bluuebunny/crossref_metadata_2025_split huggingface dataset:
P711 Decreased steroid exposure and disease-related hospitalizations in patients with newly diagnosed inflammatory bowel disease in the era of newer biologic agents – A multi-centre experience in Singapore
Authors: Yeo G D D , Qui M , Pak W C W , Tan C K , Tay S W , Lim C T T , Tan T K M , Ong W C , Lim T G , Ng Y T V , Wong S Y A , Salazar E 
Published: January 2023

Abstract

Background
The expanding therapeutic armamentarium for inflammatory bowel disease (IBD) has drastically improved the clinical outcomes of patients with both Crohn’s Disease (CD), and Ulcerative Colitis (UC). However, data of clinical outcomes in newly diagnosed IBD in the era of biologics in recent decades remains limited. We aim to compare the clinical outcomes of newly diagnosed IBD patients in Singapore between the era of conventional biologics (originator Anti-TNF) with those diagnosed during the era of newer biologics over a 14-year period.

Methods
This is a multi-centre retrospective observational cohort study. Baseline demographics and treatment histories were obtained from the registries of two tertiary centres in Singapore. Clinical outcomes such as systemic steroid use, IBD-related hospitalizations and IBD-related surgeries were obtained. Anti-TNF, anti-integrin, anti-IL-12/23 and biosimilars were approved for IBD management in 2006, 2016 and 2018 respectively in Singapore. Patients diagnosed with IBD from 2006 to 2019 were included and further subdivided into two cohorts: Pre-2013 (from 2006 to 2012) and post-2013 (from 2013-2019).

Results
During the study period, 725 patients [CD: 331 (46%), UC: 394 (54%), pre-2013: 291 (40%), post-2013: 434 (60%)] were newly diagnosed with IBD. 625 (86%), 475 (65%), and 241 (33%) patients were exposed to 5-ASA, immunomodulators, and biologics respectively. Compared to the pre-2013 cohort, patients from the post-2013 cohort had less exposure to 5-ASA [277 (95%) vs 348 (80%), p&lt;0.001], and immunomodulators [219 (75.3%) vs 256 (58.9%), p&lt; 0.001].
In patients who were started on biologics, the overall median time from diagnosis to biologic initiation was 2.8 (1.1 – 6.3) years. 196 (81.3%) patients started on biologics were initiated from 2016 onwards. Median time to biologic initiation was shorter for the post-2013 cohort, compared to the pre-2013 cohort. (1.4 (0.5 – 2.8) vs 6.9 (4.3 – 9.1) years, p&lt;0.001). This was observed in both patients with CD [1.2 (0.3 – 2.4) vs 6.9 (4.7 – 8.6) years, p&lt;0.001] and UC [2.3 (0.9 – 3.4) vs 7.1 (3.8 – 9.2) years, p&lt;0.001].
Steroid exposure and IBD-related hospitalizations were higher in the pre-2013 cohort [(OR 1.7 (95% 1.2 – 2.5, p=0.001) and (OR 1.6 (95% 1.2 – 2.3, p=0.003) respectively], but no difference was found in the number of IBD-related surgeries between both cohorts (OR -0.02 (95% -0.4 – 0.4, p=0.934).

Conclusion
Paralleled with earlier, and increased initiation of biologic agents, there is significant reduction of steroid exposure and IBD-related hospitalizations in patients newly diagnosed with IBD in the era of newer biologics, despite a reduction in 5-ASA and immunomodulator exposure.
P713 Proactive therapeutic infliximab monitoring during induction phase in inflammatory bowel disease
Authors: Gonzalez Vivo M , Carballo Martinez N , Padulles Zamora N , Colominas Gonzalez E , Murciano Gonzalo F , Abril Rodriguez L , Marquez-Mosquera L 
Published: January 2023

Abstract

Background
Therapeutic drug monitoring (TDM) of infliximab (IFX) in patients with Crohn’s disease (CD) and ulcerative colitis (UC) is increasingly used in clinical routine, although proactive TDM is still controversial. Nevertheless, disease activity and drug clearance are higher at the induction phase leading to an increased risk of inadequate drug exposure and treatment failure.
The aim of the study was to evaluate the efficacy of the implementation of an early proactive TDM strategy, comparing clinical remission (CR) and biochemical remission (BR) at week 14 and 52, and endoscopic improvement (EI) between two groups.

Methods
Retrospective cohort study conducted in an Inflammatory Bowel Disease (IBD) unit of a tertiary care hospital. Biologic-naïve patients diagnosed of CD or UC who initiated IFX from 2019 to 2021 (p-TDM group) and from 2016 to 2019 (no-TDM group) were included.
In the p-TDM group, proactive IFX trough levels and antidrug antibodies were measured since week 2 and dose adjustment since week 6 was performed using a previously validated population pharmacokinetic model (Fasanmade et al. Clinical Therapeutics 2011).
In the no-TDM group, dose escalation was performed considering symptoms, blood, or stool results.
CR was defined as Harvey-Bradshaw Index &lt;5 in CD and partial Mayo clinic score &lt;3 in UC. BR was stablished as fecal calprotectin (FCP) &lt;150 mcg/g or c-reactive protein &lt;0.5 mg/dL. EI was defined as lack of ulcerations in CD and Mayo endoscopic score 0-1 in UC. A combined variable to evaluate objective remission (OR) at week 52 was defined as: FCP &lt;150 mcg/g or EI in UC, and EI or radiologic improvement (MRI) in CD.
Moreover, surgery, hospitalization and treatment discontinuation rates were compared between both groups.

Results
30 patients were included in each group: 13 UC, 16 CD and 1 IBD unclassified. There were no statistical differences in baseline characteristic between groups (table 1).

Outcomes at week 14 and 52 are shown in table 2.

At week 14, CR rate was significantly higher in p-TDM than in no-TDM (86.7% vs 56.7%, p=0.01). Although BR rate at week 14 was numerically higher in p-TDM, it did not achieve statistical significance (61.1% in p-TDM vs 50.0% in no-TDM, p=0.59). However, limitations in blood and stool collection were considerable at this timepoint.
During first year, hospitalizations tend to be fewer in p-TDM group. There were no statistically differences in CR and BR or in EI between groups at week 52. Although OR rate was higher in p-TDM than in no-TDM, it did not reach statistical significance (60.9% vs 33.3%, p=0.06).

Conclusion
Proactive TDM during induction phase, especially in naïve patients, could be a useful tool to obtain optimal IFX trough levels and to classify correctly primary failure.
P714 Mucosal healing in CD with vedolizumab versus other biologics: endoscopic outcomes during long-term routine care in a multinational observational study
Authors: Siegel C , Sebastian S , Siegmund B , Zhou J , Jones S , Adsul S , Louis E 
Published: January 2023

Abstract

Background
Mucosal healing (MH) is considered an important treatment target for patients (pts) with moderate to severe Crohn’s disease (CD). The aim of this analysis was to evaluate rates of MH achieved during treatment with vedolizumab (VDZ) or other biologics in pts with CD who underwent endoscopic assessments during routine clinical practice in a long-term observational study across a number of multinational study centres.

Methods
Data were analysed from a long-term prospective, multicentre, post-authorization safety study (PASS; NCT02674308, EUPAS6469) cohort of pts with CD. This secondary outcome was evaluated in pts initiating treatment with VDZ or other biologics, including infliximab, adalimumab and ustekinumab. Pts received treatment under routine standard of care with clinical decisions at the discretion of treating physicians, treatment could be modified or changed without the need to withdraw from the study. For pts with available endoscopy data, rates of MH (simple endoscopy score [SES-CD] ≤ 2) at baseline and 12-months were compared in biologic-naïve or biologic-experienced pts treated with VDZ versus other biologics.

Results
MH was analysed in pts with CD who had endoscopic assessment. In those pts who were biologic-naïve and had baseline endoscopy (VDZ n=76, other biologics n=239), MH rates at baseline were 11.8% (9/76) versus 12.1% (29/239), respectively. After 12-months’ treatment, MH rates in biologic-naïve pts who had endoscopy data at month 12 (VDZ n=48, other biologics n=108) were 70.8% (34/48) in VDZ-treated pts versus 60.2% (65/108) in pts treated with other biologics (Table 1). In pts who received biologic treatment prior to study entry (biologic-experienced) and had baseline endoscopy (VDZ n=151, other biologic n=146), MH rates at baseline were 11.9% (18/151) versus 16.4% (24/146), and 51.1% (45/88) versus 31.4% (27/86) after 12 months of treatment in the VDZ and other biologic cohorts, respectively.

Conclusion
These real-world data from a multinational observational study show that VDZ was effective at achieving MH, particularly as a first-line biologic treatment, and also in biologic-experienced pts.
P718 A Phase I Study of Ex Vivo Expanded Allogeneic Bone Marrow Derived Mesenchymal Stem Cells for the Treatment of Pediatric Perianal Fistulizing Crohn’s Disease
Authors: Otero Piñeiro A , Lightner A L , Reese J , Ream J , Nachand D , Adams A , VanDenBossche A , Kurowski J 
Published: January 2023

Abstract

Background
Background: Mesenchymal stem cells have been used for the treatment of perianal Crohn’s fistulizing disease by direction injection. However, no studies to date have included pediatric patients.

Objective
To determine safety and efficacy of mesenchymal stem cells for pediatric perianal fistulizing Crohn’s disease.

Methods
Design: Phase I safety trial

Settings
Tertiary inflammatory bowel disease referral center

Patients
Crohn’s patients aged 13-17 with perianal fistulizing disease.

Intervention
75 million mesenchymal stem cells were administered with a 22G needle by direct injection after curettage and primary closure of the fistula tract. A repeat injection of 75 million mesenchymal stem cells at 3 months was given if complete clinical and radiographic healing were not achieved.

Main outcomes measures
Adverse and serious adverse events at post procedure day 1, week 2, week 6, month 3, month 6 and month 12. Clinical healing, radiographic healing per magnetic resonance imaging, and patient reported outcomes at the same time points.

Results
Results: A total of 7 pediatric patients were enrolled and treated (6 male; median age of 16.7 years). There were no adverse or serious adverse events reported related to investigational product. At six months, 83% had complete clinical and radiographic healing. The perianal Crohn’s disease activity index, Wexner incontinence score, and VanAssche score had all decreased at six months.

Limitations
Single institution and open label.

Conclusion
Bone marrow derived mesenchymal stem cells offer a safe, and likely effective, alternative treatment approach for pediatric perianal fistulizing Crohn’s disease.
P727 Effectiveness and Safety of Vedolizumab in Inflammatory Bowel Disease: A Comprehensive Meta-analysis of Observational Studies
Authors: Macaluso F S , Ventimiglia M , Orlando A 
Published: January 2023

Abstract

Background
Many observational studies on the use of vedolizumab (VDZ) in patients with Crohn’s disease (CD) and ulcerative colitis (UC) have been published in the last few years. We aimed to comprehensively summarize its effectiveness and safety by pooling data only from observational studies.

Methods
PubMed/Medline and Embase were systematically searched for observational studies on patients with CD and UC treated with VDZ through December 2021. The rates of clinical remission and overall adverse events were the primary outcomes. The rates of steroid-free clinical remission, clinical response, mucosal healing, C-reactive protein normalization, loss of response, colectomy, serious adverse events, infections, and malignancies were considered as secondary outcomes.

Results
Eighty-eight studies comprising 25,678 patients (13,663 with CD and 12,015 with UC) met the inclusion criteria. In patients with CD, the pooled estimate rates of clinical remission were 36% at induction and 39% at maintenance. In patients with UC, the pooled estimate rates of clinical remission were 40% at induction and 45% at maintenance. The pooled estimate of incidence rate of adverse events was 34.6 per 100 person-years. At multivariable meta-regression analysis, studies with increased male proportion were independently associated with higher rates of clinical remission and steroid-free clinical remission at both induction and maintenance, and clinical response at maintenance in patients with CD. Studies with increased disease duration were independently associated with higher mucosal healing rates at maintenance in patients with UC.

Conclusion
Observational studies demonstrated extensively the effectiveness of VDZ, with a reassuring safety profile.
P728 Real world evidence for adalimumab biosimilar, MSB 11022, therapy in inflammatory bowel diseases: Adherence analysis
Authors: Cheung S , Truong D 
Published: January 2023

Abstract

Background
Adherence to medication is crucial for maintaining remission in patients with inflammatory bowel diseases (IBD). Patient-support program (PSP) plays a significant role in education for patients on medication adherence. The objective of this project was to analyze the data collected by Fresenius Kabi PSP (KabiCare) in IBD patients population on their adherence to an adalimumab biosimilar, MSB 11022, in real world practice in Canada.

Methods
Patients with IBD enrolled in KabiCare and received at least one dose of adalimumab biosimilar, MSB 11022, were follow-up from Feb 2021 to Nov 2022 in Canada. Medication initiation date and stop date, disease types (Crohn’s disease [CD], and ulcerative colitis [UC]) and patient treatment (categorized by naïve to biologic, or switched from other biologics) were recorded in the database. The stop date was the date when KabiCare was informed that medication was discontinued. The patients continuing medication were censored at the maximal follow-up date of analysis, November 9, 2022. Log-rank tests were used for KM (Kaplan-Meier) plot comparison to examine if there were differences in medication adherence between CD and UC, and between naïve group vs. switch group by disease.

Results
The study sample consisted of 836 patients, 670 (80.0%) of whom had CD, and 266 (31.8%) were in naïve group. KabiCare followed patients for a median time of 291 days (interquartile range: 190-392 days; maximum: 622 days). At 600 days after starting the medicine, the adherence probability was similar for patients with CD and UC (At day-600: 83.4% vs. 82.2%, P=0.26); however, the adherence probability was higher in the switch group compared to naïve group (At day-600: 87.9% vs. 73.5%, P=0.0001). Among patients with CD, the adherence probability was higher with switch group compared to naïve group (At day-600: 88.8% vs. 71.7%, P=0.0001). Among patients with UC, the adherence probably was similar between switch group compared to naïve group (At day-600: 90.5% vs. 76.5%, P=0.11).

Conclusion
The adherence probability of adalimumab biosimilar, MSB 11022, was over 80% 600-day after initiating therapy, regardless of the type of IBD disease. Compared to patients in naïve group, patients in switch group were more likely to stay on adalimumab therapy. As far as we know, this is the first report of using adalimumab biosimilar, MSB 11022, in real world clinical practice of IBD.
P729 Evaluation of hepatobiliary pathologies using transient elastography in patients with inflammatory bowel disease: What about the effect of drugs?
Authors: Ağargün B F , Şenkal İ V , Rustamzade A , Nuriyev K , İstemihan Z , İmanov Z , Genç S , Çelik B , Şahutoğulları D , Çavuş B , Çifcibaşı Örmeci A , Demir K , Beşışık S F , Kaymakoğlu S , Akyüz F 
Published: January 2023

Abstract

Background
In this study, we evaluated hepatobiliary involvement in inflammatory bowel disease (IBD) with FibroScan® (transient elastography) and examined drug effects on liver fibrosis and steatosis. We particularly focused on the effect of azathioprine (AZT) on spleen stiffness (SS).

Methods
A total of 352 subjects were included in this study, including 298 IBD patients and 54 healthy controls. LSM (liver stiffness measurement), SS, and CAP™ (controlled attenuation parameter) scores were measured by FibroScan®. In addition to disease and patient characteristics; laboratory tests, and effect of the drugs were evaluated and compared within the groups.

Results
The patient and control groups were similar in terms of age and gender. The characteristics of the groups are shown in Table 1. Mean LSM (5.2±3.1kPa vs 4.5±1,1kPa), mean SS (22.69±13,10kPa vs 17.96±7,44kPa), CAP™ score (hepatosteatosis) (233±56dB/m vs 224±47dB/m) were significantly higher in the patients with IBD than in the control group (p&lt;0.05). Liver fibrosis and steatosis grades are shown in Figure 1. A positive correlation was found between CAP™ score and male gender, hypertension, diabetes, BMI, smoking, penetrating disease, GGT, triglyceride, LSM, and SS (p&lt;0.05). LSM (5.7±3,1kPa vs 5.0±3,1kPa) was significantly higher in patients with extraintestinal involvement (p&lt;0.05). In patients with significant liver fibrosis (F2-3-4), the frequency of anti-TNF treatment was lower (44,4% vs 69,5%; p=0,008) (Figure 2). In patients who use alcohol regularly compared to nondrinkers (25.54±14,83kPa vs 21.05±11,24kPa) SS was significantly higher (p&lt;0.05). Additionally, in patients using AZT≥100 mg/day compared to those using AZT&lt;100 mg/day (23.48±14,61kPa vs 19.99±11,84kPa; p&lt;0,05) SS was significantly higher (Figure 3). AZT dose was positively correlated with SS (Spearman analysis; r=0.182 and p=0.013); however, no correlation was found with the duration or cumulative dose of AZT. The mean level of platelets was significantly higher in patients with IBD than in controls (300±104x10³/µL vs 251±52x10³/µL, p=0,001); however, there was no correlation between SS and trombosit level (p&gt;0,05). 83% of patients were in clinical remission (Mayo score≤2/CDAI&lt;150). No positive correlation was found between disease activity and SS in IBD patients. AZT-associated non-cirrhotic portal hypertension was detected in only one patient.

Conclusion
In this study, fatty liver, liver fibrosis, and SS were found to be significantly higher in IBD patients than in healthy controls. Although there is no relationship with the duration of AZT therapy, AZT dose was positively correlated with SS. We recommend that spleen stiffness should be evaluated in patients who use high doses of AZT (≥100 mg/day).
P733 Novelties of COVID-19 vaccination beyond efficacy: Nationwide experiences with trough levels, durability, and disease activity among inflammatory bowel disease patients
Authors: Resál T , Horváth M , Bacsur P , Szántó K , Rutka M , Bálint A , Fábián A , Bor R , Szepes Z , Fekete J , Miheller P , Molnár T 
Published: January 2023

Abstract

Background
The SARS-CoV-2 pandemic has raised issues in the management of inflammatory bowel diseases (IBD). This study aimed to assess the efficacy of different anti-SARS-CoV-2 vaccines under different treatments in IBD patients and identify predictive factors associated with lower serological response, including anti-TNF drug levels.

Methods
A prospective, multicentre study of IBD patients was conducted following mRNA and non-mRNA anti-SARS-CoV-2 vaccination. Healthy control (HC) patients were enrolled to reduce bias. Baseline and week 14 samples were obtained following the second dose to assess the impact of conventional and biological treatments. Clinical and biochemical activity, serological response level, and anti-TNF drug levels were measured.

Results
This study included 199 IBD (Table 1.; mean age, 40.9 ± 12.72 years) and 77 HC participants. Most patients (76.9%) and all HCs received mRNA vaccines. Half of the IBD patients were on biological treatment (Table 2.; anti-TNF 68.7%). Combined immunomodulation and biological treatment were associated with lower serological response (Figure 1.; p&lt;0.001), and mRNA vaccination promoted better antibody levels (p&lt;0.001). Higher adalimumab levels caused lower serological response (p=0.006). W8 persistence of anti-SARS-CoV-2 level was equal in IBD and HC groups (Figure 2.; p&gt;0.05). Vaccination had no impact on disease activity.

Conclusion
Anti-SARS-CoV-2 vaccination is considerably efficacious in IBD patients, with mRNA vaccines promoting better antibody levels. The negative impact of combined biological treatment, especially with high adalimumab drug levels, on serological response to vaccination should be considered. Although mid-term durability of vaccination is encouraging, more data are needed to expand existing understanding on this issue.
P737 Intensification with intravenous ustekinumab in refractory Crohn′s disease
Authors: Arroyo Argüelles J M , Suárez Ferrer C , Rueda García J L , Martín-Arranz E , Poza Cordón J , Sánchez-Azofra M , García-Ramírez L , Martin-Arranz M D 
Published: January 2023

Abstract

Background
There is little scientific evidence available about the results in terms of clinical and biochemical response after intensification with intravenous (IV) ustekinumab (UST) as a therapeutic strategy to be used in patients with refractory Crohn’s disease (CD) who are receiving subcutaneous (SC) treatment with said drug.

Methods
Patients with CD in stable follow-up at Hospital Universitario La Paz (Madrid), who were undergoing intensified treatment with IV UST, were recruited. The objective of the study was to assess the clinical and analytical response and drug levels 12 weeks after the change from subcutaneous to intravenous UST.

Results
27 patients were retrospectively included, all of them with previous treatment with UST SC. In Table 1 baseline characteristics are collected.

Out of the 27 patients included, 4/27 were under treatment with UST in first line, 10/27 in second line, 9/27 in third line and 4/27 had failed to three biologics.
The reason for intensification with IV UST was the lack of response to treatment in the 27 patients, 7 of them (25.93%) being found in the context of post-surgical recurrence. On the other hand, 10 patients (37.03%) were already under treatment with intensified SC UST, while the remaining 17 patients (62.96%) were under treatment with a standard schedule of SC UST every 8 weeks.
At the baseline visit, prior to the change to IV UST, differences in levels were observed between intensified and non-intensified patients (7216 vs 2842, p=0,00005). However, no significant differences were appreciated between these two groups 12 weeks after IV intensification (7949 vs 7937; p=0,99).
In patients with intensified UST SC was observed a decrease in fecal calprotectin 12 weeks after starting IV intensification, going from a mean of 1463 to 751, although the differences were not significant (p=0,14).
In Figure 1 is shown improvement in fecal calprotectin levels and in Figure 2 improvement in UST levels in blood is reflected, both parameters quantified 12 weeks after intravenous intensification of the drug.

In Table 2 data derived from the analysis of the clinical activity and determinations of CRP and calprotectin are collected, before performing the intensification with UST IV and 12 weeks after it.

Conclusion
In our experience, change to intravenous ustekinumab in maintenance led to an improvement in the clinical and biochemical response in patients with Crohn’s disease (even in patients already intensified). Likewise, an increase in drug levels was observed 12 weeks after the change from subcutaneous to intravenous treatment.