Abstract Background Small bowel capsule endoscopy (SBCE) has the highest sensitivity and specificity for identifying Crohn’s disease (CD) affecting the small bowel. The recent CURE-CD study demonstrated that proactive treatment optimisation with SBCE monitoring led to improved outcomes. [1] We performed a retrospective cohort study at a tertiary centre in the UK to evaluate the impact of SBCE in the management of Crohn’s disease. Methods We reviewed the capsule database from December 2021 – December 2022. 181 SBCE were performed in this time period. We included patients who were either newly diagnosed with CD following SBCE or patients with known CD undergoing SBCE as part of disease reassessment. All patients included had no/minimal changes on imaging and/or endoscopy to justify treatment initiation/escalation for ongoing symptoms. Data was extracted from their electronic health record. Correlations were analysed using Spearman’s ranked test. Results 96 patients met the inclusion criteria. 67 patients (69.8%) with known CD underwent SBCE as part of disease reassessment and 29 patients (30.2%) were newly diagnosed with CD following SBCE. Their baseline demographics pre-SBCE are illustrated by table 1. Small bowel visualisation was adequate in 93 (96.8%) and the median transit time for a SBCE study was 4hrs and 36 minutes. The median Lewis Score (LS) was 423. 71 (73.9%) patients had active SB Crohn’s disease (defined as a LS >135). Of these, 26 (36.6%) had moderate to severe disease (LS>790). There was a poor correlation between inflammatory biomarkers and symptoms of diarrhoea/abdominal pain with active CD on SBCE with none of these reaching a correlation level greater than 0.3. The impact of SBCE on the management of patients is showed by figure 1. 47 (48.9%) had a repeat SBCE for disease reassessment with a median time of 449 days between the first and second SBCE. The median LS for the repeat SBCE was 112. There was a significant reduction in moderate-to-severe active disease at the follow-up SBCE (baseline 26/96, 27.1% to follow-up 8/47, 17%). Repeat SBCE identified more patients in remission defined as LS <135 (baseline SBCE remission 25/96, 26% vs repeat SBCE remission 27/47, 57.4%, p=0.005). No cases of capsule retention occurred. Conclusion In a large cohort of patients with minimal/no changes on conventional investigative modalities for Crohn’s disease, SBCE led to a change in treatment in 63.5%. Repeat SBCE showed significantly higher proportion of patients in endoscopic remission. Conventional non-invasive markers of inflammation and symptoms correlated poorly with activity on SBCE further highlighting the importance for clinicians to consider SBCE in both the workup and reassessment of disease activity in patients with Crohn’s disease. References 1.S Ben-Horin, A Lahat, B Ungar, O Ukashi, D Yablecovitch, M M Amitai, Y Haberman, L Selinger, A Talan-Asher, O Kriger-Sharabi, T Naftali, Y Ron, H Yanai, I Dotan, U Kopylov, R Eliakim, The Israeli IBD Research Nucleus (IIRN), DOP29 Capsule endoscopy-guided proactive treatment versus standard treatment of patients with quiescent Crohn’s Disease: The CURE-CD randomized controlled trial, Journal of Crohn’s and Colitis, Volume 18, Issue Supplement_1, January 2024, Pages i125–i126,

Abstract Background Inflammatory bowel disease (IBD) has an impact on pregnancy outcomes due to disease activity and medication use. We conducted a retrospective cohort study to evaluate pregnancy outcomes at a large tertiary IBD centre in the UK. Methods Pregnant IBD patients at our unit are managed by a multidisciplinary team with joint obstetric medicine and gastroenterology review. Consecutive patients from January 2023 to December 2023 were included. Data was extracted from EPIC electronic health record. Multiple logistic regression analysis was performed using Prism version 10.4 Results 90 unique women were included in the study. 55 (61.1%) had Crohn’s disease (CD), 32 (35.6%) had ulcerative colitis (UC) and 3 (3.3%) had IBD-U. 9 (10%) had either prior or active perianal disease. Median disease duration was 8 years and the median age at conception was 35 years. Median preconception BMI was 23.1kg/m2. At conception, 37 (41.1%) were on biologics, 9 (10.0%) were on thiopurines, 25 (27.8%) were on mesalazine, 4 (4.4%) were on oral steroids and 22 (24.4%) were not on any treatment. A flare was defined as a faecal calprotectin of ≥250ug/g or exacerbation of symptoms (SCCAI >2 or HBI >4). 43 (47.8%) experienced a flare during pregnancy. Flares were treated with mesalazine (n = 20, 22.2%) and/or systemic corticosteroids (n=12, 13.3%) with 5 (5.6%) patients initiated on biologic therapy during pregnancy. Biologics were stopped in the third trimester in only 6 (16.2%) patients. 86 (96%) patients had a live singleton birth. There were 3 (3.3%) miscarriages and 1 (1.1%) termination of pregnancy due to fetal anomalies. The majority of women had a vaginal delivery (n=36, 41.8%) or an elective caesarean section (n=31, 36.0%). There were 3 (3.4%) preterm births and the median gestational age at birth was 39 weeks. The median birth weight was 3282g. There were 5 (5.8%) neonates with a low birth weight and 5 (5.8%) had fetal macrosomia. Maternal infections occurred in 5 (5.6%) with the majority being intrapartum sepsis (n=3). One neonate was admitted to neonatal intensive care due to complications from an emergency vaginal breech delivery. Gestational diabetes (GDM) occurred in 20 women (22.2%) which was higher than the European prevalence of 5%. [1] Based on multivariable logistic regression analysis, the higher rates of GDM was independent of steroid exposure, baseline BMI and active disease in pregnancy. Conclusion IBD flares were common in our cohort which reflects the complexity of patients referred to our service. Obstetric and neonatal outcomes were similar to the general population. We observed a higher rate of GDM which was independent of steroid exposure, BMI and disease activity. References 1.Eades CE, Cameron DM, Evans JMM. Prevalence of gestational diabetes mellitus in Europe: A meta-analysis. Diabetes Res Clin Pract. 2017 Jul;129:173-181. doi: 10.1016/j.diabres.2017.03.030. Epub 2017 May 9. PMID: 28531829.

Abstract Background Intestinal ultrasound is an accurate tool for assessing inflammatory bowel disease activity1. Previous studies showed point-of-care ultrasound (POCUS) can impact treatment decisions in 48% of appointments2. Early diagnosis and treatment improves outcomes in Crohn’s disease (CD). We aimed to investigate if POCUS in the IBD clinic led to earlier initiation of advanced therapies using a randomised controlled trial. Methods Patients attending an IBD clinic at a UK tertiary referral centre with known or suspected IBD (with a high likelihood) were eligible. During the primary clinic appointment clinicians’ investigation and treatment decisions were recorded. Immediately following this they were randomised 1:1 to POCUS or standard of care (SOC). The POCUS group then had further review with an option to alter treatment decisions. The primary end-point was time to initiating definitive therapy (in days) (new/changed immunomodulator, advanced therapy or surgery only). Secondary end-points included clinical score (HBI, SCCAI), calprotectin and patient tolerability. Patients were followed for 12 months. Results 122 patients were enrolled between 1st June and 1st November 2023. Median age was 25 years (16-79) and 50% male with a final diagnosis of 87 CD, 23 UC, 4 IBD-U and 8 non IBD (new referrals). 63 had POCUS and 59 SOC. POCUS was performed by one of two sonographers (one gastroenterologist and one radiologist). 65 (53%) were on advanced therapy or immunomodulators at baseline. 99 (81%) had advanced therapy, immunomodulators or surgery during the study period. Mean time to definitive treatment decision was 43 days with POCUS compared to 92 days in SOC (p<0.01). 65 (53%) patients had a change of, or started a new therapy and mean time to treatment initiation was also significantly shorter in the POCUS group, 75 days, compared to SOC, 131 days (p=0.033). In a sub-group of 20 new referrals, 12 were diagnosed with IBD. Mean time to treatment initiation was shorter with POCUS (82 vs 151 days). Steroid prescriptions at the baseline appointment were significantly higher in the POCUS group, 11/63 vs 2/59 (p = 0.012). Any change to treatment in the POCUS group occurred in 29/63 (46%) patients. Scans took an average of 7.5 minutes with 100% patient acceptability. Conclusion POCUS leads to earlier IBD-related decision making which translates into earlier initiation of effective therapy. This should, in turn, lead to improved care with shorter time to remission and reduced complications. Pathways to incorporate POCUS into routine clinical practice to optimise its effectiveness need further evaluation. This will require collaborative training and working across multiple specialties to effectively deliver this service. References (1)Taylor SA, Mallett S, Bhatnagar G, et al. Diagnostic accuracy of magnetic resonance enterography and small bowel ultrasound for the extent and activity of newly diagnosed and relapsed Crohn’s disease (METRIC): a multicentre trial. Lancet Gastroenterol Hepatol. 2018;3(8):548-558. doi:10.1016/S2468-1253(18)30161-4 (2)Bots S, De Voogd F, De Jong M, et al. Point-of-care Intestinal Ultrasound in IBD Patients: Disease Management and Diagnostic Yield in a Real-world Cohort and Proposal of a Point-of-care Algorithm. J Crohns Colitis. 2022;16(4):606-615. doi:10.1093/ecco-jcc/jjab175

Abstract Background Small bowel & colon capsule endoscopy have been established in their use to visualise the gastrointestinal (GI) tract. The Panenteric Crohn’s Capsule (PCC) is an evolution of these capsules enabling simultaneous assessment of both the small & large bowel with dual cameras for expanded mucosal coverage. This study investigates the use of PCC in patients suspected for inflammatory bowel disease (IBD), specifically Crohn's disease (CD), and in reassessing patients with established CD. The primary objective is to evaluate the impact of PCC results on patients’ management. Methods All consecutive patients who had PCC for suspected or established CD were included in the study. Those at risk of capsule retention (previous surgery, obstructive symptoms, stricturing disease) underwent a patency capsule, unless MR enterography was done within six months of PCC. Data was collected prospectively and included demographics, indication, procedural information such as completion rates, bowel cleansing & need for subsequent colonoscopy. PCC findings were recorded and the clinical outcome based on those was assessed at the subsequent clinic follow up. Results In this prospective single-centre study, 95 patients (average age 34 years, range 14-84) underwent PCC from November 2020 to May 2023, 61 were females (64%). 43 procedures were conducted remotely, 52 in-hospital, & 5 as inpatients. The primary indications were suspicion of IBD (n=54, 57%) and reassessment of established CD (n=41, 43%). Among the 95 patients,68 (72%) had successful PCC procedures. 18% (17/95) required a subsequent colonoscopy, primarily for biopsy (7,7.4%). PCC findings revealed inflammation in 41 patients (43.2%), diverticular disease in 13 (13.7%), & polyps in 15 (15.8%). The data demonstrated a 51% change in management post-PCC, including treatment escalation (15.8%), treatment de-escalation due to IBD remission (10.5%), exclusion of IBD with redirection for other pathologies or IBS diagnoses (15.8%), new IBD diagnoses (5.3%), & discharged due to normal investigation without need of further investigation (3.2%). Particularly in patients undergoing PCC for CD reassessment, 66% experienced a change in the treatment plan (14 escalated treatment, 7 de-escalated treatment due to remission, 3 achieved IBD treatment response & 3 treated for symptoms found to be caused by other pathologies). Conclusion PCC is a single, one-stop, non-invasive GI examination, ideal for suspected or established CD patients requiring pan-gut assessment. Despite suboptimal completion rates, PCC spared a colonoscopy in 82% of patients and resulted in change of management in over half of the patients and in 2/3 of those with established CD, suggesting a promising future role in diagnosing and monitoring CD.

Objectives To assess current transition practice in a London foundation Trust delivering secondary, tertiary and quaternary care to young people(YP) 13–18 years, with> 43,000 outpatient episodes/year. To determine whether the services meet quality standards for care of YP. Methods A retrospective review of developmentally appropriate healthcare (DAH) and transition process was performed against the DoH ‘You’re Welcome’ quality criteria(1) and NICE guideline ‘Transition from children’s to adults’. A questionnaire was co-designed by a YP steering group; a multidisciplinary team across paediatric, adolescent, and adult services, which was circulated and completed electronically. Results 56 services across the Trust responded. 68% of respondents reported that they provided a Transition service, 35% of services had a transition lead (consultant 48% ; CNS 35%),with 57% running multidisciplinary team (MDT) clinics for YP. The average age for transition process to start was 13 years (13–20) into adolescent services, 17 years into adult services. Transfer to adolescent service mean age 17 years ( 13–17), and to adult services 18 years ( 16–24yrs). Despite transition clinics being held, 8/25 services describe only 10% will go into the pathway and 90% will be transferred with letter only. Table 3 describes issues identified with the transition process. Table 4 describes adherence to You’re welcome criteria (young person’s centred approach) No service had a clear idea of how to support YP with learning difficulties. There was no common trust policy regarding adolescents DNAs. 21% had involved YP in designing their process and 18% had asked for feedback on their services. Conclusion Many services reported offering a transition service, and there were areas of excellent practice in dedicated young people’s services, including developmentally appropriate healthcare practices. However transfer into adult services is often occurring without adequate transition., DAH is not universal. Engagement with YP is low. Going forwards the following work streams were identified: Develop YP steering board Creation of policy and guidelines with regular audit and PPIE review Identify transition leads and key workers to support each service Recognise where specialist support from psychology, social work and learning disability teams required Develop and improve use of resources to engage and prepare YP Develop staff training and education programme

Background Biosimilar tumour necrosis factor inhibitors (TNFi) are increasingly used to treat inflammatory immune-mediated disorders as they cost less than the originator biologic drug. More women are therefore becoming pregnant on biosimilar TNFi. This is the first paper to explore the safety and efficacy of biosimilar therapies in pregnancy. Methods A retrospective review of clinical data reviewed pregnancy outcomes and inflammatory disease activity in 18 pregnancies where the mother was using a biosimilar TNFi at conception. Results Biosimilar therapy was not associated with congenital abnormalities, preterm birth or other adverse pregnancy outcomes. Stopping biosimilar TNFi in pregnancy was associated with childbirth at an earlier gestation, as well as a flare of inflammatory disease in pregnancy or post-partum. Conclusions Women and clinicians should feel confident in using biosimilar TNFi in early pregnancy, and continuing them through pregnancy to prevent flares in late pregnancy or the early post-partum.

Abstract Background Patient healthcare portals can empower IBD patients by allowing access to their electronic health record and provide opportunities for active participation in their care. We built 3 patient-entered symptom questionnaires in EPIC MyChart using existing validated IBD symptom scores (HBI, SCCAI, IBD Control). Patients were invited to complete these prior to clinic using the MyChart patient portal. In this study we examine the feasibility and accuracy of patient entered scores compared to the physician’s impression of disease activity and the potential impact on healthcare delivery. Methods Between September 2020 and January 2021 consecutive patients were invited to complete 2 questionnaires reporting disease activity on the EPIC MyChart portal using the IBD Control (Bodger et al. 2014) and either HBI or SCCAI (for Crohn’s disease and UC respectively). Only patients who completed these scores were included in this study. A retrospective review of the notes was completed to determine the physician’s impression of disease activity and actions taken by the physician in the outpatient clinic. Results 107 patients with Crohn’s and 80 with UC were included in the study. 60% of CD and 56% of UC patients were in remission by HBI (<5) or SCCAI (<3). Patient reported disease activity correlated well with clinical impression of disease activity. 88% of CD patients and 98% of UC patients in HBI or SCCAI remission were also deemed to be in remission on physician’s clinical impression (r= 0.54, p <0.001 and r= 0.74, p <0.001). Both CD and UC had lower rates of remission by IBD Control (49% and 53%). This score also captures fatigue and mood. Furthermore, the IBD Control identified a specific question to be addressed at the upcoming clinic visit for 76% of patients with CD and 64% with UC. Importantly, 24% of all UC patients (n=19) in remission by SCCAI and IBD Control, had no questions they wanted addressed, and all of these patients had no further actions triggered by clinic attendance. Conversely in the 18% patients with moderate to severe disease by HBI or SCCAI, 50% required a blood test or calprotectin prior to further clinical decisions. Conclusion Patient-entered symptom scores correlate closely with physician’s impression of disease activity and patients are able to accurately record these using the EPIC MyChart portal. Importantly, it is possible to identify a cohort of patients who are well, where there are opportunities to optimise follow-up, and conversely a group of patients with active disease where key investigations can be arranged prior to clinical review to prevent delays in treatment. These patients can also be prioritised for face-to-face clinics, at a time when reducing social contacts is imperative.

Abstract Background Drug choice and order in Inflammatory Bowel Disease (IBD) is an important challenge and is becoming increasingly complex. There are few studies comparing head-to-head outcomes in second line treatments in Ulcerative Colitis (UC). It is unclear if using anti-Tumour Necrosis Factor-a (anti-TNF) therapy following vedolizumab (VDZ) or VDZ after anti-TNF has a more favourable outcome in UC in a real-world outpatient setting. Methods Patients with UC who were exposed to first-line anti-TNF (adalimumab/ADA or infliximab/IFX) or VDZ who subsequently switched to the alternate class between May 2013-August 2020 were identified following a review of databases at 10 hospitals. 88 VDZ and 39 anti-TNF (12 ADA,27 IFX) second line patients were eligible. Data was collected retrospectively. Baseline demographics, disease activity indices, colectomy rates, treatment persistence and healthcare resource utilisation composite endpoint (HRUC) were examined over a 52 week period for the second line biologic. HRUC included unplanned emergency hospital attendance or hospital admission. The primary endpoints of 52 week treatment persistence, HRUC survival and colectomy free survival were analysed with Kaplan Meier method, statistical significance between the survival curves was assessed with Log Rank test. Propensity score matching (PSM) was applied to survival curves (tolerance level 0.1). For a subset where SCCAI scores available, week 52 corticosteroid free clinical response/remission rates were calculated (response: reduction of SCCAI ≥3 and remission: SCCAI ≤2).: Results The second line anti-TNF group had a significantly higher baseline endoscopic Mayo score (p=0.035) and lower concomitant immunomodulator use (p=0.001). Second line week 52 treatment persistence was higher in the VDZ group 71/80 (89%) vs. Anti-TNF 15/36 (42%) ,p<0.0001 (Figure 1). Second line week 52 HRUC survival was higher in the VDZ group 68/81 (84%) vs. anti-TNF 20/33 (61%), p=0.003 (Figure 2). Week 52 colectomy free survival VDZ 77/80 (96%) vs. anti-TNF 26/32 (81%), p= <0.011 (Figure 3). For treatment persistence and colectomy free survival statistical significance was maintained with PSM. Week 52 corticosteroid free clinical remission rates VDZ 22/32 (69%) vs. anti-TNF 5/19 (25%) p=0.004 (Figure 4). Conclusion The VDZ second line cohort had significantly higher 52-week treatment persistence, lower HRUC and lower colectomy rates and higher corticosteroid free clinical remission rates. This data suggests that VDZ is an effective biologic in UC in a second line therapy after anti-TNF exposure. It highlights the effect of biologic sequencing on clinically important outcomes in an outpatient setting. Larger prospective studies are required to confirm these findings.

Abstract Background Patient portals are available on most major electronic health record (EHR) platforms and present many opportunities to improve patient engagement with services, the quality of data captured and therefore healthcare outcomes and patient satisfaction. Our centre looks after 5100 patients with IBD. We recently adopted the EPIC Systems patient portal MyChart which allows patients to view results, letters and complete patient reported outcomes (PRO). At baseline, few patients were registered for this platform. Our aim was to compare patient engagement with MyChart using a low and higher cost approach and to evaluate patient satisfaction with the platform. Methods 160 consecutive patients were invited to join MyChart between September and October 2020. The low-intensity intervention group were invited to join MyChart via a standardised email without further communication. Newly registered patients and active patients were sent a portal message with disease-specific PRO questionnaire 7 days prior to clinic (HBI, SCCAI and IBD Control). Patients in the high-intensity intervention group received a telephone reminder to encourage completion at each step, which took on average 2 minutes, in addition to email. Engagement with the platform was measured prospectively. After clinic a patient-experience questionnaire was sent to all patients who signed up to the platform. Results 72 patients were included in the low intensity group and 88 in the high intensity group. At baseline only 33% patients were already signed up to MyChart. Significantly more patients newly registered with the patient portal following the high intensity intervention compared to the low (75% vs. 30%, p <0.0001). Overall, patients in the high intensity group were significantly more likely to complete the PRO compared to the low (53% vs. 28%, p=0.002). Patients already registered were 5 times more likely to complete the PRO in the high intensity group compared to low (p=0.017). Platform engagement was not significantly impacted by gender or ethnicity. There was a trend toward lower engagement in patients over 65. 63 patients provided feedback. 87% found MyChart easy to use and 94% said they would complete the PRO questionnaires again. Conclusion In our patient cohort, a higher intensity strategy significantly increased patient registration and engagement with a new patient portal at a minimal cost of time and resource. Healthcare providers can facilitate patient engagement with patient portals and overcome barriers to adoption to unlock transformative opportunities for better quality IBD care, disease monitoring and population-based research.

Abstract Background Ustekinumab is effective at inducing and maintaining remission of Crohn’s disease (CD) in clinical trials. However real-world practice may vary regarding use of concomitant immunomodulator (IM), dosing schedule and patient selection. We present the largest UK real-world, multi-centre study of effectiveness. Methods The cohort comprised adult patients initiated on ustekinumab for CD from October 2016–18 at 3 tertiary London centres. Clinical endpoints were (i) remission (Harvey Bradshaw Index (HBI) ≤4) (ii) response, (reduction in HBI of ≥3 or sustained HBI≤4 points) at 3, 6 and 12 months. Biological endpoints were remission and response (CRP <5mg/l in patients with a baseline CRP>5mg/l, and 50% reduction in CRP, respectively). Results 211 patients were included (Table 1), of whom 207 (98%) were biologic exposed and 59 (28%) had failed 3 biologics. All patients received i.v. induction and 203 (96%) received a s.c. dose at week 8. At 6 and 12 months, 133 (74.8%) and 109 (73.6%) patients, respectively, were on 8 weekly dosing. Dosing schedule did not impact clinical and biological outcome at 6 and 12 months. Discontinuation occurred in 4 (1.9%), 20 (9.5%) and 50 (23.7%) patients by 3, 6 and 12 months respectively. Reasons for stopping included: drug reactions (4(1.9%)), partial response (4 (1.9%)), loss of response (10 (4.7%)) and primary non-response. (24 (11.4%)). Clinical and biological outcomes at 3, 6 and 12 months are shown in Figure 1. Adverse events occurred in 27 (12.8%) patients. IM were prescribed in 49 (23%) at baseline and continued in 46 (21.8%), 36 (17.1%), 27 (12.8%) at 3, 6 and12 months respectively. There was no significant difference in median persistence (months) on ustekinumab between patients who were on an IM at baseline vs. those not (15.2 (95% CI 0–32.2) vs. 23.3 (17.3–29.4) months, p = 0.4). Likewise, there was no significant difference in clinical or biological outcome between patients with colonic vs. ileocolonic or ileal disease. Finally, there was no significant difference in median persistence on ustekinumab between patients with and without a history of perianal disease (19.5 (95% CI 9.2–29.8) vs. 22.9 (18.6–27.2) months, p = 0.8). Conclusion Ustekinumab is effective in a real-world cohort. In keeping with trial data, we did not find evidence of improved outcomes with the use of a concomitant IM, nor differential outcomes when considering perianal and isolated colonic disease.

Background Ustekinumab is effective in inducing and maintaining remission of Crohn’s disease (CD) in clinical trials. We present the first UK realworld, multicentre study of effectiveness. Methods Data was collected for patients started on ustekinumab for CD from September 2015 to May 2018 at 3 tertiary London centres. Clinical endpoints were (i) remission (Harvey Bradshaw Index (HBI) ≤4 points) and (ii) response (reduction in HBI of ≥3 points or sustained HBI≤4 points) at week 8 and 32. Biological endpoints were (i) remission (CRP < 5 mg/L in patients with a baseline CRP >5 mg/L) and (ii) response (50% reduction in CRP) at weeks 8 and 32. Results Baseline characteristics of the 149 patients analysed are shown in table 1. The majority (146 (98%)) had failed anti TNF therapy. All patients received i.v. induction and 147 (99%) received a s.c. dose at week 8. At week 32, 91 (75.8%) patients were on 8 weekly dosing. Discontinuation occurred in 24 (16.1%) patients due to: primary nonresponse (14 (9.4%)), drug reactions (2 (1.3%)), side effects (2 (1.3%)), and other causes (6 (4.0%)). Followup to week 32 was available for 125 (83.8%) patients. Adverse events occurred in 16 (10.7%) patients. Dosing schedule did not impact clinical and biological outcome at week 32. Where paired data was available, mean (SD) HBI decreased significantly from baseline (6.2(4.9)) to week 8 (4.6(4.4), n=99, p=0.016) and was sustained at week 32 (4.7(4.1), n=56, p<0.001). Mean (SD) CRP decreased significantly from baseline (18.1 mg/L(21.9)) to week 8 (11.9 mg/L(17.2), n=122, p=0.002), but did not sustain significant improvement at wk 32 (12.9 mg/L(17.4), n=93, p=0.158). At weeks 8 and 32, clinical rates of (i) response, (ii) remission, and (iii) steroid-free remission were (i) 68 and 63%, (ii) 53 and 38%, (iii) 45 and 36% respectively. At weeks 8 and 32, biological rates of (i) response and (ii) remission were (i) 45 and 34%, (ii) 24 and 20% respectively. Clinical remission at week 8 was significantly associated with remission at week 32: clinical remission (n=34, p=0.013, RR 3.16, 95%CI 1.238.13), and biological remission (n=56, p=0.027, RR1.95, 95% CI 1.213.13). Biological remission at week 8 was significantly associated with outcome at week 32: biological response (n=62, p=0.003, RR 4.72, 95%CI 0.65 – 13.51), and biological remission (n=62, p=0.003, RR 4.41, 95%CI 1.78–10.87). Conclusions Ustekinumab is effective in a realworld cohort with response sustained at 6 months. Clinical and biological remission at week 8 predicted both clinical and biological outcomes at week 32.

Iron deficiency anaemia (IDA) is a common complication of pIBD affecting cognitive development and quality of life, and its oral treatment might be is hampered by as poor compliance and efficacy. Intravenous FCM has been shown to be effective and safe for IDA in adult patients, but paediatric studies are limited. Aim: To study the safety and efficacy of FCM in the treatment of IDA in pIBD. Retrospective review of all pIBD patients with IDA treated with FCM between 2013 and 2018 in two tertiary care paediatric IBD centres. IDA was diagnosed by combining haemoglobin (HB), haematocrit (HCT), mean cell volume (MCV), iron levels, total iron binding capacity (TIBC), transferrin saturation (TSAT), and ferritin. Inflammatory biomarkers (C-reactive protein [CRP] and faecal calprotectin [FC]) were also assessed. Patients received 500–1500 mg of FCM according to body weight. Bloods were repeated 4–6 weeks after each infusion. Patient and disease characteristics are expressed as percentage and mean ± SD. Paired samples t-test was used for statistical analysis, and significance was set at the p < 0.05 level. A total of 213 infusions were administered to 132 pIBD patients with IDA, 70 males (53%), Crohn’s disease = 90 (68.2%), ulcerative colitis = 25 (18.9%), inflammatory bowel disease unclassified = 17 (12.9%). Mean age at the first injection was 12.53 years (SD 3.811, range 3–18). Four–six after first FCM injection, a significant improvement was found in HB (107.36 ± 15.899 vs. 122.34 ± SD, p < 0.001), HTC (0.333 ± 0.4 vs. 0.375 ± 0.375; p < 0.001), MCV (75.94 ± 6.8 vs. 80.35 ± 6.82, p < 0.001), iron (7.37 ± 5.03 vs. 11.96 ± 7.21 μmol/l, p < 0.001), TIBC (63.71 ± 18.02 vs. 54 ± 49.80 μmol/l, p < 0.001) TSAT (12.16 ± 8.14 vs. 24.19 ± 13.64%, p < 0.001) and ferritin (64.32 ± 168.45 vs. 215.77 ± 195.43 μg/l, p < 0.001) was shown. No statistical difference was observed pre and post infusion for CRP and FC. Only 3 patients showed an adverse reaction: one developed an anaphylactic reaction, the remaining 2 itch and transient fever. No adverse events were recorded in patients under 6 years old (n = 11). FCM administration is safe and effective for routine management in children with IBD, including those who are under 6 years old

Crohn’s disease (CD) is frequently diagnosed in childhood and follows a more aggressive course when compared with adults. In this population, anti-TNF treatments are well established, but little is known about the efficacy and safety of ustekinumab. We report our experience in its use for paediatric Crohn’s disease across two London hospitals. Paediatric patients (<18 years) commenced on ustekinumab were identified from University College London Hospital (UCLH) and The Royal London Hospital (RLH). A retrospective case note review was conducted and data collected on disease phenotype, prior treatment, prior surgery, CRP and weight. Biological response at Week 8 was defined as a 50% reduction in CRP where the baseline CRP was >5 mg/l. Ten patients with CD were commenced on ustekinumab under the age of 18. The baseline characteristics are summarised in Table 1. All patients had failed at least one anti-TNF and 8 patients had failed two. The mean CRP at baseline was 38 mg/l. Patients received intravenous drug at baseline and 8 weekly subcutaneous dosing thereafter. Two patients discontinued treatment prior to Week 16 owing to primary non-response, both requiring intestinal resection. Four patients had reached Week 16 at the time of analysis. One patient had been followed up for 29 weeks at the time of analysis. No adverse events were reported. Where paired data were available, there was a significant increase in mean weight from baseline (38.9 kg, n = 7) to Week 8 (42.7 kg, n = 7, p = 0.003) and Week 16 (44.0 kg, n = 3, p = 0.001). Where paired data were available, mean CRP (mg/l) improved from 38 at baseline (n = 7) to 22 at Week 8, and 9 at Week 16 (n = 4), although this did not reach significance. The biological response rate was 50% at Week 8. Both patients on steroids at baseline had discontinued these by Week 8. Table 1. Baseline characteristics of paediatric patients treated with ustekinumab. We report on the use of ustekinumab to treat anti-TNF refractory Crohn’s disease in 10 paediatric patients. This was well tolerated with no adverse events reported. We found a mean reduction in CRP and significant weight gain at Week 8 which was sustained at Week 16, suggesting clinical benefit. Further studies are needed to establish the safety and efficacy of its use in the paediatric population.

Combination therapy (CT) with infliximab (IFX) and azathioprine (Aza) appears more clinically effective than either alone in IBD.1,2 However, IFX antibody (Ab) formation can be as high as 73% (3). CT can significantly reduce this3 and may allow IFX dose reduction.4 Less data exist regarding methotrexate (MTX) than Aza in this context. Although the COMMIT trial of CT with IFX and MTX did not show clinical superiority of CT over monotherapy in Crohn’s disease, it did demonstrate lower IFX antibody (Ab) levels in the CT arm.5 The role of MTX in reducing immunogenicity of IFX and adalimumab (Ada) in IBD treatment remains undefined. We sought to review the characteristics of patients at our centre receiving CT with MTX and either IFX or Ada. A retrospective analysis was performed of all patients actively prescribed MTX in combination with IFX or Ada at UCLH. Patients’ demographics, previous treatment, laboratory data, Harvey Bradshaw Index (HBI) scores and clinical outcomes were recorded. Drug levels and Abs, treatment escalations or alterations and adverse events were also noted. Fifty-nine patients were identified (51 CD, 6 UC, and 2 IBD-U). Mean age was 30 years (range 16–70), 62% were male, with median disease duration of 10 years. MTX was oral in 50 of 59, subcutaneous in 9 of 59, and in combination with Ada in 41 of 59 (69%), IFX in 17 of 59 (29%), and vedolizumab in 1 of 59. Of 59, 18 (31%) were anti-TNFα naïve prior to commencing CT. All were prescribed concomitant folic acid. During the observation period (median 33 months), 27% (16/59) developed a flare requiring steroids or hospital admission and 17% (10/59) had an IBD-related complication requiring antibiotics or surgery. 83% (49/59) had drug levels and Abs measured on CT, with 7/49 having detectable Abs (3 to IFX, 4 to Ada). Four of seven of those with positive Abs were anti-TNFα naïve prior to CT, and four necessitated a dose escalation. One patient lost Abs after the addition of MTX to IFX. Ada drug levels were lower in those who had suffered a flare requiring admission (mean 8.49 vs. 12.24, z-score 1.99, p = 0.045). CRP levels before CT (within 3 months) and at ≥6 months after commencing CT, were not significantly different (z-score 1.07, p = 0.28). HBI scores (in 22/59) were significantly improved once established on CT (mean 7.2 vs. 4.4; z score −2.14, p = 0.032). In this cohort, CT with MTX and IFX or Ada was associated with improvement in disease activity scores. The prevalence of detectable anti-drug antibodies (IFX 20% (3/15), Ada 12% (4/34)) was comparable to other published data.5 Ada drug levels were lower in those who had a flare and 1 patient was seen to seroconvert, in keeping with the possible role for MTX in reducing the development of IFX or Ada immunogenicity. 1. Colombel JF, et al. Infliximab, azathioprine, or combination therapy for Crohn’s disease. New Eng J Med, 2010. 2. Panaccione, R, et al. Combination therapy with infliximab and azathioprine is superior to monotherapy with either agent in ulcerative colitis. Gastroenterology, 2014. 3. Vermeire, S, et al. Effectiveness of concomitant immunosuppressive therapy in suppressing the formation of antibodies to infliximab in Crohn’s disease. Gut, 2007. 4. Sokol, H, et al. Usefulness of co-treatment with immunomodulators in patients with inflammatory bowel disease treated with scheduled infliximab maintenance therapy. Gut, 2010. 5. Feagan, BG, et al. Methotrexate in combination with infliximab is no more effective than infliximab alone in patients with Crohn’s disease. Gastroenterology, 2014.

Vedolizumab is α4β7 integrin antagonist licenced to treat moderate to severely active Crohn’s disease (CD) as well as ulcerative colitis. The aim of this study was to examine the efficacy of vedolizumab in patients with CD at a single tertiary IBD centre in the UK, and whether efficacy varies depending on disease location in this heterogeneous condition. Clinical records of patients with CD commenced on vedolizumab between 11/05/2015 and 01/12/2016 were examined retrospectively. Clinicopathological features and disease activity using Harvey Bradshaw Activity Index (HBAI) were collected at baseline, and at Weeks 14, 30 and at Week 52. Response to vedolizumab was defined as reduction in HBAI score ≤3 compared with baseline, and remission was defined as HBAI score ≤4 at these time points. For patients with a stoma, response was defined as a reduction in CRP ≥ 20% or radiological improvement, and remission was defined as normalisation of CRP ≤ 10 mg/l or radiological resolution of disease activity. Forty patients with CD were commenced on vedolizumab during the study period. Out of the 40 patients, 8 were excluded from the data analysis due to incomplete data. Eighteen patients (57%) had ileocolonic disease, 11 patients (34%) had colonic disease, and 3 patients (9%) had small-bowel disease. Mean age at the time of first Vedolizumab infusion was 29.3. Mean age at diagnosis was 18.1 with mean time between diagnosis and first vedolizumab infusion of 10.1 years. Twenty-one patients (66%) were taking immunomodulator (IM) and only 1 patient was anti-TNF naïve (3%) at the time of the first vedolizumab infusion. Sixteen patients had undergone previous surgery. Mean faecal calprotectin at baseline was 1948 μg/g. At Week 14, 3 patients responded (9%), 14 (44%) were in remission and 15 (47%) did not respond. Out of 23 patients who continued vedolizumab to Week 30, 1 patient responded (4%), 14 were in remission (61%), and 8 (35%) did not show response. Out of 18 patients who continued vedolizumab for 1 year, 10 (56%) were in remission. Out of these 10 patients, 4 had colonic disease and 6 had ileocolonic disease. The three patients with small-bowel disease were all non-responders. The rate of remission at 1 year was lower in the patients with concomitant use of IM (n = 5/21, 24%) compared with IM (n = 5 of 11, 45%). Six patients underwent surgery within 1 year of receiving their first vedolizumab infusion. CD patients treated with vedolizumab achieved remission in 44% at Week 14, in 44% at 30 weeks and in 31% at Week 52. Vedolizumab was most effective at maintaining remission at 52 weeks in patients with colonic disease (n = 4 of 9, 44%) compared with patients with ileocolic disease (n = 6 of 20, 30%) and patients with small-bowel disease (n = 0 of 3, 0%).

Vedolizumab is an α4β7 integrin antagonist which blocks gut-specific leucocyte migration. It is indicated for induction and maintenance of remission in moderate to severe ulcerative colitis (UC) and Crohn’s disease.1 The aim of this study was to characterise the use and efficacy of vedolizumab in the induction and maintenance of remission in UC patients at University College London Hospital, a tertiary UK IBD centre. A retrospective review of all UC patients initiated on vedolizumab from October 2015 to November 2016 was completed. A 52-week follow-up was completed on all patients. Patient characteristics and clinical review data with SCCAI score were collected. Clinical response was defined as a reduction of SCCAI to <3 from baseline at Week 14, 30 and Week 52. Clinical remission was defined as SCCAI ≤2 or endoscopic evidence of quiescent disease. Forty-five UC patient records were examined; six patients were excluded due to incomplete data for Weeks 0–14 outcomes. Clinical review at 1 year of excluded patients showed five patients in clinical remission. Complete data were reviewed for 39 patients, 26 male, 13 female. Montreal classification identified 19 patients with pancolitis (E3), 14 with left sided disease (E2) and 6 with proctitis (E1). Average age at diagnosis was 26 and age at starting vedolizumab was 32 with average duration of disease 6.23 years. 43% had failed at least one previous tumour necrosis factor antagonist (anti-TNF). Concomitant immunomodulators were used in 69% of patients, 19 with a thiopurine analogue, and 8 using methotrexate. Average number of vedolizumab infusions to clinical response was 2.41. Average faecal calprotectin reduced from 2163 to 828. No difference was identified in number of infusions required to induce clinical remission between anti-TNF naive and exposed patients (2.5 vs. 2.18). 10 patients were primary non-responders at 14 weeks. Three patients required colectomy with one planned. Anti-TNF therapy was used in six patients of which only one patient has responded well. No difference was identified in average SCCAI scores at Week 0 between responders and primary non-responders. Clinical response at Week 14 predicted remission in all but five patients at Week 52 review. This real-world study demonstrates that vedolizumab is equally efficacious in anti-TNF therapy naive and exposed UC patients. Clinical response at 14 weeks predicts the likelihood of maintaining clinical remission at 52 weeks. Use of anti-TNF medication to induce remission in UC patients after failure of vedolizumab may not be of benefit. 1. Feagan B et al. Vedolizumab as induction and maintenance therapy for ulcerative colitis. New Eng J Med, 2013;369: 699–710, doi:10.1056/NEJMoa1215734.

Background: Paediatric patients with IBD move from family-oriented paediatric to individual-oriented adult gastroenterology services at a time of significant physical and psychological change. There is some evidence that coordinated transition programmes may improve outcomes in IBD when transferring to adult services. The health-related quality of life (HRQoL) of adolescent/young adults following transfer to adult services has not been described. Methods: An observational, multi-centre, mixed methodology study of adolescent/young adult patients (age ≥16 years) with a confirmed diagnosis of IBD before age 16 who had been under the care of adult services for ≥12 months at recruitment was conducted in 11 UK centres. Transition visits were defined as those involving clinical staff from both paediatric and adult services; transition patients had attended ≥2 transition visits and non-transition patients attended none. Patients completed the following questionnaires at recruitment: Short Inflammatory Bowel Disease Questionnaire (SIBDQ), Inflammatory Bowel Disease Control Questionnaire (IBDCQ-8 and IBDCQ-VAS [visual analogue scale]), Hospital Anxiety and Depression Scale (HADS), Work Productivity and Activity Index (WPAI) and self-reported days of education lost due to IBD. Socioeconomic status was measured using the English Index of Multiple Deprivation (IMD). Results: Transition (n=95) and non-transition (n=34) patients were similar in terms of demographic and clinical characteristics at recruitment (transition: median age 19.6 years; 47% female; 78% CD; median 2.1 years since index visit) and non-transition patients (n=34; median age 19.3 years; 41% female; 74% CD; median 2.3 years since index visit; all p>0.05). Overall, patient-reported quality of life and perceived IBD control were similar in transition and non-transition patients (all p>0.05; see table). Significant symptoms of anxiety and depression were reported by 20% and 2%, respectively, of transition patients and by 13% and 0%, respectively, of non-transition patients (p>0.05; see table). Of those in employment, 16% of transition and 27% of non-transition patients had time off work in the previous week. Time lost from education and socioeconomic status were similar in transition and non-transition patients (both p>0.05; see table). Conclusions: Surveys collected from at least 120 adolescent/young adult patients with IBD taking part in this study describe health related quality of life at this time point.

Background: Rare loss-of-function mutations in IL10 or its receptors (IL10R) cause severe infantile IBD in humans suggesting that the IL10/IL10R pathway is indispensable for mucosal homeostasis in the infant gut.We have previously shown that mice deficient in IL10R develop microbiota-driven spontaneous colitis between 3-4 weeks which is associated with the increases in inflammatory gene expression and CCR2-dependent recruitment of Ly6C + inflammatory monocytes (Mo) and Ly6C + MHCII + macrophages (MΦ) into the colon of infant IL10R KO mice.However, the precise role of recruited intestinal MΦs in driving colonic inflammation in infant IL10R KO mice remains elusive.Here using several complementary approaches, we determined whether colonic inflammation in infant IL10R KO mice required CCR2-dependent MΦ recruitment.Methods: Three-week-old Il10rb -/- mice were treated with liposomal-Clodronate to deplete intestinal MΦs.The role of Ly6C + proinflammatory Mo/MΦ in driving colonic inflammation was assessed by using a CCR2-blocking antibody.The transcriptional signature of anti-inflammatory Ly6C - MHCII + MΦs from 1, 3, and 12 week old Il10rb -/- and control mice was evaluated by RNA-seq analysis.We generated Rag -/- mice that lack IL10R (Il10rb -/- Rag -/- ) and CCR2 (Il10rb -/- Rag -/- Ccr2 -/- ) to assess the development of colitis following transfer of wild-type CD4 + T cells.Finally, we analyzed the development of colitis in crosses between C57BL/6 mice lacking IL10Rα in MΦ (Il10ra fl/ fl LysM Cre) and those carrying a genetic locus driving colitis susceptibility, Cdcs1, neither of which independently develop colitis.Results: Clodronate treatment led to significantly reduced colonic inflammation in infant 129SvEv Il10rb -/- mice.However, the inhibition of Ly6C + inflammatory Mo/ MΦ recruitment by anti-CCR2 antibody did not inhibit inflammation in the colons of Il10rb -/- mice.The inability of CCR2 blockade to interfere with inflammation in IL10R deficiency was verified by demonstrating that colitis in Il10rb -/- Rag -/- Ccr2 -/- mice was as severe as colitis observed in Il10rb -/- Rag -/- control mice following transfer of wild-type CD4 + T cells, despite a marked reduction in inflammatory and resident MΦ in the absence of CCR2.Finally, we observed severe colitis in Cdcs1 +/+ Il10ra fl/fl LysM Cre mice between 3-4 weeks of age but not in control Cdcs1 +/+ LysM Cre mice, confirming IL10R signaling on MΦ is essential to prevent spontaneous colitis.Conclusion: These results suggest that CCR2-independent mechanisms are responsible for driving colitis in infant IL10R deficient mice.These findings raise the possibility that IL10R competent macrophages are necessary to prevent colitis but may not necessarily be required to drive inflammation.We propose that mechanistic studies using these models could have significant implications for our understanding of pathogenic pathways in infantile IBD.

Background: The early inflammatory response in ulcerative colitis (UC) has been shown to be protracted. We used an in vivo bacterial challenge model to determine the cellular and molecular determinants and consequences of this perturbed acute inflammatory response in patients with UC. Methods: Acute inflammation was provoked in 26 UC patients off treatment or on 5-aminosalicylates, and 17 healthy controls (HC), by intradermal injection with UV-killed E. coli or S. pneumoniae. The local vascular reaction was quantified using laser Doppler imaging. The early and resolving inflammatory exudates were sampled by raising suction blisters over inoculation sites after 4h or 48h. Cells were characterised by polychromatic flow cytometry; cytokines by multiplex array; and lipid mediators by mass spectrometry. In vivo findings were confirmed by in vitro stimulation experiments on cultured peripheral blood-derived neutrophils and macrophages. Results: UC patients off treatment demonstrated enhanced local blood flow within 24h of bacterial exposure, with impaired resolution, to both Gram-negative and Gram-positive bacteria (p=0.01). Neutrophil accumulation within 4h of inoculation was almost double that of HC (115,217 vs 67,760 cells/blister, p=0.04). This was associated with elevated PGE2 production (p=0.02), and did not appear to be a cytokine-driven phenomenon. At 48h, the excess of neutrophils in UC persisted (5,402 vs 494 cells, p=0.001), accompanied by T lymphocytes (7,713 vs 3,670 cells, p=0.03) of an effector memory phenotype. The exaggerated onset was normalised in UC patients taking 5-aminosalicylates; these individuals had greater numbers of macrophages present at 48h (5,044 vs 1875 cells, p=0.03), consistent with their role in inflammation resolution and tissue healing. Excess PGE2 production and normal cytokine secretion were replicated in cultured UC macrophages stimulated with E. coliin vitro, supporting the primary impact of these abnormalities in the generation of the excessive acute inflammatory response. Conclusions: The acute inflammatory response to bacteria in UC is exaggerated, and slow to resolve, with immunological findings mirroring those seen in acute disease flares. This phenomenon was not restricted to Gram-negative bacterial stimuli, and is associated with abnormalities in inflammatory lipid mediators. 5-aminosalicylates normalise this process, likely through harnessing novel pro-resolution mechanisms. This method also provides a platform to investigate disturbed inflammation in UC, and the impact of novel therapies on this.

Introduction Acute inflammation in ulcerative colitis (UC) is protracted. Using an in vivo bacterial challenge model, we characterised the cellular and molecular determinants and consequences of the early inflammatory response in UC, and the functional impacts of 5-ASA on this process. Method Acute inflammation was provoked in 23 healthy controls (HC) and 26 UC patients off treatment or on 5-ASAs, by intradermal injection with killed E. coli or S. pneumoniae. Local vascular reactions were quantified by laser Doppler. Early and resolving inflammatory exudates were sampled by raising suction blisters over inoculation sites after 4 hour or 48 hour. Cells were characterised by polychromatic flow cytometry; cytokines by multiplex array; and lipid mediators by mass spectrometry. In vivo findings were confirmed by in vitro stimulation of cultured peripheral blood-derived macrophages with killed E. coli. Results UC patients had enhanced local blood flow within 24 hour of bacterial exposure, and impaired inflammation resolution, to both Gram-negative and Gram-positive bacteria (p=0.01). Neutrophil accumulation (p=0.04) and PGE2 production (p=0.02) were increased within 4 hour, and were not cytokine-driven phenomena. At 48 hour, UC patients had persistent neutrophils (p=0.001) and T lymphocytes (p=0.03). Findings were replicated in cultured macrophages, which also exhibited higher COX-1 up-regulation, supporting the primary impact of these abnormalities. Exaggerated onset was normalised in patients taking 5-ASAs, although these individuals had greater numbers of macrophages at 48 hour (p=0.03). This was accompanied by increased concentrations of the hydroxy fatty acids 9-oxo-octadecadienoic acid (OxoODE) and 13-OxoODE. To characterise their effects, macrophages were co-incubated with E. coli and these mediators. Both led to dose-dependent suppression of TNF-α (p=0.0001 and p=0.01, respectively), at concentrations reflective of those in vivo. These effects were completely reversed by GW9662, a PPARγ antagonist (p=0.006). The in vivo profile of lipid mediators in HC treated with 5-ASAs differed from UC, with subtle differences in resolving inflammatory cellular and cytokine constituents; this has important implications for understanding generation of these hydroxy fatty acids in vivo. Conclusion Acute inflammation in UC is exaggerated and slow to resolve, associated with perturbed production of inflammatory lipid mediators. 5-ASAs normalise this reaction, partly through generation of hydroxy fatty acids that act through the PPAR-γ receptor. Disclosure of Interest None Declared