bluuebunny/crossref_metadata_2025_split huggingface dataset:
P697 De-escalating therapy in inflammatory bowel disease: Results from an observational study in clinical practice.
Authors: Arenas A , Moreta M J , Ordás I , Fernández-Clotet A , Caballol B , Gallego M , Vara A , Barastegui R , Giner A , Prieto C , Masamunt M C , Ricart* E 
Published: January 2023

Abstract

Background
Combination therapy with an immunomodulator (IMM) and an anti-TNF agent (specifically infliximab) is recommended in Crohn’s disease (CD) and ulcerative colitis (UC) patients to improve efficacy and reduce anti-TNF immunogenicity. Combo therapy increases the risk of adverse events and therefore attempts are made to de-escalate therapy in clinical practice. There are scarce data about relapse rates after discontinuation of either IMM or anti-TNF among patients with long-term remission under combination therapy. The aims of this study were to assess the risk of relapse in a cohort of UC and CD patients with long-standing remission after discontinuation of IMM or anti-TNF and to identify predictive factors for relapse.

Methods
This is a retrospective unicentric study that included patients with UC or CD on combination therapy and sustained clinical remission at least for 6 months. IMM or anti-TNF were stopped upon treating-physician decision and data were collected until relapse or last follow-up. Relapse was defined as the onset of clinical, biological, endoscopic or radiological activity, leading to therapeutic intervention. The survival without relapse is represented by Kaplan–Meier curve and analyzed by log rank test. Hazard ratios (HR) for relapse were estimated by Cox proportional hazard regression analyses and are reported with 95% confidence intervals (CI).

Results
Eighty-eight patients (60 CD (68.2%), 28 UC (31.8%) were included. Demographic data and clinical characteristics are shown in tables 1 and 2. Forty-eight patients (54.5%) discontinued IMM and 40 (45.5%) anti-TNF. Median time of follow-up was 33 months (IQR 18.00-55.75). During follow-up, relapse rate was 16.7% in the IMM discontinuation group and 52.5% in the anti-TNF discontinuation group (p&lt;0.001) (Figure 1). Median time without relapse after discontinuation of IMM and anti-TNF was 38.50 (IQR 19.75-58.5) and 24.50 months (IQR 10.25-42.75), respectively (p=0.036). In the multivariate analysis, only discontinuation of anti-TNF was a predictive factor for relapse (HR=4.99; 95% CI=1.11–14.07) (Table 3). Among patients who relapsed after anti-TNF discontinuation, clinical response after reintroduction of the drug was achieved in 78.6% (11/14) without safety issues.

Conclusion
Discontinuation of anti-TNF in patients on combination therapy with IMM and anti-TNF and long-standing remission led to significantly higher relapse rates compared to discontinuation of IMM. Retreatment after anti-TNF discontinuation was effective and safe.
P700 Perceptions towards established and emerging dietary therapies for Crohn’s disease management among the adult patients: results from a questionnaire survey
Authors: Jatkowska A , White B , Jaskolski P , Brownson E , Clowe J , Seenan J P , Gerasimidis K , MacDonald J 
Published: January 2023

Abstract

Background
Exclusive enteral nutrition (EEN) and partial enteral nutrition (PEN), replacing at least 50% of the energy intake with formula, remain the only evidence-based dietary therapies in the management of Crohn’s disease (CD). Nonetheless, emerging solid food-based dietary therapies are being researched to offer equally effective, but more palatable alternatives. We assessed the perceptions of adults with CD towards EEN, 50% PEN, and novel dietary therapies within a cross-sectional questionnaire survey.

Methods
The 26-question anonymous survey with a pre-paid return envelope was mailed to 300 adult patients with CD treated with biologics under the care of the NHS Greater Glasgow & Clyde. A reminder was resent three months later. Responses to open-ended questions regarding concerns about 50% PEN use were analysed independently by two researchers using thematic analysis.

Results
One-hundred and sixty patients (85/160, 53% female) completed and returned the survey (response rate: 53%). Forty-two percent (67/158) had already followed some form of an exclusion diet, with low spice (32/158, 20%) and low fibre (24/158, 15%) diets being the most popular. Although only a quarter of patients believed that EEN or PEN could help with their CD (42/157, 27%), the majority believed that diet could help (84/157, 54%), with another 13% (21/157) reporting already using diet for CD management. Although only around half of the patients were willing to try EEN (80/157, 51%), the majority were willing to try PEN instead (124/157, 79%) (EEN vs. PEN chi-square: P&lt;.001). Most patients preferred to follow an exclusion diet meal plan to prepare at home (65/154, 42%) compared to EEN or PEN (53/153, 34%). Similarly, most patients preferred to follow a meal plan to prepare at home (76/151, 50%) rather than a meal plan with pre-made meals delivered (59/151, 39%). When asked about preferences related to PEN use, most patients reported that they would prefer to follow a flexible meal plan, allowing them to choose meals to replace to fit their lifestyle (92/153, 60%). The most commonly reported concerns about PEN identified within the thematic analysis were taste/palatability (25%, 34/136), satiety/hunger (22%, 30/136), taste fatigue (14%, 19/136), and impact on social life (14%, 19/136).

Conclusion
Most adult patients would prefer to follow an exclusion diet meal plan rather than EEN or 50% PEN. However, the majority would try 50% PEN which allows for more flexibility and may be easier to comply with than EEN.
P715 Achievement and maintenance of endoscopic, histologic, and combined outcomes after extended induction in Week 10 nonresponders of ozanimod: 2-year interim analysis of the True North open-label extension study
Authors: Vermeire S , Colombel J F , Rubin D T , Ghosh S , Jain A , Lawlor G , Osterman M T , Wu H , Canavan J B , Chiorean M V 
Published: January 2023

Abstract

Background
Ozanimod, a novel oral therapeutic option for patients with moderately to severely active ulcerative colitis, demonstrated significant improvements in clinical, endoscopic, and histologic endpoints in the phase 3, 52-week, double-blind True North (TN) study. Approximately one-third of the patients did not achieve clinical response to ozanimod after 10 weeks of TN induction therapy. However, a delayed response was observed in a subset of these nonresponders upon extended induction with ozanimod. The present analysis evaluated ozanimod efficacy on endoscopic and histologic endpoints in these delayed responders in the TN open-label extension (OLE) study.

Methods
Data were analysed for the overall delayed responder population and separately for the blinded (Cohort 1) and open-label (Cohort 2) cohorts (data cutoff: 10 January 2022, the point at which patient disposition was available for all patients up to OLE Week 94). Endpoints included endoscopic improvement (defined as an endoscopy subscore of ≤1 point), histologic remission (defined as Geboes index score &lt;2.0), and mucosal healing (defined as endoscopy subscore of ≤1 point and Geboes index score of &lt;2.0) up to OLE Week 94. The endpoints were evaluated using observed case (OC) and nonresponder imputation (NRI) analyses.

Results
A total of 226 patients (Cohort 1, n=150; Cohort 2, n=76) were nonresponders at Week 10 and entered the OLE (67% male; mean [standard deviation] age, 39.6 [13.6] years). At OLE entry, 24% of patients had moderate disease (Mayo endoscopic score [MES]=2) and 73% had severe disease (MES=3). Approximately half of these patients achieved symptomatic clinical response as early as 5 weeks of ozanimod open-label treatment. In OC analysis at OLE Week 46, 30% of patients achieved endoscopic improvement, 42% achieved histologic remission, and 24% achieved mucosal healing that further increased to 48%, 48%, and 39%, respectively, by OLE Week 94 (Figure 1A). In NRI analysis, the following patient proportions were observed at OLE Weeks 46 and 94: 18% and 19% (endoscopic improvement), 22% and 14% (histologic remission), and 13% and 11% (mucosal healing) (Figure 1B). Data were generally similar in Cohorts 1 and 2.

Conclusion
Delayed responders to ozanimod achieved and maintained mucosal healing over 2 years of continuous ozanimod treatment. Ozanimod treatment resulted in the healing of intestinal mucosal lesions, even in patients with moderate to severe disease who may have an initial delayed response to ozanimod.
P719 Symptomatic improvement and long-term stability of ulcerative colitis symptoms over 3 years of ozanimod treatment
Authors: Danese S , Abreu M T , Afzali A , Canavan J B , Jain A , Wu H , Petersen A , Panaccione R , Wolf D C 
Published: January 2023

Abstract

Background
The phase 3 True North (TN) study demonstrated the efficacy and safety of ozanimod over 52 weeks in patients (pts) with moderately to severely active ulcerative colitis (UC). Pts completing 52 weeks of TN were eligible for the ongoing TN open-label extension (OLE) assessing the long-term efficacy and safety of ozanimod. Presented here is the interim analysis of the TN OLE focused on the symptomatic efficacy of ozanimod in pts with approximately 3 years of continuous ozanimod treatment.

Methods
Pts who achieved clinical response after receiving 52 weeks of continuous ozanimod during TN and subsequently entered the TN OLE were evaluated (data cutoff: 10 January 2022, at which point the OLE Week 94 disposition was available for pts). Patient-reported (rectal bleeding subscore [RBS] and stool frequency subscore [SFS]) and clinician-reported (Physician’s Global Assessment) symptomatic outcomes were determined. Symptomatic clinical response (partial Mayo score [PMS] ≥1 point and ≥30% reduction in PMS with ≥1-point decrease in RBS or absolute RBS of ≤1) and symptomatic clinical remission (RBS=0 and SFS ≤1 [and decrease of ≥1 point from baseline SFS]) were evaluated at OLE Week 5 through OLE Week 94 (146 weeks of continuous ozanimod treatment) using observed case (OC) and nonresponder imputation (NRI) analyses. PMS, RBS, and SFS were assessed from TN baseline to OLE Week 94.

Results
In all, 131 pts entered the OLE after achieving clinical response following 52 weeks of continuous ozanimod during TN. At data cutoff, 87.0% completed OLE Week 46 (98 weeks of continuous ozanimod) and 71.8% completed OLE Week 94 (146 weeks of continuous ozanimod). Pts had a mean age of 44 years and 52% were female. Most (68%) had left-sided UC disease, 24% had concomitant corticosteroid use at TN baseline, and 32% had prior exposure to tumor necrosis factor inhibitors. Symptomatic clinical response and symptomatic clinical remission were observed in 100.0% (Figure 1A) and 84.4% (Figure 2A) of pts, respectively, at OLE Week 5 in the OC analysis (93.1% [Figure 1B] and 78.6% [Figure 2B] in the NRI analysis). Rates of symptomatic clinical response and symptomatic clinical remission were maintained through OLE Week 94 in the OC analysis and decreased slightly over time in the NRI analysis. Reductions in mean PMS from baseline were observed during TN and sustained through OLE Week 94. Reductions from TN baseline in RBS (Figure 3) and SFS (Figure 4) were also observed through OLE Week 94.

Conclusion
This interim analysis of the TN OLE focusing on symptomatic endpoints found that most pts who achieved clinical response after 1 year of ozanimod sustained symptom control for another 2 years.
P720 Drug survival of first-line biologics in inflammatory bowel disease: large single-centre experience from UR-CARE
Authors: Hanzel J , Supovec E , Smrekar N , Koželj M , Kurent T , Štabuc B , Novak G , Drobne D ,   SING (Slovenian National IBD Study Group)
Published: January 2023

Abstract

Background
The expanding therapeutic armamentarium for inflammatory bowel disease (IBD) has led to uncertainty about the optimal first-line biological therapy for a given patient. Given the paucity of dedicated head-to-head trials, treatment decisions can be supported by network meta-analyses or real-world data. Our aim was to assess the drug survival of first-line biologics by drug class (anti-tumour necrosis factor [TNF] agents, anti-integrin, anti-interleukin [IL]-12/23) and identify potential predictors for prolonged drug survival in our cohort of IBD patients, supported by the United Registries for Clinical Assessment and Research (UR-CARE).

Methods
We prospectively included all adult patients with IBD treated with biological drugs and at least one follow-up visit between October 2021 and August 2022 at our tertiary referral centre. Patient data were collected retrospectively from records and included demographics, disease characteristics and drug survival. Data were collected in UR-CARE with data lock on August 1, 2022. Cox regression was used to assess the association of patient and disease characteristics with drug survival of first-line biologic drugs by drug class.

Results
We included 1047 adult patients with IBD (644 Crohn’s disease [CD], 403 ulcerative colitis [UC]) (Table 1). Among TNF antagonists, adalimumab was most frequently used in CD (280/644, 43.5%; infliximab: 241/644, 37.4%), infliximab was most frequently used in UC (169/403, 41.9%; adalimumab: 55/403, 13.6%; golimumab: 52/403, 12.9%). Unadjusted median drug survival of the first-line biologic did not differ by medication class in CD, but was significantly longer for vedolizumab than for anti-TNF agents in UC (hazard ratio [HR] for discontinuation 0.585, 95% confidence interval [CI] 0.41–0.84; P = 0.003) (Table 2). Disease duration and extent were not associated with drug survival. In CD, isolated ileal disease was associated with longer drug survival (HR 0.83, 95% CI 0.70–0.99; P = 0.04). Findings for both CD and UC were consistent in a sensitivity analysis of patients (CD 228, UC 202) started on biologics after January 1, 2019 when all three drug classes could be prescribed first line without limitations.

Conclusion
In our cohort of 1047 patients with IBD, the drug survival of first-line biologics was comparable regardless of drug class in CD. In UC, first-line vedolizumab was associated with longer drug survival. Disease location and duration did not impact drug survival.
P731 Effect on direct and indirect costs of switching Inflammatory Bowel Disease patients from intravenous to subcutaneous infliximab (CT-P13)
Authors: Carbery I , Broglio G , Clark T , Greer D , Alakkari A , Selinger C P 
Published: January 2023

Abstract

Background
Infliximab has transformed the management of Inflammatory Bowel Disease (IBD) however it has a significant cost burden. Additionally, demand on our IBD day case infusion unit has tripled in the last 7 years leading to long delays in treatment initiation. Switching patients from intravenous (IV) to subcutaneous (SC) infliximab reduces the demand on infusion units and offers patients more flexibility. We aim to compare the real-life direct (drug price and administration costs) and indirect costs (travel costs and time lost to work for patients) associated with switching patients from IV to SC CT-P13, an infliximab biosimilar, in a tertiary UK IBD centre.

Methods
We analysed data from all adult IBD patients at Leeds Teaching Hospitals Trust who had been identified as eligible to switch from IV to SC CT-P13. All patients were on a standard dosing regimen (5mg/kg 8 weekly) and were invited to switch via a letter from the IBD lead clinician. Patients were classified as IV or SC based on their decision to switch within 3 months. Figure one demonstrates how direct and indirect costs were calculated. We then compared the calculated annual costs by intention-to-treat (i.e. if all patients had switched from IV to SC) and as-treated (comparing all on IV pre-switch to some on IV and some SC post switch).

Results
169 patients were identified as eligible to switch to SC CT-P13, 98 (58%) switched within 3 months. One patient was excluded as they had subsequently moved out of area. Prior to switching, total annual IV cost for 168 patients was calculated as £689,507.04 (direct = £653,671.20, indirect = £35,835.84). In the as-treated analysis after the switch, IV cost for 70 patients was £285,490.02 (direct = £272,363, indirect = £13,127.02) and SC cost for 98 patients was £389,432.81 (direct = £382,200, indirect = £7,232.81) giving a total annual cost for 168 patients of £674,922.83. In this analysis, after a proportion of patients switched to SC CT-P13, annual direct costs to the health service were £891.80 more per year, however indirect costs or cost to the patient were lower resulting in a lower total spend. See figure 2 for a breakdown of direct and indirect costs.

Conclusion
Our real-world analysis demonstrates that a switch from IV to SC CT-P13 is broadly cost neutral to the health service. Whilst the SC option has higher drug costs, a switch to SC allows for more efficient running of IV induction therapies by reducing demand on the infusion unit and reduces costs to the patient in terms of travel, parking and potential loss of working hours.
P754 Beyond Paneth cell metaplasia: Small intestinal metaplasia of the sigmoid colon in patients with Inflammatory Bowel Disease
Authors: Koehne de Gonzalez A , del Portillo A 
Published: January 2023

Abstract

Background
Paneth cells are normally found in the small intestine, and when found in the left colon, they represent Paneth cell metaplasia (PCM). This finding indicates a chronic inflammatory state and is seen in some patients with inflammatory bowel disease (IBD). However, small intestinal differentiation beyond PCM has not been reported. We report a broader range of small intestinal metaplasia in the sigmoid colon in patients with IBD, including loss of expression of the colonic marker SATB2, presence of a brush border and villous architecture, and gain of expression of the small intestinal markers CD10 and HepPar1. We perform a pilot study to investigate the frequency, staining patterns, and clinical correlates of this metaplastic phenomenon.

Methods
A database search for sigmoid biopsies for the words “Paneth cell metaplasia” from 2010-2018 returned 862 cases. The 100 most recent consecutive cases with a history of IBD were reviewed and confirmed to have PCM in non-neoplastic sigmoid biopsies in 96 cases. Of these, 94 blocks from 91 patients (age range 7-88, median age 43, 53% male, 74% ulcerative colitis (UC), 23% Crohn’s disease, 3% IBD) were on file. IHC staining for HepPar1, CD10, and SATB2 was performed on each case.

Results
Of the 94 cases, 13 (13.8%) had HepPar1 positivity, 5 (5.3%) had CD10 positivity, 2 (2.1%) had SATB2 loss, 1 (1.1%) had reduced SATB2 expression, and 2 showed villous architectural features. Extensive positivity for CD10 was seen in 3 (3.2%) cases, and one case showed all 3 IHC markers of small intestinal metaplasia. Of the CD10+ cases, there were 3 UC, 1 Crohn's, and 1 IBD (Table 1). The index case (sigmoid colon) showed a brush border (Figure 1) and intermixed small (Figure 2, red arrows) and large bowel (Figure 2, black arrows) differentiation.

Conclusion
A range of small intestinal differentiation may be seen in the left colon in IBD patients, including PCM, the presence of brush border, villous architecture, CD10 and HepPar1 positivity, and reduced or lost SATB2 expression. Since the frequency of HepPar1+&gt;CD10+&gt;SATB2 loss, there may be a sequence of small intestinal metaplasia, with PCM occurring first, and loss of SATB2 reflecting more advanced metaplasia. Previous studies suggest that SATB2 and HepPar1 are helpful in distinguishing between inflamed ileal pouch vs rectal cuff in patients with IBD, and that CD10 could be used to distinguish between ileum and colon in anastomoses, but our data refute these claims. SATB2 loss has been described in dysplastic lesions in patients with IBD, and thus these markers could serve as biomarkers of progression to dysplasia.
P763 Role of quality of life in patients with Inflammatory Bowel Disease
Authors: Kaltenbach T , Schulte L A , Kranzeder A , Klaus J , Sularz M 
Published: January 2023

Abstract

Background
Complaints like diarrhea, incontinence, frequent hospitalizations etc. can affect quality of life (QoL) in IBD patients (IBDP). QoL plays a central role in patient care. We investigated in which aspects patients with high quality of life (HQL) differ from patients with low quality of life (LQL).

Methods
This study was based on an anonymous questionnaire. IBDP of specialized outpatient clinics in three hospitals in Germany participated. Using questions about IBD/ lifestyle, disease activity (Harvey-Bradshaw-Index (HBI)/ Partial Mayo Score (PMS)) and psychological tests (Hospital Anxiety and Depression Scale (HADS), State-Trait-Anxiety Inventory (STAI), Social Support Questionnaire (F-SozU), Complaints-list (BL-R'), NEO-Five-Factor Inventory (NEO-FFI), differences between IBDP with HQL (SIBDQ≥50) vs. LQL (SIBDQ&lt;50) were investigated.

Results
Overall, 103 (36%) patients had LQL and 183 (64%) had HQL. In general, LQL patients are more likely to be female (p=0.013), to worry about course of disease (p&lt;0.001), to engage in irregular or no exercise (p=0.044), to have anal discomfort (p&lt;0.001), to have extraintestinal symptoms, such as joint (p&lt;0.001) or eye (p=0.004) disorders, and they are more likely to be taking cortisone (p&lt;0.001).Furthermore LQL patients have higher number of general complaints (p&lt;0.001) and are more often in active state of disease (HBI/CAI) (p&lt;0.001 / p&lt;0.001) or have higher disease activity than HQL patients. LQL patients rated the effect of their current medication poorer (p&lt;0.001).Investigation of psychological parameters showed that LQL patients had higher scores on depression scale (p&lt;0.001) and anxiety scale (p&lt;0.001) of HADS-D. Both trait anxiety (p&lt;0.001) and state anxiety (p&lt;0.001) of STAI are significantly higher in LQL patients and they experience less social support (p=0.011). LQL patients are particularly likely to exhibit the personality trait neuroticism (p&lt;0.001) in NEO-FFI, whereas HQL patients exhibit extraversion (p&lt;0.001) and conscientiousness (p=0.007).

Conclusion
IBD patients with LQL differ from IBD patients with HQL in several factors. Inter alia, concerning disease in terms of higher disease activity, poorer effect of medication and additional extraintestinal manifestations. But also in terms of psychological factors such as anxiousness, depressiveness, and regarding extend of social support. By paying attention to and working on these factors affecting QOL physician and IBD-patient may improve this very important therapeutic goal together.