bluuebunny/crossref_metadata_2025_split huggingface dataset:
P161 The impact of biologic therapies on Extra-Intestinal Manifestations in Inflammatory Bowel Disease: a multicentre observational study
Authors: Ferretti F , Monico M C , Cannatelli R , Lenti M V , Di Sabatino A , Carmagnola S , Conforti F , Pastorelli L , Caprioli F , Bezzio C , Saibeni S , Mazza S , Vecchi M , Maconi G , Ardizzone S 
Published: May 2021

Abstract

Background
A high proportion of Inflammatory Bowel Disease (IBD) patients will develop extraintestinal manifestations (EIMs). Choosing the most appropriate therapeutic strategy among currently available biologics for each patient may often be challenging. Data regarding the effects of gut-selective therapies such as vedolizumab (VDZ) on new-onset and pre-existing EIMs are scarce and often discordant. The main aims of this study were to assess the cumulative incidence of new-onset EIMs and the course of pre-existing EIMs in a large cohort of IBD patients treated with VDZ compared to non-gut selective biologic agents.

Methods
This multicenter retrospective study collected data of IBD patients on biologic therapy in clinical follow-up at 6 tertiary referral IBD units in Lombardy. Clinical and demographic data of IBD patients were collected. We calculated the cumulative incidence of new-onset EIMs since the introduction of the ongoing biologic therapy, comparing patients on VDZ with patients on non-gut selective therapies. Furthermore, we analyzed the course of pre-existing and new-onset EIMs in these two cohorts of patients.

Results
Data about 973 IBD patients (624 CD, 339 UC, 10 IBD-U; median age 46 years; 59% males) on biologic therapy were collected. Of them, 215 were on VDZ and 758 were on non-gut-selective agents, with a median treatment duration with the ongoing therapy of 3 years. The overall prevalence of EIMs in this IBD cohort of patients was 19.8% (193/973 patients). The overall cumulative incidence of new-onset EIMs was of 4.1 % (40/973): 13 on VDZ (13/215) versus 27 (27/758) in the non-gut selective group (6% vs 3.6%, p = 0.1). Regardless of the type of biologic agents, the female sex and the duration of the ongoing biologic treatment were statistically associated with a higher risk of developing EIMs. About 17% of IBD patients reported a pre-existing EIM. Compared to non-gut selective therapies, patients on VDZ showed a significantly higher rate of worsening or absence of response (8.1% vs 19.4%, 12/148 vs 7/36, p=0.04). However, in both groups, a modification of the therapeutic protocol has been necessary with the introduction of adjunctive therapy, the switch, or the optimisation of the ongoing biologic therapy (27.8% patients on VDZ versus 25% on non-gut selective therapies, p=0.7).

Conclusion
Our study suggests that the type of biologic treatment does not affect the risk of new-onset of EIMs. However, in the case of pre-existing EIMs, a subtle higher risk of worsening can be speculated after starting VDZ, even if the proportion of patients who will need adjunctive therapy, the optimisation or switch of the ongoing treatment would be similar between gut-selective and non-gut selective therapies.
P182 Bowel wall thickness as seen on point-of-care intestinal ultrasound correlates with endoscopic severity in children with Inflammatory Bowel Disease: A North American diagnostic cross-sectional study
Authors: Chavannes M , Hart L , Dillman J R , Marachelian A , Polk D B 
Published: May 2021

Abstract

Background
In pediatric patients with Inflammatory bowel disease (IBD), delay in diagnosis can lead to progression of disease and bowel damage. In North America, the current methods to visually assess disease activity are limited to ileocolonoscopies and MR enterography. Point-of-care intestinal ultrasound (IUS) is a non-invasive, cost-efficient tool for assessing intestinal inflammation. We aim to evaluate the correlation between IUS and endoscopic disease activity in children suspected to have IBD.

Methods
In this cross-sectional study, we recruited consecutive patients newly diagnosed with IBD, presenting to the IBD outpatient clinic, or hospitalized in our pediatric center between August 2020 and February 2021. In addition to ileocolonoscopy, they underwent IUS performed by one gastroenterologist who was blinded to ileocolonoscopy results at the time of performing IUS. Bowel wall thickness (BWT) was measured systematically across different bowel segments (terminal ileum, ascending, transverse, descending, sigmoid colon, and rectum) and recorded twice in longitudinal view and twice in axial view. An average segmental BWT of more than 3 mm was considered inflamed. The inflammation seen on endoscopy was graded using segmental scores of the SES-CD for patients with Crohn’s disease (CD) and the UCEIS for patients with ulcerative colitis (UC). Segments were classified as healed, mild, moderate, or severe disease activity. The association between the BWT and disease severity on endoscopy was assessed using the Kruskal-Wallis test. Numerical correlation between BWT and continuous values of the endoscopic scores was performed using Kendall’s Tau-b.

Results
Fifteen patients completed both IUS and ileocolonoscopy. A total of 74 bowel segments were assessed. There were 7 girls, median age of 15 years (IQR 12.5–15.5 years). 8 patients were diagnosed with CD, 5 with UC, and 2 had a normal endoscopy. Median PCDAI was 32.5 (IQR 30.0–40.0), and median PUCAI was 70 (IQR 70–75). The Kruskal-Wallis test showed that BWT was significantly associated with disease severity as measured by the SES-CD (chi-square = 14.3, p &lt;0.001, df = 2) for patients with CD, and that the BWT was also significantly associated with disease severity as measured by the UCEIS (chi-squared=12.0, p&lt;0.001, df=3). The numerical correlation between BWT and SES-CD for all segments was 0.43 (p&lt;0.001, 95%CI 0.3–0.58), while the correlation with the UCEIS was 0.52 (p&lt;0.001, 95%CI 0.4–0.66).

Conclusion
In pediatric patients with IBD, we found that endoscopic disease severity correlates with the degree of BWT seen on IUS. These findings support the use of IUS as an evaluation tool of disease activity in North American pediatric clinical practice.
P196 Colon-involving versus non-colon-involving Crohn’s disease classification: is the Montreal classification outdated?
Authors: Capela T , Macedo Silva V , Freitas M , Cúrdia Gonçalves T , Dias de Castro F , Moreira M J , Cotter J 
Published: May 2021

Abstract

Background
An appropriate disease classification is essential for the management of Crohn’s disease (CD) patients. Recently, a new classification of colon-involving versus non-colon-involving disease extension was considered to be more predictive of adverse outcomes than the Montreal classification (MRC). We aimed to investigate the association of a colon-based classification with clinically relevant outcomes in patients with CD compared with the MRC.

Methods
Retrospective cohort-study which consecutively included adult CD patients with at least 1 year of follow-up. Patients were categorized into colon-involving and non-colon-involving disease and according to the MRC. Patients’ demographic, clinical, biochemical, and imaging data were recorded and compared between the two classifications. The primary outcome was the need for treatment with steroids or biologics, hospitalization and major abdominal surgery.

Results
Of 327 patients, 52.3% were female with a mean age of 43.3±13.1 years. The most common disease location according to MRC was L1 (48.9%), followed by L3 (41.3%) and L2 (9.8%). Overall, 51.1% of patients had colon-involving disease. Although patients with colon-involvement at diagnosis had higher frequency of perianal lesions (27.5% vs 16.9%, P&lt;0.05) and serum inflammatory biomarkers (lower hemoglobin, and higher leucocyte and platelet counts, c-reactive protein and erythrocyte sedimentation rate), this classification was not predictive of relevant outcomes. Considering the two types of colon-involving disease (L2, L3), patients with L2 disease had higher extraintestinal manifestations (43.8% vs 20.7%, respectively, P&lt;0.05), higher B1 disease behavior (87.5% vs 58.5%, respectively, P&lt;0.05) and lower B2 disease behavior (6.25% vs 22.2%, respectively, P&lt;0.05). Disease location according to MRC was predictive of the need for treatment with biologics, hospitalization and major abdominal surgery in univariate analysis, but not in multivariate analysis.

Conclusion
Although simpler, defining Crohn’s disease extension by colon-involving versus non-colon-involving is not more predictive of adverse outcomes than the Montreal classification. Therefore, the use of Montreal Classification should still be considered essential in the adequate management of IBD patients.
P224 Regular physical activity on IBD patients: impact on IBD natural history and related comorbidities
Authors: Arias-Loste M T , Salcines L , Rodriguez-Duque J C , García García M J , Iruzubieta P , Rivas C , Castro B , Rivero M , Crespo J 
Published: May 2021

Abstract

Background
Regular physical activity (PA) has a potential antioxidant and anti-inflammatory effect that is mainly exerted on adipose tissue, skeletal muscle, and the immune and cardiovascular systems. Thus, PA is known to be beneficial in different pro-inflammatory conditions. Nevertheless, data on the role of PA in IBD patients is scarce. The aim of our study is to analyse the association of PA with clinical outcomes in IBD patients.

Methods
Cross-sectional prospective study including all consecutive IBD patients attended at a university hospital was performed. Data on physical activity was recorded through the International Physical Activity Questionnaire (IPAQ). Metabolic Equivalent Task (MET) hours per week were calculated according to the combination of walking, moderate-intensity or vigorous intensity activity, and patients were categorized into low, moderate or high PA according to a previously validated method. Data on IBD phenotype, activity indexes, natural history, current and past treatments, together with liver evaluation, and history of cardiovascular risk factors were also collected.

Results
831 patients were included in the study. Study flow chart is depicted in figure and clinical characteristics in table 1. IBD patients with a low or moderate PA showed a tendency to a higher proportion of IBD-related complications and higher scores in disease activity indexes than those with high PA. PA was strongly associated to the metabolic profile. Patients with a low/moderate PA were more frequently obese, hypertense, diabetic and had dyslipidaemia. Regarding liver disease, PA was significantly associated to the presence of non-alcoholic fatty liver disease (NAFLD), but not with advanced liver fibrosis.

Conclusion
Insufficient PA can negatively impact clinical outcomes in IBD patients, probably not because of a direct effect on IBD-pathogenesis, but due to its strong association with cardiovascular risk factors and NAFLD.
P236 Low Social support and distinct anxiety as a crucial feature in depressive IBD patients
Authors: Klaus J , Kretschmer M , Schulte L , Kaltenbach T , Rauschek L , Sularz M 
Published: May 2021

Abstract

Background
Depression is a common comorbidity of Inflammatory Bowel Disease (IBD) which leads to deterioration of the state of disease. The physician needs to know which psychiatric and temperamental characteristics have to be met in order to adapt his treatment to depressive patients. Therefore we compared patients with elevated depressive scores to those with normal scores.

Methods
291 IBD patients in 3 specialized IBD clinics in Germany (Ulm, Blaubeuren, Biberach) answered an anonymous questionnaire on their disease itself, on socio-demographic parameters and 6 psychological tests (HADS, STAI-S, STAI-T, FSozU, Neo-FFI, BL-R).

Results
The questionnaire was completed by 139 (47,3%) male and 155 (52,7%) female patients, 185 (63,4%) with Crohn’s disease and 107 (36,6%) with ulcerative colitis. 229 patients (79,0%) had a normal depression score (=NormD) (HADS-D), 59 (21,0%) had a borderline to very severe elevated score (elevated depression score = ElevD).
We characterized ElevD patients with the aid of a personality test (Neo-FFI) as more neurotic (p&lt;0.001), but less extroverted (p&lt;0.001), open for experience (p=0.042), agreeable (p=0.004) and conscientious (p=0.001) than patients with NormD. The Hospital Anxiety and Depression Scale (HADS-D) revealed them as more anxious (p&lt;0.001). This was confirmed by the State Trait Anxiety Inventory (STAI-S/-T) which showed ElevD patients to be more anxious as a state (p&lt;0.001) and as a trait (p&lt;0.001).
Moreover patients with ElevD percieve their social support as little as seen in the FSozU (p&lt;0.001). In addition there are lower scores in the Short Inflammatory Bowel Disease Questionnaire (SIBDQ) (p&lt;0.001), the Complaints List (B-LR) (p&lt;0.001) and the fact that most of the patients with ElevD had an active disease (43 (75,4%)) of the group.

Conclusion
IBD patients with an elevated depression score are more neurotic and less extroverted, open for experience, agreeable and conscientious than other patients. They are anxious and have little social support combined with many complaints and low quality of life. To improve their situation or to prevent it, the treating physician needs to be more sensitive to the patient’s state of mind and inquire more about their general complaints and especially their social support system so he is able to intervene and optimize the quality of life.
P242 Newly diagnosed Inflammatory Bowel Disease patients referred via the Straight To Test Lower GI two week wait pathway, Single Centre Study
Authors: Samarasinghe M , Chariah F , Desilva C , Koutsoumpas A 
Published: May 2021

Abstract

Background
Fast track or 2-week wait Lower GI pathways (2ww LGI), including Straight To Test or Straight To Colonoscopy 2ww LGI (2ww LGI STT) for patients with suspected Colorectal Cancer (CRC), have been extensively implemented in the UK. Approximately 3.9% of patients referred via the 2ww LGI will get a new diagnosis of IBD; once CRC has been excluded however, there is no standardised pathway for the management of those newly IBD pts. We implemented in 2019 in our Trust a new service structure for rapid access of those new IBD patients to IBD clinics, with emphasis to Nurse Led IBD clinics. In this study we aimed to look at real world data for the management of those new IBD pts in a large district hospital.

Methods
Retrospective analysis of prospectively collected data for all newly (endoscopically) diagnosed IBD patients referred from the 2ww LGI STT service, between January 2019 and March 2020, at Chase Farm and Barnet Hospitals (BCF).

Results
There has been a steady increase over time in the number of new IBD pts identified via the 2ww LGI STT and referred to BCF IBD service. A total of 168 patients were referred to BCF IBD service via this pathway over the above 14 months. Within the first 2–4 weeks after colonoscopy, 86% patients were seen in the IBD Nurse led clinic. The remaining patients were seen within 6–8 weeks either in IBD Nurse or Consultants clinics.
Approximately 11% of patients were not started on any medication at the time of colonoscopy. The remaining patients were commenced on either Steroid or 5ASAs post colonoscopy, in accordance with our local pathway. Biologic treatments or immunosuppressants were required for 18% of those patients during the above timeframe.

Conclusion
2ww LGI STT identifies a significant number of newly diagnosed IBD patients in our Trust. 2WW LGI endoscopists of different levels and backgrounds (medical, surgical, nurses, fellows, insourced) should be aware of the first line IBD therapies and relevant IBD pathways, and prescribe those in Endoscopy Unit. Advanced Nurse IBD clinics are an integral part of the IBD service, especially for newly diagnosed IBD patients via the 2ww LGI STT.
P267 Sequencing of anti-TNF agents and gut-selective anti-lymphocyte trafficking (GSALT) therapy in the treatment of Crohn’s disease (CD)
Authors: Huang Z , Ba Y , Kamble P , Wang S 
Published: May 2021

Abstract

Background
Anti-TNF agents and GSALT therapy (MAdCAM α4β7 blocker) are available treatment options for patients (pts) with moderate-to-severe CD. There are limited data on the optimal sequencing of these two mechanisms of action (MOAs) from the first line (1L) to second line (2L) biologic treatment of CD to inform clinician’s decision making.

Methods
This retrospective study used the Truven Health MarketScan administrative claims database to assess treatment pathways in a large U.S. insured population. Biologic naïve adult CD pts (identified using ICD-9 and 10 codes) who initiated (date of initiation defined as an index date) 1L biologic treatment (adalimumab [ADA], infliximab [IFX], certolizumab pegol [CTZ], or vedolizumab [VDZ] between 09/2016 and 09/2019) with at least 6 months of continuous health benefits enrolment post biologics initiation were included. Pts treated with biologics of different MOAs in 1L and 2L setting were identified to evaluate the treatment sequencing of either VDZ to anti-TNF or anti-TNF to VDZ. Treatment persistence was defined as time to index drug discontinuation with a pre-defined gap or switch to other biologic drugs.

Results
In the 1L, 474 VDZ and 4173 anti-TNF (2648 ADA, 1446 IFX, and 79 CTZ) pts were included. Among the 1L VDZ pts, only 33 switched to anti-TNF as 2L biologic treatment (VDZ to anti-TNF). Among the 1L anti-TNF pts, 221 switched to VDZ as 2L biologic therapy (anti-TNF to VDZ). In the VDZ to anti-TNF group, only proportion of 6 months treatment persistence was assessed due to the small number of pts in 2L. Median 1L treatment persistence was 842 days in VDZ pts and 557 days in anti-TNF pts (log rank p=0.041). The median treatment persistence in 2L VDZ post anti-TNF was 625 days (anti-TNF to VDZ). The 6 months treatment persistence to 2L was estimated as 85.1% (95% CI 59.1–95.2) in VDZ to anti-TNF group and 80.1% (95% CI 73.8–85.1) in anti-TNF to VDZ group. The 6 months treatment persistence was estimated as 74.8% (95% CI 73.4–76.1) in 1L anti-TNF and 85.1% (95% CI 59.1–95.2) in 2L anti-TNF post VDZ (VDZ to anti-TNF).

Conclusion
VDZ in 1L biologic treatment of CD was associated with significantly improved treatment persistence compared with anti-TNF agents. The sequencing of VDZ to anti-TNF had higher treatment persistence in both 1L and the first 6 months of 2L compared with the sequencing of anti-TNF to VDZ. The use of VDZ before anti-TNF agents led to higher persistence to anti-TNF in 2L than if anti-TNF was used in 1L during 6 months period of time. VDZ used in 2L post anti-TNF showed lower treatment persistence than if VDZ was used in 1L. This real-world evidence from U.S. large database suggests the use of GSALT prior to anti-TNF agents in biologic naïve pts with CD.
P312 Erythrocyte methotrexate polyglutamate concentrations in patients with Crohn’s Disease: towards a new therapeutic drug monitoring tool
Authors: Van de Meeberg M , Lin M , Seinen M , Fidder H , Oldenburg B , Bouma G , de Jonge R , Bulatović Ćalasan M 
Published: May 2021

Abstract

Background
Methotrexate (MTX) is an immunomodulatory drug for patients with Crohn’s Disease (CD), used as first-line therapy, as a second-line in case of failure to thiopurine, and concomitantly with anti-TNFα agents to decrease production of anti-drug antibodies. Nevertheless, MTX is underutilised in the treatment of CD, despite its proven efficacy and good safety profile. This is for a large part due to the lack of therapeutic drug monitoring (TDM) of MTX because no stable plasma MTX levels are reached. Intracellular MTX-polyglutamates (MTX-PGs), formed after folylpolyglutamate synthetase attaches glutamate residues to MTX, could be used as a TDM tool as MTX-PG is thought to mediate MTX’s efficacy. We present the results of our cross-sectional study in CD patients, aiming to gain insight into erythrocyte MTX-PG levels.

Methods
CD adults on MTX treatment who visited the outpatient clinic of Amsterdam UMC between May 2019 and February 2020 were included consecutively. An established LC-ESI-MS/MS method1 was used to measure erythrocyte MTX-PGs.

Results
Nineteen patients were included. Mean disease duration was 17 years (SD±13.7). Montreal disease location and behaviour were as follows (n=): L1 = 2, L2 = 4, L3 = 13; B1 = 11, B2 = 5, B3 = 3. Only 4 patients had a flare according to Physician Global Assessment. Twelve patients received MTX monotherapy, whereas 7 patients were on concomitant anti-TNFα agents. The mean dose of MTX was 15.5 mg (SD±2.8) and 12 (63%) patients had subcutaneous (sc.) MTX. We successfully measured MTX-PG2-5 in 18 patients, showing substantial variability in measured concentrations of total MTX-PG(tot) and the individual species. The median MTX-PGtot was 117.1 nmol/L [min:46.4-max:358.7] with preferential accumulation of MTX-PG3 (43.1 [15.3-96.1]); the least predominant species being MTX-PG5 (9.4 [1.1-24.1]). Patients on sc. compared to oral MTX had higher MTX-PGtot levels (177.8 [58.8-358.7] vs. 93.2 [46.4-120.8] nmol/L, p=0.067) and significantly higher long-chain MTX-PG4-5 levels (55 [3.7-84.3] vs. 8.9 [2.4-15.0] nmol/L, p=0.010); see figure.

Conclusion
We showed that erythrocyte MTX-PGs can be measured in CD patients by tandem MS. Large variability in concentrations was demonstrated, similar to our previously published results in rheumatoid and juvenile arthritis2,3 which is a pre-requisite for MTX-PG use as a TDM tool. We showed for the first time that MTX-PG accumulation was higher in sc. MTX vs. oral MTX treatment. This work provides the first step towards establishing TDM for MTX in CD, a goal we aim to realize in our upcoming longitudinal study.

References