bluuebunny/crossref_metadata_2025_split huggingface dataset:
P624 Investigating the symptom burden among European patients with moderate-to-severe Crohn’s disease using a real-world survey
Authors: Burisch J , Hart A , Sturm A , Knight H , Rudolph C , Meadows R , Oortwijn A , Weatherby S , Rolph R , Dawod F , Armuzzi A 
Published: January 2023

Abstract

Background
Despite treatment, patients with Crohn’s disease (CD) experience symptoms that affect their health-related quality of life (HRQoL). Understanding how CD affects HRQoL reveals valuable insight into disease impact. We aimed to examine the disease burden in patients with moderate-to-severe CD in remission vs not in remission using real-world, gastroenterologist (GE)- and patient-reported data.

Methods
Data were drawn from the Adelphi Inflammatory Bowel Disease (IBD) Disease Specific Programme,1 a point-in-time survey conducted in France, Germany, Italy and Spain from October 2020 to March 2021. GEs collected data from the next 5–8 consecutive patients (≥18 years old, not involved in clinical trials) with a CD diagnosis who they saw in clinical practice. GEs reported patient demographics, clinical characteristics (including remission status) and treatment history. Patients completed questionnaires on their treatment satisfaction, symptoms and HRQoL (Short Inflammatory Bowel Disease Questionnaire [SIBDQ] and EQ-5D scores). Scores were compared among patients in remission vs not in remission using propensity score matching (PSM).

Results
Overall, 133 GEs reported on 538 patients with CD (Table 1). Overall, 66.0% of patients were employed, and of those not working, 24.3% were not working due to CD. Most patients (70.9%) had received ≥2 lines of treatment and 43.3% of patients were receiving a tumour necrosis factor (TNF) inhibitor. Of 427 patients from whom complete data were available and were therefore included in PSM analyses, 70.0% (n=299) were in remission. Although patients in remission were generally less likely than those not in remission to experience CD symptoms, they were still moderately likely to experience symptoms such as fatigue/tiredness and abdominal pain (Figure 1). Similarly, whilst patients in remission had better mean SIBDQ and EQ-5D scores than those not in remission, their scores still indicated diminished HRQoL (Figure 2). Of patients for whom symptom data were provided, 39.2% were either not satisfied with their current treatment or believed that better disease control could be achieved. A higher proportion of patients who were dissatisfied with their treatment reported residual symptoms than those who were satisfied, especially abdominal pain, non-bloody diarrhoea and fatigue/tiredness (Figure 3). Characteristics of patients in remission with mucosal healing were similar regardless of whether remission was confirmed by endoscopy.

Conclusion
A substantial proportion of patients with CD, even those in remission, experience high symptom burden and diminished HRQoL despite treatment. There is a need for therapies that provide more comprehensive disease control.
1. Anderson P et al. Curr Med Res Opin 2008:24;3063–72.
P631 Long-term safety of vedolizumab versus other biologic agents in ulcerative colitis (UC) and Crohn’s Disease (CD): Results from a large multinational prospective observational study
Authors: Louis E , Sebastien S , Siegmund B , Bossuyt P , Danese S , de Boer N , Loftus E , Moum B , Peyrin-Biroulet L , Schreiber S , Zhou J , Wernicke J , Angellotti E , Siegel C 
Published: January 2023

Abstract

Background
Vedolizumab (VDZ) is a gut-selective humanised monoclonal anti-α4β7 integrin antibody for treatment of UC and CD. This post-authorization safety study (PASS) compared long-term safety in patients (pts) treated with VDZ or other biologics for UC or CD.

Methods
This was a prospective, observational, multicentre, cohort study in pts with UC or CD starting treatment with VDZ or other biologics (NCT02674308, EUPAS6469). Pts were biologic naïve (VDZ=35%, Other biologic=65%) or had prior exposure to biologics other than VDZ and were followed for up to 7 yrs. Pts were treated under usual standard of care as directed by their physician with no discontinuation from the study due to physician-directed treatment changes. The primary safety outcome was serious infections and was compared between cohorts using a Cox proportional hazards model adjusted by propensity score (with other biologics as reference). Secondary safety outcomes were adverse events (AE) of special interest (AESI) as listed in Tables 2 and 3.

Results
In total, 5208 patients were enrolled across 21 countries between Mar 2015 and Jul 2019. The full analysis set comprised 5008 pts (VDZ=2502; other biologic=2506) and mean (SD) study duration was 37.4 (14.1) months. Consistent with the observational nature of the study and the current standard of care, the baseline characteristics in the two cohorts were imbalanced (Table 1). The overall treatment-emergent Adverse Event (AE) rate was 61.3% (VDZ) and 59.5% (other biologic), with serious AEs in 27.5% (VDZ) and 25.7% (other biologic), respectively. In UC pts, the incidence rate (IR) of serious infections were: 0.014 (95% CI: 0.010, 0.019) [VDZ] and 0.015 (0.010, 0.023) [other biologic], with a hazard ratio (HR) of 1.018 (0.931, 1.114), p=0.70 (Table 2). In CD pts, corresponding findings were 0.012 (95% CI: 0.008, 0.017) [VDZ] and 0.006 (95% CI: 0.004, 0.009) [other biologic] with HR of 1.035 (0.959, 1.117), p=0.38 (Table 3). The incidence of primary and secondary safety outcomes is reported in Table 2 for UC and Table 3 for CD. There were no safety issues relating to pregnancy and no cases of PML observed. There were 19 deaths in the VDZ cohort (1 case of pneumonia deemed as treatment-related); and 13 deaths in the other biologic cohort, 2 cases deemed treatment-related (one case septic shock and pneumonia; one case non-small cell lung cancer). Clinical outcomes and quality of life (QoL) measures were comparable between cohorts.

Conclusion
In this long-term, prospective, real-world observational study of a large multinational population under routine standard of care there was no new safety signal identified in relation to VDZ. Results are consistent with the known safety profile of VDZ.
P638 Effectiveness and safety of risankizumab induction therapy for 100 patients with Crohn’s disease: a GETAID multicentre cohort study
Authors: Fumery M , Defrance A , Roblin X , Altwegg R , Caron B , Hebuterne X , Carmen S , Meyer A , Nachury M , Laharie D , Nancey S , Le Berre C , Serrero M , Geyl S , Gilletta C , Ah Soune P , Duveau N , Uzza M , Abitbol V , Biron A , Tran Minh M L , Paupard T , Vuitton L , Elgharabawy Y , Peyrin-biroulet L ,   GETAID
Published: January 2023

Abstract

Background
Phase III trials have demonstrated the efficacy of risankizumab in moderate-to-severe Crohn’s disease (CD), but no real-world data are currently available. We aimed to assess the short-term effectiveness and safety of risankizumab in patients with CD.

Methods
From May 2021 to May 2022, all patients with refractory luminal CD treated with risankizumab in 22 French GETAID centers were retrospectively included. The primary endpoint was steroid-free clinical remission at week 12 (Harvey-Bradshaw (HB) score &lt; 5). Secondary endpoints included clinical response (≥ 3-point decrease of HB score and/or (HB) score &lt; 5), biological remission (CRP ≤ 5 mg/L), need for CD-related surgery, and adverse events.

Results
Among the 100 patients included, all have been previously exposed to anti-TNF agents, 94 to vedolizumab, 98 to ustekinumab (all exposed to at least three biologics) and 61 had previous intestinal resection. All but three (97%) received a 600 mg risankizumab intravenous induction at weeks 0-4-8. At week 12, steroid-free clinical remission was observed in 45.8% of patients, clinical remission in 58% and clinical response in 78.5%. Absence/mild abdominal pain with normal stool frequency was noted in 50% of patients at week 12. Biological remission was observed in 50% of patients. Six patients discontinued risankizumab before the week 12 visit due to lack of efficacy. CD-related hospitalization was needed in six patients, and three underwent intestinal resection. In multivariable analysis, only a history of ustekinumab loss of response (vs primary failure) (Odds Ratio (OR), 2.80 ; 95%CI, 1.07 – 7.82; p=0.041) was significantly associated with clinical remission at week 12. Twenty adverse events (AE) occurred in 20 patients including 7 serious AE corresponding to 6 CD exacerbation and one severe hypertension.

Conclusion
In a cohort of highly refractory patients with luminal CD and multiple prior drug failures including ustekinumab, risankizumab induction provided clinical response in about 3 out of 4 patients and steroid-free clinical remission in about half of patients.
P639 Percutaneous drainage vs surgery as definitive treatment for anastomotic leak after intestinal resection in patients with Crohn’s disease.
Authors: Belvedere A , Dajti G , Larotonda C , Angelicchio L , Rizzello F , Gionchetti P , Poggioli G , Rottoli M 
Published: January 2023

Abstract

Background
Anastomotic leak remains one of the most relevant complications after intestinal resection for Crohn’s disease (CD). While surgery has always been considered the standard treatment for perianastomotic abscess or collection, percutaneous drainage (PD) has been proposed as a potential alternative.
The aim of this study was therefore to compare the success rate of percutaneous drainage with that of surgery for the management of anastomotic leak in CD patients.

Methods
Retrospective, single-centre study including all consecutive patients who were diagnosed with an anastomotic leak as a complication of intestinal resection for CD between 2004 and 2022. Patients requiring emergency surgery due to generalised peritonitis or clinical instability were excluded. Anastomotic leak was defined as a perianastomotic fluid collection confirmed by radiological findings within 30 days from surgery. Patients underwent either PD or surgery as a primary treatment for the complication. The success after PD was defined as the removal of the drainage with clinical and radiological resolution of the complication. The need for further surgical treatment was considered as a failure in both groups.
Primary aim: to compare the success rate of PD vs surgery. Secondary aims: to compare the outcomes at 90 days after the procedures; to identify the variables associated with the indication to PD.

Results
Among the 47 patients included, 25 (53%) underwent PD and 22 (47%) surgery. Table 1 shows the outcomes by the procedure.

Success rate was 84% in PD and 95% in surgery group (p=0.20). The median time to success was 14 days after PD (drainage removal) and 12.5 days after surgery (discharge) (p=0.92). Similar rates of post-procedure medical (12% vs 18%, p=0.55) and surgical (24% vs 36%, p=0.62) complications were shown. An ileostomy was required in 91% of surgery cases. At 90 days, similar rates of discharges (100% vs 95%, p=0.28), readmissions (8% vs 0%, p=0.18) and reoperations (16% vs 9%, p=0.48) were observed between PD and surgery cases, respectively.
In the multivariate analysis (Table 2), PD was more likely to be performed in patients whose anastomotic leak was diagnosed later after surgery (OR 1.25, 95%CI 1.03-1.53, p=0.027), in those who underwent an ileo-colic anastomosis alone (OR 3.72, 95%CI 2.29-12.45, p=0.034) and in those who were treated after 2016 (OR 6.36, 95%CI 1.04-39.03, p=0.046).

Conclusion
The present study confirms that PD is a safe and effective procedure to treat anastomotic leak and perianastomotic abscess in CD patients. Surgery, in particular, is associated with a high risk of stoma formation, which would require a subsequent operation. PD should be indicated in all eligible patients as an effective alternative to surgery.
P655 MadCAM1 Negativity of Lamina Propria Endothelial Cells is Associated with Non-Response to Vedolizumab in Inflammatory Bowel Disease Patients
Authors: Zelinkova Z , Podmanicky D , Berakova K , Kadleckova B 
Published: January 2023

Abstract

Background
Vedolizumab (VDZ), a monoclonal antibody against α4β7 integrin has been shown to be effective in inducing and maintaining remission in inflammatory bowel disease (IBD). By blocking α4β7, it is preventing the homing of lymphocytes through binding to mucosal vascular adressin cell adhesion molecule 1 (MadCAM1) localised on the intestinal endothelial cells. We have previously reported that MadCAM1 is expressed to various extent on lamina propria endothelial cells of IBD patients and that this expression is stable over time. The aim of the present study was to analyse whether expression of MadCAM1 was related to the response to VDZ in IBD patients.

Methods
All IBD patients treated with VDZ in one referral IBD centre were included. The biopsies or resection specimen from the inflamed intestinal tissue were stained by immunohistochemistry for MadCAM1 expression. Clinical response to vedolizumab was assessed in patients with the minimal treatment duration of 10 weeks and the response rate between patients with positive and negative MadCAM1 were analyzed by Fisher`s exact test.

Results
In total, 92 IBD patients were treated with VDZ; for 83 of them intestinal biopsies or surgical specimen were available for assessment of MadCAM1 expression. In four patients (5%) no expression of MadCAM1 was detected, remaining 79 patients expressed MadCAM1 to various extent.
Overal, 30 patients (36%) were non-responders to VDZ treatment. With regards to MadCAM1 expression, 67% of patients expressing MadCAM1 responded to VDZ (53 patients) while none of the patients negative for MadCAM1 responded to treatment (p=0.0171).

Conclusion
Lack of MadCAM1 expression in intestinal endothelium is associated with clinical non-response to vedolizumab.
P660 Body composition and health-related quality of life in adult Crohn’s Disease during clinical remission: The INTICO2 cohort study
Authors: McDonnell M , Sartain S , Westoby C , Katarachia V , Davis C , Cummings F , Wootton S 
Published: January 2023

Abstract

Background
A reduction in the absolute or relative mass of lean tissue or muscle mass in the context of disease and/or malnutrition are well-described features associated with poor prognosis. Conversely, excessive adiposity may lead to metabolic disease, increased inflammation and has been linked to adverse CD outcomes. Bioelectrical impedance analysis (BIA) allows estimation of fat-mass index (FMi kg/m2) and fat-free mass index (FFMi kg/m2) which can be expressed standardised as Z scores using device-specific age and gender reference ranges. Here we report the body composition and relationship between BMI, elevated FMi and reduced FFMi Z scores and patient reported outcome measures in an adult cohort in CD clinical remission.

Methods
194 adult CD outpatients in clinical and biochemical remission were recruited from a single tertiary IBD service (Harvey Bradshaw Index &lt;5 and calprotectin &lt;250µg) as part of the INTICO2 observational study. 55 had undergone previous intestinal resection, 81 were on biological therapy, 67 immunomodulator and 33 both. Subjects needed to be in intestinal continuity and not currently receiving either exclusive or partial EN or IV nutrition. Body composition was assessed using BIA (seca mBCA 515) and expressed as FMi and FFMi Z scores. Health and disease-related quality of life was assessed using Short Form 36 (SF36) and the fatigue-specific PROM FACIT-F.

Results
The Median BMI of the cohort was 26.1 (18.0-48.9) Kg/m2. One subject was underweight (≤18.5) by BMI, 37% of patients (71/194) were overweight (BMI ≥25), of which 47 (24% of cohort) were obese (BMI≥30). 16/97 of men and 11/97 of women were below the 5th centile (SDS score &lt;-2) for age and sex matched values for FFMi, respectively. Of the 27 individuals with reduced lean mass, 20 had a normal BMI (20-25), 2 were overweight (25-30). 14/97 and 21/97 of women were above the 95th centile for FMI Z-scores (SDS score &gt;2), all had BMI over 30. Excessive fatigue was present among the population affecting 25% (49/194). FMiz was correlated to excessive fatigue among women (r- 0.236 p&lt;0.05), but there was no relationship to FFMiZ among either sex.

Conclusion
While weight loss is a recognised presentation of CD, this characterisation of a large outpatient adult cohort in remission found the commonest BMI-defined malnutritional states to be overweight or obese. In the population of individuals with predominantly normal or elevated BMI, sarcopenia was common, masked by excessive adiposity and may not have been appreciated without BIA assessment of body composition. Body composition analysis estimates of excessive age and sex matched adiposity was correlated to excessive fatigue, which was common in the population.
P691 Disparate care: rates of treat to target among patients with inflammatory bowel disease
Authors: Haydek J , Oonk A , Cheng D , Ahmed W , Click B , Fennimore B , Gerich M , Hou J , Scott F 
Published: January 2023

Abstract

Background
Inflammatory bowel diseases (IBD) therapies are limited by low response rates and risks of loss of response. Treat to target (T2T) algorithms aim to maximize the benefit of therapies by establishing a framework for assessing patient reported outcomes, biochemical evaluation (C-reactive protein (CRP) or fecal calprotectin (FC)), and structural assessment via endoscopy or enterography. There are limited data on adoption rates of T2T in real-world clinical practice. We aimed to describe rates of T2T utilization in a large regional medical system in the United States.

Methods
A retrospective cohort study was conducted from 2015-2021. Individuals with IBD starting a new biologic therapy were identified. Collected data included demographics, laboratory data, current medications, and procedure and imaging data. Patients were categorized based on whether they completed T2T, defined as CRP or FC testing at 2-4 months after starting a new therapy, and structural assessment, defined as colonoscopy, sigmoidoscopy, capsule endoscopy, or enterography within 6-12 months after starting a new therapy. Complete adherence was defined as both of these criteria being met. Social deprivation index (SDI), with higher values associated with higher rates of social deprivation, was derived using mail codes. T-tests, Pearson chi-square tests, ANOVA and multivariable logistic regression were used for comparisons.

Results
7,962 patients were identified (Table 1). Rates of T2T were low; only 7.81% of patients completed biochemical monitoring at 2-4 months (0.83% FC, 8.65% CRP, 1.76% both), 9.80% completed structural assessment, and 3.43% completed both. In univariable logistic regression, higher age (OR 0.98, p&lt;0.01), IBD type (UC OR: 0.69, p&lt;0.01), having no insurance (OR 0.84, p=0.02) and low social deprivation index (SDI) (OR 1.004, p&lt;0.01) were associated with lower T2T completion rates.
In multivariable logistic regression, ulcerative colitis (UC), younger age, and lower SDI score were significantly associated with likelihood of completing any T2T (Table 2). When considering biochemical monitoring at 2-4 months, Asian race, UC diagnosis, age, SDI score and year were significantly associated with completion (Table 3). UC diagnosis, year and age were significantly associated with completion of structural assessment (Table 4).

Conclusion
Treat to target completion rates among patients with IBD starting biologic therapies were low in this large cohort. Age and UC diagnosis were negatively associated with completing T2T. Social deprivation score was positively associated with biochemical monitoring. Further research is required to understand barriers to T2T monitoring.
P695 Effectiveness and Safety of Combination Biologic or Small Molecule Therapy in Inflammatory Bowel Disease
Authors: McShane C , Varley R , Fennessy A , Campion J , Ring E , Kelly O , Slattery E , Doherty G , McCarthy J , Kevans D ,   INITIative Network
Published: January 2023

Abstract

Background
Biologic and small molecule therapies have revolutionised the treatment of inflammatory bowel disease (IBD). Despite these advances, there appears to be a therapeutic ceiling with single agent therapy with up to 50% of patients failing to achieve long term remission. Combination of two biologic therapies or a biologic therapy and small molecule agent, with differing mechanisms of action, has the potential to improve IBD therapy outcomes. Information on the effectiveness and safety of this treatment strategy in IBD remains limited.

Methods
A retrospective, multicentre study was carried out at five Irish Academic Centres within the Initiative Network. Combination biologic or small molecule use was defined as concomitant use of two biologics or one biologic and small molecule therapy licenced or undergoing clinical trial assessment for treatment of IBD. Patients who had received combination therapy were identified from institutional databases. Review of clinical records was performed and demographic data collected. Combination therapy persistence was considered a proxy for successful therapy outcome. Adverse events were documented. P values &lt; 0.05 were considered significant in analyses.

Results
The study cohort included 85 patients; 70% Crohn’s disease (CD), 30% ulcerative colitis (UC); median (IQR) number of prior biologic therapies 3 (2 – 3); median (IQR) study follow up 40.71 weeks (13.68 – 82.86). Further baseline characteristics are described in Figure 1. 97 combination therapy trials were undertaken in 85 patients. 13 different combination therapy regimes were utilised with ustekinumab & vedolizumab being the most common regimen. 76.5% (n=65 patients) remained on combination therapy at last follow up. Higher rates of combination therapy discontinuation (p=0.04) and shorter time to combination therapy discontinuation were observed in UC compared with with CD (HR 0.48 [95% CI 0.21-1.11], p&lt;0.05). 3.1% of the study cohort developed a serious or opportunistic infection. No deaths or intensive care unit admissions occurred during study follow up.

Conclusion
Combination therapy is an effective therapeutic strategy with an acceptable safety profile in refractory IBD patients. Randomised controlled trials are required to clearly define the role of combination therapy in the management of IBD.