bluuebunny/crossref_metadata_2025 huggingface dataset:
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

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

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 > 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

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 <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

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

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 < .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

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

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

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 < 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.
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

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

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

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 < 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

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 >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

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

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 >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 < 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 < 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

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 < 0.0001). Within 10 year, 63% of 5-ASA intolerant and 20% of tolerant patients received immunomodulators (log-rank test < 0.0001); and 37% of 5-ASA intolerant and 11% of tolerant patients received biologic therapy (log-rank test < 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

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.
P679 What is the best strategy after failure to anti-TNF? Ustekinumab or other anti-TNF?
Authors: Cerpa Arencibia A , Suarez Ferrer C , Poza Cordón J , Martín Arranz E , Ramírez L , Martín Arranz M D
Published: January 2020

Background

After the appearance of new biologics are more treatment options for first and second-line individualising according to the characteristics of each patient. The efficacy of a second anti-TNF is lower than the initial treatment so a more efficient strategy could change the therapeutic target.

Methods

We included patients with an established diagnosis of Crohn’s disease who were on second-line biological treatment (ustekinumab or anti-TNF) after failure of a first anti-TNF (adalimumab or infliximab) treatment. Only patients in whom the indication was the ‘induction of remission of inflammatory activity’ so those patients in whom the indication was different from the intestinal activity (intestinal manifestations, perianal disease etc.) were selected were not considered valid for analysis. Patients who had undergone intestinal resection alone were included in the study if the indication of second-line biologic treatment was already established and no recurrence prophylaxis thereof.

Results

A total of 56 patients with an established diagnosis of Crohn’s disease stable tracking unit EII La Paz Hospital who were treated with second-line ustekinumab (21 patients, 37.5%) or anti-TNF (35 patients were included, 62.5%) for remission induction. Baseline characteristics of patients and their IBD are summarised in Table 1. The duration of biological treatment at the time of analysis was 1.48 years (SD: 1.2) for ustekinumab group and 3.55 years (SD 3.3) for the anti-TNF group. Ustekinumab group in 16/21 (76.2%) achieved clinical remission, 3/21 (14.3%) had no response while achieving remission (note that in one patient occurred exitus otherwise cause adenocarcinoma páncreas- unable to properly assess drug response), 2/21 patients (9.5%) did not answer. In the group of anti-TNF, 15/35 patients (42.8%) achieved clinical remission, 12/35 patients (34.3%) had response without remission, 8/35 patients (22.9%) No response. These differences between groups reached statistical significance (p = 0.015). Among patients who achieved a response / clinical remission included those wherein assessed by endoscopy identifying intestinal activity no statistically significant differences between groups vs. anti-TNF ustekinumab both SESCD (average 2 vs. 6.3 p = 0, 39) to the Ruttgerts in (mean 2.5 vs. 2, p = 0.67) postsurgical stage. Regarding the response/biological remission found no significant differences in CRP between ustekinumab and anti-TNF (4.55 vs. 5.79, p = 0.68) or with fecal calprotectin (276.25 vs. 268.82, p = 0.94).

Conclusion

In our experience, the second-line treatment with ustekinumab after the failure of a first anti-TNF has better remission rates and response to treatment with a second anti-TNF.
P681 Efficacy of vedolizumab for the prevention of postoperative recurrence in Crohn’s disease: Data from clinical practice from the ENEIDA registry
Authors: Mañosa Ciria M , Hinojosa E , Carbajo A , Castro J , Manceñido N , Calvo M , Núñez Alonso A , P Gisbert J , Nos P , Guardiola J , Sainz E , Sánchez-Rodríguez E , Cañete F , Calafat M , Domènech E
Published: January 2020

Background

Anti-TNF and thiopurines are the only drugs that demonstrated efficacy in preventing postoperative recurrence (POR) in Crohn’s disease (CD). However, in some cases, these drugs are contraindicated or have previously failed. Vedolizumab was licensed for CD some years ago but scarce data on its efficacy for the prevention of POR is available.

Methods

All CD patients in whom vedolizumab was prescribed for primary prevention of POR within the first 3 months after ileocecal or ileocolonic resection with anastomosis were identified from the ENEIDA registry (a large, prospectively maintained database of the Spanish Working Group in IBD, GETECCU). We evaluated the rates of Endoscopic, clinical or surgical POR in the first 18 months. Endoscopic POR was defined by a Rutgeerts score >i1 and advanced endoscopic POR by >i2.

Results

Twenty-three patients were included; vedolizumab was started after a median time of 23 days (IIQ21-73). Concomitant immunosuppressants were used in 17%; 18% received an additional 3-month course of metronidazole after surgery. Regarding risk factors for POR: 13% were active smokers, 62% had prior resections, 33% had penetrating CD behaviour, and 22% had a history of perianal disease. Thirty-four per cent had been exposed to vedolizumab prior to the index surgery (26% within the last 6 months). The median time of follow-up on ustekinumab was 26 months (IQR 11–31). Eighty-three per cent of patients had at least one endoscopic assessment within 18 months after surgery: 40 % had endoscopic POR and 15% advanced endoscopic POR. Additionally, 22% presented clinical POR at the discretion of the treating physician and 9% developed surgical POR.

Conclusion

In a small clinical practice cohort, vedolizumab showed similar efficacy as that reported with anti-TNF in the prevention of endoscopic POR.