bluuebunny/crossref_metadata_2025 huggingface dataset:
P440 Myenteric plexitis and active inflammation at surgical margins are high-risk predictors for postoperative clinical recurrence of Crohn’s disease
Authors: Okano S , Abe K , Sonoda A , Iwamoto S , Sako M , Okamoto K , Yamana T , Fukata M
Published: January 2024

Background

Preventing postoperative recurrence is an important issue for clinical management of Crohn’s disease (CD). Identification of practical risk factors and an effective prophylactic treatment strategy has been desired for the prevention of postoperative recurrence. Although some of the clinical risk factors have been applied to select candidates for prophylactic treatments, these attempts have not fully prevented postoperative recurrence. In this study, we investigate the histological features at resected margins which predicted postoperative recurrence, and whether the initiation of prophylactic treatments could prevent postoperative recurrence in these cases.

Methods

We retrospectively reviewed the clinical recurrence rate in CD patients who underwent intestinal resection between January 2019 and December 2021. Clinical recurrence was defined by combination of serological, radiographic, and endoscopic findings or treatment escalation. To assess the histological risk factors for postoperative recurrence, resection margins of the surgical specimens were evaluated for the presence of myenteric plexitis, granulomas, and active inflammation. Each histological feature was evaluated from Grade 0 to 3. We also examined the ability of prophylactic treatments to prevent postoperative recurrence stratified with histological findings related to clinical recurrence rates.

Results

Of the 141 patients included in this study, 61.9% had plexitis (grade 3:Inflammatory cells at myenteric plexus, 10>HPF) at the proximal margin and 13.5% had active inflammation (grade 3: erosion or ulcer) at the distal margin. Log rank test identified the presence of plexitis (Grade3) (HR:1.84, 95%CI [1.05-3.22], p=0.029) at the proximal margin and active inflammation (Grade3) at the distal margin (HR:1.29, 95%CI [1.05-1.58], p=0.012) as possible risks of clinical recurrence (Figure). Multivariate analysis confirmed that the presence of plexitis (Grade3) at the proximal margin (HR 1.82, 95% CI 1.04-3.21, P=0.038) and active inflammation (Grade 3) at the distal margin (HR 2.31, 95% CI 1.18-4.46, P=0.013) were associated with postoperative clinical recurrence. Prophylactic use of immunomodulators (IM) and biologics did not show a significant reduction of clinical recurrence compared to treatment without IM and/or biologics in patient with histological risk factors (Table).

Conclusion

Our results indicate that the presence of plexitis in the proximal margin and active inflammation in the distal margin of the resected intestine are risk factors for postoperative recurrence. In these cases, initiation of prophylactic treatments with biologics and/or IM may not prevent the clinical recurrence.
P442 Renal lithogenic risk in patients with Inflammatory Bowel Diseases correlates with microbiota composition, urinary profile and dietary intake
Authors: Mignini I , Blasi V , Masucci L , De Maio F , Agrillo C , Monzo F R , Laterza L , Scaldaferri F , Napolitano D , Schiavoni E , D' Amato D , De Ninno G , Baroni S , Mele M C , Grassi F , Cintoni M , Garcovich M , Riccardi L , Gasbarrini A , Ferraro P M , Papa A
Published: January 2024

Background

Nephrolithiasis (NL) is a common extra-intestinal complication of inflammatory bowel diseases (IBD), often related to enteric hyperoxaluria. Growing evidence highlights the association between NL and gut microbiota, but no data are available on the urinary microbiota in IBD patients. Our study aims to analyse the relationship between diet, urinary lithogenic profile, and gut and urinary microbiota in patients with IBD.

Methods

We prospectively enrolled consecutive adult patients with IBD. All patients underwent abdominal ultrasound, blood tests and 24h-urine collection for lithogenic profile analysis. Moreover, a nutritional evaluation was performed, and all patients underwent bioimpedance measurement. Urinary and gut microbiota were analysed through 16S rRNA sequencing.

Results

60 patients were enrolled: 32 with Crohn’s disease (CD) and 28 with ulcerative colitis (UC). NL was more frequent in CD than in UC (28% vs 14%). In patients with NL, gut microbiota analysis showed a lower relative abundance of Agathobacter (p<0.05) and a reduction in alpha diversity (p<0.05) [figure 1]. No statistically significant difference was found in urinary microbiota composition comparing patients with the presence or absence of NL. Protein (g/die) and phosphorus (mg/die) dietary intake were significantly associated with oxaluria (mg/L) (p=0.032 and p=0.007, respectively). At the same time, protein and calcium (mg/day) intake were significantly associated with NL (p= 0.018 and p= 0.023, respectively). Oxaluria and calcium oxalate relative saturation ratio (RSRCaOx) were significantly higher in CD compared to UC [Table 1].

Conclusion

Patients with IBD and NL have distinctive gut microbiota features. CD patients showed a higher prevalence of NL and oxaluria levels than UC. In addition, NL occurrence and oxaluria correlated with some nutritional parameters. Further studies are needed to identify patients with IBD at greater risk of NL by connecting the parameters of the gut microbiota, urinary profile and dietary intake to act on modifiable factors aiming to reduce this risk.
P458 Diagnostic accuracy of patency capsule and cross-sectional imaging for capsule endoscopy retention: A systematic review and meta-analysis
Authors: Kim Y E , Kim P H , Yoon H M , Lee J S , Jung A Y , Cho Y A , Oh S H , Kim K M
Published: January 2024

Background

Although small bowel capsule endoscopy (SBCE) has been widely used to evaluate small bowel lesions including Crohn’s disease, there is a risk of capsule retention that can cause obstructive symptoms potentially necessitating surgical treatment. We conducted a systematic review and meta-analysis to evaluate the accuracy of patency capsule (PC) and cross-sectional imaging (CSI) for predicting capsule retention.

Methods

MEDLINE/PubMed, EMBASE, Web of science, and the Cochrane library databases were searched for articles that invested the diagnostic accuracy of PC or CSI for predicting capsule retention up to August 15, 2023. Pooled sensitivity and specificity were calculated using a bivariate random-effects model. Considering that SBCE was generally not performed when capsule retention was suspected on PC, the false-negative rates of PC and CSI were separately analyzed and compared using a single-proportion meta-analysis based on random-effects modeling. Quality assessment of the selected studies was performed using the revised Quality Assessment of Diagnostic Accuracy Studies-2 tool.

Results

A total of 22 peer-reviewed articles, including 17 articles for PC (covering 2,234 patients) and 7 articles for CSI (covering 302 patients) were included in this systematic review. The pooled sensitivity and specificity for predicting capsule retention with CSI were 64% [95% confidence interval (CI), 31%–87%] and 85% [95% CI, 62%–95%], respectively. The pooled sensitivity and specificity for predicting capsule retention with PC were 75% [95% CI, 43%–92%] and 94% [95% CI, 90%–96%], respectively (Figure 1, Table 1). Although there was no statistically significant difference in prediction accuracy between PC and CSI on the bivariate random-effects model (P=0.14), the pooled false-negative rate was significantly lower in the PC compared to CSI (2.5% [95% CI, 1.4%–4.7%] vs. 11.0% [95% CI, 5.2%–21.8%]; P=0.003) (Table 1).

Conclusion

Cross-sectional imaging showed good specificity, but showed moderate sensitivity in predicting capsule retention. In contrast, patency capsule showed good sensitivity and excellent specificity, with a significantly lower false-negative rate compared to cross-sectional imaging. Therefore, in patients with clinically suspicious small bowel stenosis, the patency capsule is a more reliable modality for predicting capsule retention.
P459 The prevalence and characteristics of inflammatory bowel disease-related ocular involvement in children
Authors: Ben-Tov A , Achler T , Patalon T , Gazit S , Yanai H , Shulman S , Assa A
Published: January 2024

Background

Ocular manifestations (OM) in patients with inflammatory bowel disease (IBD) are uncommon, particularly in children. We aimed to explore the prevalence, characteristics and risk factors of IBD associated OM in a large epidemiologic cohort-based study.

Methods

A cross-sectional study was performed using the Maccabi Healthcare Services (MHS) database. The eligible population included all patients diagnosed with IBD as children (<18 years) between January 2005 and July 2023. An additional analysis was conducted on patients diagnosed with ocular disease during childhood (<18 years) and IBD during childhood or adulthood.

Results

Out of 2,567 children with IBD (males 55%, Crohn’s disease 64%), 78 (3%) were diagnosed with OM at any time during disease course. In 54 patients (69%), the OM occurred after IBD diagnosis with a median time of 2.6 (0.47-7) years between the two events, whereas in 24 patients (31%) OM preceded IBD diagnosis with a median time of 2.1 (0.6-5.7) years. OM was significantly associated with Crohn’s disease, compared with ulcerative colitis (78.2% vs. 63.6% in the entire cohort; p=0.03). The presence of OM was associated with increased usage of systemic corticosteroids (p<0.001), biologic agents (p=0.04) and longer duration since IBD diagnosis (p=0.04). There were 55 patients with OM during childhood who were ever diagnosed with IBD. In this population OM was also associated with increased usage of systemic corticosteroids (p<0.001) and increased hospitalization rate per year (p=0.048). The annual prevalence of OM increased gradually from 10/1000 patients in 2005 to 22/1000 patients in 2022 (p=0.55).

Conclusion

Ocular involvement in children with IBD is rare and more common in patients with Crohn’s disease with a stable prevalence rate. It is associated with a longer duration of disease, greater usage of systemic corticosteroids and biologic agents and with a higher rate of hospitalizations, potentially representing a more severe disease course.
P478 Fatigue, physical fitness, and physical activity in patients with inflammatory bowel disease
Authors: Demers K , Bongers B C , Jonkers D M A E , Pierik M J , Stassen L P S
Published: January 2024

Background

Fatigue is a common and debilitating symptom in patients with Inflammatory Bowel Disease (IBD) with a great impact on quality of life and work productivity. A better comprehension of the contributing factors to fatigue could potentially pave the way for more targeted and effective strategies for managing fatigue in IBD. Fatigue may be associated with lower levels of physical activity and reduced physical fitness. Yet, the interaction between these factors in IBD, measured with validated tests, is not fully understood. Therefore, this study aimed to investigate the association between fatigue and physical fitness and physical activity in patients with IBD.

Methods

Adult patients with IBD in remission or with mild-to-moderate clinical disease activity with an ASA Physical Status <III were eligible for inclusion. Fatigue was defined as a Checklist Individual Strength-fatigue subscale score ≥35. Patient and clinical characteristics were collected, including age, sex, body mass index, comorbidities, disease duration, disease location and behavior, clinical and biochemical disease activity, smoking status, previous intestinal resection, and medication use. Cardiorespiratory fitness was measured using cardiopulmonary exercise testing to assess the oxygen uptake at peak exercise (VO2peak). Muscular strength (peak torque at 60°/s) and endurance (fatigue rate as percentage decline in peak torque over 30 repetitions at 180°/s) of the knee extensor and flexor muscles were assessed using an isokinetic dynamometer. Objective physical activity data were collected continuously for seven consecutive days utilizing the MOX accelerometer, with activities categorized into sedentary, standing, light (LPA), moderate (MPA), and vigorous physical activity (VPA) levels.

Results

In total, 50 patients were included, with 17 being classified as fatigued. Fatigued patients had significantly higher BMIs, a higher frequency of clinical disease activity, and a higher prevalence of smoking (Table 1). They also exhibited significantly lower VO2peak (mean [±SD] 28.1 [±7.9] vs. 36.0 [±9.8] mL·kg-1·min-1, p=0.007) and higher knee extensor fatigue rate (mean [±SD] 39.0% [±8.8] vs. 31.1% [±10.4], p=0.010) compared to non-fatigued patients. There was no statistical significant difference in physical activity between fatigued and non-fatigued patients.

Conclusion

Although physical activity did not differ between patients with and without fatigue, fatigued patients exhibited lower cardiorespiratory fitness and knee extensor muscular endurance. A larger population is needed to further investigate the influence of patient and disease characteristics on this relationship to work towards more targeted and effective strategies for managing fatigue in patients with IBD.
P483 Fatigue and brain morphology in active and remitted Crohn’s Disease
Authors: Thomann A , Schmitgen M , Szabo K , Ebert M , Reindl W , Wolf C
Published: January 2024

Background

Extraintestinal symptoms like fatigue and psychosocial impairments are highly prevalent in IBD, especially during active phases of the disease. They not only significantly impair patients’ quality of life, but can also alter the disease course. Disturbances of brain-gut-interactions may contribute to these symptoms. The aim of this study was to examine associations between brain structure, inflammatory biomarkers and symptoms of fatigue, depression and anxiety in persons with Crohn’s Disease (CD) in different disease states.

Methods

We prospectively enrolled n=109 participants (n=67 persons with CD, n=42 healthy controls). All participants underwent cranial magnetic resonance imaging at 3Tesla, provided stool samples for analysis of faecal calprotectin and completed questionnaires to assess symptoms of fatigue, depression and anxiety. We analysed differences in grey matter volume (GMV) between patients and controls and associations between regional GMV alterations, neuropsychiatric symptoms and faecal calprotectin.

Results

Symptoms of fatigue, depression and anxiety were increased in patients with CD compared to controls, with the highest scores in active CD (Table 1). Patients exhibited regionally reduced GMV in cortical and subcortical sensorimotor regions, occipitotemporal and medial frontal areas. GMV in some of these regions showed a significant negative association with fatigue, but not with depression or anxiety (Fig. 1a). Subgroup analyses revealed symptom-GMV-associations for fatigue in remitted (Fig. 1b), but not in active CD (Fig. 1c), while fatigue was positively associated with fCal in active (Fig. 1c), but not remitted disease (Fig. 1b).

Conclusion

Our findings support disturbances of brain-gut-interactions in the development extraintestinal symptoms in CD, which may be particularly relevant for fatigue during remitted disease. Reduced GMV in the precentral gyrus and other sensorimotor areas could reflect key contributions to fatigue pathophysiology in CD. A sensorimotor model of fatigue in CD could also pave the way for novel treatment approaches, such as targeted noninvasive brain stimulation. Moreover, differences in gut-brain-disturbances between active and remitted disease with regard to fatigue may indicate the need for differential therapeutic approaches dependent on the disease state.
P486 Chronic kidney disease in inflammatory bowel disease: systematic review and meta-analysis
Authors: Innocenti T , Zadora W , Meijers B , Verstockt B
Published: January 2024

Background

Chronic kidney disease (CKD) is defined by a reduction in kidney function (estimated glomerular filtration rate < 60 mL/min/1.73m2) and/or damage markers that are present for at least three months, regardless of the underlying aetiology. Case reports and cohort studies suggest that inflammatory bowel disease (IBD) is associated with CKD. The extent and magnitude of a potential association between IBD and CKD is currently unknown.

Methods

A comprehensive search was conducted in EMBASE, MEDLINE, Web of Science, the Cochrane database, and SCOPUS. Two separate reviewers were involved in the process of article selection and evaluation. In studies where a comparison between an IBD population and a non-IBD control population was available, odds ratios were calculated to quantify the association. To derive an overall estimate of the effect, the Mantel–Haenszel test was employed, utilising a random effect model. This systematic review was registered with PROSPERO (ID RD42023381927).

Results

Fifty-four articles were included in the review [Table].

Eight articles compared an IBD population with a healthy control population (102.230 total patients with IBD and 762.432 total non-IBD controls) and were included in the meta-analysis, although with high heterogeneity (I2 88%). An increased risk of CKD in the IBD population was observed, with an overall odds ratio of 1.59 (95% CI 1.31-1.93) [Figure].

Importantly, this effect was independent of 5-aminosalicylic acid use. Data on other therapies was sparse, except for known nephrotoxic medication like tacrolimus and cyclosporine. Interestingly, several studies reported a decreasing relative risk with increasing age, potentially reflecting an increased baseline risk in this ageing population.

Conclusion

The existing evidence on CKD in IBD was systematically reviewed, including all human epidemiological studies. An increased CKD prevalence in IBD was found, independent of medication. Hence, we suggest regular measurements of kidney function by determination of baseline serum creatinine for all patients with IBD, irrespective of the therapeutic regimen. For patients having a normal baseline function, we would recommend annual follow-up. A more systematic research approach regarding CKD and IBD is warranted.
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

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 > 90% accuracy, and the bowel preparation model, performing at > 95% accuracy compared to the labels provided by human annotators. Second, MES sub-score prediction currently performs with >75% accuracy for 4-level Mayo sub-score prediction and >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

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 < .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

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 <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 <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 <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 <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 <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 <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

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

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<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<0.001) or SC administration every 4–12 weeks (1.30 [1.14–1.48], P<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

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 < 5, clinical response was defined as reduction in the HBI by ≥3 points and biochemical remission as FCP < 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 >2.2 µg/ml and <=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

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

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.
P625 Electronic patient-reported outcomes in Inflammatory Bowel Diseases on vedolizumab therapy: Interim analysis of the non-interventional German LISTEN II study
Authors: Teich N , Stallmach A , Schulze H , Cavlar T , Knop J , Henneberger S
Published: January 2024

Background

Integrating systematic monitoring of patient-reported outcomes (PROs) with clinical information may enhance disease management and improve patient outcomes. Vedolizumab (VDZ) is approved for treating patients with ulcerative colitis (UC) and Crohn’s disease (CD). The German, multicentre, prospective, non-interventional LISTEN II study evaluates patient characteristics and effectiveness of VDZ treatment in real-world clinical practice, focusing on PROs.

Methods

Adult UC or CD patients, who either initiate VDZ intravenously (IV) or switch from IV maintenance to subcutaneous (SC) formulation, are enrolled. Data on patient characteristics, modalities of VDZ use and disease activity are recorded quarterly over one year. PROs are recorded via weekly questionnaires in app (ePRO). Sustained ePRO use was defined as proportion of patients reporting at least one PRO for ≥80% of available questionnaires. Interim data up to 9 months follow-up are presented.

Results

Data of 299 UC and 174 CD patients (51% and 59% female, respectively) with a mean age of 40 years were analysed. VDZ treatment was newly initiated IV (start) in 259 UC and 151 CD patients and switched from IV to SC application (switch) by 40 UC and 23 CD patients at baseline. Total mean pMayo score decreased in UC start-patients from 5.0 to 1.7 and from 1.1 to 0.8 in switch-patients. In CD start-patients HBI score decreased from 5.5 to 2.5 and from 3.1 to 2.3 in switch-patients.

The ePRO was initially utilized by 226 UC and 124 CD patients (51% and 61% female, 57% and 52% sustained ePRO users, respectively) with a mean age of 39 years; 86% were start- and 14% switch-patients. Disease activity at baseline was comparable to the overall population, showing a total mean pMayo score of 4.5 for UC and a HBI of 5.3 for CD patients. Most UC (82%) and CD patients (88%) used a patient support program for the first time. ePRO use declined to approx. 40% usage within the second quarter and to 30% during further follow-up.

Overall, mean symptom scores reported via the ePRO declined during the 9-month follow-up period. The most notable improvements (baseline to month 9) were reported for the symptom impact on work productivity (from 3.9 to 1.7 points) in UC patients and for sick leave (from 1.3 to 0.4 points) in CD patients (Table). For most PROs reduction in symptom scores was apparent within the first week of ePRO-use (Figure).

Conclusion

LISTEN II real-world data confirm VDZ effectiveness in UC and CD patients, with reduction in disease activity in IV starters and maintained effectiveness in IV-to-SC switchers. Both UC and CD patients reported sustained symptom improvement under VDZ treatment, with scores indicating improvement within the first week of ePRO-use.
P642 Effect of prior vedolizumab treatment on ustekinumab time-on-treatment in Crohn’s disease: a targeted literature review and statistical analyses
Authors: Owen G , Harvey R , Shields G , Jenkins A , Robertson J , Eaton J
Published: January 2024

Background

Ustekinumab, vedolizumab and anti-TNFα therapies are all biologics that are licensed to treat moderate-to-severe Crohn’s disease (CD). With many new therapies available in moderate-to-severe CD, the question of the optimal sequence in which to administer biologics becomes more pertinent. In this study, we aimed to determine if ustekinumab treatment effectiveness was affected by prior vedolizumab treatment in patients with CD.

Methods

We conducted a targeted literature review to identify evidence for ustekinumab effectiveness both with and without prior vedolizumab treatment. The population of interest was patients with moderate-to-severe CD treated with prior anti-TNFα. Studies were required to report single lines of treatment (e.g., specify second-line or state after one anti-TNF). Ustekinumab time-on-treatment (ToT) Kaplan-Meier (KM) data were recreated using digitisation methods and grouped into 2 categories (based on prior vedolizumab exposure) for subsequent statistical analysis. We compared ToT over a 34-month period (maximum follow-up period observed across all studies). A log-rank test was performed to identify whether there was a statistically significant difference in ToT between to the two groups across the follow-up period and Cox regression modelling was used to identify the direction of trends through estimation of a hazard ratio (HR).

Results

We identified 4 studies (n=495) that reported ustekinumab ToT after 1 anti-TNFα and 2 studies (n=69) that reported ustekinumab ToT after 1 anti-TNFα and vedolizumab. Based on the KM curves pooled across studies, the analysis showed the probability of remaining on treatment for ustekinumab following 1 anti-TNFα and vedolizumab was higher than following just 1 anti-TNFα. The log-rank test demonstrated a statistically significant difference between these two groups (HR=0.523; 95% CI: [0.310, 0.883]; log-rank p-value=0.014).

We identified a further 3 studies (n=1,017) that reported ustekinumab ToT after ≥1 anti-TNFα, and a further 2 studies (n=441) that reported ustekinumab ToT after ≥1 anti-TNFα and vedolizumab. Although these studies stated second line treatment of ustekinumab, some patients had received ≥2 prior anti-TNFα, which may have biased ToT results. There was no statistically significant difference in ToT for ustekinumab following ≥1 anti-TNFα and vedolizumab compared to following ≥1 anti-TNFα (HR=1.167; 95% Cl: [0.971, 1.1404]; log-rank p-value=0.098)

Conclusion

Our research shows that prior vedolizumab treatment does not negatively impact ustekinumab ToT in CD, which may have implications for the sequencing of biologics in moderate-to-severe CD and should be considered when deciding on the most appropriate treatment for patients.