bluuebunny/crossref_metadata_2025_split huggingface dataset:
P480 Ustekinumab Dose Intensification Is Effective in One-Third of Asian Inflammatory Bowel Disease Patients, Results From A Tertiary Inflammatory Bowel Disease Centre
Authors: Lim C T , Tay S W , Lim G H , Salazar E , Ong W C , Chan W P W , Tan M T K 
Published: January 2023

Abstract

Background
Ustekinumab (UST) is an effective biologic for treatment of Inflammatory Bowel Disease (IBD). However, some patients treated with UST have suboptimal clinical response with standard induction and maintenance doses. In some patients, strategies such as dose intensification (DI) and reinduction have been used to improve response. The aims of this study are to identify factors associated with DI for our IBD cohort and also effectiveness of reinduction during DI.

Methods
This was a retrospective cohort study on patients with Crohn’s disease (CD) and ulcerative colitis (UC) who received UST from September 2017 to October 2022 in a tertiary center. Patients were identified from a prospectively maintained IBD registry. Patient’s demographics, biochemical profile, disease phenotype, UST intervals and previous use of biologics were retrieved. Statistical analysis was performed to identify factors which are predictive of UST DI and effectiveness of UST DI.

Results
A total of 63 patients with IBD on UST were identified, with most being bio-experienced (76.2%). Forty two patients (34 CD, 8 UC) underwent UST DI to either 6-weekly (n=19, 45.2%) or 4-weekly (n=23, 35.9%). The median duration of UST treatment is 108.0 weeks (IQR 44.7-185.9) while the median time to intensification was 31.1 weeks (IQR 17.8-65.7). Presence of perianal disease in CD (HR 4.9; 1.47 – 16.4) was associated with DI. However, prior usage of biologics (HR 1.61; 0.80 - 3.24) and usage of steroids during induction (HR 1.85; 0.69 – 4.91) were not significant factors for DI.
After DI, there were 14 (33.3%) patients who achieved treatment end points (corticosteroid-free clinical remission, biochemical remission, endoscopic healing (for UC) or transmural healing (for CD) by week 52. In patients who had UST DI, UST re-induction was given to 13 (10 CD, 3 UC) and 4 achieved treatment endpoints but this was not statistically significant (p=0.99). There were 26 patients who failed to achieved end point at week 52 of which 8 patients were continued on UST at dose intensified regime while 11 patients were switched to other biologics.

Conclusion
Two third of IBD patients undergo DI while on UST treatment and the median time to DI is about 6 months after induction. CD patients with perianal disease is more likely to undergo DI. One third of dose intensified patients achieved remission at week 52 while reinduction of UST during DI did not improve outcome for patients.
P482 The experiences of people with IBD and comorbid anxiety or depression and their views on an online intervention for people with long term conditions (COMPASS): A qualitative framework analysis
Authors: Harston E 
Published: January 2023

Abstract

Background
IBD has high levels of comorbid mental health conditions, with anxiety and depression being more common in patients with IBD than the general population. Despite this, few studies have qualitatively explored the experience of IBD and comorbid anxiety and depression together, and little is known about how the population would experience a long-term condition (LTC) specific psychological intervention. An online, digital, transdiagnostic therapy for LTCs (COMPASS) has been trialled in a range of health conditions, and the current study aims to qualitatively evaluate the experience of COMPASS from the perspective of IBD patients.

Methods
n=22 adults with IBD and comorbid anxiety/depression that is felt to be related or part-related to their IBD who participated in the intervention arm of the COMPASS parallel-group randomised control trial were interviewed. The interviews covered both their experience of living with IBD and comorbid anxiety or depression, in addition to their experience of the COMPASS intervention. The data was analysed using framework analysis.

Results
'Embarrassment, shame and stigma' was found to be an overarching theme from the experience of adults living with IBD and comorbid anxiety or depression. This theme influenced the core themes of 'isolation', 'identity changes' and the 'perceived lack of control'. The experience of COMPASS was qualitatively reported as being beneficial, in addition to reducing scores on the PHQ-ADS from baseline (M=21.78 SD=9.20) to the end of the intervention (M=11.36, SD=6.05 at 12 weeks). Themes highlighted from the experience of COMPASS included a sense of 'connection and support', 'practical benefits of COMPASS' and 'the empowering process', in addition to highlighting areas of improvement. The themes from these two areas were found to compliment each other and were mapped together to illustrate the potential interaction.

Conclusion
This study highlighted the cyclical, interconnected nature of IBD and anxiety/depression, with participants noting bidirectional influence between their physical and mental health. Participants found the COMPASS intervention to be accessible for people with IBD and felt it addressed the need for psychological support within IBD care. Future research could tailor the COMPASS intervention to further suit the needs of the IBD population, focusing more on IBD-specific anxieties relating to incontinence and toilet access, hypervigilance around physical symptoms and fear of recurrence and progression, as well as doing more to address embarrassment, shame and stigma in this population.
P510 Comparative effectiveness of Ustekinumab against other biologics in Inflammatory Bowel Disease: a propensity score analysis.
Authors: Matos Coelho Bernardo S , Fernandes S , Serrazina J , Rodrigues I , Botto I , Bronze S , Gonçalves A R , Valente A , Santos P M D , Tato Marinho R , Correia L 
Published: January 2023

Abstract

Background
Background: Increasing evidence supports the use of Ustekinumab (USTK) in patients with moderate to severe Crohn’s disease (CD) and Ulcerative colitis (UC). Comparison of USTK against other biologics is still lacking.

Methods
AIMS: to perform a propensity score analysis (PSA) for comparison of USTK against conventional Infliximab (IFX), proactive IFX and vedolizumab in CD and UC

Methods
retrospective study including patients under Ustekinumab (n=71), Vedolizumab (n=98), conventional IFX (n=70) and proactive IFX (n=148). PSA correcting for age, gender, IBD subtype, previous biologic exposure was performed for each comparison. We compared the rates of fecal calprotectin (Fc) remission (&lt;150 µg/g), treatment discontinuation, hospitalization, and surgery at 52 weeks of treatment. Primary non-responders were excluded.

Results
Results: after PSP, ustekinumab showed lower rates of treatment discontinuation compared to vedolizumab (7.4% vs 37%, P&lt; 0.001) with a trend for higher rates of Fc remission (42.6% vs 25.9%, P=0.104). Ustekinumab showed higher rates of Fc remission compared to conventional IFX (53.8% vs 19.2%, P= 0.020) with a trend for lower rates of hospitalization (7.7% vs 30.8%, P= 0.075). There were no differences between ustekinumab and proactive IFX in any of the clinical outcomes.

Conclusion
Conclusion: taking into account the potential limitations of PSP, our results suggest that ustekinumab may be as effective as proactive IFX with some benefits compared to vedolizumab and conventional IFX.
P514 Serum levels of Klotho in inflammatory bowel disease: an exploratory study
Authors: Hernandez-Camba A , Rodriguez-Jimenez J , Carrillo Palau M , Ramos Lopez L , Perez-Mendez L , Martin-Nuñez E , Alonso I , Vela M , Hernandez Alverez Builla N , Arranz L , Hernandez A , Ferraz Amaro I , Navarro-Gonzalez J F 
Published: January 2023

Abstract

Background
Alpha klotho (α-Klotho) is an anti-aging protein recognized as a humoral factor with anti-oxidant and anti-inflammatory effects, showing a bidirectional relationship with inflammation, a main pathophysiologic factor in atherosclerosis. A decrease in Klotho has been associated to cardiovascular disease (CVD), but no previous studies have investigated the relationship between inflammatory bowel disease (IBD), a risk factor for CVD, and Klotho levels. Therefore, we assessed if the serum levels of Klotho differ between patients with IBD and controls, and how this protein is related to the clinical and laboratory characteristics of the disease, subclinical atherosclerosis and metabolic risk factors.

Methods
Cross-sectional multicentric study that included 251 individuals: 191 IBD patients and 60 healthy controls was conducted. Serum Klotho levels were determined by commercial ELISA immunoassay (IBL International GmbH Laboratories). In the IBD patients disease activity was evaluated using CDAI for Crohn’s disease, partial Mayo (pMayo) for ulcerative colitis, specific laboratory parameters, determination of the Systematic Coronary Risk Evaluation (SCORE), and the presence of subclinical atherosclerosis was assessed using carotid ultrasound for identifying carotid plaque and measurement of carotid intima-media thickness.

Results
Serum Klotho levels were significantly higher in the IBD group: 734.31 pg/ml vs. 484.17 pg/ml (p&lt;0.001) compared with controls. In the IBD group, no significant differences in the serum Klotho levels were found between the type of IBD (p=0.911), time from diagnosis (p=0.126), disease activity: CDAI (p=0.277), pMayo (p=0.916), type of treatment (0.76), the presence of plaque (p=0.101) or the intima media thickness (p=0.429). However, a significant inverse correlation between serum Klotho and the SCORE was observed in IBD patients: r = -0.176 (p= 0.014) (figure 1)

Conclusion
Patients with IBD had higher Klotho levels than healthy controls, with an inverse and significant relationship with the SCORE in the IBD patients. Further studies are necessary to clarify the role of Klotho in IBD.
P516 Humoral immune responses to SARS-CoV-2 vaccines in an ozanimod open-label extension study
Authors: Caldera F , Maddux R , Ungaro R , Kaur A , Brown E , Hu S , Sheffield J K , Silva D , Harris S , Cree B A C 
Published: January 2023

Abstract

Background
Ozanimod, an oral sphingosine 1-phosphate receptor modulator, is approved in the European Union and United States for the treatment of moderately to severely active ulcerative colitis (UC) and relapsing multiple sclerosis (RMS). A previous analysis of data from UC and multiple sclerosis (MS) open-label extension (OLE) studies showed that most patients with confirmed coronavirus infection (COVID-19) had nonserious infections, recovered, and did not require ozanimod discontinuation. Some immunomodulators and biologics may attenuate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine response; therefore, this analysis evaluated humoral immune responses and predictors of response to SARS-CoV-2 vaccination in patients with RMS treated with ozanimod.

Methods
RMS participants who completed a phase 1–3 ozanimod trial could enter an OLE trial (DAYBREAK; NCT02576717) of ozanimod 0.92 mg/d. This analysis (January 2020‒October 2021) included DAYBREAK participants receiving mRNA or non-mRNA SARS-CoV-2 vaccines (1–2 doses, vaccine-dependent) with no evidence of recent infection (ie, nucleocapsid antibody negative). Receptor binding domain (RBD) antibody titers were analysed (Elecsys Anti-SARS-CoV-2 assay; Roche Diagnostics, Basel, Switzerland) prevaccination, after 1 dose, and &lt;4, 4–8, 8–12, and &gt;12 weeks after full vaccination. Fisher’s exact tests and regression models determined association with seroconversion and log2 antibody levels.

Results
Demographics were similar between the mRNA and non-mRNA vaccine recipients (Table). Seroconversion (≥0.8 U/mL spike RBD antibody) occurred in 100% (80/80) of fully vaccinated mRNA recipients and 62% (18/29) of fully vaccinated non-mRNA vaccine recipients. Higher spike RBD antibody levels were seen with mRNA (grand mean: 512.6 U/mL, range: 1.3–4572.0) vs non-mRNA (grand mean: 39.3 U/mL, range: 0.4–368.5) vaccines at all time points studied. Vaccination with a non-mRNA vaccine predicted lower antibody levels (beta: –5.90 [95% CI: –6.99 to –4.82]; P&lt;0.0001) and less seroconversion (Fisher’s exact: P&lt;0.0001), whereas age, sex, body mass index, and absolute lymphocyte count (ALC) did not.

Conclusion
Participants receiving ozanimod developed humoral immune response to SARS-CoV-2 vaccines, with 100% seroconversion after mRNA vaccination; this was independent of demographic characteristics and ALC levels at time of vaccination. However, some participants developed lower antibody concentrations and may benefit from booster doses. These findings provide important information for physicians managing ozanimod-treated patients with UC or MS.
P520 Thromboembolic and major adverse cardiovascular events among patients in the filgotinib clinical trial programme
Authors: van der Woude J , Schreiber S , Peyrin-Biroulet L , Szekanecz Z , Choy E H , Stiers P J , Van Hoek P , Van Beneden K , de Haas A , Rudolph C , ten Cate H 
Published: January 2023

Abstract

Background
The once-daily, oral, Janus kinase 1 preferential inhibitor filgotinib (FIL) is approved for the treatment of moderately to severely active rheumatoid arthritis (RA) and ulcerative colitis (UC) in the UK, the EU and Japan.1 To further understand the safety profile of FIL across indications, we evaluated the risk of major adverse cardiovascular events (MACEs) and venous thromboembolic events (VTEs) in patients treated with FIL 200 mg (FIL200) or FIL 100 mg (FIL100).

Methods
An integrated analysis was conducted with RA data from five phase 2/3 trials and two long-term extension (LTE) trials of FIL, and UC data from two phase 2/3 trials and one LTE trial of FIL (herein termed ‘overall’ data). Subgroup analyses by age and cardiovascular (CV) risk factors (excluding age) were conducted. Real-world data were extracted from a systematic literature review. Exposure-adjusted incidence rates (EAIRs) or incidence rates per 100 patient-years of exposure and 95% confidence intervals (CIs) were estimated for MACEs and VTEs. For clinical trial data, MACEs and VTEs included positively adjudicated events only.

Results
In pooled data, baseline characteristics were generally similar across treatment arms for RA and UC (Tables 1 and 2). In the RA data, MACE EAIRs were 0.29 and 0.41 for the overall FIL200 and FIL100 arms, respectively (Figure 1). MACE IRs were 0.45–0.77 for the general RA population. Higher MACE EAIRs were reported in the subgroup of patients with RA aged ≥65 years vs &lt;65 years. In the RA subgroup with CV risk, MACE EAIRs were 0.53 for FIL200 and 0.64 for FIL100. VTE rates were 0.19 for both FIL200 and FIL100 overall in patients with RA, and 0.32–0.44 for the general RA population. Numerically higher VTE EAIRs with overlapping CIs were seen in patients with RA aged ≥65 years vs &lt;65 years, and in those with vs without CV risk.
In the UC data, MACE rates were 0.29, 0.35 and 0.87 in the overall FIL200 and FIL100 arms and in the general UC population, respectively (Figure 2). VTE rates were 0.08, 0.18 and 0.39 in the overall FIL200 and FIL100 arms and in the general UC population, respectively. For both MACE and VTE EAIRs, wide CIs were reported in patients with UC aged ≥65 years and in those with CV risk, owing to low numbers of events and/or patients in these subgroups.

Conclusion
No association was identified between FIL200 treatment and an increased risk of MACEs or VTEs compared with the general RA or UC population. Patients aged ≥65 years or with CV risk had slightly higher rates of MACEs and VTEs than those in other subgroups; however, overlapping CIs suggested no real difference. Further work should examine real-world data from FIL-treated patients and longer follow-up.
1. https://www.ema.europa.eu/en/medicines/human/EPAR/jyseleca
P540 The opinions and needs of patients living with refractory ulcerative proctitis, and the health care professionals who care for them; A Delphi consensus survey
Authors: Radford S , Kyriacou M , Moran G 
Published: January 2023

Abstract

Background
Refractory ulcerative proctitis presents a huge clinical challenge not only for the patients living with this chronic, progressive form of inflammatory bowel disease (IBD) but also for the professionals who care for them. Currently, there is limited research and evidence-based guidance on this condition, resulting in the large majority of patients living with the symptomatic burden of disease and reduced quality of life. The aim of this study was to establish a consensus on the thoughts and opinions surrounding refractory proctitis disease burden and management.

Methods
A three-round Delphi consensus survey was conducted among patients living with refractory proctitis and the healthcare experts with knowledge on this disease. A brainstorming stage which involved a focus group where the participants came up with an initial list of fourteen statements was completed. Following this, there were three rounds of Delphi surveys in which the participants were asked to rank the statements in order of importance alongside providing any additional comments or clarifications. Calculation of mean scores, analysis of comments and revision of statements was performed by the research team after each survey round. Statements meeting the pre-defined consensual mean score of at least 7 out of 10 were included in the final list of statements.

Results
In total, fourteen statements were suggested by the focus group at the initial creation stage. Based on these suggestions, the statements were presented to the participants and following completion of three Delphi survey rounds, all fourteen statements reached consensus following appropriate revision. The total response rate for the third Delphi round was 100% (21 out of 21 participants). Statements consider treatment options, areas for further research and clinical decision making factors.

Conclusion
This is the first study of its kind to provide a list of consensual statements on the opinions and needs of those living with refractory ulcerative proctitis. We established consensus on the thoughts and opinions surrounding refractory proctitis from both the experts who manage this disease and the patients living with it. These statements represent the first step towards providing more clinical research date and ultimately guidance aimed at this specific patient group.
P542 Short term efficacy, safety and thromboembolic risk of tofacitinib in moderate to severe Ulcerative Colitis
Authors: Cingolani L , Barberio B , Zelante A , Ribaldone D , Testa G , Bertani L , Buda A , Zingone F , Savarino E V 
Published: January 2023

Abstract

Background
Tofacitinib is a small oral molecule approved to treat moderate to severe ulcerative colitis (UC), which effectiveness and safety is still poorly known in UC patients. Recent concerns have been raised regarding its administration at high dosage in UC patients because of a likely higher incidence of drug-related thromboembolic events.

Methods
The aim of this study was to evaluate short-term effectiveness and safety of tofacitinib. As secondary aim, we analyzed the state of blood coagulation at baseline in order to evaluate whether it could predict thromboembolic events in relation to demographic, clinical and biochemical characteristics.
A multicenter, retrospective, observational study was conducted, including patients from March 2021 to October 2022; a prospective single-centre sub-study concerning the thromboembolic risk was performed. At baseline, demographic, clinical, biochemical and endoscopic data, and previous therapies were recorded; quality of life was evaluated through IBD-Disability Index (IBD-DI) and Pittsburgh Sleep Quality Index (PSQI). In a subgroup of patients, a thrombophilic screening and a Rotational Thromboelastometry (ROTEM) were performed at baseline. Patients were reassessed after 8 weeks, 6 months and 1 year, evaluating for each timepoint clinical and biochemical characteristics, IBD-DI and PSQI, and reporting adverse events (AEs) and discontinuation of therapy. The following clinical outcomes were considered: benefit, steroid-free remission and response.

Results
44 adult patients were enrolled. The overall clinical benefit was 54.2%, summing up 45.8% of subjects in steroid-free clinical remission and 8.3% with clinical response; significant short-term improvement of IBD-DI and PSQI scores (p=0.000 in both cases after 6 months of therapy) was observed. Patients previously treated with less than two different biological therapies had major rates of clinical benefit at 6 months (p=0.045). Ten AEs, including one venous thrombosis, were reported; global therapy failure rate was 31.4%. In the subgroup with additional data on coagulation (17 patients), we did not observe significant alterations of coagulating factors or inhibitors, nor of ROTEM parameters, although some coagulation features were significantly increased in obese patients (FII, p=0.030; FIX, p=0.000; FX, p=0.000; fibrinogen blood levels, p=0.030) and subjects older than 40 years old (FVIII, p=0.020). We did not find significant correlation with gender, smoking habit, concomitant steroid therapy, CRP, fecal calprotectin.

Conclusion
Our data confirm literature ones on effectiveness and safety of tofacitinib in UC patients, while the risk of thrombosis needs to be better evaluated in larger longitudinal studies.