bluuebunny/crossref_metadata_2025_split huggingface dataset:
P207 Colonic location at diagnosis of pediatric-onset Crohn’s disease is associated with a pejorative disease course: a two decades population-based study
Authors: Fumery M , Savoye G , Ley D , Dupont-Lucas C , Bertrand V , Wils P , Guillon N , Sarter H , Gower-Rousseau C , Turck D , Leroyer A ,   EPIMAD
Published: January 2023

Abstract

Background
Crohn's disease (CD) location would influence the risk of complications and therapeutic strategies. The objective of this study was to compare the clinical presentation at diagnosis and the natural history of colonic CD in comparison to ileal CD and ulcerative colitis (UC) in pediatric-onset inflammatory bowel disease.

Methods
All children (&lt; 17 years) with a diagnosis of CD or UC made between 1988 and 2011 in a population-based registry were followed retrospectively until 2013. Presentation at diagnosis, risks of complicated disease, surgery, hospitalization and exposure to treatments in ileal CD (L1), colonic CD (L2) and UC were compared. Disease location was defined at diagnosis. In case of extension of the disease (L1 or L2 to L3), follow-up was censored.

Results
A total of 215 L1 patients, 234 L2 patients and 337 UC patients were included. At diagnosis, the proportion of males (L1 53.5%; L2 53.4%; UC 42.7%; p=0.012), age at diagnosis (15.0; 13.7; 14.0 years; p=0.003), family history of IBD (12.6%; 12.7%; 5.0%; p=0.005), diagnostic delay (3.0; 3.0; 2.0 months; p=0.001) and smoking prevalence (11.6%; 8.1%; 5.6%; p=0.041) were different between the three groups. Bloody stool and diarrhea at diagnosis was observed in respectively 14.9%, 44.4%, and 91.1% (p &lt; 0.001) and 47.0%, 71.8%, and 65.0% (p &lt; 0.001) of L1, L2 and UC. At diagnosis, granuloma was identified in 12.6% of L1 patients and 31.2% of L2 patients (p&lt;0.001). The risk of extension to L3 was significantly higher in the L2 group than in the L1 group (at 5 years - 37% vs. 14%, p&lt;0.001). Compared to L1 location, L2 was associated with a lower risk of luminal fistula (HR 0.41 [0.21-0.79], p=0.008) but a higher risk of anoperineal lesion (HR 2.11 [1.29-3.45], p=0.003). The prevalence of extra-intestinal manifestations, articular (p&lt;0.001) and cutaneous (p&lt;0.001) was higher in L2. While the risk of surgery was significantly higher in case of L1 (at 5 years – L1 37%, L2 13% and UC 13%; p&lt;0.001), the risk of hospitalization (at 5 years - 22%, 39% and 33%; p=0.01), exposure to corticosteroids (at 5 years - 55%, 69% and 67%; p&lt;0.001), immunosuppressants (at 5 years - 47%, 61% and 42% - p&lt;0.001) and anti-TNF (at 5 years - 16%, 35% and 22%; p&lt;0.001) were higher in case of L2.

Conclusion
The clinical presentation at diagnosis and natural history of ileal and colonic CD differ significantly. Colonic location is associated with a high risk of perianal CD, extra-intestinal manifestations, hospitalization as well as exposure to steroids, immunosuppressants and anti-TNF. These differences may justify different therapeutic strategies in the future.
P247 Oncostatin M and its receptor are markers of endoscopic and histological disease activity in Inflammatory Bowel Disease
Authors: Nguyen A , Sturm G , Plattner C , Trajanoski Z , Atreya R , IBDome Consortium I C , Siegmund B , Hegazy A N ,   IBDome Consortium
Published: January 2023

Abstract

Background
Oncostatin M (OSM) and its receptor (OSMR) have been associated with active disease in patients with inflammatory bowel disease (IBD). This study compared the expression of OSM and OSMR in intestinal tissue according to clinical, endoscopic, and histological disease activity.

Methods
A multi-centre IBD database containing RNA-sequencing datasets, was used to analyse OSM and OSMR expression in ileal and/or colonic tissue, expressed as transcripts per million (TPM). Clinical scoring systems included the Harvey Bradshaw Index for Crohn’s disease (CD) and partial Mayo score for ulcerative colitis (UC). Endoscopic scoring systems included the simple endoscopic score for CD (SES-CD) and UC endoscopic index of severity (UCEIS). Histological scoring included the modified Naini and Cortina, and Riley scores. Graphs were presented in log transformed TPM+1 values.

Results
155 patients (108 CD, 47 UC) and 38 controls were included. For IBD patients, 49% were men, median age was 35 years and intestinal tissue was collected at endoscopy (73%) and surgery (27%). Compared to controls, patients with CD and UC had significantly elevated median expression of OSM (0.08, 0.29 and 0.34 TPM respectively) and OSMR (1.21, 1.69 and 3.53 TPM respectively). OSMR expression was higher in UC patients than CD (p&lt;0.001). There was no difference in OSM or OSMR between Harvey Bradshaw Index categories (0-4 vs 5-7 vs 8-16) or partial Mayo scores (0 vs 1-3 vs 4-7). Endoscopically, OSM was higher for SES-CD scores of 16-51 (1.11 TPM), compared to SES-CD scores of 0-3 (0.14 TPM, p=0.003) and controls (0.08 TPM, p&lt;0.0001). Median OSMR increased non-significantly with increasing SES-CD scores (score 0-3: 1.59 TPM; score 4-15: 1.90 TPM; score 16-51: 2.04 TPM). There was no difference in OSM and OSMR expression between UCEIS scores, but the most severe disease (UCEIS score 5-8) had higher expression than controls for both OSM (3.92 vs 0.08 TPM, p&lt;0.001) and OSMR (6.10 vs 1.21 TPM, p&lt;0.0001). Increasing expression of OSM and OSMR was found with increasing histological scores, see Figure. Using the modified Naini and Cortina score for CD, OSM and OSMR were most expressed in the highest scores compared to the lowest scores (OSM: 1.48 vs 0.09 TPM, p&lt;0.001; OSMR: 5.50 vs 1.27 TPM, p=0.003). For the modified Riley score for UC, both OSM and OSMR were also able to differentiate between the highest and lowest score groups (OSM: 3.14 vs 0.12 TPM, p=0.0001; OSMR: 6.61 vs 1.58 TPM, p&lt;0.0001).

Conclusion
This study showed that OSM and OSMR expression in intestinal tissue is associated with inflammation both histologically and endoscopically. Further investigations are needed to confirm our observations and explore the OSM pathway’s relevance in intestinal inflammation.
P389 Switching infliximab to subcutaneous from intravenous therapy (SWIMSUIT) – A prospective, real-world, single centre, phase IV interventional study.
Authors: Rahmany S , Young D , Moyses H , Gonclaves J , Latter S , Cummings F 
Published: January 2023

Abstract

Background
Subcutaneous (SC) infliximab (CT-P13) was approved in 2020 by the EMA for use in IBD. This offers patients greater choice, flexibility and the convenience of administering their treatment at home as well as other potential therapeutic benefits. We aim to evaluate the clinical outcomes of patients switching from intravenous (IV) infliximab to SC CT-P13.

Methods
We offered IBD patients established on IV infliximab (&gt;4 doses) the opportunity to switch to SC CT-P13. Patients who agreed to switch were followed up every 12 weeks for 24 weeks. Demographics, disease history, disease activity scores, IBD CONTROL PROM, SF36, calprotectin, standard blood tests, infliximab drug levels, antidrug antibodies (ADA) and adverse events were collected at each visit. The primary endpoint was the maintenance of clinical status at week 24 (W24). A failure to maintain clinical status was defined as an increase in disease activity scores (mHBI or SCCAI) of ≥3, and/or a decline in IBD-Control PROM score of ≥4 points at any time during the study period.

Results
We approached 204 patients receiving IV infliximab, of which 120 patients switched to SC CT-P13 (75.8% CD, 22.5% UC, 1.7% IBDU). 24 patients had perianal disease at baseline. Median age was 38. The median time taken by patients (leaving home to returning home) to receive their infusions was 180 minutes (range 60 to 660). 96 participants were on concomitant immunomodulators (79 thiopurines, 17 methotrexate) and 105 were treated with SB2 preswitch. The median duration of IV infliximab prior to switching was 45 months. 70 (58%) of the patients were on the standard dosing (5mg/kg Q8W) regimen. All patients were switched to 120mg of SC CT-P13 every other week, regardless of their baseline regimen. 11 (9.2%) patients discontinued the treatment prior to finishing the study. 75% (CI 0.65, 0.82) of the whole cohort reached the primary endpoint of maintaining clinical status at week 24. There was no statistically significant difference in disease activity scores or IBD-Control PROM between baseline and W24. 31 (25.8%) of the patients had evidence of immunogenicity at baseline (ADA of &gt; 50ng/ml). Of the 89 patients with no immunogenicity at baseline, 69 (77.5%) maintained this at W24. The median serum infliximab levels increased by 72.8 % from baseline to W24 (3.05 µg/ml to 5.27 µg/ml (figure 1)). Median ADA levels increased from 8.46 ng/ml at baseline to 10.6 ng/ml at W24 (figure 2). Patient satisfaction with SC CT-P13 was very high (figure 3).

Conclusion
Switching patients from IV to SC CT-P13 is safe, effective, and well-accepted with higher infliximab serum levels. The majority of the patients with no immunogenicity at baseline maintained this at W24.
P405 Long-term safety of 3 years of ozanimod in moderately to severely active ulcerative colitis: an interim analysis of the True North open-label extension
Authors: Panaccione R , Danese S , Wolf D C , Canavan J B , Jain A , Wu H , Petersen A , Charles L , Afzali A , Abreu M T 
Published: January 2023

Abstract

Background
The phase 3, randomised True North (TN) study demonstrated the efficacy and safety of ozanimod for up to 52 weeks in patients (pts) with moderately to severely active ulcerative colitis (UC). The ongoing TN open-label extension (OLE) aims to assess the long-term efficacy and safety of ozanimod in UC. This analysis evaluated the cumulative long-term safety of ozanimod in these studies, which included pts with up to ~3 years of treatment exposure.

Methods
In TN, pts were randomised to once-daily ozanimod 0.92 mg or placebo, or to open-label ozanimod for a 10-week induction period. Ozanimod clinical responders were rerandomised at Week 10 to ozanimod or placebo in the maintenance period through Week 52. TN pts were eligible to enrol in the OLE and receive ozanimod if they did not achieve clinical response at the end of induction (Week 10), lost response during maintenance, or completed maintenance at Week 52. This interim analysis of the TN OLE (data cutoff: 10 January 2022) included all pts who entered the OLE from TN (n=823). Safety was monitored from the first dose of ozanimod in TN and throughout the subsequent OLE. Exposure-adjusted incidence rates per 100 patient-years (PY) were calculated.

Results
The average age of TN OLE study participants was 41.7 years (±13.6), 41% were female, 62% had left-sided UC disease, and 35% had prior exposure to tumor necrosis factor inhibitors. Total PY exposure to ozanimod was 2219 years (mean [SD] exposure = 2.7 [1.6]). The most frequent treatment-emergent adverse events (TEAEs) reported through OLE Week 94 (up to 146 weeks of continuous treatment) are listed in the Table. Most TEAEs were nonserious; TEAEs leading to discontinuation were uncommon. Bradycardia was reported in 3 pts (0.4%; EAIR 0.1/100 PY; 2 in TN and 1 in OLE; no pts were discontinued from treatment). Macular edema was reported in 2 (0.2%; EAIR 0.1/100 PY) pts. Reductions in ALC were common (470 [57.1%] had ALC &lt; 500 cells/mm3), as previously described, but ALC reductions were not associated with the occurrence of TEAEs. Malignancies were uncommon (n=13 [1.6%]; EAIR 0.6/100 PY), and included 6 basal cell carcinomas and 3 colorectal neoplasms. Two deaths were reported: 1 due to COVID-19 and 1 sudden death. Investigators deemed both to be unrelated to treatment. Ozanimod was not associated with an increased risk of ischemic heart disease or thromboembolic events.

Conclusion
Long-term exposure to ozanimod for up to 3 years was well tolerated in pts with moderately to severely active UC. No new safety signals were observed with long-term ozanimod use in UC (2219 PY exposure). Safety findings are consistent with previous reports from the UC and multiple sclerosis development programs (&gt;16,512 PY exposure).
P434 Upadacitinib improved fatigue and health-related quality of life in patients with moderately to severely active Crohn’s disease: Results from induction and maintenance phase 3 trials
Authors: Ghosh S , Feagan B , Parra R S , Lopes S , Steinlauf A , Kakuta Y , Joshi N , Lee W J , Remple V , Lacerda A P , Zhou Q , Xuan S , Louis E 
Published: January 2023

Abstract

Background
Upadacitinib (UPA) demonstrated efficacy and safety in the phase 3 U-EXCEED (NCT03345836) and U-EXCEL (NCT03345849) induction, and U-ENDURE (NCT03345823) maintenance trials in patients (pts) with moderately to severely active Crohn’s disease (CD). We evaluated the impact of UPA on health-related quality of life (QoL) in pts with CD.

Methods
Clinical responders to UPA 45 mg (UPA45) in U-EXCEED and U-EXCEL induction trials were re-randomised at Week 12 (1:1:1) to UPA 15 mg (UPA15), UPA 30 mg (UPA30), or placebo (PBO) for 52 weeks of maintenance treatment in U-ENDURE; data from these induction and maintenance trials were included in this analysis. Endpoints included the percentage of pts who achieved an Inflammatory Bowel Disease Questionnaire (IBDQ) response (≥16 points), IBDQ remission (≥170 points), a meaningful within-person change (MWPC) from baseline of ≥9 points on the Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT-F), and of ≥4.1 and ≥3.9 points on the 36-item Short-Form Health Survey (SF-36) physical (PCS) and mental (MCS) component summary scores, respectively, at Weeks 4/12 of induction and Week 52 of maintenance. Adjusted risk differences compared to PBO, 95% confidence intervals, and p-values were calculated based on the Cochran-Mantel-Haenszel test.

Results
In U-EXCEED (n=324 UPA; 171 PBO) and U-EXCEL (n=350 UPA; 176 PBO), a greater proportion of UPA45- vs PBO-treated pts had an IBDQ response at Weeks 4 (U-EXCEED: 71.6% vs 47.6%; U-EXCEL: 71.0% vs 50.2%; p≤0.001) and 12 (U-EXCEED: 63.9% vs 44.4%; U-EXCEL: 68.4% vs 46.5%; p≤0.001; Figure 1). In UPA- vs PBO-treated pts, a greater proportion achieved IBDQ remission at Weeks 4 (U-EXCEED: 41.4% vs 22.4%; U-EXCEL: 44.2% vs 23.7%; p≤0.001) and 12 (all p≤0.001; Figure 1). At Week 12, a significantly greater proportion of UPA-treated pts vs PBO demonstrated a MWPC in FACIT-F, and SF-36 PCS and MCS from baseline (p≤0.001; Figure 1). Similar results for UPA45 vs PBO were achieved as early as Week 4 in FACIT-F (U-EXCEED: 42.3% vs 20.0%; U-EXCEL: 42.0% vs 27.0%), SF-36 PCS (U-EXCEED: 56.6% vs 37.2%; U-EXCEL: 53.0% vs 37.5%; p≤0.001) and MCS (p≤0.05). In the maintenance study U-ENDURE (n=168 UPA30; 169 UPA15; 165 PBO), a greater proportion of pts receiving UPA15 and UPA30 vs PBO achieved an IBDQ response (39.1%, 53.5% vs 20.4%), IBDQ remission (36.1%, 45.2% vs 13.5%), and a meaningful improvement from baseline in FACIT-F, SF-36 PCS and MCS through 52 weeks (p≤0.01; Figure 2).

Conclusion
In pts with moderately to severely active CD, UPA treatment significantly improved fatigue, disease-specific and generic QoL, compared with PBO, as early as Week 4 of induction. The effects were sustained through 52 weeks of maintenance treatment.
P446 The INTESTINE study: INtended TEmporary STomas In crohN’s diseasE
Authors: Perrott C , Calini G , Gori A , Rottoli M , Garoufalia Z , Wexner S , Celentano V ,   The INTESTINE Study Group
Published: January 2023

Abstract

Background
Patients with ileocolic Crohn’s disease may require surgery resulting in temporary stoma formation. The impact on quality of life and morbidity related to stomas is well recognised and timely reversal should be targeted to alleviate this affect. This study aims to determine the proportion of stomas reversed, the timing and reasons for non-reversal in patients with Crohn’s disease.

Methods
This international retrospective trainee-led observational study included patients who underwent surgery for ileocolic Crohn’s disease between January 2017 and December 2020. Patients undergoing proctectomy or proctocolectomy were excluded. The primary outcome was the proportion of patients who still had a stoma at 18 months post-operatively. Secondary outcomes included: interval between formation and reversal of stoma, assessing complications and risk factors from non-reversal of the stoma. Evaluation of these outcomes were documented for short-term (6 months) and mid-term (18 months).

Results
Currently there are 38 collaborating centres collecting data across 18 countries. We present an intermediate analysis, with full results available in January 2023.
Baseline and surgical characteristics are described in Tables 1 and 2. The intermediate analysis included 110 patients of which 37% had their stoma reversed at 6 month follow up (mean time to reversal 3.2 ± 1.4 months), and 56% reversed at 18 months (mean 5.9 ± 4.0 months). Reasons for non-reversal at 6 months included: ongoing Crohn’s disease (30%), patient unfit for surgery (14%), waiting lists (9%) and patient’s preference (8%). Stoma related complications at 6 months were reported in 16% of patients, consisting of: high output (6%), parastomal hernia (5%), stoma stenosis (3%) and peristomal cutaneous lesions (1%). 30-day postoperative outcomes and follow up at 6 and 18 months are reported in Tables 3 and 4.

Conclusion
This trainee-led international study will provide information on the proportion of stomas that are reversed and the reasons for non-reversal of stomas in Crohn’s disease. Preliminary results demonstrate that 18 months after stoma formation, 1 in 2 patients still had a stoma.
P464 Effects of ozanimod on histologic remission and mucosal healing over 3 years of continuous treatment in patients with ulcerative colitis
Authors: Panaccione R , Danese S , Wolf D C , Canavan J B , Jain A , Wu H , Petersen A , Afzali A , Abreu M T 
Published: January 2023

Abstract

Background
Ozanimod is approved in the European Union, United States, and other countries for the treatment of moderately to severely active ulcerative colitis in adults (UC). The phase 3, randomised True North (TN) study demonstrated the efficacy and safety of ozanimod for up to 52 weeks in patients with moderately to severely active UC. The ongoing TN open-label extension (OLE) aims to assess the long-term efficacy and safety of ozanimod. This interim analysis of the TN OLE evaluated the efficacy of ozanimod on histologic remission (HR) and mucosal healing (MH) in patients who received approximately 3 years of continuous ozanimod treatment.

Methods
In TN, patients were randomised to once-daily ozanimod 0.92 mg (equivalent to ozanimod HCl 1 mg) or placebo (Cohort 1) or to open-label ozanimod (Cohort 2) for a 10-week induction period. Ozanimod clinical responders were rerandomised at Week 10 to ozanimod or placebo for a 42-week maintenance period (MP). Patients with clinical response to ozanimod at Week 52 in TN were eligible to continue receiving ozanimod in the ongoing OLE. This interim analysis of the OLE (data cutoff: 10 January 2022, the point at which patient disposition was available for patients until OLE Week 94) included all patients on continuous ozanimod in the TN MP who achieved clinical response at Week 52 and enrolled in the OLE (n=131). Endoscopic and histologic endpoints were evaluated at OLE Weeks 46 and 94 (98 and 146 weeks of continuous ozanimod treatment, respectively) and reported using observed case analysis. Mean Mayo endoscopy scores were evaluated from TN baseline to OLE Week 94.

Results
Of the 131 total patients included in this analysis, 87% completed OLE Week 46 (98 weeks of continuous ozanimod) and 72% completed OLE Week 94 (146 weeks of continuous ozanimod). Patients had a mean age of 44 years and 52% were female. Most patients (68%) had left-sided UC, 69% had prior use of corticosteroids, 99% had prior use of 5-aminosalicylic acid, and 32% had prior use of tumor necrosis factor inhibitors. Most TN Week 52 clinical responders achieved endoscopic improvement (EI), HR, and MH at OLE Weeks 46 and 94 (Figure 1). Ozanimod treatment was associated with a reduction in mean Mayo endoscopy score to 1.0 at TN Week 52; this was sustained through OLE Week 94 (Figure 2).

Conclusion
In this interim analysis of the TN OLE, a large proportion of clinical responders after 1 year of ozanimod who remained on ozanimod for up to 2 years thereafter, achieved EI, HR, and MH after 2 and 3 years of continuous treatment. Long-term ozanimod use may be associated with sustained endoscopic and histologic benefits in patients with UC.
P476 Characterization of cardiac conduction abnormalities reported in the phase 3 ELEVATE programme
Authors: Vermeire S , Yarur A , Rubin D T , Dubinsky M C , Regueiro M , Irving P , Peyrin-Biroulet L , Goetsch M , Gu G , Wu J , Modesto I , McDonnell A , Rabbat C J , Green J , Anthopoulos P 
Published: January 2023

Abstract

Background
Etrasimod is an investigational, once-daily, oral, selective sphingosine 1-phosphate receptor 1,4,5 (S1P1,4,5) modulator in development for the treatment of moderately to severely active ulcerative colitis (UC). First-dose, transient heart rate (HR) reduction and cardiac conduction aberrations are a known, on-target effect of S1P receptor modulators. Here, we report characteristics of patients for whom adverse events (AEs) of bradycardia or atrioventricular (AV) block were reported in the phase 3 ELEVATE programme.

Methods
In ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369), patients (16-80 years) with moderately to severely active UC were randomised 2:1 to once-daily etrasimod 2 mg or placebo on study day 1 with no dose titration regimen. Cardiac conduction was evaluated in all patients with a 12-lead ECG during the screening period, prior to randomisation on day 1 (baseline), and 4-hours post-dose. Bradycardia was considered an AE of special interest if the HR was &lt;40 bpm, or &lt;50 bpm with associated symptoms, or the event led to study discontinuation. AV conduction delays were considered an AE of special interest if second degree AV block (Mobitz Type I/II) or higher, first degree AV block with PR interval &gt;230 ms, or if associated with clinical symptoms.

Results
A total of 9 events of bradycardia were reported in patients receiving etrasimod across both trials (Table 1). All but 1 event (8/9) were first reported on day 1 of treatment, with the remaining first reported on day 2 (none reported after day 2). Seven of 9 events were asymptomatic; the 2 symptomatic events (moderate dizziness; mild dizziness, palpitations) led to therapy discontinuation and resolved without additional intervention. No serious or severe events of bradycardia or hemodynamic changes were reported. Three AEs of AV block were reported in patients on etrasimod across both trials. All events occurred on day 1 during in-clinic ECG monitoring per study protocol and were nonserious, asymptomatic, and resolved without interventional treatment. Two events were first degree, one of which was pre-existing (treatment was discontinued); the other patient continued treatment and completed the study. The third event was second-degree (Mobitz Type I) (treatment was discontinued). Among the small sample size of 11 patients who experienced ≥1 AE of bradycardia or AV block, there were no baseline characteristics that could be used to predict these events (Table 2).

Conclusion
Cardiac AEs with etrasimod were generally rare, mild, asymptomatic, and occurred on day 1 in association with the first dose. This is consistent with other S1P receptor modulators. Data from the ongoing 5-year open-label extension will further characterize the etrasimod safety profile.