bluuebunny/crossref_metadata_2025_split huggingface dataset:
OP11 Ileocecal resection for recently diagnosed ileocecal Crohn’s disease is associated with improved long-term outcomes compared to anti-tumor necrosis factor therapy: a population-based study
Authors: Agrawal M , Ebert A , Poulsen G , Ungaro R , Faye A , Jess T , Colombel J F , Allin K 
Published: January 2023

Abstract

Background
Early treatment of Crohn’s disease (CD) often involves biologics such as anti-tumor necrosis factor (anti-TNF) agents. Ileocecal resection (ICR), while a therapeutic option in early CD, is generally reserved for complicated CD or when medical treatment fails. We aimed to compare long-term outcomes of ICR and anti-TNF therapy as index treatment for ileocecal CD, initiated within one year of diagnosis, in the Danish nationwide cohort.

Methods
Using cross-linked nationwide registers, we identified all individuals who lived in Denmark and were diagnosed with ileal CD between 2003 and 2018. We included individuals who underwent ICR or received anti-TNF drugs as index treatment for ileocecal CD within one year of diagnosis. We excluded patients who did not have pathology information confirming disease in the ileocecal region. The primary outcome was a composite of CD-related hospitalization, systemic corticosteroid exposure, CD-related surgery, and perianal CD diagnosis. We conducted Cox proportional hazards regression analyses to compare outcomes in the two groups after adjusting for potential confounders. We also determined the proportion of individuals initiated on immunomodulator (IMM), anti-TNF, or no therapy at 5 years after ICR.

Results
Of the 16,443 individuals diagnosed with ileocecal CD between 2003 and 2018, 581 (3.5%) and 698 (4.2%) individuals with confirmed disease in the ileocecal region underwent ICR and received anti-TNF as the index treatment, respectively. The composite outcome occurred in 273 individuals (IR 110.3/100,0 person years (PY)) in the ICR group and in 318 individuals (IR 201.9/100,0 PY) in the anti-TNF group. The risk of the composite outcome was 33% lower in the ICR group compared to the anti-TNF group (aHR 0.67; 95% CI 0.54, 0.83), after adjusting for demographic and clinical variables. On analysis of individual outcomes, ICR was associated with reduced risk of systemic corticosteroid exposure and CD-related surgery, but not CD-related hospitalization or perianal CD diagnosis. Of individuals who underwent ICR, the proportion that was initiated on IMM, anti-TNF treatment or no treatment at 5 years of follow up was 47.5%, 17.1%, and 50.3%, respectively.

Conclusion
These data support the role of ICR as an index treatment for ileocecal CD and challenge the current paradigm of reserving surgery for complicated CD refractory or intolerant to medications. Further studies will help identify characteristics of individuals who needed no treatment after ICR.
OP14 Prevention of postoperative recurrence of Crohn's disease with vedolizumab: First results of the prospective placebo-controlled randomised trial REPREVIO
Authors: D'Haens G , Taxonera C , Lopez-Sanroman A , Nos Mateu P , Danese S , Armuzzi A , Roblin X , Peyrin-Biroulet L , West R , Witteman B , Duijvestein M , Gecse K , Hulshoff M , Mostafavi N , Clasquin E , Bouhnik Y , Laharie D 
Published: January 2023

Abstract

Background
Crohn’s disease (CD) is a chronic, immune-mediated inflammatory condition of the intestine, for which the majority of patients still needs to undergo surgical resection. Following the most common intervention ileocolonic resection, the vast majority of patients suffers from recurrence of CD in the neoterminal ileum. Endoscopic lesions usually precede symptoms in the first months after resection and predict the severity of the further disease course. No treatments have been approved for recurrence-prevention of CD. REPREVIO is a prospective placebo-controlled randomized trial investigating the preventive effect of vedolizumab, an anti-integrin antibody, on recurrence of CD.

Methods
Following ileocolonic resection, patients were treated with vedolizumab (300 mg IV at week 0,8,16 and 24) or PLC (1:1) at 12 sites in the Netherlands, France, Italy and Spain. Treatment was initiated within 4 weeks following ileocolonic resection with anastomosis. Six months following surgery, patients underwent ileocolonoscopy for assessment of recurrent lesions. Video recordings were centrally scored using the modified Rutgeerts’ score by 2 readers with adjudication in case of disagreement. The primary endpoint was endoscopic recurrence (ER) of CD (non-parametric); secondary endpoints were the proportion of patients with ER &gt;i2a and clinical recurrence. Adverse events were recorded.

Results
95 pts were screened and 80 randomized. All patients have reached month 6 and the videos are being analysed. We will receive the results of all statistical analysis in December, 2022.

Conclusion
The efficacy of vedolizumab postoperative recurrence-prevention treatment was studied in the REPREVIO study.
OP16 Endoscopic and clinical outcomes of upadacitinib in patients with moderately to severely active Crohn’s disease by number and type of prior biologics
Authors: Peyrin-Biroulet L , Parkes G , Rodríguez C , Siffledeen J , Wright J , Broide E , Ford S , Lacerda A P , Oomen J , Garrison A , Berg S , Rubin D T 
Published: January 2023

Abstract

Background
Biologic therapies are used to treat moderate-to-severe Crohn’s Disease (CD), but many patients eventually lose response to them. With new potential therapies for CD, understanding their efficacy after patients undergo biologic treatment is important for clinical decision-making. This post hoc analysis assessed the outcomes of upadacitinib (UPA), an oral selective Janus kinase inhibitor, in patients with CD who had failed a biologic, by the number and type of prior biologic therapies.

Methods
In the 2 induction studies, U-EXCEL (NCT03345849) and U-EXCEED (NCT03345836), patients with moderate-to-severe CD received oral UPA 45 mg once daily (QD) therapy or placebo (PBO) for 12 weeks. Patients achieving clinical response to UPA induction were re-randomised in the maintenance study, U-ENDURE (NCT03345823), to receive UPA 15 mg QD, UPA 30 mg QD, or PBO for 52 weeks. This analysis assessed clinical, endoscopic, and safety outcomes in patients with inadequate response or intolerance to biologic therapy by number and type of biologics failed. Data from the U-EXCEL and U-EXCEED studies were pooled.

Results
At baseline, patient (n=733) characteristics were similar for UPA vs PBO within each subgroup by number of prior biologics (1, n=279; 2, n=223; &gt;2, n=231); patients who received ≥ 2 prior biologics had longer disease duration (median, years: 1, 6.2; 2, 9.4; &gt;2, 12.9) and were more likely to have used steroids (1, 27.7%; 2, 40.4%; &gt;2, 45.0%). Across subgroups, greater proportions of patients receiving UPA vs PBO achieved clinical remission (Figure 1) and endoscopic response and remission (Figure 2) at week 12 of induction and week 52 of maintenance; response rates were generally higher for patients who had failed fewer biologics. When analyzed by type of prior biologic (tumor necrosis factor inhibitor [yes/no], n=704/29; ustekinumab [yes/no], n=272/461; vedolizumab or natalizumab [yes/no], n=220/513), the proportion of patients achieving clinical and endoscopic outcomes was slightly higher for those without prior exposure to each biologic. Adverse events (AEs) occurred at numerically higher rates for patients who had failed multiple biologics in the induction and maintenance studies across both PBO and UPA treatment arms. AEs of special interest occurred at similar rates across subgroups. No non-melanoma skin cancers, major adverse cardiovascular events, or venous thromboembolic events were reported.

Conclusion
Clinical and endoscopic improvements were observed with UPA induction and maintenance therapy in patients with moderate-to-severe CD, regardless of number and type of prior biologics failed; greater benefits and fewer AEs were observed in patients who failed fewer biologic therapies.
OP20 The effects of upadacitinib on ulcerative colitis symptom resolution and fatigue normalization in patients with moderately to severely active ulcerative colitis: Phase 3 U-ACHIEVE and U-ACCOMPLISH results
Authors: D'Haens G , Tran J , Danese S , Rubin D T , Aoyama N , Lügering A , Klaff J , Xuan S , Ilo D , Sanchez Gonzalez Y , Panes J 
Published: January 2023

Abstract

Background
Abdominal pain (AP), bowel urgency (BU), stool frequency (SF), rectal bleeding (RB) and fatigue are debilitating symptoms that reduce quality of life in patients with ulcerative colitis (UC). Results from two Phase 3 induction trials and one maintenance trial (U-ACHIEVE [NCT02819635] and U-ACCOMPLISH [NCT03653026]) showed significant and clinically meaningful improvements in these symptoms following induction and maintenance treatment with upadacitinib (UPA) in patients with moderately to severely active UC. We evaluated the effects of 8-week UPA induction and 52-week UPA maintenance treatment on UC symptom resolution, defined as no BU, no AP, and symptomatic remission (no RB, SF≤1), and normalization of fatigue, defined as achievement of a Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT–F) score ≥ 40.1.

Methods
A total of 988 patients were randomized in the U-ACHIEVE and U-ACCOMPLISH induction studies to receive UPA 45 mg once daily (QD; n=660) or placebo (PBO) QD (n=328). Patients who achieved a clinical response after 8 weeks of induction (n=451) were enrolled in the U-ACHIEVE maintenance study and re-randomised 1:1:1 to UPA 15 mg QD (n=148), UPA 30 mg QD (n=154), or PBO QD (n=149). Symptom resolution was assessed at induction Weeks 0, 2, 4, 6, 8 and maintenance Weeks 0, 4, 8, 12, 20, 28, 36, 44, and 52. A more stringent assessment of symptom resolution and normalization of fatigue was conducted at Weeks 0, 2, and 8 of induction and Weeks 0 and 52 of maintenance.

Results
A higher percentage of patients achieved symptom resolution during induction treatment as early as Week 2 with UPA 45 mg vs PBO (11.1% vs 0.9%, p &lt;0.001; Figure 1), and sustained through Week 8 (31.2% vs 7.9%, p&lt;0.001). This difference was also observed during maintenance treatment among clinical responders starting at Week 8 with UPA (15 mg: 43.2%; 30 mg: 42.2% vs PBO: 30.2%, p&lt;0.01 and p&lt;0.05, respectively; Figure 2) and sustained through Week 52 (15 mg: 37.2%; 30 mg: 46.1% vs PBO: 12.8%, p&lt;0.001 for both). Furthermore, the percentage of patients who achieved symptom resolution and fatigue normalization was greater with UPA vs PBO at Week 8 of induction (45 mg: 23.4% vs PBO: 6.7%, p &lt;0.001; Figure 3) and Week 52 of maintenance (15 mg: 24.3%; 30 mg: 36.4% vs PBO: 12.1%, p&lt;0.01 and p&lt;0.001, respectively).

Conclusion
Patients with moderately to severely active UC were more likely to achieve symptom resolution and normalization of fatigue during induction treatment with UPA compared to PBO, and these benefits were sustained during maintenance therapy.
OP35 Efficacy and safety outcomes up to ~4 years of treatment with filgotinib 200 mg among patients with Ulcerative Colitis: Results from the SELECTIONLTE study
Authors: Feagan B G , Matsuoka K , Rogler G , Faes M , Oortwijn A , de Haas A , Rudolph C , Peyrin-Biroulet L 
Published: January 2023

Abstract

Background
Filgotinib (FIL) is a once-daily, oral, Janus kinase 1 preferential inhibitor approved for the treatment of ulcerative colitis (UC). FIL 200 mg (FIL200) was effective in inducing and maintaining clinical remission vs placebo (PBO) and well tolerated in patients with UC in the randomized, phase 2b/3 SELECTION trial (NCT02914522).1 The efficacy and safety of continued FIL200 therapy are being assessed in the continuing SELECTION long-term extension (LTE) study.

Methods
The SELECTION programme comprises SELECTION and the associated LTE study (SELECTIONLTE; NCT02914535). In SELECTION, adults with moderately to severely active UC received induction (IND) FIL200, FIL 100 mg (FIL100) or PBO once daily for 11 weeks. Patients in clinical remission or with a Mayo Clinic Score (MCS) response at week 10 (responders) could enter the 47-week Maintenance (MNT) Study. SELECTIONLTE enrolled patients who completed IND and MNT (completers), patients who were not responders at IND week 10 (non-responders), and patients with disease worsening during MNT. This interim analysis assessed the efficacy and safety of open-label FIL200 through LTE week 144 in completers and LTE week 192 in non-responders, respectively, representing a total of 3.9 years of treatment each (completers: 58 + 144 weeks; non-responders 10 + 192 weeks). The cut-off date was 24 February 2022. Continuous measures of partial MCS (pMCS) and proportions of patients achieving the minimal clinically important difference (MCID) in total IBDQ score (≥16-point increase vs baseline) were assessed without imputation (as observed). Safety was assessed by the exposure-adjusted incidence rate per 100 patient-years of exposure (PYE) for treatment-emergent adverse events (TEAEs) and TEAEs of interest.

Results
This analysis included 148 completers and 372 non-responders (IND FIL100, n=212; IND FIL200, n=160). Among completers, the reductions in mean pMCS in SELECTION over weeks 0–10 were maintained up to LTE week 144 (Figure 1). In non-responders, mean pMCS decreased from LTE baseline to week 192 (Figure 2). High proportions of completers (&gt;90%) and non-responders (&gt;60%) achieved the MCID in IBDQ score; proportions were maintained over time (Table 1). Safety events among all patients treated with open-label FIL200 in the LTE study (total PYE=2055.5) are reported in Table 2.

Conclusion: FIL200 was effective in maintaining symptomatic remission and health-related quality of life for up to ~4 years. No new safety signals were observed over ~4 years of treatment, and safety events were comparable with those seen in previous analyses.2
1. Feagan BG et al. Lancet 2021;397:2372–84.
2. Feagan BG et al. J Crohns Colitis 2022;16(Suppl1):i456–7.
DOP21 Disease activity patterns of paediatric Inflammatory Bowel Disease – A Danish nationwide cohort study 1996-2018
Authors: Wewer M D , Jansson S , Malham M , Burisch J , Wewer V 
Published: January 2023

Abstract

Background
Inflammatory bowel diseases (IBD) are heterogenous diseases in terms of their clinical presentation including frequency and severity of flares.
We aimed to describe disease activity (DA) patterns in a Danish nationwide cohort including all IBD patients diagnosed &lt; 18 years of age between 1996 and 2018.

Methods
Paediatric patients diagnosed with Crohn’s disease (pCD) or ulcerative colitis (pUC) were identified from national registers (Danish Civil Registration System, National Patient Registry, Danish National Prescription Registry and Danish Pathology Data Bank). DA was assessed in both incident and prevalent pIBD patients and categorised as mild-moderate in case of a course of topical corticosteroids, oral budesonide, or topical 5-ASA. Episodes were categorised as severe if they involved hospitalization, surgery, oral corticosteroids or biological therapy.
DA patterns in incident patients were assessed for 5- and 10-year periods from diagnosis as follows:
The 5-year DA pattern: A) No years with DA. B) 1 or 2 years with at least one episode of DA in each year. C) 3 or 4 years with at least one episode of DA in each year. D) All 5 years with at least one yearly episode of DA.
The 10-year DA pattern: A) Decreasing: First 5 years with 2 or more years with DA; following 5 years with 2 years or less with DA. B) Increasing: First 5 years with less than 2 years with DA; following 5 years with 2 or more years with DA. C) Chronic continuous: First 10 years with at least 8 years with DA. D) Quiescent: First 10 years with one year or less with DA. E) Chronic intermittent: DA pattern that does not meet the criteria above.

Results
1,965 pCD and 1,838 pUC incident patients were included. At diagnosis severe DA was found in 87% in pCD and 80% in pUC, in addition to 6.1% of pUC patients who had a colectomy the first year. After 5 years of disease the annual proportion of pCD and pUC with no DA 70% and 61%. This remained constant after 10 years (pCD:72% and pUC: 64%). In pUC, 12% and 16% required colectomy 5 and 10 years after diagnosis.
In prevalent pCD (N=2,515) and pUC (N=2,428) the proportion with no DA each calendar year was stable (pCD: 59%-73% and pUC: 50%-60%, prior to 2010). The majority of both pCD and pUC patients experienced one or two years with at least one episode of DA within the first five years (pCD: 51%, pUC: 53%). During the first 10 years from diagnosis, the decreasing DA pattern was the most common in both pCD and pUC (43% and 47%, respectively) (Figure).

Conclusion
DA patterns in pIBD are characterised by a high proportion of severe activity initially with a decreasing pattern after 5 and 10 years follow-up. No change in the proportion of patients with no DA was seen despite the introduction of biologic therapy in the period.
DOP24 Early life exposures and risk for inflammatory bowel disease: a nested case-control study in Quebec, Canada
Authors: Fantodji C , Rousseau M C , Nicolau B , Madathil S , Benedetti A , Jantchou P 
Published: January 2023

Abstract

Background
Early childhood is an important period for the establishment of gut microbiota. Most early life risks or protective factors for inflammatory bowel disease are likely to act through an effect on the gut microbiota. The aim of this study was to estimate the associations between exposures in infancy (birth until 3 years of age) such as breastfeeding, antibiotic treatment, presence of domestic pets, and passive smoking, and the occurrence of inflammatory bowel diseases.

Methods
This case-control study was nested within the Quebec Birth Cohort on Immunity and Health. Cases and controls were identified among persons born in Quebec in 1970-1974 based on their health services from 1983 to 2014 using validated algorithms. All cases and randomly selected controls were invited to participate in a web or telephone questionnaire. Participation rates were 47% among controls (n=946), and respectively 52% (n=1212) and 55% (n=570) among cases of Crohn’s disease and ulcerative colitis. Logistic regression models were used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI), separately for Crohn’s disease and ulcerative colitis. Each exposure was analyzed in a multiple regression model adjusted for relevant covariates identified with a directed acyclic graph.

Results
Adjusting for perinatal and sociodemographic characteristics, the risk for Crohn’s disease or ulcerative colitis did not differ in subjects who were exclusively breastfed compared to non-breastfed subjects. Partial breastfeeding (breastfeeding combined with infant formula) was not associated with Crohn’s disease (OR=1.03, 95% CI: 0.76-1.40), but an increase in the odds of ulcerative colitis (OR=1.40, 95% CI: 0.99-1.99) was observed as compared with no breastfeeding. Early introduction of solid foods was associated with higher odds of Crohn’s disease (introduction at 3-6 months compared with &gt;6 months: OR=1.35; 95% CI: 1.05-1.78), but not of ulcerative colitis (OR=1.06; 95% CI: 0.77-1.46). Antibiotic use and the presence of domestic pets were not associated with either Crohn’s disease or ulcerative colitis. Passive smoking was associated with increased odds of Crohn’s disease (OR=1.23; 95% CI: 1.00-1.51), but not ulcerative colitis (OR=0.96; 95% CI: 0.75-1.22).

Conclusion
Differences were noticed in early childhood risk factors for Crohn’s disease and ulcerative colitis. Early introduction of solid foods and passive smoking increased the risk of Crohn’s disease, whereas there was a trend of increased risk of ulcerative colitis with partial as compared with no breastfeeding. The results for partial breastfeeding and early introduction of solid foods are novel and will require further investigation.
DOP32 Crohn’s disease stricture matrisome analysis reveals the anti-fibrotic activity of milk-fat globule-epidermal growth factor 8 (MFGE8)
Authors: Lin S , Wang J , Mukherjee P , Mao R , West G , Czarnecki D , Zhao S , Elias M , Nguyen Q T , Chandra J , Le T H N , Chen M H , Dejanovic D , Holubar S , Olman M , Southern B , Hu S , Gordon I O , Atabai K , Fiocchi C , Rieder F 
Published: January 2023

Abstract

Background
Intestinal fibrosis is considered an inevitable consequence of chronic inflammatory bowel disease (IBD), leading to stricture formation and need for surgery. During the process of fibrogenesis, extracellular matrix (ECM) components critically regulate the function of mesenchymal cells. We characterized the composition and function of the ECM in fibrostenosing Crohn’s disease (CD) and control tissues.

Methods
Decellularized full thickness intestinal tissue platforms were tested using three different protocols and ECM composition in different tissue phenotypes was explored by proteomics and validated by quantitative polymerase chain reaction (qPCR) and immunohistochemistry. Primary human intestinal myofibroblasts (HIMF) treated with Milk Fat Globule-Epidermal growth factor 8 (MFGE8) were evaluated regarding mechanism of their anti-fibrotic response, and the action of MFGE8 was tested in experimental intestinal fibrosis.

Results
We established and validated an optimal decellularization protocol for intestinal IBD tissues. Matrisome analysis revealed elevated MFGE8 expression in CD strictured tissue (CDs), which was confirmed at the mRNA and protein levels. Treatment with MFGE8 inhibited ECM production in normal control (NL) HIMF but not CDs HIMF. Next generation sequencing (NGS) uncovered functionally relevant integrin-mediated signaling pathways, and blockade of integrin αvβ5 and focal adhesion kinase rendered HIMF non-responsive to MFGE8. MFGE8 prevented and reversed experimental intestinal fibrosis in vitro and in vivo.

Conclusion
MFGE8 displays anti-fibrotic effects, and its administration may represent a future therapeutic approach for prevention of IBD-induced intestinal strictures.