bluuebunny/crossref_metadata_2025_split huggingface dataset:
P628 Histological remission does not offer additional benefit for ulcerative colitis patients in endoscopic remission
Authors: Narula N , Alshahrani A A , Fadida M , Al-Saedi M , Marshall J K , Rubin D T , Christensen B 
Published: January 2020

Abstract

Background
Histologic remission appears to be associated with positive outcomes in ulcerative colitis (UC) patients. However, it is not clear whether UC patients in endoscopic remission have additional benefit from achieving histologic remission. The objective of the study was to assess the relationship between time to relapse and histological activity among UC patients who are in endoscopic remission.

Methods
This was a retrospective observational study conducted at McMaster University Medical Centre in Hamilton, ON, Canada and University of Chicago Hospital, Chicago, IL. UC patients from an ongoing observational database who had achieved endoscopic remission (Mayo score 0) were included. Index colonoscopy was the first colonoscopy where Mayo 0 was achieved. These patients were classified based on their histologic activity: normal (no architectural changes or evidence of UC), inactive colitis (architectural changes but absence of acute inflammation), or active colitis (neutrophils in epithelium, crypt destruction, and/or erosions/ulcers). The primary outcome was time to relapse (defined as symptomatic flare with escalation of medical therapy, UC-related hospitalisation, colectomy, or development of colorectal cancer/dysplasia). Secondary outcomes included reasons for relapse and the association between other baseline variables and risk of relapse. A Cox proportional hazards model was used to evaluate the association of baseline factors with the outcome of relapse.

Results
269 patients with UC and endoscopic remission were included in this study. According to a Kaplan–Meier survival curve analysis, there was no significant difference based on histologic activity with regards to time to relapse (log-rank p = 0.96)(See Figure). Patients with active colitis on histology did not have a higher relapse rate compared with those with inactive colitis (hazard ratio 1.11, p = 0.77), after adjustment for covariates. Older age, 5-aminosalicylate use, and disease location (both left-sided and pan-colitis) were found to be significantly associated with a lower rate of relapse. Symptomatic flare with an escalation of medical therapy accounted for the majority of relapses (80.4%).

Conclusion
Histologic remission did not impact time to relapse in UC patients who had achieved endoscopic remission. This suggests against targeting histologic remission in patients who have achieved endoscopic remission.
P634 Predictors of response and course in patients with inflammatory bowel disease treated with biological therapy: The Danish IBD-Biobank project
Authors: Zhao M , Bendtsen F , Petersen A M , Larsen L , Jess T , Dige A , Hvas C , Seidelin J , Burisch J 
Published: January 2020

Abstract

Background
Biologic treatment has revolutionised the treatment of inflammatory bowel diseases (IBD) and has been shown to reduce surgery and hospitalisation rates in patients with severe disease. Up to one-third of patients do not respond to first-line biologic drugs and another third loses response with time. This highlights an unmet need for optimising the use of biologics and for predicting treatment response to biologics. We present the initial recruitment stages and experimental pipeline for The Danish IBD Biobank which aims to identify predictive biomarkers of response and disease course in patients with IBD who receive biologics.

Methods
The Danish IBD Biobank constitutes a multicenter prospective cohort study aiming to include 840 biological-naïve adult patients with IBD who initiate biologic therapy in a three-year period from May 2019 and onwards. Primary outcomes are the occurrence of primary non-response (PNR) evaluated at week 14–16 and loss of response (LOR) evaluated during the entire follow-up. Patients will be followed with clinical data for at least one year or until May 2022 and sampled for blood, stool and intestinal tissue during the first year of treatment. Blood and stool samples are collected at each visit for biologic treatment and upon change in drug type, dosing or discontinuation. Intestinal tissue is sampled whenever an endoscopy is performed and after one year of treatment (Figure 1).

Results
As of 15 November 2019, 132 patients have been recruited to the cohort. Biologic treatment was indicated due to acute severe ulcerative colitis (UC) or chronic active UC in 13% and 43% of patients, respectively, while 38% and 6% received treatment for luminal Crohn’s disease (CD) and perianal CD. In accordance with national guidelines issued by the Danish Medicines Council, infliximab was the most commonly used first-line drug (98%), followed by vedolizumab (2%) and adalimumab (0.8%). Among 68 patients who have completed induction therapy so far, PNR occurred in 35% (62% UC, 38% CD). Among those with PNR, 50% switched class, 21% discontinued treatment and 29% underwent surgery. Blood and stool samples and intestinal biopsies are stored in a biobank awaiting characterisation of RNA and protein expression using multiplex immunoassay, 16S and Illumina sequencing, and characterisation of mucosal gene and protein expression (Figure 2).

Conclusion
The Danish IBD Biobank project aiming to identify predictive transcriptomic, microbial and proteomic biomarkers associated with treatment response and outcomes to biological therapy in a prospective cohort of biological-naïve IBD patients has been successfully launched.

Funding
This study is funded by an unrestricted grant from Takeda A/S and public fund hosted by Hvidovre Hospital.
P635 Superior outcomes with early biologic-combination treatment in Crohn’s Disease: Data from an international inception cohort
Authors: Matheeuwsen M , Vermeijden K , Bossuyt P , Pouillon L , Baert F , de Boer N , Duijvestein M , Löwenberg M , Ponsioen C , Bemelman W , D’Haens G , Gecse K 
Published: January 2020

Abstract

Background
Crohn’s disease (CD) is characterised by intestinal inflammation leading to progressive bowel damage. Over the past years, treatment goals have evolved from clinical remission to prevention of structural bowel damage. It is currently unknown which treatment options and sequences lead to superior outcomes in patients with newly diagnosed CD.

Methods
The aim of this study was to compare different treatment strategies and associated outcomes in newly CD. We performed a retrospective study in adult patients diagnosed with CD in Amsterdam (The Netherlands), Bonheiden or Roeselare (Belgium) between 2009 and 2019. Based on first-line treatment choice, patients were assigned to one of the five pre-defined treatment strategies. The primary outcome was time to treatment failure, defined as a switch to another CD treatment, escalating CD treatment, need for endoscopic balloon dilation or CD-related surgery, CD-related hospitalisation or a new perianal fistula. Time to treatment failure was compared between different treatment groups using Kaplan–Meier analysis and Cox proportional hazard models.

Results
In total, 188 newly diagnosed patients were included. Treatment with corticosteroids only as first-line treatment (group 1) was started in 35 patients, immunomodulators (azathioprine, 6-mercaptopurine or methotrexate; group 2) in 87 patients, biological therapy (infliximab, adalimumab or vedolizumab; group 3) in 26 patients, and biological therapy in combination with an immunomodulator (group 4) in 25 patients. Fifteen patients underwent direct surgery (group 5). Baseline characteristics (C-reactive protein, CD Endoscopic Index of Severity, Simple Endoscopic Score for CD, smoking status) were similar between the different treatment groups, although group 5 had significantly more patients with stricturing (Montreal B2) and penetrating (Montreal B3) disease subtypes [Table1]. Log-rank test revealed significantly longer median time to treatment failure in group 5 (573 days; 95% confidence interval (CI) 0, 1274; hazard ratio (HR) 0.37), group 4 (1077 days; 95% CI 436, 1717; HR 0.26) and group 3 (337 days; 95% CI 270, 403; HR 0.40) compared with group 2 (121 days; 95% CI 88, 153) (p ≤ 0.01). Median time to treatment failure in group 4 (1077 days; 95% CI 436, 1717; HR 0.35) was significantly longer compared with group 1 (195 days; 95% CI 141, 248) (p &lt; 0.01) (Table 2; Figure 1).

CD Endoscopic Index of Severity (CDEIS), Simple Endoscopic Score for CD (SES-CD), *based on n = x patients.

Conclusion
These real-world data seem to show superior treatment survival in newly diagnosed CD patients receiving first-line treatment with biologicals (as mono- and combination therapy) and early surgery compared with patients receiving first-line treatment with immunomodulators alone.
P644 Post-operative Crohn’s disease recurrence in Glasgow: How common is it and does deprivation matter?
Authors: Brownson E , Shields S , Derakhshan M H , Macdonald J , Nicholson G , Seenan J P 
Published: January 2020

Abstract

Background
50% of patients with Crohn’s disease (CD) will have surgery within the first 10 years, with 35% requiring additional surgery in the following decade. The REMIND cohort-linked male gender, smoking and previous resection to recurrence1. The link between CD and deprivation is debated, while its influence on recurrence is unknown. We aimed to define our local post-operative CD population, highlighting recurrence rates and associated risk factors.

Methods
CD resections between 2008 and 2014 were identified from NHS Greater Glasgow and Clyde Pathology Archive. Data including gender, age at diagnosis/resection, Montreal classification and smoking status was obtained from the Electronic Patient Record (EPR). Scottish Index of Multiple Deprivation (SIMD) score was determined by postcode and was ranked 1–5 (most to least deprived). Five years of follow-up data were collected. The type of recurrence was recorded as clinical recurrence - symptom flare requiring a course of steroids or inpatient admission; biochemical recurrence—faecal calprotectin &gt;250 µg/l; endoscopic recurrence; or surgical recurrence—the need for further Crohn’s disease-related surgery.

Results
304 patients (59.5% female) were included. Median age at diagnosis was 29 (range 3–82 years) and at resection was 43 (range 17–85 years). 52.9% of patients were never-smokers, 16.5% were ex-smokers and 30.6% were current smokers. 33.6% of patients had a SIMD score of 1. Eighty-two per cent had ileal, colonic or ileocolonic involvement. 46.7% of patients had clinical recurrence, 48.7% biochemical recurrence and 31.6% endoscopic recurrence. 15.8% required further surgery for CD.
For clinical recurrence, younger age at diagnosis (p = 0.012, and younger age at resection (p = 0.002) were significant determinants. Gender, smoking and SIMD were not significantly associated with recurrence. Chemical recurrence showed similar associations. Similarly, for surgical recurrence, younger age at diagnosis (p = 0.030, and younger age at resection (p = 0.003) were significant determinants. Male gender was the only risk factor for endoscopic recurrence (OR=1.88, 95% CI: 1.13–3.08).

Conclusion
Our data suggest rates of post-operative recurrence in line with published data. Risk factors were similar to those identified in the REMIND study, with younger age at diagnosis/resection associated with higher rates of recurrence. Our data suggest sociodemographic deprivation does not influence recurrence rates; however,, more work is needed to validate this.

References
P654 Influence of the interval of time between anti-TNF and vedolizumab or ustekinumab in the response to treatment in patients with inflammatory bowel disease
Authors: Bastón Rey I , Costa M , Calviño-Suarez C , Mauriz-Barreiro V , De la Iglesia D , Gonzalez J , Ferreiro-Iglesias R , Dominguez- Munoz J E , Barreiro-de Acosta M 
Published: January 2020

Abstract

Background
There is no evidence about the time that it is reasonable to wait until starting Vedolizumab (VDZ) or Ustekinumab (UST) in case of loss of response to anti-TNF therapy. The aim of our study was to evaluate whether the time between the change from any anti-TNF drug to VDZ or UST had an influence on the risk of treatment failure and the rate of adverse events or severe infections.

Methods
A retrospective, observational single-centre study was designed. Inclusion criteria were all adult patients with moderate-to-severe IBD who started treatment with VDZ or UST due to loss of response to anti-TNF (Infliximab or Adalimumab). Exclusion criteria were patients who had received treatment for different indications such as prevention of recurrence or extra-intestinal manifestations. Patients that changed directly from VDZ to UST or from UST to VDZ were also excluded. We defined two groups of periods based on the interval of time between the last dose of anti-TNF and the first dose of VDZ or UST: Group A: early (≤30 days), Group B: late (31–60 days). Patients that had a waiting time of over 60 days were also excluded. Treatment failure after the initiation of VDZ or UST was defined as the need for dose intensification, surgical resection, therapy removal for ineffectiveness or adverse reaction. The existence of infections was also evaluated. Results are shown as percentages, median, range and Hazard Ratio (CI 95%). Fisher test and Cox Regression analysis were also performed.

Results
46 patients (45.6% CD) were consecutively included (mean age 47.6 years). 17 had initially been treated with Infliximab and 29 with Adalimumab. Thirty patients were changed to VDZ and 16 to UST. Twenty-three patients were included in Group A and 23 in Group B. Treatment failure was observed in 20 patients: 9/23 in group A and 11/23 in group B with a mean follow-up of 323 days (range 152–432). The duration of the interval of time between stopping anti-TNF and starting VDZ or UST was not associated with increased risk of treatment failure (p = 0.25) with a median of time until loss of response of 252 days (range 98–432 days) in Group A and 168 days (range 131–418 days) in group B (Figure 1). No differences were found between patients with CD or UC (p = 0.23) and no differences were found in starting with VDZ or UST. There was 1 adverse event that forced a stopping of treatment in group A. No infections that required hospitalisation were observed.

Conclusion
The interval of time between anti-TNF and VDZ or UST had no influence on the rates of treatment failure, adverse events or infections in our cohort.
P661 Post-operative prophylaxis with anti-TNF in patients with Crohn’s disease who are anti-TNF experienced is associated with higher rates of prophylaxis failure
Authors: Aharoni Golan M , Ollech J , Avni Biron I , Broitman Y , Snir Y , Banai Eran H , Leibovitzh H , Goren I , Wasserberg N , Dotan I , Yanai H 
Published: January 2020

Abstract

Background
Anti-TNF therapy is the most effective strategy for post-operative prophylaxis in patients with Crohn’s disease (CD) who are considered to be at high risk for recurrence. However, some patients fail to maintain long-term remission under these therapies. We aimed to assess predictors for the efficacy of post-operative anti-TNF therapy.

Methods
Patients with CD who underwent a curative bowel resection and were given post-operative anti-TNF prophylaxis between 2010 and 2019 were identified, and their data analysed retrospectively. Patients were assessed for disease recurrence at their first post-operative colonoscopy, a Rutgeerts score of &gt;2a or clinically active disease that required a change in treatment was considered prophylaxis failure.

Results
Overall, 51 patients were included in our analysis. Male: 23 (45%); most of them had a penetrating complication (n = 23, 63%) that required surgery. Median age at surgery: 32 years (IQR 26–46). Anti-TNF therapy was started within a median of 9 weeks (IQR 6–14) post-surgery. Anti-TNF naïve: 14/51; 37/51 were anti-TNF experienced; of whom, 23 (62%) were treated with the same anti-TNF given before surgery. Disease recurrence occurred in 23 patients (45%) within a median follow-up of 13 months (IQR 8–26). Of the patients with disease recurrence, 10 (43%) were male, the median age of CD diagnosis was 26 years (IQR 15–49), 15 (65%) had penetrating disease, 5 (21%) had previous surgery, and 5 (21%) were active smokers. Disease recurrence was more common among patients operated at an older age (43 vs 33 years, p &lt; 0.05) and in patients who had previous exposure to anti-TNF agents (56% vs. 14%, p = 0.01). In a multivariate Cox regression analysis, previous anti-TNF exposure was predictive of disease recurrence after surgery (HR 5.5, 95% CI 1.3–24, p &lt; 0.05).

Conclusion
Post-operative prophylaxis using anti-TNF therapy in patients with CD who are anti-TNF experienced is associated with high rates of disease recurrence. This failure might be attributed to immunogenicity or pharmacodynamic failure. Closer monitoring and early treatment modifications should be considered in anti-TNF experienced patients.
P671 Natural history and clinical outcomes of patients with ulcerative colitis who are intolerant to 5-aminosalicylic acid agents: A multi-centre cohort study
Authors: Madarame A , Kinoshita H , Yamaguchi T , Izumi Y , Nishikawa Y , Shonai S , Tatsuno M , Ishii Y , Yaguchi K , Nakamori Y , Ikeda A , Araki K , Hirayama A , Ogashiwa T , Fuji A , Suzuki R , Kimura H , Kunisaki R 
Published: January 2020

Abstract

Background
Five-aminosalicylic acid (5-ASA) compounds are used as the primary treatment for ulcerative colitis (UC); however, some patients are intolerant to this drug. There have been few studies on the natural history and clinical outcomes of 5-ASA intolerant patients. The aim of this study was to elucidate the clinical outcomes of 5-ASA intolerant patients in terms of colectomy, immunomodulator use, and biologic (anti-tumour necrosis factor (TNF) and Vedolizumab) therapy.

Methods
Data were obtained by a retrospective review of the charts of 2065 consecutive patients with UC who were treated with 5-ASA compounds at our tertiary referral inflammatory bowel disease (IBD) centre and a related IBD clinic from 2010 to 2020. Patients were considered to be intolerant to 5-ASA if they discontinued the drug because of any type of adverse effect. The cumulative rates of immunomodulator-, biologic- and colectomy-free survival rates in 5-ASA tolerant and intolerant patients were calculated using the Kaplan–Meier method. Additionally, Cox regression was used to analyse other factors besides 5-ASA intolerance contributing to clinical outcomes.

Results
Intolerance to 5-ASA was identified in 268 patients. The cumulative probability of colectomy within 10 years in 5-ASA intolerant patients was 23%, which is significantly higher than that in tolerant patients, 10% (log-rank test &lt; 0.0001). Within 10 year, 63% of 5-ASA intolerant and 20% of tolerant patients received immunomodulators (log-rank test &lt; 0.0001); and 37% of 5-ASA intolerant and 11% of tolerant patients received biologic therapy (log-rank test &lt; 0.0001). Cox regression multivariate analysis identified that younger age, disease extent and 5-ASA intolerance were predictors of colectomy.

Conclusion
In this retrospective cohort study, 5-ASA intolerant patients had worse clinical outcomes than those who tolerated 5-ASA treatment. This is the first report on the long-term prognosis of 5-ASA intolerant patients.
P678 Effect of accelerated infliximab induction on short-term outcomes of paediatric acute severe ulcerative colitis
Authors: Coronel-Arismendi M B , Pujol Muncunill G , Minguez-Rodríguez B , Feo-Ortego S , Guevara-Caviedes L N , Vila-Miravet V , Martin De Carpi F J 
Published: January 2020

Abstract

Background
Due to a higher inflammatory burden and a rapid clearance of infliximab (IFX) in Acute Severe ulcerative colitis (ASUC), the accelerated IFX induction may be considered (IFX up to 10 mg/kg per dose, at week 0, 1 and 4–5) in those patients who need to start second-line treatment. The aim of our study is to describe the short-term outcomes of ASUC pediatric patients who have received an accelerated IFX induction regimen in our Unit.

Methods
In a retrospective study we collected data from patients with ASUC who received treatment with accelerated IFX induction. We analyzed demographic, clinical and analytical data as well as treatment adverse events from medical records. The short-term outcomes (at the end of the induction and at 3 months) were analyzed based in the Paediatric Ulcerative Activity Index (PUCAI)) and analytical parameters (haemoglobin, C reactive protein (CRP), erythrocyte sedimentation rate (ESR) and albumin.

Results
Six patients with ASUC who received accelerated IFX induction were included (5 male; median age at diagnosis 10.5 years (IQR: 2–15); mean time from diagnosis to ASUC flare: 1.8 years (IQR: 0–9 years)). At disease onset, 5/6 patients presented with pancolonic involvement (E4) with an average PUCAI of 55 points. At ASUC flare all of them presented pancolonic involvement with a PUCAI over 65 points, 50% of them had anaemia, 66.6% elevation of inflammatory markers (CRP and/or ESR) and 50% hypoalbuminemia. The patients received an accelerated IFX induction with IFX at 10 mg/kg at 0, 1 and 4 - 5 weeks without adverse events. After accelerated IFX induction regimen 5/6 patients showed clinical response and normalisation of laboratory tests (haemoglobin, inflammatory markers and albumin). One patient presented treatment failure needing surgery (colectomy rate 16.6%). At 3 months follow-up, no new patients needed colectomy. One patient had an infusional reaction and was changed to Vedolizumab treatment maintaining remission, the other 4 patients were maintained on IFX treatment (1 clinical remission, 3 mild clinical activity). The overall colectomy rate after accelerated IFX induction remained in 16,6%.

Conclusion
In our cohort of ASUC patients treated with an accelerated IFX induction regimen we observed an 83.3% free colectomy rate at short-term, being this regimen a valid therapeutic option to avoid surgery. Prospective and comparative studies are needed to determine the efficacy of this strategy in reducing the colectomy rate, both in the short-and long-term follow-up.