bluuebunny/crossref_metadata_2025 huggingface dataset:
P953 Establishment and Internal Validation of a Clinical Risk Score to Predict the Efficacy of Adalimumab in Crohn's Disease
Authors: Wang F , Liang J
Published: January 2024

Background

Adalimumab (ADA) plays a crucial role in treating Crohn's disease (CD), but not all patients benefit from it. This study aimed to analyze the factors affecting the treatment effectiveness of ADA for CD and then establish an efficacy prediction model with internal validation.

Methods

Retrospectively collected data from CD patients receiving ADA at Xijing Hospital from October 2020 to February 2023. Collect clinical data of patients and use FITC-labeled ADA to perform immunofluorescence staining on paraffin tissue sections of CD patients before ADA treatment. The data were randomly split into training and validation. Single-factor and multiple-factor logistic regression models were used to analyze the factors influencing the 12-week clinical remission of CD patients treated with ADA in the training, determining the optimal predictive model. A line chart prediction model was established and the model's discrimination and calibration were tested. Finally, the model was internally validated in the validation set.

Results

A total of 68 patients were included in the study. The clinical remission rate of CD patients treated with ADA at 12 weeks was 55.88% (38/68). The results showed that baseline endoscopic stenosis [OR=0.019, 95% confidence interval (95% CI) 0.019-0.993], disease course [OR=0.966, 95% CI 0.940-0.993], and the number of FITC-labeled ADA-positive cells [OR=1.109, 95% CI 1.025-1.201] were factors affecting the therapeutic effect of ADA in CD patients (p<0.05) which used to establish the efficacy prediction model. The AUC of the prediction model in the training and validation were 0.868 (95% CI 0.769-0.977) and 0.802 (95% CI 0.604-1) (p<0.05), respectively. The clinical decision curve analysis showed that the prediction model had significant clinical benefits in both the training and validation.

Conclusion

The prediction model can provide reference for clinicians to make treatment decisions.
P958 Comparison of Paediatric Patients and Young Adults with Moderately to Severely Active Crohn’s Disease Treated with Ustekinumab in the REALITI Real-World Evidence Effectiveness Study
Authors: Steiner S , Shehzad S , Adler J , Colletti R B , Strauss R , Heile J , Adedokun O , Sheahan A , Zhang R , Lo K H , Kim L , Xiao Y , Volger S
Published: January 2024

Background

Few approved treatment options exist for paediatric patients (pts) with Crohn’s disease (CD). Paediatric inflammatory bowel disease (IBD) medication approvals are delayed nearly 7 years after adult approvals,1 resulting in off-label use and potential for incorrect dosing. The REALITI Study evaluated the effectiveness and safety of ustekinumab (UST) in routine clinical care in paediatric pts (age 2-<18) and young adults (age 18-25) with moderately to severely active CD (Short Paediatric CD activity [sPCDAI] score ≥30) using data from the ImproveCareNow (ICN) Registry.

Methods

Effectiveness data from pts with CD treated with UST were extracted from the ICN Registry between 10 January 2010 and 29 February 2020. A supplemental, retrospective chart review was conducted to collect data not in the ICN Registry. The primary endpoint was clinical remission (sPCDAI≤10) at Week (Wk) 52. All data were summarized descriptively, and the proportion of pts achieving clinical remission and associated 2-sided 95% confidence interval were calculated across multiple populations. Rates of discontinuations, IBD-related hospitalizations, surgeries, and serious infections were also calculated.

Results

A total of 479 CD pts in ICN were treated with UST, including 348 paediatric pts and 131 young adults. We report an analysis of 114 paediatric pts who weighed >40 kg and had a sPCDAI ≥30. All pts were treatment refractory; 99.1% had not responded to prior biologic therapies, with less than 1% biologic naïve. Results were compared to 51 ICN young adults with moderately to severely active CD, a population for which UST is approved. Clinical remission at Wk 52 was achieved in 22.8% (26/114; 95% CI: 16.1%, 31.3%) of paediatric pts vs 21.6% (11/51; 95% CI:12.5%, 34.6%) of young adults (Figure 1A). Discontinuation rates through Wk 52 were similar between paediatric pts (25.4%) and young adults (25.5%; Figure 1B).

Overall, 36.0% of paediatric pts and 21.6% of young adults had IBD-related hospitalizations. IBD-related surgery was reported in 14.0% of paediatric pts and 11.8% of young adults. Serious infections occurred in 9.6% of paediatric pts and 3.9% of young adults. Opportunistic infections occurred in 1.8% of paediatric pts and 0% of young adults. No events of tuberculosis, malignancy, or anaphylaxis requiring UST discontinuation occurred in either group. No deaths were reported.

Conclusion

This study of real-world data from the ICN Registry found similar remissions rates in paediatric pts and young adults with CD treated with UST, suggesting comparable effectiveness of UST in both age groups. No new safety signals were identified. (Crowley E, et al. J Crohns Colitis. 2022 Feb 23;16(2):331-335.)
P960 Comparison of clinical outcomes by induction therapy response status in patients with Inflammatory Bowel Disease (IBD) treated with subcutaneous (SC) versus intravenous (IV) infliximab (IFX): Post hoc analysis of a pivotal, randomised controlled trial
Authors: Vuitton L , Mathieu N , Ye B D , Kim D H , Jeong A L , Lee Y N , Schreiber S
Published: January 2024

Background

Clinical associations between initial response and long-term outcome are well established for IV IFX in IBD.1,2 In 2020, SC IFX was approved in Europe for treating moderate-to-severe Crohn’s disease (CD) or ulcerative colitis (UC), based on a pivotal randomised trial (NCT02883452) comparing SC and IV IFX.3 This post hoc analysis investigated clinical outcomes in patients (pts) treated with SC or IV IFX, by response to IV IFX induction.

Methods

In the pivotal trial, adults with active CD or UC received IV IFX induction (5 mg/kg; Week [W] 0 and W2), before randomisation to SC (n=66) or IV (n=65) arms. W6 clinical response (≥70-point decrease in Crohn’s Disease Activity Index [CDAI] score [CD]; ≥2-point decrease in partial Mayo score with ≥1-point decrease in rectal bleeding subscore or an absolute rectal bleeding subscore of 0 or 1 [UC]) was a stratification factor. The SC arm received SC IFX (120/240 mg for pts weighing <80/≥80 kg) every 2 weeks from W6–54; the IV arm received IV IFX 5 mg/kg every 8 weeks (W6–22), then switched to SC IFX (W30–54). Rates of clinical remission (CDAI score <150 [CD]; partial Mayo score ≤1 [UC]) and trough IFX concentrations (Ctrough) were assessed at W6, W30 and W54. Analyses were descriptive.

Results

There were 101 induction responders (IRs) to IV IFX, who were randomised to the SC arm (n=49, 74.2%; SC-IR subset) or the IV arm (n=52, 80.0%; IV-IR subset). Correspondingly, there were 17 (25.8%) and 13 (20.0%) induction non-responders (INRs; SC-INR and IV-INR subsets, respectively). In both study arms, IRs had higher clinical remission rates than INRs at both W30 and W54 (Figure A). Comparing by formulation, the SC-INR subset had nearly twice the W30 clinical remission rate of the IV-INR subset (58.8% vs. 30.8%; p=0.159 [Fisher exact test]). In addition, IV-INR subset clinical remission rates numerically increased after pts switched to SC IFX (W30: 30.8% vs. W54: 46.2%; p=0.476 [McNemar test]). These observations were generally consistent with Ctrough findings (Figure B); median Ctrough in the IV-INR subset increased from 1.5 to 18.3 µg/mL (p=0.005 [Wilcoxon signe-drank test]) after switching to SC IFX.

Conclusion

Findings suggested associations between initial response to IFX induction therapy and positive long-term outcomes for both SC and IV IFX, and supported potential benefits with SC IFX maintenance therapy for INRs, compared with the option of IV IFX maintenance. Given the post hoc nature of the analysis and the small analysis population (thus statistical inconclusiveness), investigation in larger studies is warranted.

1Murthy SK et al. Inflamm Bowel Dis 2015;21:2090–6.

2Wong ECL et al. J Crohns Colitis 2021;15:1114–9.

3Schreiber S et al. Gastroenterology 2021;160:2340–53.
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

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

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

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

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

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 < 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

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>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)>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<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

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

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<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

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 < 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.
P1046 Home calprotectin testing: An east London experience
Authors: Blakey L , Ronquillo F L V , King J J , Vinayaga-pavan M , Tai C K , Jawad N
Published: January 2024

Background

Monitoring of inflammatory bowel disease (IBD) using home faecal calprotectin (FCP) testing kits was adopted widely during the Sars-Cov-2 pandemic. CalproSmart is a kit which allows patients to measure FCP at home and upload the results to a smart phone application allowing remote monitoring. Recent NHS long term recovery plan has highlighted the importance of ensuring equity of access with service development1. Following the British Society of Gastroenterology guidance during the pandemic we introduced the system to our hospital in Newham, one of the most ethnically diverse regions of the UK2. The aim of this pilot study was to evaluate the uptake of the kits, patient acceptability and how they impacted on IBD care.

Methods

62 patients with stable IBD were invited to take part in the study over a 12 month period. They were sent four FCP tests and instructions on how to enrol onto the CalproSmart portal. The participants who enrolled on the portal were then sent a post-study questionnaire.

Results

28 of the 62 patients invited (45%) enrolled onto the CalproSmart portal. 14 of these 28 patients (50%) completed the post-study questionnaire.

The patients invited to take part were from a variety of ethnic backgrounds, the average age was 36 and there were a mix of Ulcerative Colitis (60%) and Crohn’s (40%) diagnoses. When comparing those invited and those who used the home kit, uptake varied according to gender and ethnicity. 57% of women invited used the home kit compared to 34% of males. Additionally, despite 69% of the borough’s population being non-white, 50% of those using the home tests were white (see table 1).

The post –study questionnaire showed that both the sample kit and the application were found easy to use by 12 (86%) and 13 (93%) of the patients, respectively. 11 patients (79%) reported they found the results of the FCP home kit helpful and 6 patients (50%) felt the FCP home kit improved the treatment of their disease (see figure 1).10 patients (71%) reported they preferred a home test to dropping stool samples at the hospital. The reasons for this were the convenience of not having to visit the hospital (90%) and the speed in which they got the results (80%).

Conclusion

This study demonstrates that home FCP tests are an easy-to-use tool and patients prefer them to attending the hospital. The home kit was well received in a diverse area of London with a mix of ethnic groups and socio-economic backgrounds.

However, the ethnicity of patients using the home tests did not reflect the diversity of the invited participants or the borough. This suggests there needs to be additional exploration into their barriers to access and consider any extra support needed to improve uptake of patient initiated monitoring.
P1047 Observational study of tofacitinib in Ulcerative Colitis in Sweden (ODEN) – Interim analysis of health-related quality of life and fatigue
Authors: Nyberg L , Söderling J , Olén O , Strid H , Jäghult S , Halfvarson J , Hedin C , Jónsdóttir S , Hjortswang H , Cappelleri J C , Henrohn D , Seddighzadeh M , Marsal J , Grip O
Published: January 2024

Background

Ulcerative colitis (UC) has a major impact on daily life. The Janus Kinas (JAK) inhibitor tofacitinib is effective in achieving remission in UC, but prospective real-world evidence concerning the effect on health-related quality of life (HRQoL) and fatigue are still scarce. Fatigue is a component of UC that is notoriously difficult to treat and not unambiguously related to inflammatory activity. ODEN is an ongoing Swedish multicentre prospective observational study of tofacitinib in UC. In this interim analysis, we assessed the effectiveness on HRQoL and fatigue during the first 16 weeks.

Methods

Patients with UC and active inflammation were enrolled 2020-2023 when starting tofacitinib as per clinical indication. To measure various aspects of impairment of daily life, the validated questionnaires Short Health Scale (SHS), EQ-5D-5L [Swedish value set], and IBD-fatigue scale (IBD-F) were used. These data and information concerning clinical, biochemical, and endoscopic outcomes were collected in an e-CRF linked to the Swedish National Quality Registry for Inflammatory Bowel Disease (SWIBREG). For HRQoL outcomes, per protocol analysis was applied. Paired t-test and Wilcoxon’s signed-rank test were used for mean and median differences, respectively.

Results

In total, 103 patients were included. Baseline data are shown in Table 1a. For patients still on tofacitinib treatment, all four dimensions of the SHS (symptoms, social function, disease related worry, and general well-being) improved significantly, Table 1b. A median decrease of one point from baseline was seen at week 8 in each of the parameters, which was maintained through week 16 with a tendency towards further improvement. EQ-5D-5L showed an impairment mainly in the aspects of pain/discomfort and ability to participate in common daily activities. Improvement in these dimensions was seen from baseline to week 16. The overall EQ-5D-5L index improved significantly from baseline (0.80) to week 8 (0.86) and week 16 (0.89), as did the EQ VAS 0-100 reflecting overall health (58, 71, and 74, respectively). A significant improvement in IBD-F part 1 and 2 was seen at week 8 and 16, Figure 1.

Conclusion

This study demonstrates that tofacitinib treatment covariates with positive changes in a variety of measures of patients’ quality of life, including improvements in self-assessed overall wellbeing. Finally, fatigue significantly improved during tofacitinib treatment. Thus, tofacitinib treatment shows association with meaningful improvements in multiple aspects of quality of life during the first 16 weeks of treatment.
P1059 Use of preoperative transjugular intrahepatic portosystemic shunt (TIPS) in patients with Inflammatory Bowel Disease and cirrhosis
Authors: Karime C , Vattikonda A , Hashash J G , Merchea A , Stocchi L , Farraye F A
Published: January 2024

Background

Colorectal surgery in patients with inflammatory bowel disease (IBD) and cirrhosis is associated with high morbidity related to portal hypertension. Thought to reduce surgical risk, transjugular intrahepatic portosystemic shunt (TIPS) may be used to decrease portal pressures. In this study, we aimed to characterize surgical outcomes of patients with IBD and cirrhosis who underwent preoperative TIPS at a large tertiary care center.

Methods

We retrospectively identified patients with IBD and cirrhosis who had undergone TIPS between 2010-2023 for portal decompression prior to colorectal surgery. All other indications for TIPS led to patient exclusion. Demographic and medical data was collected, including surgical indication and portal pressure measurement. Data on surgical outcomes were compiled through chart review.

Results

We identified 10 patients (60% male) with IBD and history of decompensated cirrhosis who underwent preoperative TIPS for portal decompression (Table 1). Surgical indications were colonic dysplasia (50%), refractory IBD (50%), and stenosis or stricture (30%). All patients were deemed nonsurgical candidates due to significant surgical risk from portal hypertension. Following multidisciplinary coordination, patients underwent TIPS for portal decompression at a median of 47 days (IQR 34-80) prior to colorectal surgery. TIPS was associated with significant reduction in portal pressure (22.5 vs 18.5mmHg, p<0.01) and portosystemic gradient (12.5 vs 5.5mmHg, p<0.01) in all patients. Of 10 patients, 30% had TIPS-related complications (transient fluid overload and encephalopathy). In terms of surgical complications, 40% of patients required intraoperative blood transfusion (range: 1-4 units). Postoperatively, 30% of patients had surgical site bleeding and 10% had wound dehiscence, although none required reoperation. Systemic complications occurred in 30% of patients, with systemic signs of infection being the most common. Transaminitis (50%) and coagulopathy (40%) were also common. Median hospital stay was 7 days (IQR 5.5-9.3), with 40% of patients being readmitted within 30 days. Most common cause of readmission was systemic infection (75%), abdominal abscess (50%), or electrolyte abnormality (50%), with one patient requiring reoperation for wound dehiscence. Ninety-day and 1-year survival was 100% and 90% respectively.

Conclusion

In our series of patients with IBD and cirrhosis requiring surgery but deemed nonsurgical candidates, preoperative TIPS lead to portal decompression and facilitated successful surgical intervention despite heightened risk. Nevertheless, significant operative and postoperative complications were noted. Future studies are needed to determine optimal surgical timing following TIPS placement.
P1065 Endoscopic Submucosal Dissection for High-Risk Colorectal Colitis-Associated Neoplasia in Inflammatory Bowel Disease: a Real-World Multicenter Study
Authors: Maselli R , de Sire R , Barbaro F , Cecinato P , Andrisani G , Rosa Rizzotto E , Sferrazza S , Fiori G , Azzolini F , Pugliese F , Facciorusso A , Repici A , Armuzzi A
Published: January 2024

Background

Inflammatory bowel disease (IBD) patients have a 2-3-fold increased risk of developing colorectal cancer. High-risk colorectal colitis-associated neoplasia (HR-CAN), including non-polypoid lesions and large non-pedunculated colon polyps, are often not amenable to conventional resection techniques. Aim of this study was to evaluate effectiveness and safety of endoscopic submucosal dissection (ESD) of HR-CANs.

Methods

In this real-world, multicenter, retrospective study, we included consecutive IBD patients referred to nine Tertiary Italian Endoscopy Centers (January 2014 - April 2023) to undergo an ESD or a hybrid-ESD (hESD), for HR-CANs. The primary outcome was rate of en bloc, R0 resection and adverse events (AEs). The secondary outcome was rate of local recurrence, metachronous lesions, and post-dissection surgery.

Results

96 HR-CANs (89.6% non-polypoid, 79.2% left-side colon, 34.8 mm ± 16.2 mm, 15.6% invasive pit-pattern) in 91 patients with colonic IBD (58.2% male, 60.8 ± 12.2 years, 83.4% ulcerative colitis, disease duration of 183 ± 104 months, 14.3% endoscopic activity) were included. ESD and hESD were performed in 82.3% and 17.7% of cases. The final histopathological diagnoses were serrated sessile lesions in 14.6%, low-grade dysplasia in 32.3%, high-grade dysplasia in 38.5%, adenocarcinoma in 14.6%. Overall, en bloc and R0 resection were achieved in 95.9% and 85.4% of cases. AEs occurred in 12.5% of cases, all managed endoscopically and conservatively. After a mean follow-up of 23.4 months, local recurrence and metachronous lesions occurred each in 3.1% (n=3) of cases. Post-dissection surgery was required in 11.5% (n=11) of cases (7 for histopathology, 2 for recurrences, 2 for refractory IBD). At univariate analysis the left site was identified as a predictor of higher rate of en bloc resection (OR 0.07; 0.007-0.77; p=0.02), while the female sex as a predictor of lower rate of AEs (OR 0.17; 0.03-0.81; p=0.02). Further, the invasive pit pattern was associated with higher rate of post-dissection surgery (OR 6.25; 1.6-24.3; p=0.008).

Conclusion

Our findings showed that ESD of HR-CANs, when performed in Tertiary Endoscopy Centers, was effective and safe in patients with colonic IBD. However, further prospective studies including a long-term follow-up are still required to highlight the impact of ESD for IBD patients’ dysplasia-free survival.
P1077 Patients’ and Gastroenterologists’ Preferences on Outcomes and Medication Attributes for Ulcerative colitis
Authors: Katsoula A , Paschos P , Giouleme O , Toumbalidou M , Mainou M , Malandris K , Tsapas A
Published: January 2024

Background

Gastroenterologists’ perceptions regarding importance of treatment outcomes and medication attributes for ulcerative colitis (UC) may differ from inflammatory bowel disease (IBD) patients’ preferences. The objective of the study was to explore and compare patients’ and health care professionals’ attitudes in the decision-making process for available UC treatments.

Methods

A qualitative study was conducted using patients’ focus groups and gastroenterologists’ interviews. Participants who had been diagnosed with ulcerative colitis were recruited for the purposes of this study. Gastroenterologists (GIs) were identified from the Hellenic Group for the study of IBD. Focus groups discussions and interviews were audiotaped and transcribed verbatim. Thematic analysis was used to identify patients’ and clinicians’ important outcomes.

Results

Eight gastroenterologists and 23 individuals with IBD participated in semi-structured interviews and focus-group discussions, respectively. Categories that emerged from the data analysis included outcomes related to UC, the impact of UC on daily life, drug-related attributes, and the patient-doctor relationship. Within these themes, divergences between the opinions of GIs and patients were observed on two primary issues. In terms of UC-related outcomes, physicians aimed for clinical remission and focused on long-term objectives such as mucosal healing defined by endoscopic improvement and histologic remission. In contrast, patients' expectations were of shorter term and focused on symptomatic response, defined as early and sustained relief of the symptoms and improvement in quality of life. Regarding specific drug attributes, patients were mainly focused on the impact on daily life, considering factors such as route of drug administration, dosage, and the need for daily hospitalization. In contrast, GIs appeared more concerned about drug adverse events and the risk of losing responsiveness.

Conclusion

Individuals receiving healthcare and healthcare providers may have varying views on the significance of different treatment outcomes and features of medications. Patients often prioritize factors that directly impact their quality of life. It is crucial to address these concerns and preferences in clinical discussions when determining the most suitable treatment approach for ulcerative colitis.