bluuebunny/crossref_metadata_2025 huggingface dataset:
P310 Intestinal ultrasound as a tool to assess treatment response in patients with Inflammatory Bowel Diseases
Authors: Katsaros M , Katsoula A , Kalogirou M , Paschos P , Papagiannakis P , Tsionis T , Giouleme O
Published: January 2024

Background

The assessment of treatment response in patients with Inflammatory Bowel Disease (IBD) is often based on clinical indices [Harvey Bradshaw index (HBI), Partial Mayo score (PMS)] and biomarkers [C - reactive protein (CRP)]. Intestinal ultrasound (IUS) has been proposed as a modality capable of objectively evaluating therapeutic response. We investigated the utility of the IUS as a tool to assess treatment response, as well as its association with HBI, PMS and CRP.

Methods

We included patients with an established diagnosis of IBD who initiated biologic agent (infliximab, adalimumab, ustekinumab, vedolizumab) or tofacitinib. Active disease on IUS was defined as an increase in bowel wall thickness (BWT) >3 mm in the most affected bowel segment, while the presence of a Doppler signal (CDS) in the bowel wall was also assessed. Treatment response on IUS was defined according to the International Bowel Ultrasound Group (IBUS) criteria: reduction in bowel wall thickness (in continuous measurements) >25% or >2.0 mm or >1.0 mm with concomitant reduction in CDS by 1 unit at week 14 ± 2 from the initiation of treatment.

Results

A total of 19 patients (11 men, 11 with Crohn's disease) underwent IUS at week 0 and week 14 ± 2, while CRP, HBI and PMS were calculated at the same time points. We included bio-naïve as well bio experienced patients (table 1). At week 0, 84.2% of patients exhibited clinical activity (HBI ≥5, PMS ≥2), median CRP was 24.7 mg /L (IQR 18.6-42.8) and median BWT was 7.1mm (IQR 6.5-7.6). At week 14 ± 2, 42.1% of patients remained clinically active, median CRP was 6.8 mg/L (IQR 4.6-20.7) and median BWT was 5.2 mm (IQR 4.6- 6.4). Overall 10/19 patients fulfilled the criteria of treatment response on IUS at week 14 ± 2. Clinical remission was observed in 8/10 patients who demonstrated therapeutic response on IUS and 3/9 patients who did not (p=0.07). Normalization of CRP value (<6mg/L) was observed in 8/10 patients who exhibited treatment response on IUS and in none of the patients who did not (p<0.001). Among the IUS parameters at baseline, a statistically significant difference was found only in the presence of fat wrapping between treatment responders and treatment non-responders (table 2). Finally, median CRP was 4.9 mg/L (IQR 2.6-6.2) in IUS treatment responders and 20.7 mg/L (IQR 10.5-28.5) in IUS treatment non-responders. (p<0.001), with median BWT being 4.7mm (IQR 3.3-5.1) and 6.4mm (IQR 6.1-6.9) respectively (p<0.001).

Conclusion

IUS represents an objective tool for evaluating treatment response in patients with IBD, which demonstrates a significant correlation with CRP but not with clinical indices of activity.
P354 Tryptophan metabolites as predictive biomarkers for dietary therapy outcomes in paediatric Crohn's disease
Authors: Ghiboub M , van der Kruk N , Sigall Boneh R , Wine E , Verburgt C M , de Meij T G J , Löwenberg M , Gecse K B , Derikx J P M , de Jonge W J , D’Haens G , Van Limbergen J E
Published: January 2024

Background

Crohn's disease (CD) exclusion diet combined with partial enteral nutrition (CDED+PEN) and exclusive enteral nutrition (EEN) are effective in inducing remission in mild-to-moderate paediatric CD. While tolerance is higher with CDED+PEN than with EEN, a subset of patients still does not achieve remission. Diet-induced remission at week 6 was associated with changes in tryptophan (Trp) metabolism.1 Our aim was to investigate whether baseline Trp metabolites could predict dietary therapy outcomes in paediatric CD.

Methods

In total, 26 mild-to-moderate treatment-naive paediatric CD patients from a prior randomized controlled trial 2, were classified as having remission 6 (R, n =19 (CDED+PEN=10 and EEN=9)) and No-Remission (NR, n=7 (CDED+PEN=3 and EEN=4)) following 6 weeks of CDED+PEN or EEN therapy, based on the Paediatric Crohn’s Disease Activity Index (PDCAI) score (≤10 remission, >10 no remission). We performed targeted quantitative analysis of 21 tryptophan metabolites in baseline faecal samples from both groups, utilizing liquid chromatography coupled with quadrupole mass spectrometry. Receiving Operator Characteristic Curve (ROC) and Random Forest Analysis were used to assess the predictive power of Trp metabolites for dietary outcomes.

Results

Baseline clinical characteristics were comparable between R and NR. Baseline fecal kynurenine was significantly higher in NR compared to R for CDED+PEN (p=0.02) (Fig 1A) and EEN (p=0.04) (Fig 2A). ROC analysis highlighted the robust predictive power of kynurenine for CDED+PEN (area under the curve (AUC)=0.97) (Fig 1B) and EEN (AUC=0.88) (Fig 2B) induced remission. Random Forest analysis corroborated these observations. Ratios of Trp metabolites were compared to investigate different downstream Trp pathways. The ratio serotonin/kynurenine was the strongest predictor of CDED+PEN-induced remission (AUC=1) (Fig 1C). The ratio 5-OH-Tryptophan/kynurenine (AUC=0.88) (Fig 2C) predicted EEN-induced remission. When data from CDED+PEN and EEN were combined, kynurenine (AUC=0.91) and the ratios of quinolinic acid/kynurenine (AUC=0.93) and kynurenine/indole-3-acetic acid (AUC=0.88) demonstrated strong predictive performance for dietary therapy in general (Fig 3A,B and C).

Conclusion

Baseline faecal kynurenine has potential as a prognostic biomarker for dietary therapies. Trp metabolite ratios, notably serotonin/kynurenine for CDED+PEN and 5-OH-tryptophan/kynurenine for EEN, showed promising predictive capabilities. If confirmed in validation studies, baseline faecal Trp markers may be able to provide much needed guidance to personalize dietary intervention within the management of paediatric CD.

References

1. Gastroenterology. 2022 Oct;163(4):922-936. 2. Gastroenterology. 2019 Aug;157(2):440-450.
P375 Histological activity predicts the risk of colectomy after biological treatment in biological-naive patients with Ulcerative Colitis
Authors: Zhao M , Riis L B , Lo B , Attauabi M , Ovesen P D , Wewer M D , Larsen L , Dige A , Hvas C L , Poulsen A , Christiansen D , Gassem Nagras Z , Dahlin P , Petersen A M , Bendtsen F , Seidelin J , Burisch J ,   The Danish IBD Biobank Project Group
Published: January 2024

Background

Treatment failure with biological agents is common in patients with ulcerative colitis (UC), but the impact of baseline histological disease activity is unknown. We aimed to investigate the predictive role of histopathological findings for biological treatment failure in UC patients.

Methods

This is a sub-study of the Danish IBD Biobank Project. Adult bio-naïve patients with UC (n=129) were followed prospectively while undergoing biological treatment. Histological activity was assessed using the Nancy Index and the Geboes score in intestinal biopsies sampled before treatment. Endoscopic activity was assessed using the Mayo Endoscopic Subscore, and clinical activity was measured using the Simple Clinical Colitis Activity Index (SCCAI). Associations between histological activity and treatment outcomes were assessed in multivariable models which incorporated the following fixed covariates: age, gender, disease duration, body mass index >30, disease extent, the SCCAI, and the Mayo Endoscopic Subscore. Correlations between histological, endoscopic, clinical, and biochemical activity were assessed using Spearman’s rank correlation.

Results

Colectomy was needed in 17.1% (n=22) of UC patients during follow-up (Table 1). Histological activity at baseline measured using the Nancy Index was the only significant predictor of the risk of colectomy during follow-up (Nancy 2 vs. 4: HR 0.14, 95% CI 0.02-0.84, p=0.03; Nancy 3 vs. 4: HR 0.11, 95% CI 0.02-0.53, p=0.01) beside baseline haemoglobin concentration (HR 0.32, 95% CI 0.16-0.64, p<0.01. Figure 1). The risk of colectomy was also significantly predicted by a Geboes grade above 5.0 at baseline (HR 2.72, 95% CI 1.14-6.50, p=0.02). In contrast, endoscopic and clinical activity did not predict the risk of colectomy. At baseline, the Nancy Index and the Geboes score were moderately correlated to endoscopic activity, and weakly, but significantly correlated to biochemical markers haemoglobin, albumin, and C-reactive protein. Meanwhile, poor correlations were found between histological activity and clinical activity.

Conclusion

The risk of colectomy during biological treatment in bio-naïve UC patients was significantly predicted by histological disease activity, but not endoscopic or clinical disease activity. Our study suggests that histological assessment before initiating biological treatment should be encouraged in UC patients.

Funding

This study is funded by a restricted grant from Takeda A/S, Louis-Hansen Fonden, and a public fund hosted by Hvidovre Hospital.
P386 Persistence of bowel urgency despite clinical remission after induction therapy is associated with unfavorable long-term outcomes in patients with ulcerative colitis: results from the multicenter UC-RGENCY study
Authors: Buisson A , Amiot A , Nachury M , Altwegg R , Serrero M , Guilmoteau T , Treton X , Caillo L , Vuitton L , Bouguen G , Pereira B , Fumery M
Published: January 2024

Background

STRIDE 2 recommendations define clinical remission as no rectal bleeding and normalization of stool frequency in patients with ulcerative colitis (UC), without including bowel urgency (BU) despite its negative impact on quality of life.

In this large multicenter cohort, we aimed to assess whether the persistence of BU after induction therapy is independently associated with poor long-term outcomes in patients with UC.

Methods

From a multicenter retrospective study, we included consecutive UC adult patients previously exposed to at least one anti-TNF agent, with partial Mayo score (pMS) > 2, who started biologics or small molecules between Jan2019 and June2022. BU was defined as a binary criterion based on the SCCAI definition.

The primary endpoint was the time to drug discontinuation due to active UC. Secondary endpoints were time to relapse, time to colectomy as well as steroid-free clinical remission (pMS ≤ 2) (CFREM), endoscopic remission (CFREM + Mayo endoscopic score (MES) ≤ 1), and mucosal healing (CFREM + MES ≤ 1 + histological remission i.e. Nancy index ≤ 1) at last follow-up.

Results

Among 473 patients with UC, 270 were assessed for BU after induction therapy (week 16) (mean age 43.0±17.0 years-old, median UC duration 6 [3-11] years, female gender=54.0%, pancolitis=45.9%). The median follow-up was 14 [8-22] months.

The rate of CFREM after induction therapy was 54.4% (147/270) while 21.5% (58/270) had remaining bowel urgencies after induction therapy. Among the 147 patients achieving remission after induction therapy, 12 had persistent BU (8.2%), while 62.6% (77/123) of patients with no CFREM after induction therapy did not have any BU.

The agreements between BU and rectal bleeding (75.2%, κ-coefficient = 0.33±0.06) or normalization of stools frequency (67.9%,κ-coefficient = 0.35±0.05) were mild. Among the patients with persistent BU after induction therapy, only 3.7% had no endoscopic activity (MES = 0).

In multivariable analyses including CFREM at week 16, persistence of BU after induction therapy was independently associated with the time to drug discontinuation (HR=2.0[1.1-3.5], p=0.016) and colectomy (HR=4.4[2.3-8.4], p<0.001), and absence of mucosal healing (OR = 5.0[1.1-24.8], p=0.046) at last follow-up. A trend was also observed regarding the association between remaining BU after induction therapy and no CFREM (OR=6.1[0.8-48.0], p=0.085) or absence of endoscopic remission (OR=2.4[0.9-6.1], p=0.077) at last follow-up.

Conclusion

Persistence of BU despite clinical remission is associated with higher risk of drug discontinuation due to active UC, colectomy and lower likelihood of mucosal healing.

Bowel urgency should be implemented into international guidelines to define clinical remission in patients with UC.
P410 Intraoperative Ultrasonography of the Small Bowel in the evaluation of resection margins during surgery for Crohn's Disease
Authors: Sacchetti F , Pizzolante F , Giambusso M , Nesci C , Giannarelli D , Galiandro F , Pugliese D , Scaldaferri F , Potenza A E , Sofo L
Published: January 2024

Background

Histological involvement of surgical resection margins in Crohn’s Disease (CD) is considered an important risk factor for disease recurrence after surgery. The extent of resection is currently left to preoperative investigations and surgeon's experience. Aim of the study is to evaluate usefulness of intra-operative ultrasonography (IOUS) of the small bowel to best identify the surgical site of resection and reduce the risk of histological involvement of resection margins.

Methods

Consecutive patients who underwent surgery for CD (ileocaecal or ileal resections for first or repeated surgery) from April 2022 to April 2023 were prospectively enrolled (IOUS group). All patients underwent to IOUS through a small mini-laparotomy with a linear wireless probe performed by an expert gastroenterologist and the location of the proximal ileal resection was decided considering the absence of intraoperative small bowel ultrasonographic signs of CD (wall thickness, mucosal, submucosal and muscular layer thickness, echogenicity of the wall stratification and mesenteric fat). A control group from the historical cohort of patients undergoing the same surgical procedures was included; for whom the site of the proximal ileal resection was decided only on the basis of the absence of macroscopic signs of disease as usually assessed.

To minimize the selection bias, a propensity score analysis was performed identifying a subgroup of the historical cohort (non-IOUS group) matched for location of disease and repeated surgery.

The primary endpoint was histological involvement of the resection margins, judged positive in case of granulomas or signs of active ulcerative inflammation.

Results

27 patients (59% male, mean age 39.3 y [SD 16.5], mean BMI 21.24 [SD 2.03]) were consecutively enrolled in the IOUS group. A 1:1 propensity score matching analysis was performed identifying 27 patients included in the non-IOUS group .

The two groups were homogeneous in terms of gender, age, smoking, BMI, behavior of disease and surgical technique (laparoscopic or open technique).

IOUS group presented a lower rate of histological positive margins compared to the non-IOUS group (18.5% vs 48.1% p = 0.021).

No significant differences were found in terms of mean duration of surgery between the two groups (254.2 min vs 225 min [49.3-77.8]; p = 0.11) or in terms of mean length of surgical specimen (24.1 cm vs 34.1 cm [SD 13.5 -23.1]; p = 0.058)

Conclusion

IOUS of the small bowel appears to be a useful tool for IBD-surgeon in order to obtain a lower rate of histologically positive margins with a comparable duration of the surgery and no significant difference in length of the intestinal specimen.
P424 Analysis of the intestinal microbiome using an Endoscopic Brush in Ulcerative colitis
Authors: Lee B , Keum B , Kim S , Jeon H , Jeen Y , Hoonjai C
Published: January 2024

Background

The precise pathogenesis of the Ulcerative colitis is still yet unknown, but one of its cause is known to be microbial dysbiosis.

The mucosa-associated microbiota are more deeply involved in the pathogenesis of UC. However, the optimal sampling of mucosa-associated microbiome has yet to be investigated.

In this study, we investigated the mucosa-associated microbiome in patients with ulcerative colitis, using endoscopic brush samples. We hypothesized that endoscopic brushing is precise and noninvasive method to get sample of mucosa-associated microbiome.

Methods

Patients with UC who visited the gastroenterology department of Korea University Anam hospital were screened for this study.

Clinical data such as medical records, colonoscopy and fecal samples were reviewed.

Using a stool and saliva sample collector kit respectively, the subjects provided stool and saliva samples. Brushing samples were collected during the sigmoidoscopy procedure with 3-4 brush strokes on the colon mucosa using the cytology brush.

The samples were analyzed for microbiome in the Korea University Medical Center.

Results

From July 2022 to January 2023, we prospectively enrolled 19 patients with UC.

Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria were the most common species in microbiota of brush, stool and saliva.(Fig.1-1)

The microbiome between stool and brush was no significant difference in alpha and beta diversities.(Fig.1-2)

However, Oral microbiome was different from stool and brush in beta diversities.(Fig.1-3) Patients were categorized into to analyze the oral microbiome. A trend was observed where increased disease severity was associated with an increase in Firmicutes.(Fig.1-4)

Conclusion

The microbiome of stool and brush was no significantly different. However, the novel sampling of mucosa-associated microbiome, endoscopic brush, is not inferior compared to currently used sampling of stool.

Also the analysis of the oral microbiome suggested that Firmicutes could be considered a useful biomarker for assessing disease severity. Therefore, it is necessary to conduct followup research by increasing the number of subjects.
P425 Clinical Characteristics of Steroid-Dependent Ulcerative Colitis Patients after Acute Severe Ulcerative Colitis Treatment in East Asia and Australia/New Zealand: AOCC and ANZIBDC collaboration study
Authors: Kim D H , Park S H , Kim H S , Kim S J , Kim K O , Lee Y J , Song E M , Kim E S , Lee H S , An Y K , Begun J , Ruddick-Collins L , Fernandes R , Liu J , Cao Q , Kobayashi T , Wei S C
Published: January 2024

Background

Intravenous steroid therapy (IVS) is the main initial treatment for acute severe ulcerative colitis (ASUC). The study aimed to assess corticosteroid dependency after treating ASUC and to explore potential differences between East Asian and Caucasian populations within the steroid-dependent group.

Methods

Patients from East Asia (China, Japan, South Korea, and Taiwan) and Australia/New Zealand diagnosed with ASUC based on the Trulove and Witts criteria from January 2015 to September 2022 were retrospectively included in the study. We specifically chose individuals responsive to intravenous corticosteroid treatment and divided them into two groups based on steroid dependency. "Steroid dependency" was defined as the inability to reduce steroid medication to a dosage below 10 mg/d (equivalent to prednisolone) within three months of initiating steroid treatment or experiencing a relapse within three months of discontinuing steroid therapy. Patients with a history of biologics or small molecules and those currently receiving them were excluded.

Results

Among 861 patients with ASUC (430 from East Asia and 431 from Australia/New Zealand), 626 received initial IVS, and 381 showed steroid response. Among these steroid responders, 102 patients (26.7%) were classified as steroid-dependent with no significant difference between East Asians and Caucasians (28.3% vs. 24.1%, p=0.44). For 1 year after ASUC, the colectomy rate (7.8% vs. 2.9%, p=0.04) and ASUC relapse rate (18.6% vs. 10.2%, p=0.03) were higher in the steroid-dependent than non-dependent group. For the management of steroid dependency, East Asians mainly repeated steroid treatment (60.9%), while Caucasians mostly switched to infliximab (57.1%). In the Cox regression analysis of 3-year follow-up data for the steroid-dependent group, Caucasians showed a significant increase in colectomy rates (adjusted hazard ratio [aHR] 1.59, 95% confidential interval [CI] 1.12-2.25, p<0.01) compared to East Asians. Additionally, relapse rates increased in Caucasians (aHR 1.37, 95% CI 1.13-1.65, p<0.01), while relapse rates decreased in thiopurine users (aHR 0.32, 95% CI 0.12-0.87, p=0.03).

Conclusion

Around one-fourth of patients with ASUC who initially responded to IVS became steroid-dependent. East Asians showed a more favorable prognosis compared with Caucasian in this steroid-dependent group.
P435 Plasma inflammation-related proteins as markers of anxiety and depression disorders in inflammatory bowel disease patients
Authors: Zhou M S , Dang Y , Xu F , Xu C Y , Wang Z , Wang C S E , Zhu S Y , Li P , Wu J , Shi H Y
Published: January 2024

Background

Up to 25%-35% of patients with inflammatory bowel disease (IBD) suffer from anxiety or depression. Inflammatory and immune response processes may play an important role in the co-occurrence of IBD and mood disorders. We aimed to investigate the plasma inflammation-related proteins that can characterize the anxiety and depression disorders in IBD patients.

Methods

Plasma was collected from 61 IBD patients, and the OLINK panel (Target 96 Inflammation) was used to quantify the expression levels of 92 inflammation-related proteins. The Hospital Anxiety and Depression Scale (HADS) was used to assess the anxiety and depression symptoms.

Results

Among the involved IBD patients (median age 37, 40.98% female), 26.23% had anxiety and 29.51% had depression. Compared with IBD patients without mental disorders, the plasma level of FGF-23 was significantly increased in IBD patients with anxiety or depression disorders (P=0.035). Besides, the levels of CCL20 (P=0.039) and CXCL1 (P=0.021) were up regulated in IBD patients with anxiety and depression, respectively (Figure 1). Correlation analysis showed that the plasma level of CXCL1 (r=0.254, P=0.047) and FGF-23 (r=0.318, P=0.012) were positively correlated with the total degree of anxiety and depression disorders, while DNER (r=-0.300, P=0.018) appeared a reverse correlation trend. On the other hand, the plasma level of FGF-23 (r=0.351, P<0.01) was positively correlated with anxiety degree in IBD patients. As for the depression disorder, we found a positive correlation in plasma CXCL1 (r=0.296, P=0.020) level, and negative correlations were found in levels of IL-8(r=-0.256, P=0.045), uPA (r=-0.264, P=0.038), IL-20 (r=-0.290, P=0.022) and DNER (r=-0.353, P<0.01) (Figure 2).

Conclusion

We found specific plasma inflammation-related proteins for anxiety and depression disorders in IBD patients. The high incidence of anxiety and depression in IBD patients may be attributed to the stimulation of high levels of inflammatory factors.
P496 Interdisciplinary student-led screening clinics can identify undernutrition, sarcopenia and mental health risk in ambulatory patients with Inflammatory Bowel Disease
Authors: Plush S , Burfield K , Kumar S , Bryant R , Day A
Published: January 2024

Background

The changing landscape of allied health practice has led to the emergence of student-led clinics as a resource to enable workforce capacity. Undernutrition, sarcopenia, and poor mental health are common in inflammatory bowel disease (IBD) and affect quality of life. Despite high prevalence, these co-morbidities are under-recognised due to lack of service capacity. This study aimed to determine the frequency of undernutrition, reduced physical performance and mental health risk identified by a novel student-led interdisciplinary screening clinic in ambulatory patients with IBD.

Methods

Sixteen final year dietetic, physiotherapy or exercise physiology students conducted 5-10 weekly half day interdisciplinary outpatient clinics within a tertiary IBD service between July and October 2023. Following training, students completed all aspects of the interdisciplinary consult under direct dietetic supervision. Risk screening assessments comprised of anthropometrics, depression anxiety and stress scale-21 (DASS21), subjective global assessment (SGA), short physical performance battery (SPPB), handgrip strength (HGS) and inflammatory bowel disease-nutrition screening tool (IBD-NST). Consecutive patients attending a tertiary IBD outpatient service were contacted to participate in the clinic following their gastroenterology appointment. Descriptive statistics were completed, and prevalence is presented as number (n) and percentage.

Results

Screening assessments were completed for 88 patients in the 15-week period (Table1). Patient acceptance was high with 86% of patients approached consenting to participate. High hip to waist ratio was present in 68% (n=60/88) of patients suggestive of visceral adiposity (Figure 1a). The IBD-NST identified mild nutrition risk in 5% (n=4/88) of patients and generated a referral to dietetics with a moderate nutrition risk in 21% (n=19/88) of patients (Figure 1b). Malnutrition was detected in 10% (n=8/88) of the patient population (Figure 1c). Mental health risk was elevated in 63% (n=50/79) of patients screened (Figure 1e, f, g). Physical impairment was present in 52% (n=46/88) of patients (Figure 1h &1i). The screening clinic generated 48 referrals through to varied allied health disciplines for individualised therapy.

Conclusion

A student-led interdisciplinary screening clinic ensures timely identification of patient risk for undernutrition, sarcopenia and poor mental health, improving access to early intervention opportunities. Students can act as a valuable enabler for workforce capacity at a time when the health service providers are stretched.
P524 Etrasimod shows low risk of adverse events following concomitant use with opioids or antidepressants in patients with ulcerative colitis
Authors: Afzali A , Regueiro M , Yarur A J , Zabana Y , Ng S C , Menon S S , McDonnell A , Lazin K , Keating M , Bhattacharjee A , Branquinho D , Bananis E , Peyrin-Biroulet L
Published: January 2024

Background

Etrasimod is an oral, once-daily (QD), selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). Unlike the other S1P receptor modulator approved for UC, etrasimod and its metabolites do not have a molecular structure to inhibit monoamine oxidase (MAO).1 Coadministration of drugs that inhibit MAO with opioids and antidepressants may increase the risk of adverse events (AEs), including hypertension.2 This post hoc analysis evaluated the incidence of AEs potentially related to serotonin syndrome in patients taking etrasimod and concomitant opioids or antidepressants in the phase 3 ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369) trials.

Methods

Safety data pooled from both trials were analysed in patients receiving etrasimod 2 mg QD (up to 52 weeks of exposure) with/without concomitant opioids or antidepressants. We report the proportions of patients who had ≥1 concurrent AE potentially related to serotonin syndrome, consisting of one standardised MedDRA Query, one query based on the Hunter Criteria and supplemental preferred terms (pyrexia, tachycardia and hypertension-related AEs).3

Results

Among 527 patients receiving etrasimod, 77 (14.6%) and 35 (6.6%) patients were taking concomitant opioids or antidepressants, respectively. Most patients on concomitant opioids or antidepressants were White (80.0–88.3%); male (50.6–51.4%); their median age was 35.0 (18.0–70.0) and 41.0 (19.0–74.0) years, respectively. More patients with vs without concomitant opioids or antidepressants, respectively, consumed alcohol (40.3% vs 24.7% and 48.6% vs 25.4%) and used tobacco (40.3% vs 20.9% and 34.3% vs 23.0%). The incidence of other AEs potentially related to serotonin syndrome was low and generally comparable in all subgroups; reported rates of pyrexia and tachycardia were similar in patients with/without concomitant opioids or antidepressants (Table). Hypertension-related AEs were infrequent and generally balanced. No AEs per the Hunter Criteria were reported in patients on concomitant opioids or antidepressants (Table). No reported AEs were serious or led to treatment discontinuation among patients taking these concomitant medications.

Conclusion

The incidence of AEs was low and comparable in patients receiving etrasimod with or without concomitant opioids or antidepressants. This analysis supports the low likelihood of clinically relevant drug–drug interactions between etrasimod and medications commonly prescribed to patients with UC, such as opioids or antidepressants.

References

1. Lee CA et al. Clin Pharmacol Drug Dev 2023; 12: 553–571.

2. Sands BE et al. J Crohns Colitis 2023; online ahead of print.

3. Dunkley EJC et al. QJM 2003; 96: 635–642.
P525 Utilisation of endoscopic ultrasonography for submucosal cushion measurement to determine eligibility for endoscopic submucosal dissection in ulcerative colitis-associated dysplasia: A case series
Authors: Kim K , Hong S W , Hwang S W , Park S H , Ye B D , Byeon J S , Myung S J , Yang S K , Yang D H
Published: January 2024

Background

Endoscopic submucosal dissection (ESD) has gained traction as an effective therapy for ulcerative colitis (UC)-associated dysplasia, yet identifying fitting ESD candidates is challenging by substantial submucosal (SM) fibrosis from chronic inflammation. We report our experience utilising endoscopic ultrasonography (EUS) to assess ESD eligibility by measuring SM cushion thickness.

Methods

Retrospective case-series includes nine patients who were diagnosed or referred to as UC-associated dysplasia in surveillance colonoscopies between August 2017 and October 2023. After scanning dysplastic lesions (Fig A-B), hyaluronic acid solution was injected into the SM layer (Fig C). EUS with a mini-probe quantified SM cushion beneath the dysplastic lesion (Fig D), and ESD was performed in cases with at least 2.0 mm of SM cushion thickness (Fig E-F).

Results

Among ten cases from nine patients, eight cases met the criteria and underwent ESD, while two cases (Patient 3, Patient 7) were regarded as unsuitable for ESD with SM cushion thickness less than 2.0 mm. Median disease duration was 19 years, and median age at diagnosis of UC-associated dysplasia was 50 years. Median SM cushion thickness ranged from 4.2 to 6.9 mm. Median procedure time was 50 minutes, and median size of resected specimens and lesions were 31.5 x 24.5 mm and 16.0 x 12.5 mm, respectively. en bloc resection was achieved in all cases, with an 87.5% R0 resection rate. No perforation occurred; only one required post-discharge endoscopic bleeding control after four days post-discharge.

Conclusion

EUS-measured SM cushion thickness may be a valid approach that provides an objective criterion for determining ESD eligibility in UC-associated dysplasia. This would help guide individualised treatment in UC-associated dysplasia, reducing unnecessary procedures or surgery.
P581 Age-related patterns in biological therapy use and surgery among patients with IBD: Insights from the Belgian PANTHER cohort
Authors: Celis J , Truyens M , Verstockt S , Glorieus E , De Wolf M , Lenfant M , Barbaraci M , Sabino J , Ferrante M , Geldof J , Verstockt B , Laukens D , Cleynen I , Vandermeulen L , Vermeire S , Lobaton T ,   IBD Research Unit
Published: January 2024

Background

Inflammatory bowel diseases (IBD) are predominantly diagnosed during the second to third life decade. However, the disease may manifest itself at any age and current understanding of differences in clinical presentation and therapy use among age groups is still limited. We aimed to analyse age-related patterns in biological and surgical treatment among patients with IBD.

Methods

This study utilized data from the PANTHER cohort, a prospective Belgian inception cohort including 473 adult patients with IBD from 3 Belgian referral centres. Patient inclusion took place from 2015 to 2023. Patients were categorized into groups based on the age at diagnosis: 'young adult-onset' (18-39 years), 'adult-onset' (40-59 years), and ‘elderly-onset’ (³60 years). Baseline characteristics and treatments were analysed using Chi square, Mann-Whitney U tests, log-rank tests and/or Cox regression in SPSS.

Results

Baseline characteristics are shown in Table 1. No significant differences were found between age groups in terms of IBD diagnosis, gender, median follow-up duration, and smoking status.

Use of biologics differed significantly across age groups with highest uptake in young-adult onset patients (65.8%, P<0.001). Significant differences were found in selection of first biologic with vedolizumab as most frequently selected option in the elderly compared to anti-TNF in the youngest age group (P=0.002). Time to initiation of a biological was earlier in the youngest cohort (P=0.002, Figure 1). Cox regression analysis revealed that older age at diagnosis (HR 0.987, 95%CI [0.98;0.996], P=0.006), UC (HR 0.495, 95%CI [0.50;0.39], P<0.001) and centre of follow-up (Brussels vs Leuven: HR 0.663, 95%CI [0.4;1], P=0.048) were associated with a lower risk of biological initiation. When analysing CD separately, independent risk factors associated with biological use were perianal disease (HR 2.26, 95%CI [1.6;3.2], P<0.001), L3 (HR 1.85, 95%CI [1.3;2.6], P<0.001,) and L4 (HR 12.7, 95%CI [1.6;98.7], P=0.015,) location (compared to L1 location). In UC patients, E2 (HR 7.9, 95%CI [2.8;22.4], P<0.001) and E3 (HR 6.9, 95%CI [2.4;19.3], P<0.001) were related to earlier use of biologics.

During follow-up, 19% of CD and 5.1% of UC patients required IBD-related surgery. Univariate analysis showed a higher need for surgery in younger patients (P=0.042), however, this difference was no longer significant when analysing CD (P=0.272) and UC (P=0.09) patients as separate groups.

Conclusion

Analysis of the PANTHER Biobank reveals significant age-related variation in the administration of biological therapies among IBD patients.
P591 Treatment of microscopic colitis: retrospective analysis of consecutive single centre patients
Authors: Kiudelis V , Kiudeliene E , Kupcisnkas J , Kupcinskas L
Published: January 2024

Background

Microscopic colitis (MC) is a chronic autoimmune inflammatory condition of the colon that causes watery diarrhoea along with other symptoms like bowel incontinence. MC is a benign condition with no increase in cancer risk or impact on survival but it usually requires treatment due to significantly impaired quality of life. Even though MC therapy is symptom oriented, recent studies have shown that almost half the patients require long-term medical treatment.

Methods

A retrospective analysis of consecutive MC patients treated in Lithuanian University of Health Sciences Hospital Kauno Klinikos over the last 6 years was performed. Patient characteristics and clinical information was obtained from electronic records.

Results

94 MC patients were treated in our centre since 2017, 46 (49 %) with collagenous colitis (CC), 39 (41.5 %) with lymphocytic colitis (LC), 2 (2.1 %) with incomplete CC and 7 (7.4 %) with incomplete LC. 77 patients were female (82 %). Median age was 59 years [44.8-70.3]. There was a tendency for men to be younger (median 42 [37-68]) than women (median 60 [50-70.5]) but not significantly (p>0.05).

During the 6-year period 67 patients (71.3 %) were treated with budesonide, 33 (35.1 %) received only one course and went into clinical remission while 34 (36.2 %) needed either multiple courses or continuous treatment for relapsing or chronic active disease respectively. Primary non-response to budesonide wasn’t documented in any patient. 8 patients (8.5 %) were treated with azathioprine due to budesonide dependency or intolerance but it was discontinued in all but 1 patient due to lack of response or adverse events. 3 patients (3.2 %) were treated with biological therapy. 1 patient was treated with adalimumab which was discontinued due to adverse events, 1 was treated with infliximab which was switched to vedolizumab due to loss of response, and 1 was treated with vedolizumab which was switched to adalimumab due to primary non-response. At the time of analysis 61 patients (64.9 %) were receiving no active treatment, 21 (22.3 %) were receiving intermittent courses of budesonide, 6 (6.4 %) had been prescribed budesonide on demand, 3 (3.2 %) were taking budesonide continuously, 1 (1.1 %) was taking azathioprine and 2 (2.1 %) were on biological therapy. There was no difference between CC and LC patients.Conclusion

A little less than half of the patients needed long-term medical treatment. While budesonide was widely used and usually effective, we observed a need for advanced therapies as well.
P655 The ileorectal anastomosis after a total colectomy is a feasible and valid surgical alternative in the treatment of inflammatory bowel disease
Authors: Tapiolas I , Mañosa M , Troya J , Vela S , Pares D , Mesonero F , Valera P , Riestra S , Iglesias E , Rodríguez-González E , Guardiola J , García López S , Carpio D , Vega P , Martín Arranz M D , Ramos L , Busquets D , Sierra M , Martínez Montiel P , Sicilia B , Ricart E , Garcia Planella E , Huguet J M , Vera I , Gomollon F , Rivero M , De Castro L , Barreiro de Acosta M , Rodríguez Lago I , Gisbert J P , Garcia Sepulcre M F , Calvet X , Bermejo F , Pérez Calle J L , Gutierrez A , Lucendo A J , Muñoz Vilafranca M D C , Navarro Llavat M , Calafat M , Doménech E ,   ENEIDA
Published: January 2024

Background

Colectomy is still necessary in some patients with inflammatory bowel disease (IBD). The decision of the technique for the restoration of the bowel continuity depends on the characteristics of the patient and whether it is Crohn’s disease (CD) or ulcerative colitis (UC). The options for the reconstruction are proctectomy with an ileoanal reservoir or an ileorectal anastomosis (IRa).

The aim of this study is to evaluate the need of a proctectomy with a definitive ileostomy after an ileorectal anastomosis, the associated risk factors and the need for advanced therapies.

Methods

This retrospective study includes patients with colectomy and IRa from the ENEIDA national registry. Medical treatment offered during the postoperative follow up and the need for a proctectomy and a definitive ileostomy were evaluated according to the type of IBD.

Results

Of the 394 patients who underwent an IR, 37% had UC and 63% CD with a medium age of 58 years (RIQ 48-68) and a median follow-up after the IR of 174 months (RIQ 70- 266). 17% of UC’s patients and 42% of CD’s patients had associated perianal disease (p<0.001). The cumulative probability for a definitive ileostomy in UC’s patients was 1%, 2%, and 6% at 5, 10 and 20 years respectively and 1%, 3%, and 11% at 5, 10 and 20 years respectively for the CD (p=0.035). Postoperative maintenance treatment with biologicals was left in 45% (44% UC and 47% CD; p=0.28). During follow-up, the probability of starting biological treatment was 8%, 17%, 35% at 2, 5 and 10 years in CD and 3%, 12%, 28% at 2, 5 and 10 years in UC (p=0.59).

Conclusion

The probability of requiring a definitive ileostomy/proctectomy after an IR is low, although is more frequent in patients with CD than with UC. Because of this low probability an IR is a valid alternative to the reservoir or even to the proctectomy with a definitive ileostomy in selected patients, keeping in mind one third of the patients would need advanced therapies.
P661 Ustekinumab in Crohn’s disease: A three-year multicentre prospective study from Hungary - Assessing efficacy, drug sustainability, and safety
Authors: Barkai L J , Gonczi L , Farkas K , Farkas B , Molnar T , Szamosi T , Schafer E , Golovics P , Juhasz M , Patai A , Vincze A , Sarlos P , Farkas A , Dubravcsik Z , Toth T G , Miheller P , Lakatos P L , Ilias A
Published: January 2024

Background

While randomized controlled trials have shown ustekinumab (UST) as an effective therapeutic option for Crohn’s disease (CD), there is a lack of long-term observational data in real-world CD patient settings. This prospective study seeks to evaluate the clinical effectiveness, sustainability, and safety of UST in a nationwide multicentre cohort of CD patients over three years. The aim is to bridge the gap in our understanding of UST's real-world implications for long-term CD management.

Methods

CD patients undergoing ustekinumab (UST) treatment were consecutively enrolled at nine Hungarian Inflammatory Bowel Disease centers from January 2019 to May 2020. Over a three-year period, comprehensive data on patient demographics, disease characteristics, treatment history, clinical disease activity (measured by the Harvey Bradshaw Index (HBI)), biomarkers, and endoscopic activity (evaluated using the Simple Endoscopic Score for Crohn’s Disease (SES-CD)) were systematically collected.

Results

Involving 148 patients, the cohort comprised 48.9% with complex behavior of CD and 97.2% with previous anti-TNF exposure. Pre-induction remission rates were observed at 12.2% (HBI) and 5.1% (SES-CD). Clinical remission rates (HBI) at the end of the first, second, and third years were 52.2%, 55.6%, and 50.9%, respectively. Criteria for endoscopic remission were met in 14.3%, 27.5%, and 35.3% of subjects at the end of the first, second, and third years. Dose intensification was notable, with 84.0% of patients on an 8-weekly and 29.9% on a 4-weekly regimen by the end of year 3. Throughout the follow-up period, drug sustainability stood at 76.9%, and no serious adverse events were observed.

Conclusion

Our study confirms that ustekinumab is a sustainable, effective, and safe long-term treatment for Crohn's disease patients with a severe disease phenotype and a history of high anti-TNF failure, with the need for frequent dose adjustments.
P677 The Oxford Anti-TNF Study of Immunogenicity and Sustained Response (OASIS-IBD): Analysis of 40,000 Patient Years of Anti-TNF Use
Authors: Al-Hillawi L , Liao H , Powell Doherty R , Bedke N , Azzu H , Cripps S , Prabhu A , White L , Ambrose T , Cheung V , Palmer R , Walsh A , Travis S , Ternette N , Brain O , Satsangi J ,   The Oxford Anti-TNF Study of Immunogenicity and Sustained Response (OASIS-IBD)
Published: January 2024

Background

Anti-TNF therapy is established as a mainstay in IBD management. Recent data raise controversies regarding efficacy of these agents, sustainability of response, and identification of factors that may influence outcomes, including dose escalation and need for long-term concurrent immunosuppression (Lancet Gastro.Hep.2019;4:341).

Methods

We report a retrospective cohort study of 699 IBD patients on anti-TNF at our centre between 2005-2022. Clinical data were obtained from patient records and pharmacy database (TABLE 1). Primary outcomes were overall loss of response (LOR) at any timepoint; and secondary LOR (after an initial clinical response to therapy). Cox regression analysis was performed to identify variables independently affecting outcome. Kaplan-Meyer survival curves were constructed to demonstrate overall response rates (persistence on drug) and secondary LOR (Figure 1a-d). Dose adjustments were made proactively in a Virtual Clinic.

Results

204 patients had a diagnosis of ulcerative colitis (UC), 481 Crohn’s Disease (CD) and 14 IBD-unclassified. 126 patients received both infliximab (IFX) and adalimumab (ADA). Median duration on IFX was 42 months (range 0-204); median duration on ADA was 48.5 months (range 0-180). 48% of patients on IFX underwent dose escalation, as did 40% on ADA. Overall, 58 patients (7.6%) remained on treatment at 120 months.

Overall survival rates for IFX at 12 months were 83% (82%CD vs. 82%UC); and at 36 months were 71% (69%CD vs. 74%UC). Overall survival rates for ADA at 12 months were 84% (89%CD vs. 59%UC); and at 36 months were 72% (78% CD vs. 42% UC) (Figure 1a-b).

Secondary LOR rates for IFX at 12 months were 6% (5%CD vs. 9%UC); and at 36 months were 16% (15%CD vs.19%UC). Secondary LOR rates for ADA at 12 months were 7% (5%CD vs. 19%UC); and at 36 months were 16% (12% CD vs. 42% UC) (Figure 1c-d). There was no difference in survival analysis for IFX between CD and UC.

On Cox regression analysis, for IFX, immunomodulation was associated with reduction in overall LOR (HR=0.48, p=1.07e-05) but not secondary LOR (HR=0.78, p=0.31) (Figure 1e-f). For ADA, outcomes were better for CD vs. UC for both overall LOR (HR=0.35, p=3.29e-07) and secondary LOR (HR=0.35, p=9.99e-05).

Conclusion

We demonstrate encouraging response rates in the first three years of therapy, with a small proportion remaining on therapy beyond 120 months. Survival rates on IFX were similar for UC and CD, but for ADA were significantly lower in UC. Secondary LOR was not affected by immunomodulation. Further analysis of relation to drug levels, dose escalation and genotyping is underway. This work was supported by The Leona M & Harry B Helmsley Charitable Trust.
P690 Monitoring ustekinumab levels in Inflammatory Bowel Disease in clinical practice: a window of opportunity
Authors: González Antuña J , Valdés Delgado T , Maldonado Pérez B , Castro Laria L , Merino Bohórquez V , Calleja Hernández M Á , Argüelles Arias F
Published: January 2024

Background

Ustekinumab (UST) is an effective drug in inflammatory bowel disease (IBD). Monitoring Ustekinumab trough levels in μg/mL (USTTL) can assist in the clinical management of these patients. Our objective was to analyze USTTL in patients with IBD, establish cutoff points associated with clinical response and remission, and analyze factors related to higher levels.

Methods

Observational, retrospective, and single-center study that included patients with IBD receiving UST treatment with at least one level determination.

Before the initiation of UST (baseline) and prior to level extraction (periods 1 and 2), clinical and analytical data were collected as follow: Harvey-Bradshaw Index (HBI) in Crohn's disease (CD), partial Mayo Index (pMayo) in ulcerative colitis (UC), fecal calprotectin (FC) and C-reactive protein (CRP).

Median and interquartile range (IQR) were used for quantitative variables, and percentage (%) for qualitative variables. Univariate and bivariate analyses were performed for response and clinical remission rates using ROC curves.

Results

A total of 125 patients with at least one USTTL determination were included. Figure 1 illustrates their baseline characteristics.

In period 1, 62.4% of patients were on subcutaneous maintenance, and the median USTTL was 3.1 (1.6-5.3). 64% of patients responded to treatment, with higher USTTL than non-responders [4.1 (2.0-6.2) vs. 2.1 (1.0-4.5); p=0.006]. 42.5% achieved clinical remission with higher USTTL than those who did not achieve it [4.0 (2.3-5.7) vs. 2.5 (1.2-5.2) p=0.039].

Furthermore, patients on subcutaneous maintenance* had lower USTTL than those on subcutaneous and intravenous intensification [2.2 (1.3-3.5)* vs. 7.4 (5.1-10.8) and vs. 5.3 (3.3-12); p<0.001 and p=0.03, respectively).

In the 46 patients with two determinations, statistically significant differences were found between period 1 and period 2 in USTTL [3.4 (1.9-6.4) vs. 7.2 (4.7-11.7) p<0.001], HBI [8 (4-9) vs. 4 (4-4.3); p<0.001], pMayo [4.5 (3-5) vs. 1 (1-3.3); p=0,042], FC [700 (180-2000) vs. 400 (108-1571); p=0.032), and corticosteroid use (41.3% vs. 26.1%; p=0.024).

ROC curves were calculated for response and clinical remission in period 2. The USTTL cutoff points were 4.25 and 6.025μg/mL for response and clinical remission, respectively (figure 2).

Conclusion

Similar to previously published studies with anti-TNF, high levels of USTTL are associated with increased clinical remission and response. Patients undergoing UST treatment may benefit from a change in dosage to increase levels and achieve clinical remission. The cutoff point obtained for clinical remission was 6 μg/mL.

Therefore, the determination of USTTL in daily clinical practice is a useful tool for the treatment of patients with IBD.