with UPA clinical remission in 53,1% and endoscopic remission in 56,2% of UC patients were achieved. In IUS the most affected parts of the colon were rectum and sigmoid colon. 100% of the patients had an increased bowel wall thickness (BWT)&gt;3mm in the sigmoid colon and rectum at baseline. In the first 4 weeks of the study, the percentage of patients with an increased BWT in the sigmoid colon and rectum decreased significantly and remained low at week 8. 78% of patients with normalized BWT had endoscopic remission vs 22% without endoscopic remission (p&lt;0.001). There was 74% correlation between MUC and total Mayo score (p=0,013).

Conclusion
Upadacitinib has demonstrated a positive efficacy during induction of remission in UC patients, shown as improvement in IUS parameters as well as in endoscopy improvement. Our data showed a strong correlation between normalization of BWT and endoscopic remission in patients with UC treated with upadacytynib. IUS seems to be a useful and non-invasive method for monitoring disease course and for assessing treatment response in UC patients.
P1033 Road to exit strategy in patients with inflammatory bowel disease: ready or not?
Authors: Todeschini A , Ciccocioppo R , Geccherle A , Bernuzzi M , Signoretto P , Colaci N , Barugola G , Variola A 
Published: January 2024

Abstract

Background
Whereas there is an emerging consensus on the optimal approach to initiation of a range of therapies in inflammatory bowel disease (IBD), there remains greater uncertainty about the risks, benefits, and timing of stopping treatment when patients are in stable remission on therapy. When planning an exit strategy for drug withdrawal, the risk of disease relapse must be balanced against the risk of drug-related adverse events and healthcare costs. Our study evaluated the risks of disease relapse associated with withdrawal of the biologic therapy in both ulcerative colitis (UC) and Crohn’s disease (CD).

Methods
In this is a retrospective observational study, the exit strategy was proposed to 60 patients regularly followed in two IBD referral centre from 2015 to 2023. The exit startegy was performed as: (i) discontinuation without de-escalation, (ii) progressive de-escalation and (iii) azathioprine as monotherapy. Data on medical history were collected from electronic health records. Chi-square test was used to compare categorical variables. Logistic regression was used to assess the relationship between disease-related characteristics and the onset of disease relapse after the withdrawal.

Results
60 IBD patients were enrolled, 46 patients withdrawal their biologic therapy and 14 patients were in a de-escalation stategy. These 46 patients (15 UC and 31 CD) performed discontinuation without de-escalation (65%), progressive de-escalation (26%) and azathioprine as monotherapy (9%). They withdraw anti-TNF (82%) or other biologics (18%). Most of patients (71%) were on first line of biologic therapy. The median follow-up period after drug withdrawal was 29 months. A disease relapse occurred in 14 patiens with a median period of 12 months. A good recapture of previous therapy was observed in 57% of patients. Logistic regression analysis revealed a trend of significance between biologic therapy duration (p 0.05) and absence of flare-up after exit strategy. No correlation was noticed with duration of endoscopic or clinical remission before starting the drug withdrawal.

Conclusion
There are no specific factors related to a successful exit strategy. Biologic drug discontinuation is something best considered on a case-by-case basis and determined by patient preferences and disease features. We need more specific study in order to identify patients who can stop therapy without undue risk of poor outcomes.
P1044 Mirikizumab Pharmacokinetics and Exposure-Response in a Phase 2 Study in Patients With Moderately to Severely Active Crohn’s Disease
Authors: Chua L , Otani Y , Friedrich S , Durand F , Zhang X 
Published: January 2024

Abstract

Background
Mirikizumab (miri) is a humanized anti–interleukin-23-p19 monoclonal antibody approved for the treatment of ulcerative colitis (UC) and under development for Crohn’s disease (CD). This analysis characterises miri pharmacokinetics (PK) and the relationship between miri exposure and efficacy response using data from a phase 2 trial in adults with moderately to severely active CD.

Methods
AMAG was a randomised, double-blind, placebo-controlled trial conducted in 14 countries. Patients received placebo, miri 200 mg, 600 mg, or 1000 mg as induction regimens administered intravenously (IV) every 4 weeks (Q4W) through Week 12, followed by 36 weeks of maintenance treatment with continuous treatment of miri 200 mg, 600 mg, or 1000 mg IV or miri 300 mg administered subcutaneously (SC) Q4W. PK parameters were analysed by non-linear mixed-effects modelling. Covariate effects on miri exposure were evaluated using simulation-based estimations. Exposure-response (ER) for patients achieving endoscopic response by Simple Endoscopic Score for Crohn’s Disease (SES-CD) at Weeks 12 and 52 were assessed using logistic regression models.

Results
186 patients were included. The estimated systemic clearance (CL), central volume of distribution (V), and SC bioavailability (F) were 0.022 L/hr, 3.31 L, and 33.4%, respectively. Lower baseline values for SES-CD (indicative of a less severe CD) were associated with reduced CL. Lower body weight and higher albumin levels were also associated with reduced CL. Higher body weight was associated with higher V and lower baseline body mass index correlated with higher SC F. Impacts on PK parameters were small relative to random variability and not considered clinically relevant. The model-based ER analyses for endoscopic response probability at Week 12 detected a significant treatment effect relative to placebo (p&lt;0.001) and a significant ER (p=0.001) in a dose range of 200-1000 mg. The ER analyses indicated near maximal efficacy for IV dose between 600 mg and 1000 mg during the Induction Period. There was no significant relationship between miri exposure and the probability of achieving endoscopic response by SES-CD at Week 52, indicating exposures produced by the maintenance doses provided similar efficacy.

Conclusion
Miri PK characteristics in adults with active CD were consistent with miri UC studies. Overall, none of the covariates identified as being significantly correlated with miri PK parameters were considered clinically relevant. No patient factors evaluated in this analysis justify dose adjustment. These findings support the miri induction dose 900 mg IV Q4W and maintenance dose 300 mg SC Q4W selected for phase 3 CD study.
P1045 Comparative Efficacy of Fecal Microbiota Transplantation for Clostridioides Difficile Infection in Patients with and without Inflammatory Bowel Disease: A Retrospective Cohort Study
Authors: Chen J H , Le P H , Yeh P J , Chen C C , Kuo C J , Chiu C T , Chiu C H 
Published: January 2024

Abstract

Background
Clostridioides difficile infection (CDI) significantly exacerbates and worsens the prognosis of inflammatory bowel disease (IBD). While fecal microbiota transplantation (FMT) is recognized as a safe and efficacious therapy for patients battling recurrent or refractory CDI, but comparative studies focusing on the success rates in IBD and non-IBD patients remain scarce. Our study aims to shed light on this gap in knowledge.

Methods
In this retrospective cohort study conducted at Chang Gung Memorial Hospital between April 2019 and February 2023, patients undergoing FMT via colonoscopy for recurrent or refractory CDI were enrolled. Participants were categorized into IBD and non-IBD groups based on their underlying conditions. We compared baseline characteristics and clinical outcomes at one-month and one-year follow-up intervals. CDI diagnosis was confirmed through positive CD toxin A/B genes and associated clinical symptoms. Donor specimens were sourced from Chang Gung Microbiota Therapy Center's fecal bank.

Results
Our study included 88 patients who received FMT, comprising 30 in the IBD group and 58 in the non-IBD group. The indications were recurrent CDI in 31 patients, refractory CDI in 54, and both conditions in 3 patients. Among the IBD subgroup, 20 patients had ulcerative colitis, and 10 had Crohn's disease. In the baseline comparison, the IBD group was significantly younger (mean±SD, 45.23±16.45 years vs. 61.90±24.40 years, P = 0.001) and had fewer comorbidities such as hypertension (10.0% vs. 55.2%, P &lt; 0.001), diabetes mellitus (6.7% vs. 31.0%, P = 0.014), and cancer (3.3% vs. 31.0%, P = 0.012) than the non-IBD group. Additionally, the IBD group had less prior Fidaxomin use (6.9% vs. 26.3%, P = 0.021) and fewer HMG-CoA reductase inhibitor users (0.0% vs. 15.5%, P = 0.025). Post-FMT, IBD severity indices showed significant improvement at one month. The mean partial Mayo score in the IBD group decreased by 2.9 points, the endoscopic Mayo subscore decreased by 0.7 points, and the Crohn’s Disease Activity Index decreased by 79.98 points. At this time, the IBD group showed a similar percentage of negative CDI toxin A/B tests (83.3% vs. 63.8%, P = 0.174) but had lower clinical remission rates (79.5% vs. 96.5%, P = 0.006) compared to the non-IBD group. However, at the one-year follow-up, the eradication rate (94.4% vs. 73.9%, P = 0.112) and clinical remission rate (84.2% vs. 90.3%, P = 0.661) were comparable between both groups. No safety issues or adverse effects were reported in any of the patients.

Conclusion
FMT demonstrates safety and efficacy in treating recurrent or refractory CDI in both IBD and non-IBD patients, also aiding in mitigating IBD-associated inflammation.