bluuebunny/crossref_metadata_2025_split huggingface dataset:
OP08 Mucosal healing with vedolizumab in inflammatory bowel disease patients with chronic pouchitis: Evidence from EARNEST, a randomized, double-blind, placebo-controlled trial
Authors: Jairath V , Feagan B G , Silverberg M S , Danese S , Gionchetti P , Löwenberg M , Bressler B , Ferrante M , Hart A , Lindner D , Escher A , Jones S , Shen B , Travis S 
Published: January 2023

Abstract

Background
Mucosal healing (MH) is an important treatment goal for inflammatory bowel disease (IBD). Vedolizumab (VDZ), a gut-selective anti-lymphocyte trafficking agent, has shown potential to achieve MH.1,2 EARNEST, a randomized double-blind placebo-controlled trial of VDZ in chronic pouchitis,3 offers a robust dataset systematically collected from the inflamed pouch mucosa to further explore the impact of VDZ treatment on MH.

Methods
EARNEST evaluated intravenous VDZ (300 mg) vs placebo (PBO) administered at weeks 0, 2, 6, 14, 22, and 30, in adult patients (pts) with active chronic pouchitis despite antibiotic therapy after proctocolectomy and ileal pouch-anal anastomosis for ulcerative colitis. Endoscopic imaging was captured and centrally read at baseline, Week (W) 14, and W34. Total ulceration and SES-CD (modified to apply to a single segment) were evaluated. Microscopic inflammation was also evaluated using the Pouchitis Disease Activity Index (PDAI) histological component. Pre-specified exploratory endpoints included changes in total ulceration and SES-CD remission (score ≤2); MH was defined post-hoc as SES-CD=0 plus PDAI histology score ≤1 (none/mild polymorphic nuclear leukocyte infiltration and no ulceration). Fecal calprotectin (FCP) levels were explored by MH status. PDAI remission (score &lt;7 and ≥3 point-reduction from baseline) and Inflammatory Bowel Disease Questionnaire (IBDQ) remission (score ≥170) were assessed in pts with/without MH at W14.

Results
In total, 98 pts had endoscopic evaluations (VDZ n=48; PBO n=50). Ulcers/erosions were higher in VDZ pts at baseline with a greater reduction at W14 and W34 with VDZ vs PBO (Table 1). More pts treated with VDZ vs PBO achieved reduction in ulcerated surface area, complete absence of ulceration/erosions and SES-CD remission. At W14, 7/42 (16.7%) pts had MH on VDZ vs 1/40 (2.5%) on PBO. All 7 VDZ pts with MH at W14 were in PDAI remission at W14 and W34; 6/7 (85.7%) pts achieved IBDQ remission at W14 and 5/7 (71.4%) achieved IBDQ remission at both W14 and W34. Of the 35 VDZ-treated pts without MH at W14, 11/35 (31.4%) achieved PDAI remission at W14, 11/35 (31.4%) at W34, and 9/35 (25.7%) at both W14 and W34; 13/35 (37.1%) achieved IBDQ remission at W14, 17/35 (48.6%) at W34, and 12/35 (34.3%) at both W14 and W34. MH was associated with FCP ≤250 µg/g while ~40-60% of pts without MH had FCP &gt;250 µg/g (Table 2).

Conclusion
VDZ was associated with better control of markers of inflammation vs PBO, based upon improvements in endoscopic/histologic outcomes in the pouch mucosa, as well as improved outcomes reported by pts. These effects of VDZ in the pouch mucosa are consistent with those observed in the wider patient population with IBD.
OP15 Efficacy of ustekinumab for Ulcerative Colitis through 4 years: Final clinical and endoscopy outcomes from the UNIFI long-term extension
Authors: Danese S , Afif W , Abreu M , Sandborn W , Miao Y , Zhang H , Panaccione R , Hisamatsu T , Scherl E , Leong R , Rowbotham D , Arasaradnam R , Peyrin-Biroulet L , Sands B , Marano C ,   UNIFI Investigators
Published: January 2023

Abstract

Background
Ustekinumab (UST) is an interleukin12/23p40 antagonist approved for treatment of moderate to severe Ulcerative Colitis (UC). Here we report final clinical outcomes based on the Mayo score, including the endoscopy subscore, from the UNIFI long-term extension (LTE) study through 4 years of UST treatment.

Methods
Overall, 523 intravenous UST induction responders were randomised to subcutaneous maintenance therapy: 175 placebo (PBO); 172 UST 90 mg every 12 weeks (q12w); 176 UST 90 mg q8w. A total of 284 UST patients (pts) completed week (wk)44 and continued treatment in the LTE; pts receiving PBO were discontinued after study unblinding. Starting at wk56, randomised pts with UC worsening could receive a dose adjustment: PBO to UST q8w, UST q12w to UST q8w, and UST q8w to UST q8w (sham adjustment). Outcomes based on the Mayo score (including endoscopy assessed by a local reader) were evaluated at the final efficacy visit (wk200); pts who had treatment failure (i.e., had ostomy or colectomy or discontinued UST due to lack of therapeutic effect or worsening UC) before wk200 were also included, and they were imputed as nonresponders. Clinical remission was defined as a Mayo score ≤2 points and no individual subscore &gt;1; clinical response as a decrease in Mayo score of ≥30% and ≥3 points from induction baseline with either a decrease in rectal bleeding subscore of ≥1 from induction baseline or a rectal bleeding subscore of 0 or 1; modified Mayo score (without Physician’s Global Assessment subscore) response as a decrease in modified Mayo score of ≥30% and ≥2 points from induction baseline with either a decrease in rectal bleeding subscore of ≥1 from induction baseline or a rectal bleeding subscore of 0 or 1; and endoscopic improvement as an endoscopy subscore of 0 or 1.

Results
Among 205 pts who were randomised to UST at maintenance baseline and continued treatment in the LTE, who either had Mayo score data (including endoscopy) at wk200 or had experienced treatment failure, 58.0% were in clinical remission, 80.0% were in clinical response, 79.5% were in modified Mayo score response, and 67.3% showed endoscopic improvement (Figure 1). Using an alternative “as observed case” analysis (without imputation for treatment failures), among 171 randomised pts who continued UST treatment through LTE and had an endoscopy score at wk200, 69.6% were in clinical remission, 95.9% were in clinical response, 95.3% were in modified Mayo score response, and 80.7% showed endoscopic improvement.

Conclusion
Among these pts with a history of moderate to severe UC who continued UST treatment, approximately 2/3 or more were in clinical remission, clinical response, and/or demonstrated endoscopic improvement at 4 years.
OP21 COVID-19 morbidity/mortality and vaccination against SARS-CoV-2 in patients with Inflammatory Bowel Disease in Poland: Nationwide Data
Authors: Kucha P , Walkiewicz D , Wieszczy P , Reguła J , Zagórowicz E 
Published: January 2023

Abstract

Background
According to the international recommendations, patients with inflammatory bowel disease (IBD) should be vaccinated against SARS-CoV-2 at the earliest opportunity to do so. The aim of this study was to assess the morbidity and mortality from COVID-19 in the adult IBD population in Poland with respect to their vaccination status.

Methods
We conducted a retrospective analysis of administrative health claims collected by the National Health Fund, the sole public payer in Poland. We identified adult IBD patients as of December 31th, 2021 who had at least two or more records with K50 or K51 code and two or more prescriptions for IBD drugs reimbursed or else intestinal surgery preceding the record. The vaccination status in 2021 was assessed using the database maintained by the Ministry of Health. We examined the vaccination process against SARS-CoV-2 among IBD patients along with morbidity and mortality from COVID-19. We conducted a Cox proportional hazard model analysis to determine the hazard ratio of SARS-CoV-2 infection, hospitalization and death in respect to the vaccination status during the autumn wave of the COVID-19 pandemic (October–December 2021).

Results
As of December 31th, 2021 there were 93 068 adult patients diagnosed with IBD. The vaccination rate in IBD patients was significantly higher than in the general population of Poland (72.1% vs 63.8%; p&lt;0.001) and grew with age, reaching the top value among those aged 70-79 years (88.2%) [Figure 1]. 87 353 IBD patients were included into the Cox proportional hazard analysis of autumn pandemic wave, during which there were 4 042 registered COVID-19 cases in IBD population. The peak value of a weekly average of incidence rate of COVID-19 was lower for vaccinated IBD patients (7.4/10000) than for unvaccinated ones (13.0/10000). The risk of being infected was significantly lower for vaccinated IBD patients (HR 0.53; 95%CI 0.5-0.57; p&lt;0.001). The cumulative risk of being positively tested for COVID-19 shows Figure 2. The most notable protective effect of vaccination against SARS-CoV-2 was found in patients aged 60-69 years (HR 0.47; 95%CI 0.39-0.55) and in those aged 80 years and above (HR 0.44; 95%CI 0.32-0.63). The risk of hospitalization due to COVID-19 was also significantly lower among the vaccinated IBD patients (HR 0.48; 95%CI 0.31-0.74, p&lt;0.0001). The risk of death due to COVID-19 was more than 3 times decreased in vaccinated IBD patients in comparison to the remaining IBD population (HR 0.29, 95%CI 0.17-0.43, p&lt;0.001) [Table 1].

Conclusion
Adult patients with IBD were more likely to get vaccinated against SARS-COV-2 than adults in the general population of Poland. The vaccination significantly decreased the risk of the infection, hospitalization and death due to COVID-19.
OP22 The risk of cancer in pediatric-onset immune-mediated inflammatory diseases – a nationwide Danish study from 1980-2018.
Authors: Ehrström A , Jansson S , Malham M , Wewer V 
Published: January 2023

Abstract

Background
A higher risk of cancer has been reported among patients with adult-onset immune-mediated inflammatory disease (IMID). However, data on cancer risk in paediatric-onset IMIDs (pIMID) are scarce. In this nationwide study from 1980 to 2018, we investigated the risk of cancer in the Danish pIMID population compared to controls from the background population.

Methods
PIMID was defined as patients registered in the Danish National Patient Registries with one or more of the following diagnoses: inflammatory bowel disease (pIBD), rheumatic disease (pRD), or autoimmune idiopathic liver disease (pAILD) before their 18th birthday. Each case was matched with up to 10 controls from the background population. Cancer diagnoses were verified using the Danish Cancer Registry. Risk of cancer was calculated using Cox proportional regression analysis and presented as hazard ratios (HR) with 95% confidence intervals (95% CI).

Results
We identified 13 216 cases, consisting of 5 811 pIBD (44%), 7 241 pRD (55%) and 347 pAILD (2%), and 114 502 controls. Median age at diagnosis was 12.5 years. Follow-up time was 11.1 and 10.5 years for cases and controls, respectively. The risk of overall cancer in pIMID compared to the background population was HR 2.1 (95%CI: 1.8-2.4), p&lt;0.001. The risk of cancer was HR 2.4 (95%CI: 2.0-3.0), p&lt;0.001 in pIBD, ascribed to colorectal-, liver-, skin cancer and lymphoma, HR 1.6 (95%CI: 1.2-2.1), p=0.002 in pRD, ascribed to lymphoproliferative cancer, and HR 5.7 (95%CI: 2.5-13.1), p&lt;0.001 in pAILD, ascribed to liver and skin cancer. Patients with multiple IMID had an increased risk of cancer compared to patients with only one pIMID diagnosis (HR 2.8 [95%CI: 1.9-4.1], p&lt;0.001).

Conclusion
PIMID was associated with a twofold increased risk of cancer, ascribed to colorectal cancer in pIBD, liver cancer and skin cancer in pIBD and pAILD, and lymphoproliferative cancer in pIBD and pRD.
OP28 Children and young adults with inflammatory bowel disease have an increased incidence and risk of developing mental health conditions: a UK population-based cohort study
Authors: Cooney R , Tang D , Barrett K , Russell R K 
Published: January 2023

Abstract

Background
While it is widely recognised that inflammatory bowel disease (IBD) is associated with depression and anxiety, the burden of mental health conditions in children and young adults with IBD remains unclear. This study assessed this burden using UK population-based data.

Methods
A retrospective observational study was performed using a large UK primary care dataset (Optimum Patient Care Research Database). Children and young adults aged 5–25 years diagnosed with IBD between 2010 and 2020 were propensity score matched with up to four population controls. The association between IBD and incident depression, anxiety disorder (AD), eating disorders, body image disorders, attention-deficit disorders, behavioural disorders, adjustment disorders, acute stress disorder, schizophrenia, bipolar disorder, post-traumatic stress disorder (PTSD), self-harm, parasuicide (including suicide), sleep disturbance and ‘any mental health condition’ (a composite consisting of all these mental health conditions) was investigated. Absolute risk was derived using Kaplan-Meier analysis. Relative risk of all outcomes up to 10-years in the IBD cohort versus controls was estimated using adjusted Cox proportional hazards models controlling for age, sex, socioeconomic status, ethnicity, and other conditions (asthma, atopic dermatitis, allergic rhinitis, thyroid disease, epilepsy, diabetes mellitus, cancer, juvenile idiopathic arthritis, systemic lupus erythematosus, ankylosing spondylitis, and psoriatic arthritis).

Results
3,898 young patients with incident IBD were matched to 15,571 controls. IBD patients were significantly more likely to develop PTSD (adjusted Hazard Ratio [aHR] 2.47, 95% CI 1.23-4.94), eating disorders (aHR 1.85, 95% CI 1.05-3.26), self-harm (aHR 1.49, 95% CI 1.00-2.21), sleep disturbance (aHR 1.40, 95% CI 1.15-1.71), depression (aHR 1.34, 95% CI 1.16- 1.56), AD (aHR 1.25, 95% CI 1.06-1.48), and ‘any mental health condition’ (aHR 1.28, 95% CI 1.12-1.46) (Figure 1). In subgroup analysis, male sex, and IBD patients aged 12 to 17 appear to have the greatest additional risk for developing mental health conditions (Figure 2) and Crohn’s disease had a higher risk than ulcerative colitis (aHR 1.32, 95% CI 1.10-1.58 and aHR 1.19, 95% CI 0.95-1.49 respectively).

Conclusion
Young IBD patients have a significantly higher incidence and risk of new mental health conditions. Mental health remains a critically overlooked aspect of IBD patient management. Further research into identifying optimal monitoring tools and support for these patients is required to improve patient care.
OP32 The gut virome-colonizing Orthohepadnavirus genus is associated with ulcerative colitis pathogenesis and induces intestinal inflammation in vivo
Authors: Facoetti A , Massimino L , Palmieri O , Fuggetta D , Spanò S , D'Alessio S , Furfaro F , D'Amico F , Zilli A , Fiorino G , Noviello D , Latiano A , Bossa F , Pirola A , Mologni L , Piazza R , Abbati D , Perri F , Bonini C , Peyrin-Biroulet L , Malesci A , Danese S , Ungaro F 
Published: January 2023

Abstract

Background
Ulcerative colitis (UC) is a chronic inflammatory disorder with an unknown etiology1. Over recent years, a growing body of evidence has been pinpointing gut virome dysbiosis as a fundamental component in its progression2, although its role during the early phases of chronic inflammation is far from being fully defined. Therefore, we sought to investigate the role of a virome-associated protein encoded by the Orthohepadnavirus genus, the Hepatitis B virus X protein (HBx)3, during UC aetiopathogenesis.

Methods
HBx positivity of UC patient-derived blood and gut mucosa was assessed by RT-PCR and Sanger sequencing correlated with clinical characteristics by multivariate analysis. Transcriptomics was performed on HBx-overexpressing endoscopic biopsies from healthy donors.
C57BL/6 mice underwent intramucosal injections of liposome-conjugated HBx-encoding plasmids or the control. Multidimensional flow cytometry analysis was performed on colonic samples from HBx-treated and control animals. Transepithelial electrical resistance measurement, proliferation assay, ChIP-Seq, and RNA-Seq were performed on in vitro models of the gut barrier.

Results
HBx was detected in about 45% of patients with UC (Figure 1) and found to induce colonic inflammation in mice (Figure 2A-2D), while its silencing reverted the colitis phenotype in vivo (Figure 2E-2H). HBx acts as a transcriptional regulator in epithelial cells (Figure 3), provoking barrier leakage and altering inflammatory response (Figures 3 and 4).

Conclusion
This study paves the way for the understanding of the aetiopathogenesis of UC and provides a brand-new standpoint that looks at the virome as a target for tailored treatments, possibly leading to an entirely new approach to therapeutic intervention.
References:
1. Massimino L, Lamparelli LA, Houshyar Y, et al. The Inflammatory Bowel Disease Transcriptome and Metatranscriptome Meta-Analysis (IBD TaMMA) framework. Nat Comput Sci 2021;1:511–5. doi:10.1038/s43588-021-00114-y
2. Ungaro F, Massimino L, D’Alessio S, et al. The gut virome in inflammatory bowel disease pathogenesis: From metagenomics to novel therapeutic approaches. United European Gastroenterol J 2019;7:999–1007. doi:10.1177/2050640619876787
3. Ungaro F, Massimino L, Furfaro F, et al. Metagenomic analysis of intestinal mucosa revealed a specific eukaryotic gut virome signature in early-diagnosed inflammatory bowel disease. Gut Microbes 2019;10:149–58. doi:10.1080/19490976.2018.1511664
OP34 Enteral Nutrition Compared with Steroids in Children with Crohn’s Disease – In Israel: a nationwide study from the epi-IIRN
Authors: Plotkin L , Lujan R , Focht G , Greenfeld S , Loewenberg Weisband Y , Lederman N , Matz E , Dotan I , Turner D 
Published: January 2023

Abstract

Background
Studies have shown that exclusive enteral nutrition (EEN) treatment is as effective to corticosteroids (CS) for induction of remission in pediatric Crohn's disease (CD) with fewer side effects, but long-term outcome data are scarce. In this nationwide study we aimed to compare the risk of complicated disease course (CDC) after 2 years of follow-up in children with CD receiving EEN or CS as induction therapy.

Methods
Data of children diagnosed with CD in the epi-IIRN cohort between 2005-2020 were retrieved from the 4 Israeli Health-Maintenance-Organizations covering 98% of the population. The primary outcome was CDC defined as CD-related surgery, steroid-dependency, or need for more than one biologic class during 2 years post-diagnosis. Secondary outcomes included hospitalizations, and the use of biologics (any). Additionally, anthropometrics, labs reflecting nutrition (i.e., Alb and HGB), and growth were assessed at repeated visits until 2 years thereafter. To account for confounding by indication bias, we compared children with similar baseline characteristics based on Propensity Score (PS) individual matching. Time to CDC outcome was evaluated using Kaplan-Meier survival curves and compared by the log-rank test. A Cox proportional hazard model was sought to assess the relationship between the type of induction and time to CDC outcome.

Results
A total of 785 children with CD were induced after diagnosis with either EEN (n=410) or CS (n=375); mean age 13.3±3.5 years, 59% males. PS successfully matched 116 pairs of whom 85 (36%) had CDC. The survival probability of CDC at 6, 12,18, and 24 months was higher in the CS group compared to the EEN group at all time points (5%vs4%, 12% vs 10%, 22% vs 3%, and 27% vs.16%, respectively p=0.045; fig. 1). In a Cox multivariable model adjusted by year of diagnosis, CS induction treatment was similarly associated with higher hazard of CDC by 2 years (HR 1.8 [95%CI 1.01-3.25]). The survival probability of hospitalization was also higher in the CS group at 6,12,8, and 24 months (16% vs 9%, 20% vs 12%, 25% vs 14%, and 27% vs. 15%, respectively, p=0.024; fig.2). There was no difference in time to biologics (p=0.96, n=59 (51%) in EEN, n=57 (49%) in CS) and anthropometric data (Table 1). Significant improvements were observed in HGB and Alb levels for the EEN group during the first 3 months from diagnosis compared with the CS (p=0.046 and p=0.035 respectively) (table 1).

Conclusion
EEN as induction therapy in pediatric CD is associated with a lower long-term risk of complicated disease course and larger improvement in HGB and Alb but not in growth parameters compared with CS, even when adjusting to baseline disease severity and patients characteristics.
OP36 Real-world evidence on comparative effectiveness of Ustekinumab vs anti-TNF in Crohn’s disease with propensity score adjustment: two-year maintenance phase results from the prospective observational RUN-CD study
Authors: Bokemeyer B , Plachta-Danielzik S , Deppe H , Mohl W , Teich N , Hoffstadt M , Schweitzer A , von der Ohe M , Gauss A , Atreya R , Krause T , Blumenstein I , Fajardo Salmon S , Hartmann P , Gilman E , Schreiber S 
Published: January 2023

Abstract

Background
Within the framework of the prospective real-world RUN-CD registry on the effectiveness and safety of ustekinumab (UST) in Crohn’s disease (CD), a total of 901 CD-patients undergoing a newly initiated biologics therapy were enrolled in 44 IBD-experienced centers from all over Germany between 2017-2020 with a follow-up of 3 years. Here, the results on the effectiveness of the maintenance therapy over 24 months are presented as a real-world evidence (RWE) comparison of CD-patients with UST vs anti-TNF.

Methods
After exclusion of other biologics than UST and anti-TNF and missing outcomes (HBI), the final sample consisted of 550 CD patients. Clinical remission (HBI ≤ 4) was the predefined endpoint at month 24 and additionally, switching of biologics therapy was considered as an outcome failure. Patients were analysed on a modified intent-to-treat basis (mITT; switchers considered as outcome failure). To reduce the effect of confounders, propensity score (PS) adjustment with inverse probability of treatment weighting (IPTW) was implemented. A weighted logistic regression was used, and the results were reported as odds ratio (OR) and 95% confidence interval (CI). Quality of life was assessed using the self-reported visual analogue scale (EQ-VAS) of the EQ-5D with changes from baseline to 2 years.

Results
308 UST (naïve: 27) and 242 anti-TNF (naïve: 162) CD-patients were included (ADA: 61.2%, IFX: 38.8%). The number of switches within 24 months was significantly lower with UST than with anti-TNF (27.6% vs 37.1%; p=0.038), and especially with IFX, whereby the difference between UST and IFX (27.6% vs 46.7%; p=0.003) proves to be statistically significant (Fig. 1). Clinical remission at two years was not statistically different for the overall UST vs anti-TNF groups (51.2% vs 54.4) (numerically higher in biologic-naïve UST- vs anti-TNF-patients, without statistically significance) (Tab. 1). Remission rates were similar for UST vs ADA, while they were significantly higher for UST vs IFX (54.4% vs 37.9%; p=0.008) (Tab. 2), and also significantly higher for ADA vs. IFX (58.2% vs 37.9%; p=0.003). As a sign of an improved QoL we observed a significant increase in EQ-VAS within both treatment groups. However, a similar increase in EQ-VAS was observed with UST and anti-TNF (+14.2 vs +12.3; p=0.147).

Conclusion
In this prospective two-year RWE comparison clinical remission was, also due to more frequent switches within the IFX group, significantly higher with UST when compared with IFX and higher with ADA than with IFX. Considering the effectiveness results of UST and the proven favourable safety profile, UST can be considered a first-line targeted therapy for CD.