bluuebunny/crossref_metadata_2025_split huggingface dataset:
P534 Qualitative perspectives of parent and child participants from a trial of faecal microbiota transplant for paediatric ulcerative colitis
Authors: Popov J , Hartung E , Hill L , Chauhan U , Pai N 
Published: January 2020

Abstract

Background
Faecal microbiota transplant (FMT) is being studied across a range of therapeutic indications including ulcerative colitis (UC). Pediatric patients may have unique perspectives on microbiome-based therapeutics given their younger age, fewer comorbidities, and greater susceptibility to microbial influences. We recently conducted the first randomised-controlled trial (RCT) of FMT for pediatric UC (PediFETCh Trial) and conducted qualitative interviews of child participants and their parents. This study aims to describe the experiences and perceptions of these children who received FMT, and their parents.

Methods
Participants in the PediFETCh Trial (ClinicalTrials.gov: NCT02487238) were invited to participate in face-to-face, semi-structured interviews. Interviews were audiotaped, transcribed, and analyzed using open coding (NVivo 12 Pro).

Results
8 pediatric participants and 8 parents were interviewed. Data were summarised across 4 domains and 11 composite themes (Table 1). Most children and parents saw FMT as a ‘safe, natural’ treatment. Prior to enrollment, children were concerned about receiving ‘someone else’s poo’ and potential physical discomfort, while parents were concerned about transmission of enteric infections and psychiatric diseases. Both groups felt their decision to pursue FMT was influenced by frustration with lack of response to medications, and fear of medication-related side effects. Following completion of the study, most children and parents had no concerns about potential side effects of FMT, and children reported feeling ‘completely normal’. Children were split between preferring FMT or medication therapies. The convenience of medications was valued, while others favoured FMT for its symptomatic improvement and perceived naturality. It was noted that some alternative healthcare practitioners did not support patients’ desire to pursue FMT.

Conclusion
Our study offers valuable insight into the experiences of receiving FMT in pediatric participants and their parents. This data suggest a high rate of acceptance and interest in FMT-based therapeutics in this population and offers strategies to improve the delivery of FMT in future pediatric-focused RCTs.
P538 Pregnancy outcomes in women with psoriasis, psoriatic arthritis, Crohn’s disease and ulcerative colitis treated with ustekinumab
Authors: Geldhof A , Volger S , Lin C B , O’Brien C , Tikhonov I 
Published: January 2020

Abstract

Background
Ustekinumab (UST) is indicated for psoriasis (PSO), psoriatic arthritis (PsA), Crohn’s disease (CD), and ulcerative colitis (UC). The recommended dose in CD/UC is generally higher than in PSO/PsA. No adverse pregnancy outcomes were observed in preclinical studies.1 Here we present pregnancy outcomes from spontaneous reporting, clinical studies and registries.

Methods
This dataset includes pregnancies with maternal exposure to UST during pregnancy or within 3 months prior to conception reported to the manufacturer through April 2019.

Results
Overall, 478 maternal pregnancies (334 PSO, 124 CD, 11 UC, 9 PsA) were identified. Mean maternal age was 30.5 years. Most pregnancies (71.3%) resulted in live births (LB, [including 20 preterm births; PTB]). Spontaneous abortion (SA) was reported in 18.4% of cases. Congenital anomalies (CA) were reported in 3.8% (3.3% major CA [MCA]). Pregnancies with UST exposure throughout gestation (12.1%) resulted in 55 (94.8%) LB including 4 (7.3%) PTB, and 5 (8.6%) MCA. Among pregnancies with exposure in Trimester 1 (66.5%), 207 (65.1%) LB including 11 (5.3%) PTB, and 2 (0.6%) MCA were reported. Among PSO/PsA maternal pregnancies, rates were 72.3% LB, 2.0% CA (1.4% MCA), and 16.9% SA; among CD/UC maternal pregnancies, rates were 68.9% LB, 4.4% MCA and 22.2% SA.

Conclusion
Pregnancy outcome data following maternal exposure to UST showed that the prevalence of live births, spontaneous abortions and congenital anomalies were consistent with the general population and TNFi therapies. Pregnancy outcomes in women with CD/UC and PSO/PsA were generally comparable. No apparent safety signals were noted with exposure throughout pregnancy.

Reference
P560 Incidence of joint symptoms in patients with inflammatory bowel disease on treatment with vedolizumab
Authors: RUIZ-RAMIREZ M A , Rodríguez-Merlos P , Suarez C , Plasencia-Rodríguez C , Navarro-Compán V , Poza J , Martin-Arranz E , Sanchez-Azofra M , Rueda-Garcia J L , Garcia-Ramirez L , Franco K , Bonilla G , Peiteado D , Balsa A , Martin-Arranz M D 
Published: January 2020

Abstract

Background
Vedolizumab is a monoclonal antibody that binds to an integrin resulting in gut-selective anti-inflammatory activity. It is indicated for the treatment of inflammatory bowel disease (IBD), both in Crohn’s disease (CD) and ulcerative colitis (UC), but no benefit has been proved on inflammatory joint disease. The aim of this study was to analyse the incidence of the debut of inflammatory joint disease and also analyse the prevalence of outbreak of the previously known joint disease in IBD patients during treatment with vedolizumab.

Methods
Descriptive observational study of a prospective cohort of IBD patients treated with vedolizumab. All patients met the following inclusion criteria: adults &gt; 18 years, histological diagnosis of CD or UC and having received or being currently being treated with vedolizumab. Demographic, clinical and analytical information were obtained from the Hospital’s database from both Gastroenterology and Rheumatology clinical records.

Results
A total of 44 patients (25 with CD and 19 with UC) were included. Of these, most had been pretreated with anti-TNF (41 switchers and 3 patients näive to biological therapy). The mean age of the included patients was 50 ± 15.4 years with predominantly female (54%). The mean follow-up time of patients in this study was 26 ± 10 months. In total, 13 patients (30%) presented joint symptoms during treatment with vedolizumab (8 with EC and 9 with UC). Of these 13 patients, 3 already had previous diagnosis of inflammatory joint pathology (spondyloarthritis), 6 patients debuted with inflammatory joint symptoms during treatment with vedolizumab and 4 mechanical arthralgias. Of the 6 patients with debut of inflammatory profile symptoms, inflammatory pathology was confirmed in 5 patients (spondyloarthritis) and 1 patient presented osteomuscular mechanical pathology. A total of 11 patients with the diagnosed rheumatological disease (25%) were observed in this cohort.

Conclusion
The incidence of inflammatory joint pathology in IBD patients treated with vedolizumab is similar to the one described in other cohorts regardless of the treatment received. Suspension of anti-TNF treatment to switch to vedolizumab may be associated with outbreaks of rheumatic disease. This presents a new challenge in the therapeutic approach, being crucial a multidisciplinary approach.
P577 Ustekinumab in actual clinical practice: our centre experience
Authors: LOPEZ TOBARUELA J M , Sanchez-Capilla A D , Ortega-Suazo E J , Fernandez-Cano M C , Herrador-Paredes M , Cabello-Tapia M J , Martin-Rodriguez M M 
Published: January 2020

Abstract

Background
Crohn’s disease is an entity with wide variability in its clinical manifestations, which mainly affects the gastrointestinal tract, and may also involve another organs. We have a wide variety of treatments available, being the most recent ones biological therapies. One of them is ustekinumab, which due to its innovative mechanism of action has improved the quality of life of many patients with an excellent safety profile.
Our objective was to analyze the baseline situation of 37 patients undergoing treatment with ustekinumab in our centre and the evolution of different clinical and analytical parameters at 12, 24 and 52 weeks after starting it.

Methods
37 patients currently receiving ustekinumab treatment with indication of Crohn’s disease at Virgen de las Nieves Hospital were selected (Tables 1 and 2). Clinical response was analyzed according to the Harvey–Bradshaw Index (HBI) (clinical remission &lt;4, clinical response decrease ≥3 points above the baseline), blood and stool test (CRP and calprotectin) at weeks 12, 24 and 52, need for surgery and safety profile (Table 3).

Results
There are no significant differences in HBI or baseline CRP depending on previous or not treatment with anti-TNF or vedolizumab. No differences in HBI, CRP at weeks 12, 24 and 52 depending on if previous treatment with anti-TNF or vedolizumab. The decrease in the median values of HBI was statistically significant at weeks 12, 24 and 52; as well as CRP values at weeks 24 and 52 (Table 3).
According to HBI, clinical response was obtained in 41,38%, 50% and 61,11% of patients at weeks 12, 24 and 52 and clinical remission in 20,69%, 33,33% and 27,78% respectively (Table 3). No response predictors were identified at week 12 except for non-perianal fistulas associated with a greater response (58,3% vs. 41,7%; p = 0,0459) (Table 4).

Conclusion
In this group of patients potentially difficult to treat (62% previous surgery, long-term disease, 95% previous treatment with immunomodulators and/or biological therapies (66% ≥2 anti-TNF), etc.), ustekinumab achieves clinical response in 41,38%, 50%, 61,11% at week 12, 24 and 52. Surgery was required in 2 cases and only 3 patients suffered relevant adverse effects. In a pivotal study of ustekinumab UNITI-1, 50,6% of patients who received the induction dose of 6 mg/kg had previously been treated with ≥2 anti-TNF, in our group, 65,71%. In our cohort, only 29,73% of patients received corticosteroids concomitantly at the start of ustekinumab treatment vs. 43,3% at UNITI-1. Despite these differences against our group, clinical response and remission data are similar to UNITI-1 (41,38% vs. 37,8% and 20,69% vs. 20,9% respectively). Prospective studies with more patients could identify who would benefit most from this treatment.
P580 Irritable bowel syndrome in inflammatory bowel disease after remission: correlation with remission patterns and inflammation
Authors: Sezgin O , Boztepe B , Altintas E , Çelikcan D 
Published: January 2020

Abstract

Background
The objective of the study is to establish the frequency of irritable bowel syndrome (IBS) in patients with inflammatory bowel disease in clinical and deep remission and correlation with inflammation markers.

Methods
In this study, patients with ulcerative colitis (UC), and with Crohn disease (CD) in clinical remission for at least 6 months enrolled. All of the patients underwent colonoscopy and biopsy specimens were taken to evaluate endoscopic and histopathologic remission. All of the cases were given a questionnaire using the Rome III criteria for IBS and faecal specimens for calprotectin analysis, and blood samples for CRP, sedimentation rate and fibrinogen levels were taken.

Results
IBS frequency was 20.9% in UC cases in clinical remission, 28.9% in CD cases, and did not vary by the presence or absence of endoscopic remission (20,5% vs.22,2% in UC, p:0,727, 25% vs.33,3% in CD, p:0,837) or histopathologic remission (15,7% vs.26,6% in UC, p:0,723, 21,4% vs.33,3% in CD respectively, p:0,999). The incidence of IBS did not change statistically with deepening of remission in both diseases. It was not related to inflammation markers

Conclusion
IBS frequency among IBD patients in clinical remission was 21–29% and did not vary by the presence or absence of endoscopic or histopathologic remission or by inflammation markers levels. This suggests that IBS may not be related to ongoing subclinical inflammation in IBD in remission.
P595 Feasibility and performance of a fully automated endoscopic disease severity grading tool for ulcerative colitis using unaltered multisite videos
Authors: Stidham R , Yao H , Bishu S , Rice M , Gryak J , Wilkins H J , Najarian K 
Published: January 2020

Abstract

Background
Endoscopic assessment is a core component of disease severity in ulcerative colitis (UC), but subjectivity threatens accuracy and reproducibility. We aimed to develop and test a fully-automated video analysis system for endoscopic disease severity in UC.

Methods
A developmental dataset of local high-resolution UC colonoscopy videos were generated with Mayo endoscopic scores (MES) provided by experienced local reviewers. Videos were converted into still images stacks and annotated for both sufficient image quality for scoring (informativeness) and MES grade (e.g. Mayo 0,1,2,3). Convolutional neural networks (CNNs) were used to train models to predict still image informativeness and disease severity grading with 5-fold cross-validation. Whole video MES models were developed by matching reviewer MES scores with the proportion of still image predicted scores within each video using a template matching grid search. The automated whole video MES workflow was tested in a separate endoscopic video set from an international multicenter UC clinical trial (LYC-30937-EC). Cohen’s kappa coefficient with quadratic weighting was used for agreement assessment.

Results
The developmental set included 51 high-resolution videos (Mayo 2,3 41.2%), with the multicenter clinical trial containing 264 videos (Mayo 2,3 83.7%, p &lt; .0001) from 157 subjects. In 34,810 frames, the still image informative classifier had excellent performance with an AUC of 0.961, sensitivity of 0.902, and specificity of 0.870. In high-resolution videos, agreement between reviewers and fully-automated MES was very good with correct prediction of exact MES in 78% (40/51,κ=0.84, 95% CI 0.75–0.92) of videos (Figure 1). In external clinical trial videos where dual central review was performed, reviewers agreed on exact MES in 82.8% (140/169) of videos (κ = 0.78, 95% CI 0.71–0.86). Automated MES grading of the clinical trial videos (often low resolution) correctly distinguished Mayo 0,1 vs. 2,3 in 83.7% (221/264) of videos. Agreement between automated and central reviewer on exact MES occurred in 57.1% of videos (κ=0.59, 95% CI 0.46–0.71), but improved to 69.5% when accounting for human reviewer disagreement. Automated MES was within 1-level of central scores in 93.5% of videos (247/264).
Ordinal characteristics are shown for the automated process, predicting progressively increasing disease severity. TPR, true positive rate; FPR, false-positive rate.

Conclusion
Though premature for immediate deployment, these early results support the feasibility for artificial intelligence to approach expert-level endoscopic disease grading in UC.
P599 Trimester exposure and pregnancy outcomes in women exposed to golimumab: Results from the company pharmacovigilance database
Authors: Esslinger S , Otero-Lobato M , Gabriel S , Clark M , Sheridan P , Geldhof A 
Published: January 2020

Abstract

Background
Rheumatologic disorders and inflammatory bowel disease can affect women of childbearing potential. Golimumab (GLM) is approved for several rheumatological indications and ulcerative colitis (UC). To characterise pregnancy outcomes in patients treated with GLM, data obtained from maternal exposure to GLM are presented.

Methods
These dataset includes individual patient cases reported to the manufacturer through 06 April 2019. Cases included in the analysis were medically confirmed cases of maternal exposures to GLM during pregnancy or within 3 months prior to conception, and a reported pregnancy outcome. Both prospectively reported (ie, pregnancy outcome not known when first reported) and retrospectively reported cases (ie, pregnancy outcome known when first reported) were included. Cases originated from various sources, including spontaneous reporting, clinical studies, and registries.

Results
Two hundred eight pregnancy cases (131 rheumatological; 43 UC; and 34 other) with 211 reported birth outcomes were identified. Three cases reported twin pregnancies. Of the 208 pregnancy cases, 119 were prospective and 89 were retrospective (Table 1). Average maternal age was 31.9 years. Of the 119 prospectively reported pregnancy cases, 89 (74.8%) resulted in live births, 19 (16.0%) resulted in spontaneous abortion (of these, 42.1% (8/19) received GLM in combination with methotrexate [MTX]), 10 (8.4%) resulted in induced/elective abortion, and 1 (0.8%) resulted in ectopic pregnancy. Overall, 9 congenital anomalies were reported (2 prospective/7 retrospective cases).

For 183 of the 208 pregnancy cases with-reported outcomes, the trimester of exposure to GLM was known (Table 2). Among the 110 prospectively reported cases, 82 (74.5%) were exposed during trimester 0 or 1. Of these, 19 had concomitant exposure to MTX, with the following birth outcomes: 8 live births, 8 spontaneous abortions, 3 elective/induced abortions. Eighteen of the prospectively reported cases (16.4%) were exposed to GLM throughout pregnancy (first, second and third trimester) and all resulted in live births.

Conclusion
The rates of congenital malformations and spontaneous abortions were consistent with published background rates for the general population. Persistent exposure throughout pregnancy was rare, but not associated with apparent clinical sequelae. Limitations of this analysis include the lack of a direct comparison group, the variable amount of data available in the reports, and the possible bias towards reporting more negative outcomes in retrospective cases.
P607 Cost-effectiveness of vedolizumab IV vs. adalimumab SC for moderately to severely active ulcerative colitis
Authors: Schultz R , Diakite I , Carter J , Snedecor S , Turpin R 
Published: January 2020

Abstract

Background
VARSITY (NCT02497469) is the first head-to-head trial comparing two biologic therapies, intravenous vedolizumab (VDZ IV) and subcutaneous adalimumab (ADA), in adults with moderately to severely active ulcerative colitis (UC). We evaluated the cost-effectiveness of VDZ IV vs. ADA from a US payor perspective using efficacy data from VARSITY.

Methods
We used a cohort decision tree model with a time horizon up to 2 years. Simulated cohorts included patients with or without prior biologic therapy who initiated treatment with VDZ IV (300 mg in weeks 0, 2, and 6) or ADA (day 1: 160 mg; day 15: 80 mg) for a 6-week induction period. Initial responders proceeded to maintenance treatment with VDZ IV (300 mg every 8 weeks) or ADA (40 mg every 2 weeks); maintenance phase remitters continued treatment for 2 years. Patients with inadequate response to induction or a serious adverse drug reaction (ADR) switched to treatment with biologics (tofacitinib, infliximab, or golimumab). Patients who were intolerant to biologics received corticosteroids with or without curative surgery. The relative effectiveness of VDZ IV vs. ADA was derived from network meta-analyses of published randomised controlled trials. Model outcomes included total direct medical costs associated with drug acquisition, administration, routine monitoring, toxicity management, ADRs, and cost per remission achieved. Costs (eg, drug, monitoring, healthcare resource utilisation, administration) were expressed in 2019 US$.

Results
Based on our model, VDZ IV was associated with greater induction response (52.92% vs. 45.07%) and remission 2 (21.95% vs. 14.36%) rates at year 2 compared with ADA. Total direct medical costs were $90,673 for VDZ IV and $137,007 for ADA. After 2 years of treatment, more patients in the VDZ IV cohort were in remission and for lower costs compared with ADA.

Conclusion
The clinical foundation of this model is predicated primarily on head-to-head evidence from the Phase 3 VARSITY trial. This allowed us to extrapolate clinical outcomes out to 2 years and estimate direct medical costs over that timeframe. These modelled outcomes indicate that over a 2-year time horizon adults with moderately to severely active UC are expected to achieve better clinical outcomes and incur lower direct medical costs vs. ADA.
P616 IBD reference and biosimilar adalimumab CroSS over study (iBaSS): design considerations and methodology
Authors: Young D , Freudensprung U , Harris C , Harris R , Harvey J , Addison J , Latter S , Cummings F 
Published: January 2020

Abstract

Background
Biosimilars of adalimumab (ADA) have been available in Europe since October 2018 and have the potential to generate significant cost savings. SB5 is approved in the EU as an ADA biosimilar, having demonstrated bioequivalence and similar efficacy, safety and immunogenicity to the originator molecule (Humira™) in randomised controlled trials. Given a large number of biosimilar ADA products, it is likely that patients will be asked to switch between multiple ADA products in the future. There is a paucity of published evidence on the clinical outcomes of transitions from reference to biosimilar ADA in the heterogeneous real-world populations encountered in routine clinical practice. A better understanding of these, as well as patients’ related priorities and concerns, is essential to instil confidence in healthcare professionals and patients around such transitions and to improve the transition process.

Methods
iBaSS is a phase IV single-centre, prospective, randomised, single-blind, cross-over study in adult subjects with Crohn’s disease (CD). A cross-over design was selected as it allows each patient to experience both treatments as well as a transition to a biosimilar while remaining on active treatment throughout. This pragmatic study mimics the optimal care pathway of patients transitioning to a biosimilar and enrols a representative population of patients with CD in remission or with mild disease activity. Approximately 150 patients will be exposed in two treatment periods of 24 weeks to ADA biosimilar and reference, with half experiencing two transitions over the study period.

The primary outcome measure is defined as the proportion of patients who maintain the baseline clinical status during both treatment periods as assessed by modified Harvey–Bradshaw Index and IBD-Control. The analysis will be based on a random-effects logistic regression model. Secondary outcome measurements include describing changes in inflammatory markers, immunogenicity and patient experience (captured using semi-structured interviews, Treatment Satisfaction Questionnaire for Medication and a visual analogue scale to assess injection site experience).

Results
Recruitment started in July 2019 with 56 patients recruited so far. The summary baseline characteristics are: 46% male, mean (SD) age at enrolment 42.9 years (14.5) and 84% in remission (mHBI score &lt; 5). Three patients have withdrawn to date (2 withdrew consent and 1 is lost to follow-up).

Conclusion
This describes an achievable study design for a randomised equivalence study of biosimilar transition in patients with Crohn’s disease.