bluuebunny/crossref_metadata_2025 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

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

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 <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<0.001, df=3). The numerical correlation between BWT and SES-CD for all segments was 0.43 (p<0.001, 95%CI 0.3–0.58), while the correlation with the UCEIS was 0.52 (p<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

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<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<0.05), higher B1 disease behavior (87.5% vs 58.5%, respectively, P<0.05) and lower B2 disease behavior (6.25% vs 22.2%, respectively, P<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

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

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<0.001), but less extroverted (p<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<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<0.001) and as a trait (p<0.001).

Moreover patients with ElevD percieve their social support as little as seen in the FSozU (p<0.001). In addition there are lower scores in the Short Inflammatory Bowel Disease Questionnaire (SIBDQ) (p<0.001), the Complaints List (B-LR) (p<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

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

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

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
P341 Perceived risks and psychosocial burden during the COVID-19 pandemic in a large cohort of pediatric and adult patients with Inflammatory Bowel Disease
Authors: Koletzko L , Klucker E , Le Thi G , Breiteneicher S , Rubio-Acero R , Neuhaus L , Stark R , Standl M , Hölscher M , Török H , Koletzko S , Schwerd T
Published: May 2021

Background

The COVID-19 pandemic induced restrictions in daily life and anxiety especially in vulnerable parts of the population. We investigated the psycho-social burden of the pandemic and self-perceived risk and harm in a large IBD cohort.

Methods

In this monocentric prospective observational study, pediatric (pIBD) and adult patients completed questionnaires related to their IBD (phenotype, disease activity, treatment), comorbidities, demographic and socioeconomic factors, validated tools on Perceived Stress (PSQ) and quality of life (sIBDQ). They judged perception of harm in case of acquiring COVID-19 using ratings from 1 to 7. We used number and type of established conditions for severe COVID-19 outcome to categorize patients in 5 risk groups. SARS-CoV2 antibodies were determined by Elecsys Roche anti-N pan-Ig. All comparisons were made by using t-test, Mann-Whitney-U-test or Chi-square-test where applicable with 2-sided significance levels of 5%. Univariate and multiple logistic regression was performed to determine associations between factors and perceived harm.

Results

Between mid-July to mid-October, 504 (62%) of 820 invited IBD patients and 86 pIBD parents completed the survey. Age ranged from 6-85 years, 80% received mono- or combo-therapy with immunomodulator, biologic, JAK-inhibitor or corticosteroids. Remission, mild, moderate and severe disease activity were reported by 46, 39, 12 and 3%, respectively. High harm of potential COVID-19 (>3) was perceived by 75.4%, rates increased with age (p=0.0019). After adjusting for age and gender, high perceived harm was significantly associated with immunosuppressive drugs, number/type of comorbidities, sleep disturbance, unintended gain or loss of weight, higher PSQ and lower sIBDQ scores. PSQ scored lower in males >60 years vs age matched females or younger adults, and in patients in remission vs active disease. PIBD mothers’ total PSQ was similar with even higher subscores for demands (P=0.0004) as adults with moderate/severe disease. Compared to pre-pandemic, 58-93% of pIBD decreased physical activities (at home, sports, outdoor) with minor changes in adults. SARS-CoV-2 serology was positive in 0.4% of IBD patients compared to 2% of our city population.

Conclusion

Prior to 2nd infection wave, even IBD patients aged <40 years suffer from a high degree of worries, stress and perceived harm for potential COVID-19. Most elderly patients and those with comorbidities adequately estimate their risks. In pIBD, pandemic restrictions substantially impacted on physical activity. The low seropositivity rate indicates high adherence to social distancing or altered immune response due to IBD drugs. Results of the follow up survey in March 21 are underway.
P367 Weight patterns in biologicals treated Inflammatory bowel disease cohort
Authors: Kaazan P , Tan Z , Maiyani P , Mickenbecker M , Edwards S , McIvor C , Andrews J M
Published: May 2021

Background

Biologic therapies are effective at inducing and maintaining remission in patients with inflammatory bowel disease (IBD). Previous studies have associated TNF-a inhibitors with weight gain, however it is unclear if this is a class-related effect or a manifestation of clinical remission. We performed this retrospective study to compare weight changes from baseline across different biological classes, examine weight patterns over time and assess characteristics and associations within each (sub)groups.

Methods

Adult patients with IBD who received any biological therapy for at least 12 months, between 2008 and 2020, were identified from prospectively maintained records at two IBD units in Australia. Data collected included demographics; weight and BMI at baseline, 6, 12, 24 and 48 months; IBD type and phenotype; baseline endoscopy, baseline haemoglobin, C-reactive protein (CRP) and albumin; combination or monotherapy; initial steroid therapy and frequency of biologic infusion. Patients with missing data were excluded.

A linear mixed-effects model was performed for the outcome of weight change from baseline, including the interaction of treatment group and time period. A latent class analysis was then performed, assigning patients to weight trajectory groups, and univariate ordinal logistic regressions were used to explore possible associations between membership of each group (the outcome) against various predictive factors.

Results

Of 294 patients (156 females), 165 received Infliximab (IFX), 68 Adalimumab (ADA), 36 Vedolizumab (VDZ) and 25 Ustekinumab (UST). There was a statistically significant interaction between time and treatment group with a significant weight gain over time in both the IFX and VDZ groups. After adjusting for baseline weight and inflammatory markers, significant weight gain was found for IFX vs ADA and VDZ vs ADA at most time points (Fig.1). Significantly less weight gain was seen in those with a higher initiation weight. Each 10kg increase in baseline weight resulted in 0.5kg less weight gain. This effect also held true for BMI.

Latent class analysis identified three weight trajectories: 57.4% of patients had small weight loss (-2.3kg), 37.8% small weight gain (6.6 kg) and 4.8% large weight gain (24.3 kg). Baseline BMI inversely influenced weight gain; with every 1 unit increase in BMI, reducing the odds of large weight gain by 8%. Being female, having an initiation CRP£5 or albumin>35 also reduced the odds of large weight gain.

Conclusion

Weight gain in biological-treated IBD patients appears to be associated with male gender, active baseline inflammation and the type of drug used.
P404 Healthcare utilization and expenditures for patients with Ulcerative Colitis on advanced therapies in Germany
Authors: Picker N , Bokemeyer B , Wilke T , Rosin L , Patel H
Published: May 2021

Background

Ulcerative Colitis (UC) is a chronic inflammatory condition, which significantly impacts patients’ health-related quality of life and burdens healthcare budgets. Our objective was to provide an overview of the healthcare resource use (HCRU) for the treatment of moderate to severe UC in Germany.

Methods

A retrospective analysis was conducted using claims data from a German sickness fund (AOK PLUS). Patients were included if they had ≥2 outpatient diagnoses in different quarters and/or one inpatient UC diagnosis (ICD-10: K51), were aged ≥18 years and initiated an advanced therapy (anti-TNFs, vedolizumab, tofacitinib) between 01/01/2015-30/06/2019.

HCRU associated with UC treatment was assessed in terms of outpatient visits, work-related sick leave days, and UC caused hospitalizations. Direct UC-related costs (inpatient, outpatient and medication costs based on pharmacy sales price at prescription date) were calculated from the perspective of the German statutory health insurance.

All patients were followed from the start of treatment until the end of the study period, or loss to follow-up. In case of treatment discontinuation or change of index therapy, patient follow-up was censored 90 days after the last prescription of index therapy. UC-related HCRU and cost were reported per observable patient-year (PY) and stratified according to prior use of advanced therapies (naïve vs. experienced).

Results

574 patients were included (adalimumab: 230, infliximab: 172, golimumab: 56, vedolizumab: 113, tofacitinib: 3). Mean age was 41.9 years; 53.5% were female. On average, 2.5 outpatient visits per PY were billed by general practitioners and 1.4 by gastroenterologists. 27.0% of patients had at least one UC-related hospitalization (mean length of stay: 11.2 days). The mean number of documented UC-related sick leave days amounted to 13.1 per PY. HCRU was similar in therapy-naïve vs. experienced patients (Table 1).

Inpatient costs for any cause amounted on average to €4,522/PY, with UC accounting for €3,190/PY (70.5%). Total UC costs amounted to €34.068/PY (Table 2). Expenses for prescribed UC-related drugs amounted to €28,885/PY (95.6% of total drug costs), and outpatient treatment to €511/PY with only €123/PY for Gastroenterologists’ visits (0.4% of total UC-costs/PY). In addition, indirect cost resulting from sick leave due to UC were estimated at €2,979/PY.

Conclusion

Our study indicates a high economic burden in UC patients who initiated treatment with advanced therapies. UC-related medication was identified as the main cost driver. Furthermore, a substantial proportion of UC patients required hospitalization in the first 12 months after starting new advanced therapy.
P418 Does capsule endoscopy impact clinical management in established Crohn’s Disease?
Authors: Elosua Gonzalez A , Rullan Iriarte M , Rubio Iturria S , Oquiñena Legaz S , Rodríguez Gutiérrez C , Macías Mendizábal E , Borda Martín A , Fernández-Urién Sainz I , Nantes Castillejo Ó
Published: May 2021

Background

Capsule endoscopy (SBCE) has developed a relevant role in different indications in patients with established Crohn’s Disease (CD). However, evaluation of its impact in clinical management in CD specific modification strategies has been scarce. The purpose of our study was to question therapeutic impact of SBCE in an 11-year real-life cohort of established CD patients.

Methods

Retrospective single center study including all consecutive patients with CD submitted to SBCE from January 2008 to December 2019. Small bowel patency was evaluated with patency capsule in selected patients. A conclusive procedure was defined as the one that allowed clinical decision-making. Mucosal inflammation was graded as mild (few aphtoid ulcers), moderate (multiple aphtoid ulcers/isolated deep ulcers) or severe (multiple deep ulcers/stenosis). Therapeutic impact was defined as a change in CD related treatment including escalation, de-escalation, dose adjustment or referral to surgery recommended based on SBCE results within the next 3 months after the SBCE. Patients were assigned to four groups regarding CE indication: staging, flare, post-op and remission (fig 1).

Results

From the 432 CE performed, 378 (87.5%) were conclusive and allowed clinical decision-making. SBCE results guided changes in 51.3% of patients: 199 (46.1%) with escalation and 23 (5.3%) with de-escalation of treatment. Active disease was present in 310 (71.8%) patients; 131 (30.3%) presented mild, 126 (29.2%) moderate and 53 (12.3%) severe activity. Disease activity demonstrated by SBCE correlated with therapeutic changes. With mild activity 24.1% increased therapy, whereas 77.8% and 84.9% increased therapy with moderate or severe disease, respectively (p<0.001). De-escalation was conducted in 12.8% patients with mucosal healing and 6.1% with mild disease but not in moderate or severe activity (p<0.001). Treatment before and after SBCE is shown in the table.

Conclusion

SBCE is a safe and useful tool when approaching established CD patients guiding therapeutic management in a real-life setting. Its positive impact does not limit to treatment escalation but also helps to de-escalate in patients who can benefit from it.
P432 MyChart application in addressing Inflammatory Bowel Disease patients’ concerns and impact on service utilisation
Authors: Raman K P , Agorogianni A , Hadjinicolaou A , Nightingale A , Mayhew A , Munro R , Raine T , McDermott E
Published: May 2021

Background

MyChart is a novel electronic portal within the electronic patient record provider EPIC. IBD patients were asked to complete an electronic questionnaire via MyChart prior to their infliximab infusions. A threshold was set that any patient who recorded a severe disease activity score (Mayo >/3, Harvey-Bradshaw Index (HBI) >/8) or signalled a concern created an automatic message that was routed to our clinical nurse specialists.

Methods

Electronic notes of all IBD patients who received infliximab in the month of September 2020 were reviewed. Demographics, activity status of My Chart, type of concerns raised and outcomes, number of inpatient admissions and outpatient appointments pre- and post- the introduction of the online questionnaire were recorded. Clinical remission was defined as Mayo score of <3 or HBI score of <5. Statistical comparisons were performed in GraphPad Prism software using the exact Fisher’s test and student t-test accordingly. Values were deemed significant if p<0.05.

Results

140 IBD patients on infliximab were identified; 2 were excluded due to incomplete data. The cohort comprised of 77 males (55.8%) with mean age of 27 years (SD of 15.1).110 (78.70%) patients had a diagnosis of Crohn’s disease whereas 24 (17.0%) had ulcerative colitis and 4 (2.8%) unspecified type IBD. 104 (75.1%) patients were active on MyChart and 83 (58.9% of total; n=138) completed the infliximab questionnaire.

Significantly fewer of the patients active on MyChart required scheduled outpatient reviews when compared to those that were inactive (59.6% vs 94.1%; p=0.0001; Table 1). There were no significant differences in terms of demographics, IBD type or clinical remission between the two groups.

Strikingly, patients who did not fill in the questionnaire were significantly more likely to have scheduled outpatient review in comparison to those that filled it (83.6% vs 67.4%; p=0.047) despite a higher proportion of the first being in clinical remission at baseline (86.6% vs 67.4%; p=0.047).

Furthermore, we evaluated the impact of introducing the online questionnaire by looking at the outpatient reviews and inpatient admissions before and after patients filled it in. The group was significantly less likely to require outpatient reviews (67.5% vs 87.3%; p=0.0061) or inpatient admissions (6.0% vs 17.5%; p=0.03) following introduction of the online questionnaire (Figure 1).

Conclusion

Overall, patients active on MyChart seemed to be significantly less likely to require outpatient review. This impact seemed particularly evident after filling in an online questionnaire which effectively addressed patient concerns and prevented unwarranted outpatient reviews and inpatient admissions.
P442 Serum vedolizumab trough levels are associated with remission rate but not with extra-intestinal manifestations in IBD patients
Authors: Tzadok R , Fliss-Isakov N , Aviv Cohen N , Ron Y , Maharshak N , Hirsch A
Published: May 2021

Background

The correlation between vedolizumab trough levels and inflammatory bowel diseases (IBD) remission rates has not yet been fully defined. We aimed to evaluate the association between vedolizumab serum trough levels and disease clinical and extra-intestinal manifestations (EIMs) and biomarker activity in IBD patients.

Methods

Forty-six patients (31 ulcerative colitis, 15 Crohn’s disease) who started vedolizumab therapy were retrospectively followed. Clinical and laboratory data were collected before treatment, during induction and maintenance until week 52 from initiation. Documentation of EIMs included peripheral and axial arthropathy, cutaneous and ocular manifestations and perianal disease. Clinical remission was defined as a Harvey-Bradshaw Index (HBI)<5 or a Simple Clinical Colitis Activity Index (SCCAI)<3. Biomarker normalization was defined as C-reactive protein level<5 mg/L and fecal calprotectin level<250 µg/g. Two-sample t-tests were used to find correlations between drug levels and disease activity.

Results

Higher week-2 trough serum vedolizumab levels were associated with week 14 clinical remission compared to patients with an active disease (30.55±2.22 µg/ml vs 22.28±3.57µg/ml, p=0.05) and with weeks-14 and -30 biomarker normalization (33.77±2.98 µg/ml vs 23.6±3.19 µg/ml, p=0.05 and 30.33±1.95 µg/ml vs 19.66±6.83 µg/ml, p=0.05, respectively).

Week-6 vedolizumab levels were associated with week-30 clinical remission (30.52±3.48 µg/ml vs 15.35±4.94 µg/ml, p=0.03) and biomarker normalization (28.44±2.36 µg/ml vs 15.76±4.87µg/ml, p=0.02), and week 14 vedolizumab levels were associated week 30 biomarker normalization (14.81±1.64 µg/ml vs 6.23±2.25 µg/ml, p=0.03).

Throughout the follow-up period, 24% of patients presented with EIMs (n=11). No association was found between vedolizumab levels and endoscopic outcomes or EIMs activity.

Conclusion

Trough serum vedolizumab levels at induction is associated with remission induction and maintenance but not with EIMs improvement. Assessment of early vedolizumab trough levels may be considered for prediction of response to therapy.
P447 Combined fibrin glue with infliximab therapy of postoperative anastomotic fistula in patients with Crohn’s disease: A Pilot study
Authors: Li Y , Yao D
Published: May 2021

Background

Postoperative anastomotic fistula is one of the most frequent and potentially life-threatening complications following gastrointestinal resections in patients with Crohn’s disease. The purpose of this study was to report the results of infliximab promoting healing of postoperative anastomotic fistula in patients with Crohn’s disease.

Methods

In this randomized controlled trial, 37 patients with postoperative fistula were assigned to combined(n=18) or control(n=19) groups and followed up for 6 months. The combined group received usual management protocol for fistula plus an intravenous infliximab therapy for 6 months. The control group received usual fistula protocol. The primary outcome was fistula closure time. The secondary outcome was any infectious complication such as recurrence of ECF, abdominal abscess, pneumonia, infectious diarrhea and other signs of infection.

Results

Thirty-seven patients with postoperative anastomotic fistula were evaluated. There were18 patients randomized to the combined group who received fibrin glue combined with infliximab therapy. There were 19 patients randomized to the control group who received fibrin glue sealant therapy alone. No significant differences in demographic or clinical characteristics were found between the two groups( P>0.05). The combined group had a shorter closure time than the control group(50.5±11.1 vs 76.2±26.2 days, P=0.011). The combined group did not show higher infectious complications than the control group(P=0.167).

Conclusion

Infliximab strategy with combining fibrin glue is a safe and effective treatment alternative in the management of postoperative anastomotic fistula in Crohn’s disease, offering the advantage of reduced heal time of fistula.
P469 The PROPER study: interim analysis of a pan-European real-world study of SB5 adalimumab biosimilar after transition from reference adalimumab in patients with Crohn’s disease
Authors: Dignass A , Gisbert J , Freudensprung U , Addison J
Published: May 2021

Background

SB5, a biosimilar to reference adalimumab, received EU marketing authorisation in August 2017, based on pre-clinical and clinical Phase I and III studies that demonstrated bioequivalence, similar efficacy, and comparable safety and immunogenicity to the reference. The ongoing real-world study ‘PROPER’ is designed to provide insights into outcomes of the transition from reference to SB5 outside the controlled, randomised, clinical trial setting, and under an umbrella design has enrolled 1,000 patients with immune-mediated inflammatory disease, treated at centres in Belgium, Germany, Ireland, Italy, Spain and the UK. The objective of this interim analysis is to describe clinical characteristics and outcomes in patients with Crohn’s disease transitioned from reference to biosimilar adalimumab SB5.

Methods

Eligible patients had been transitioned to SB5 as part of routine treatment following a minimum of 16 weeks’ treatment with reference adalimumab. Data are captured from patient charts retrospectively for 24 weeks prior to and prospectively and/or retrospectively for 48 weeks after SB5 initiation. This first interim analysis of the Crohn’s disease cohort reports outcome measures including baseline clinical characteristics, disease activity, persistence on SB5, clinical management and safety for patients enrolled at 32 specialist sites and followed up to the data extract date of February 5th, 2021.

Results

Of the 459 patients included in this interim analysis, at time of data extract 108 had completed 48 weeks on SB5, 45 patients had discontinued SB5, and 10 had withdrawn from study. A disease flare was reported for 29 (6.3%) of patients, of whom 22 had no subsequent change in biologic treatment; 7 had a change, of whom 5 switched to a different biologic; 2 had secondary loss of response (physician reported). Twelve patients reported 13 serious adverse events, of which 4 (anal fistula, 2 perianal abscesses and subileus) were considered by study physician to be related to SB5 administration. In Table 1 below, baseline refers to the time of SB5 initiation.

Conclusion

This interim analysis provides a first insight into clinical management of patients in a contemporary study cohort of European patients with long-standing Crohn’s disease, transitioned from reference to biosimilar adalimumab SB5 and followed in clinical practice. The majority of patients showed no meaningful difference in disease activity or SB5 dosing regimen by Week 48 post-transition, and the Covid-19 pandemic seems to have had no impact on SB5 use in this cohort. No new safety concerns were detected.
P568 Effectiveness of ustekinumab after vedolizumab failure in patients with anti-TNF-refractory Crohn’s disease
Authors: Dussias N , Rizzello F , Calabrese C , Sanna Passino A , Melotti L , Scaioli E , Belluzzi A , Gionchetti P
Published: May 2021

Background

Both vedolizumab (VDZ) and ustekinumab (UST) are indicated in the treatment of Crohn’s disease (CD) when anti-TNF treatment fails. While there are some studies regarding the efficacy of these two drugs in this setting, data are lacking regarding the effectiveness of UST in the treatment of VDZ-refractory disease. We aim to address this particularly challenging clinical picture in a real-world single-centre study.

Methods

CD patients from a single tertiary IBD referral centre receiving treatment with UST after failure to VDZ with a minimum follow-up period of 6 months were included. All patients had previously failed anti-TNF treatment. The primary outcome measure was achievement of steroid-free clinical remission, defined as HBI < 5 at 6 months. We also assessed rates of partial response, defined as a reduction in HBI by ≥ 3 points and/or cessation of steroid treatment in patients who required corticosteroids at baseline for symptom control.

Results

A total of 32 patients (20 male, mean age ± SD 40.7 ± 14.2, range 21–75) receiving UST treatment after VDZ failure were analysed. Complete steroid-free clinical remission at 6 months from starting UST therapy was achieved in 19 patients (59.4%). Nine patients (28.1%) had partial response, while in the remaining 4 patients (12.5%) no response was achieved. No adverse events were recorded during the follow-up period.

Conclusion

Preliminary results suggest that UST is effective and safe in the treatment of VDZ-refractory CD.
P580 Benchmarking IBD Pharmacy Services to optimise, strengthen and align IBD Expert Pharmacy Practice
Authors: St Clair Jones A , Meade U
Published: May 2021

Background

UK IBD Standards 2019 (ibduk.org) for the first time embed and describe Specialist Pharmacy Services (SPS) as an integral part of the IBD multidisciplinary team (MDT) and enable recognition and commissioning of Expert Pharmacists in IBD (EPharmIBD). The Benchmarking Tool, comprised of the IBD Patient Survey and Service Self-Assessment 2019/2020 provides a benchmark of expert pharmacy practice.

Methods

The Benchmarking Tool developed by IBD UK to drive quality defines A-D descriptors for all IBD standards (A=’excellent, proactive’ to D=’minimal, inadequate’ care). Descriptors for 4 (7%) standards describing SPS were developed through an e-Delphi process by IBD UK with EPharmIBD representation. Royal Pharmaceutical Society standards and SPS feedback were used to define descriptors for leadership, medicines expert role and MDT working. All UK IBD services were asked to complete the self-assessment between Oct 2019 and Jan 2020.

Results

10,222 IBD patients complete the IBD Patient Survey

166 (72%) paediatric and adult IBD services took part across the UK.

MDT Standard

46% (n=81/166) of all IBD Services have pharmacist input to the IBD MDT, but only 13% of all adult services (n = 18/134) met or exceeded the standard for 0.6 WTE EPharmIBD /250,000 population.

Leadership role

76% (n=98/129) of services with IBD leadership team work with a pharmacist of which 48% (n=47/98) work with an EPharmIBD on the annual formulary review. Of these teams 66% (n=31/47) work with an EPharmIBD on annual protocol/policy review, with actions and outcomes, actively develop pharmacy services within IBD.

Medicines expert role

Ward pharmacists in 95% (n=157/166) of IBD Services have access to an advanced generalist pharmacist for advice. Of these services 54% (n=84/157) are supported by an EPharmIBD but in only 41% (n=34/84) of these patients and ward pharmacists have access to an EPharmIBD on admission and during their stay for medication review, optimisation and personalised consultation.

Conclusion

Benchmarking shows a low level of pharmacy IBD expertise in the UK with a minority of services, ward pharmacists and patients having access to an EPharmIBD. Few IBD leadership teams work with an EPharmIBD and a small number of services have adequate EPharmIBDs commissioned.

In contrast where services report meeting the IBD Standards criteria for the number of EPharmIBDs, patients responding to the Patient Survey were more likely to be given appropriate information about potential treatments to help them make informed decisions.

This highlights the high need for advanced competencies and prioritisation of service commissioning in IBD.The pharmacy profession needs to respond urgently to this challenge to ensure high quality pharmaceutical care for IBD patients.