Results from clinical trials show that vedolizumab is an efficacious treatment for inflammatory bowel disease, namely Crohn's disease (CD) and ulcerative colitis (UC). However, there is limited evidence from real-world clinical practice, especially on early clinical experiences in the UK. To describe real-world early experiences of vedolizumab to treat CD and UC in the UK. A retrospective, chart review study of patients with CD or UC treated with vedolizumab across 5 UK hospitals. All eligible adults (= 18 years at initiation) with a diagnosis of CD and= 14 weeks of data or UC and= 10 weeks of data available following vedolizumab initiation were included. Data were analyzed for 112 patients (CD: 66; UC: 46). Patients with CD had a median of 7.4 (interquartile range 5.7-9.4) months follow-up and patients with UC had a median of 7.4 (5.6-10.2) months follow-up post-vedolizumab initiation. Most patients, 80% (53/ 66) with CD and 89% (41/ 46) with UC, remained on vedolizumab treatment at the time of data collection. No new safety signals were identified during the study. These results add to the body of evidence supporting vedolizumab as an effective and well-tolerated treatment for CD and UC in real-world clinical practice.

Drug-induced liver injury (DILI) in IBD patients is mostly attributed to thiopurines and methotrexate. Less has been reported about biologics-related DILI in IBD patients with existing data restricted to case reports. We retrospectively collected data on a multi-centre cohort of IBD patients with DILI attributed to biologics. This was a part of the European Crohn`s and Colitis Organisation (ECCO) initiated CONFER (Collaborative Network for Exceptionally Rare case reports) project. A call was made to all ECCO members to report DILI following initiation of biologics. Data were recorded on a standardised case report form and analysed with descriptive statistics. Eighteen patients with DILI attributed to biologics have so far been reported in this cohort (M: F −10:8, CD: UC- 10:8, Median age 33 years). DILI was attributed to infliximab in 15 patients, vedolizumab in 2 and adalimumab in 1. Seven patients were on concomitant immunomodulators (5 thiopurines, 2 methotrexate). Coexistent axial or peripheral arthropathy was recorded in 6 patients. Patients had a median of 3 doses (range 1–22) prior to development of DILI. Median time to DILI following last exposure to biologics was 51 days (range 12–84 days). Predominant hepatocellular pattern of liver function tests was noted in 9 patients, predominant cholestatic in 2 and mixed picture in the remaining 7. Antinuclear antibodies were present in 11/18 (3 of these anti smooth also muscle Ab positive) with elevated IgG in 9 patients. Liver biopsy was performed in 9 patients with 6 suggesting drug toxicity, 2 showing additional features of autoimmune liver disease and one showing co-existent steatohepatitis. The biologic was discontinued in all but 2 patients. Six patients had steroids following liver injury. Complete recovery of liver function was seen in 13, and partial in 3 patients following discontinuation of biologics in a median time of 35 days. Alternative biologics were started for IBD in 13 patients (10 switched from infliximab to vedolizumab, 2 from infliximab to adalimumab, and one from infliximab to ustekinemab),) with no recurrence of DILI. In a median follow-up of 17 months, 2 patients were formally diagnosed to have autoimmune liver disease requiring additional immunosuppression. DILI is reported in patients receiving biologics for IBD predominantly with Infliximab with development of autoimmunity in a subset of patients. Majority recover on stopping the offending agenda with no recurrence on switching the biologics. Results should be interpreted with caution as causality could not be certain given the retrospective nature of the study. A larger cohort is required to study DILI related to biologics in IBD.

Introduction Very few data are available about the clinical course of chronic pancreatitis caused by Cystic Fibrosis Transmembrane Conductance Regulator (CFTR-Panc) gene mutations, when compared with non-CFTR causes of chronic pancreatitis, alcohol being the commonest cause. Methods To study the clinical presentation and course of pancreatitis in patients with Cystic Fibrosis gene carrier status, compared with larger cohort of other causes of pancreatitis. A retrospective analysis of all the patients in Manchester Foundation Trust Specialist Pancreatology Unit with Chronic pancreatitis and CFTR gene carrier status between 1999 to 2018, compared with the published literature for other causes of chronic pancreatitis. Results A total number of 41 patients were heterozygous for CFTR gene mutations 29 male, Average age at presentation was 34.6 (range 11–65). Presentation varied: recurrent attacks of pancreatitis: 30 (73%); solitary attack of pancreatitis: 10 (24.3%) 1 (2.4%) patient presented with unexplained weight loss. Complications of pancreatitis occurred in (68.2%) Conclusion We report a different course and complication rate of chronic pancreatitis in CFTR carrier patients when compared to other causes of pancreatitis in the literature. In this retrospective cohort analysis, when compared with the published literature, patients with chronic pancreatitis caused by a mutation in one CFTR gene appear to have a lower incidence of diabetes, which took longer to develop. Other complications of pancreatitis - pseudocysts, pancreatic strictures and necrosis, were also less frequent in our cohort when compared to the literature, suggesting a less aggressive disease course. However, we noted no difference in the pattern of exocrine insufficiency between the two groups. Based on these findings, a larger prospective study is now required. References Ammann, et al.. Gastroenterology. 1996 Jul;111(1):224–31. Hao, et al. PLoS One. 2018 Jun 8;13(6):e0198365. doi: 10.1371/journal.pone.0198365. eCollection 2018. Lévy et al Gastroenterol Clin Biol. 2006 Jun-Jul;30(6–7):838–44.Malka et al Gastroenterology 2000; 119: 1324–1332.

The precise mechanism of hydrocortisone immune regulation in the management of colitis is poorly understood. Whilst not without limitations, its ability to suppress pathology and rapidly improve patient clinical outcome is key. We were interested in identifying early markers of therapeutic responsiveness in order to identify patients’ refractory to therapy. Chronic Th1-driven colitis was induced in AKR/J mice using a parasite infection, Trichuris muris. 35 days post infection, mice were treated with low dose hydrocortisone (2 mg/kg/) i.p. on alternate days. Response to therapy was assessed at a systemic and tissue level day 45 post infection. Histopathology, gene and protein analysis was conducted to determine cytokine and transcriptional profiles. The colonic transcriptional profile in steroid treated mice showed significant upregulation of a small subset of T cell associated genes, in particular C/EBPβ, CD4, IL7R and STAT5a. Despite no change in either transcription or protein production in downstream cytokines IFN γ, TNFα IL-17 and IL-10, hydrocortisone treatment significantly reduced colonic pathology and restored colonic length to naïve levels. As expected, steroid treatment of chronic gut inflammation generated significant immunosuppressive effects characterized by histological improvement. Low dose hydrocortisone induced significant upregulation of a subset of genes associated with T cell maintenance and regulation, including C/EBPβ. These data suggest that enhanced expression of C/EBPβ may be one of a subset of early markers demonstrating an immune regulatory response to hydrocortisone therapy, potentially by stabilization of Treg function. These observations contribute to our understanding of the immune landscape after steroid therapy, providing a potential markers of therapeutic responders and those refractory to hydrocortisone treatment.

Background Inflammatory Bowel Disease (IBD) presents challenges to psychological coping and adjustment, impacting health outcomes and disease activity. In the UK individuals with IBD have limited access to health psychology support services which can improve the quality of life and management of long-term conditions. We developed and evaluated an evidence led, integrated health psychology clinic (GastWell) within the IBD service in a large teaching hospital. Methods Anxiety, depression and illness perception data were collected from 126 patients attending an outpatient IBD nurse clinic to gain a greater understanding of the overall need for a psychological service and to assess whether the GastWell clinic is capturing all those in need of health psychology support. Specialist IBD Health Psychologists delivered brief, behaviour change focused interventions within the GastWell clinic. Following referrals from the IBD team, patients were assessed and offered assistance in adjusting to and managing their IBD, including reducing smoking and alcohol consumption. We evaluated the GastWell service using validated patient-reported outcome measures before and after intervention. Measures include the Short IBD questionnaire, Brief Illness Perceptions questionnaire and Hospital Anxiety and Depression Scale (HADs). Results 31 patients were referred to the monthly GastWell clinic between October 2016 and October 2018. The most common reason for referral was for support in adjusting to and managing IBD. Compared to the IBD population attending the outpatient IBD nurse clinic, those referred to the GastWell clinic had a more threatening view of their IBD and higher anxiety and depression scores. Patient reported outcomes suggest reductions in illness perceptions, anxiety and depression scores and an increase in health-related quality of life from pre to post intervention. Conclusion Our service evaluation suggests that those requiring health psychology support are being correctly referred into the GastWell clinic, and that the interventions are appropriate and effective in assisting patients with adjusting to and managing their IBD. In addition, we have demonstrated reductions in illness perceptions, anxiety and depression scores that are lower than the general IBD population at this site. Greater access to integrated health psychology IBD services is necessary and may benefit all individuals with IBD. *Higher score indicates higher quality of life. **Higher scores indicate a more threatening view of the illness. ***0-7 = normal; 8-10 = borderline abnormal; 11-21 = abnormal.

Background Vedolizumab (VDZ) is a gut selective α4β7 anti-integrin approved for the treatment of UC and CD. We aimed to assess one year clinical and safety outcomes of VDZ. Methods We previously reported 12 week outcomes using retrospectively collected demographic, clinical, and adverse effects data of patients treated with VDZ at 8 UK centres since 2014. We now report longer term outcomes, evaluating clinical response at week 12 and 52, using Physician Global Assessment, Harvey Bradshaw Index (HBI) and partial Mayo Score (pMS). Results Of 203 patients, 135 had CD (96% anti-TNF experienced), and 68 UC (66% anti-TNF experienced). 101 received concomitant immunomodulator therapy and 97 received steroid bridging therapy. Of 135 CD patients, 9 discontinued VDZ prior to week 12. At week 12, 38.5% were in PGA remission and 40.0% had a PGA response. Between week 12 and 52, a further 35 patients discontinued VDZ. At week 52 PGA remission and response were seen in 39.2% and 24.3% respectively. Mean HBI decreased from 9.2 (baseline) to 5.1 (week 12) and 5.2 at week 52 (p<0.01). Of 68 UC patients, 3 discontinued VDZ prior to week 12. At week 12, 48.5% were in PGA remission and 42.6% had a PGA response. Between week 12 and 52, a further 9 patients discontinued VDZ. At week 52, PGA remission and response were seen in 67.2% and 16.4% respectively. Mean pMS decreased from 6.1 (baseline) to 3.1 (week 12) and 2.2 (week 52; p<0.01). Adverse events were reported in 48 cases (24%) Of these 29 were infection related. Overall incidence of infection was 11.1 per 100 person-years of VDZ exposure. Conclusion In our cohort of refractory (predominantly anti-TNF experienced) patients, VDZ proved to be safe and effective. Although at 12 weeks response/remission rates were similar in CD and UC, VDZ appeared to be more effective at maintaining remission for UC compared to CD. The incidence of infectious complications was lower than that seen with anti-TNF therapies (average 14 per 100 person-years).

Introduction Ustekinumab (UST) binds to the p40 subunit of IL12 and IL23 to prevent IL12RB1 cell-surface receptor activation and thus inhibits downstream inflammatory signalling. It is approved for moderately to severely active Crohn’s disease (NICE TA456). We assessed the clinical outcomes and safety of UST in a ‘real-world’ cohort of refractory Crohn’s disease patients treated at a single UK centre. Methods We retrospectively collected data from the electronic records of Crohn’s disease patients treated with UST at a single UK IBD tertiary referral centre. Patient demographics and adverse events were recorded. Clinical response to UST was evaluated at baseline and follow up using Harvey-Bradshaw Index (HBI) scores, C reactive protein (CRP), and faecal calprotectin (FC). Paired Student’s T Tests were used to determine statistical significance. Results 26 patients (mean age 36 years; age 18–62 years; M:F ratio=1:1.6) with a variety of Crohn’s disease phenotypes (L1=8; L2=6; L3=12) were treated with UST. 9 patients (35%) had stricturing disease and 5 patients (19%) penetrating disease. All patients had failed at least one anti-TNF agent. 15 patients (58%) had failed two anti-TNF agents, and 11 (42%) had failed an anti-TNF and subsequent vedolizumab therapy. 7 patients (27%) received immunomodulatory co-therapy (AZA=5; MTX=2), and 11 (42%) received bridging steroids. 12 week data was available for 20 patients. At 12 weeks, mean HBI significantly improved (5 vs 9; p<0.05). There was reduction in mean FC (763 vs 1026; ns), but no change in mean CRP (14 vs 11; ns). 10 patients (50%) demonstrated subjective and objective (FC +/-CRP +/- endoscopic) response to therapy. 6 of these patients received bridging steroids, of which all had reduced and 4 had completed their steroid course. Of all treated patients 2 discontinued UST (recurrence of a transitional cell carcinoma; primary non-response to therapy requiring surgery), and side effects were reported in 2 patients (Bell’s Palsy; lower respiratory tract infection). Conclusions UST appears clinically effective and safe in this cohort of treatment-refractory Crohn’s disease patients after 12 weeks of therapy. Future work to combine ‘real world’ data and to assess longer term outcomes will help us to better understand and place the use of UST in the management of Crohn’s disease.

Background: Real-life data on vedolizumab effectiveness in inflammatory bowel disease (IBD) are still emerging. Data on the comparative safety of the gut selective profile are of particular interest. Aims: To assess clinical outcome and safety in IBD patients treated with vedolizumab. Methods: We retrospectively collected data of patients treated with vedolizumab at eight UK hospitals (August 2014-January 2018). Clinical response and remission at 14 and 52 weeks evaluated through Physician Global Assessment (PGA) and adverse events were recorded. Possible predictors of clinical response were examined. Results: Two hundred and three IBD patients (mean treatment 16 + 8 months) were included. Of these, 135 patients (mean age 40.6 + 16.0 years; F:M 1.9:1) had CD and 68 (mean age 44.5 + 18.1 years; F:M 1:1.2) had UC. According to PGA, 106/135 (78.5%) CD and 62/68 (91.2%) UC patients (p = 0.02) had a clinical response/remission at 14 weeks, whereas 76/119 (63.9%) CD and 52/63 (82.5%) UC patients (p < 0.01) showed a sustained response or remission at 52 weeks, with a high adherence rate (97%). No predictors of clinical response were found. The cumulative incidence of infectious diseases was 11.9 per 100 person years. Conclusion: Vedolizumab is an effective therapy for inducing and maintaining remission of IBD, with better results for UC, and with a good safety profile. (C) 2018 The Authors. Published by Elsevier Ltd on behalf of Editrice Gastroenterologica ltaliana S.r.l.

Monocytes are crucial immune cells involved in regulation of inflammation either directly or via differentiation into macrophages in tissues. However, many aspects of how their function is controlled in health and disease are not understood. Here we show that human blood monocytes activate high levels of the cytokine TGFβ, a pathway that is not evident in mouse monocytes. Human CD14+, but not CD16+, monocytes activate TGFβ via expression of the integrin αvβ8 and matrix metalloproteinase 14, which dampens their production of TNFα in response to LPS. Additionally, when monocytes differentiate into macrophages, integrin expression and TGFβ-activating ability are maintained in anti-inflammatory macrophages but down-regulated in pro-inflammatory macrophages. In the healthy human intestine, integrin αvβ8 is highly expressed on mature tissue macrophages, with these cells and their integrin expression being significantly reduced in active inflammatory bowel disease. Thus, our data suggest that integrin αvβ8–mediated TGFβ activation plays a key role in regulation of monocyte inflammatory responses and intestinal macrophage homeostasis.

Summary Infliximab (IFX) has been used repeatedly in mouse preclinical models with associated claims that anti-inflammatory effects are due to inhibition of mouse tumour necrosis factor (TNF)-α. However, the mechanism of action in mice remains unclear. In this study, the binding specificity of IFX for mouse TNF-α was investigated ex vivo using enzyme-linked immunosorbent assay (ELISA), flow cytometry and Western blot. Infliximab (IFX) did not bind directly to soluble or membrane-bound mouse TNF-α nor did it have any effect on TNF-α-induced nuclear factor kappa B (NF-κB) stimulation in mouse fibroblasts. The efficacy of IFX treatment was then investigated in vivo using a TNF-α-independent Trichuris muris-induced infection model of chronic colitis. Infection provoked severe transmural colonic inflammation by day 35 post-infection. Colonic pathology, macrophage phenotype and cell death were determined. As predicted from the in-vitro data, in-vivo treatment of T. muris-infected mice with IFX had no effect on clinical outcome, nor did it affect macrophage cell phenotype or number. IFX enhanced apoptosis of colonic immune cells significantly, likely to be driven by a direct effect of the humanized antibody itself. We have demonstrated that although IFX does not bind directly to TNF-α, observed anti-inflammatory effects in other mouse models may be through host cell apoptosis. We suggest that more careful consideration of xenogeneic responses should be made when utilizing IFX in preclinical models.

Introduction Reducing emergency admissions is a recognised Quality Premium outcome by the Better Care Fund (NHS England) and it is one the of outcome measures against which CCGs are required to set targets. The IBD helpline can be directly translated into in-patient beds saved and direct costs. This prospective audit measured both cost savings and income generated and also calculated A and E avoidances and in-patient beds saved. Method The aim was to measure how an IBD Nurse helpline could influence key outcomes. Between 1/1/2016-30/6/2016 all calls to the IBD helpline were prospectively audited in a large tertiary Hospital Trust. Patients were also asked what action they would take if there were no helpline available at that time point and their thoughts/concerns recorded. The tariff from the helpline, the OPDs saved, number of in- patient bed days saved and costs were calculated with the Specialist Medicine Informatics and Accountants. Results In 6 mths there were 876 IBD related appropriate and chargeable calls to the helpline. This tariff generated an income of £26 280. 741 OPD s were avoided resulting in £62 244 savings to the CCG. 76 A and E attendances were directly avoided. Based on a 5 day in-patient stay (average in-pt stay for previous 6 mths) 380 days were saved over 6mth, saving 2.1 beds per day. The 2.1 bed days per day saved equates to £96 000 over the 6mth period. Of the 90 ‘other’, 32 were given OPDs generating an income £3648. 6 patients were admitted directly from the helpline. 273 GP consultations were avoided. Conclusion IBD helplines are a vital resource for IBD patients. There is great emphasis demonstrating the value of the IBD nurse in both monetary terms and patient experience. The presence of an IBD helpline can assist NHS Trusts and CCGs to meet national targets by avoiding A and E admissions and in-patient bed stays, reducing opds whilst maintaining a high quality, efficient and optimal service. Disclosure of Interest K. Kemp Conflict with: Abbvie, MSD, Takeda, Janssen, J Brooks: None Declared, M Kirkbride: None Declared, F Birchall: None Declared, H Dutton: None Declared, S Levison: None Declared

Background: Intestinal immune cells must be poised to clear invading pathogens while remaining tolerant to the trillions of commensal bacteria present in the gut, with perturbations in this process implicated in development of inflammatory bowel disease (IBD). The cytokine transforming growth factor beta (TGFβ) is a key factor in regulating intestinal immunity, but is secreted as an inactive complex that requires activation to function. Although recent data have established important ways that TGFβ activity is controlled in the mouse, the pathways present in humans remain unclear. Here we aimed to identify mechanisms regulating TGFβ activity in the human immune system, and establish the functional importance of TGFβ activation in intestinal homeostasis. Methods: Healthy human peripheral blood mononuclear cells, monocyte-derived macrophages (MDMs), and colonic lamina propria cells from control and IBD patients were analysed by flow cytometry. Cells of interest were co-cultured with an active TGFβ reporter cell line to determine TGFβ activation. Results: Here, we show that human CD14+ blood monocytes activate high levels of TGFβ, which is not apparent with the equivalent murine monocytes. Mechanistically, we show that activation of TGFβ by CD14+ monocytes requires expression of the integrin, alpha v beta 8 (αvβ8). When monocytes are differentiated to MDMs, expression of αvβ8 and TGFβ activation was observed on MDMs cultured with M-CSF, which are proposed to represent a more anti-inflammatory macrophage population. In addition, integrin αvβ8 expression was increased on these cells by exposure to IL-10, TLR-4 and -7/8 ligands. In contrast, MDMs cultured with GM-CSF expressed lower levels of the integrin and activated minimal amounts of TGFβ. In the intestine, integrin αvβ8 is highly expressed on CD64+ macrophage population expressing CD163 and CD206, which are proposed to represent a more regulatory phenotype, and are decreased in patients with active Crohn's disease. Conclusions: Our results suggest that expression of integrin αvβ8 by CD14+ monocytes may play an important role in the induction and function of anti-inflammatory macrophages in the intestine via TGFβ activation. Further work will provide important new insights into how myeloid cells regulate immune responses in the human intestine to maintain homeostasis and prevent IBD.

Introduction Vedolizumab (VDZ) is an α4β7 anti-integrin licensed to treat UC and CD. We aimed to assess clinical outcomes and safety of VDZ in IBD patients treated in several hospitals across northern England. Method We retrospectively collected data of patients treated with VDZ at 8 UK centres since 2014. We evaluated clinical response at 12 and 52 weeks using the Physician Global Assessment (PGA), Harvey-Bradshaw Index (HBI) or Mayo score. We collected C reactive protein (CRP) and faecal calprotectin (FC) at baseline and follow-up. Fisher exact test and student’s t-test were used to determine statistical significance. Results Of 183 patients (mean 41 years, F/M ratio 1.4:1) 120 (65.6%) had CD, 61 (33.3%) UC, and 2 (1.1%) IBD-U. 18 patients were active smokers. 57 (31%) received immunomodulators, 68 (37%) steroid bridging therapy and 27 (15%) patients were anti-TNF naïve. PGA remission was observed in 33 (31%) CD, 26 (44.8%) UC and 2 (100%) IBD-U patients at 12 weeks and in 6/48 (12.5%) CD and 16/36 (44.4%) UC patients at 52 weeks. A partial response was observed in 51 (48%) CD and 25 (43.1%) UC patients at 12 weeks and in 8/48 (16.6%) CD and 10/36 (27.7%) UC patients at 52 weeks. At 52 weeks, VDZ was more effective in maintaining remission in UC than CD (p<0.05). In CD patients, mean CRP, FC and HBI significantly improved at 12 weeks, with a further improvement of HBI at 52 weeks. In UC, mean FC and Mayo score significantly decreased at 12 weeks, whereas CRP did not improve. Non-smoking status was associated with better response (p<0.05). 43 patients (23.5%) discontinued VDZ (average exposure 4.5 months). Reported side effects occurred in 21 cases (11%): 3 urticarial rashes, 6 pneumonias, 3 nasopharyngitis, 2 skin infections, 2 sepsis, 1 viral meningitis, 1 EBV infection, 1 urinary tract infection, and 2 abnormal liver function tests. Overall incidence of infection was 12 per 100 person-years of VDZ exposure. Conclusion VDZ is a safe and effective therapy even in this cohort of predominantly anti-TNF exposed patients. Induction data are similar for CD and UC, but VDZ seems to be more successful in maintaining remission for UC. The incidence of infectious complications was comparable to that seen with anti-TNF therapies (average 14 per 100 person-years). Disclosure of Interest M. Lenti: None Declared, S. Levison: None Declared, E. Eliadou: None Declared, R. Robert Willert: None Declared, K. Kemp: None Declared, C. Stansfield: None Declared, A. Assadsangabi: None Declared, S. Singh: None Declared, B. Crooks: None Declared, S. Tattersall: None Declared, C. Kenneth: None Declared, S. Subramanian: None Declared, C. Probert: None Declared, D. Storey: None Declared, B. Gregg: None Declared, P. Smith: None Declared, E. Liu: None Declared, J. Limdi: None Declared, A. Johnston: None Declared, PJ Hamlin: None Declared, C. Selinger Conflict with: Warner Chilcott, and Abbvie, Conflict with: Warner Chilcott, Dr Falk, Abbvie, Janssen and Takeda

Introduction Filgotinib (FIL), an oral, selective Janus kinase 1 (JAK1) inhibitor that blocks cytokine signalling by inhibiting STAT phosphorylation, which previously demonstrated efficacy in rheumatoid arthritis, is being evaluated in active Crohn’s disease (CD). Method 174 patients with moderate-to-severe CD and ulcerations confirmed by centrally read endoscopy were randomised 3:1 to 200 mg FIL or placebo (PBO) QD for 10 weeks. Thereafter, patients continued to receive FIL 200 mg, 100 mg or PBO QD for another 10 weeks. Immunosuppressive agents had to be discontinued, and steroid dosage was kept stable until Week 10 (W10). Key efficacy and safety data, and phosphorylation of STAT3 in intestinal biopsies from the 10 week induction period are presented. Results Mean baseline characteristics were similar between the FIL and PBO group. The primary endpoint (clinical remission CDAI pSTAT3 levels were significantly reduced at W10 in FIL-patients (−36% (95% CI: −51%, −17%)). However, in patients in clinical remission at W10, pSTAT3 levels were significantly reduced irrespective of treatment (PBO −62% (95% CI: −83%, −16%) and FIL −42% (95% CI: −57%,−21%)). In patients without clinical remission, pSTAT3 levels numerically decreased with FIL (−28% (95% CI: −51%,+7%)) and not with PBO (+12% (95% CI:−21%,+94%). Conclusion Filgotinib is the first JAK inhibitor to demonstrate clinical efficacy in CD, as demonstrated by induction of clinical remission and response, and is associated with a significant reduction in pSTAT3 levels, suggesting that pSTAT3 behaves both as a pharmacodynamic marker for filgotinib and a disease activity marker. Disclosure of Interest S. Keshav Conflict with: Abbvie, ChemoCentryx, GSK, Merck, Conflict with: Abbvie, Allergan, Astra-Zeneca, Boehringer Ingelheim, ChemoCentryx, Dr Falk Pharma, Ferring, Gilead, GSK, Merck, Mitsubishi Tanabe Pharma, Pharmacosmos, Pfizer, Takeda, Vifor Pharma, J. Goh: None Declared, A. Hart: None Declared, S. Levison: None Declared, S. McLaughlin Conflict with: AbbVie, Conflict with: AbbVie, A. Van der Aa Conflict with: Galapagos NV, R. Galien Conflict with: Galapagos SASU, Y. Pan Conflict with: Gilead Sciences Inc, L. Meuleners Conflict with: Galapagos NV, C. Jamoul Conflict with: Galapagos NV, C. Tasset Conflict with: Galapagos NV, P. Harrison Conflict with: Galapagos NV, S. Vermeire Conflict with: AbbVie, Galapagos, MSD, Takeda, Conflict with: AbbVie, Galapagos, MSD, Takeda, Ferring, Genentech/Roche, Shire, Pfizer,Mundipharma, Hospira, Celgene, Second genome, Janssen, Conflict with: AbbVie

Introduction Increasing demands on IBD services have led to innovations in the way we interact with and deliver care to patients. IBD teams must work proactively to develop an efficient and cost effective service that enhances a patient’s experience. Optimising the care of our patients can incorporate direct or ‘virtual’ interactions. Method To standardise and improve the care of IBD patients requiring immunosuppression therapy (Aza, 6-MP, MTX) we developed a weekly virtual immunosuppressant clinic (VIC). Irrespective of their referring consultant, any IBD patient commencing therapy in our large teaching hospital between 19/5/2016- 12/1/2017 was included. To streamline the workload, all patients requiring scheduled blood test monitoring with therapy were offered blood tests on a Tues/Weds. Patients were then phoned during the VIC on a Thursday evening and their dose adjusted as/if needed. The scheduling of the next blood tests, and the measurement of AZA metabolite levels at week 12, were co-ordinated via the VIC. Stable patients were then transferred to the GP, under a Shared-Care pathway. The tariff from the VIC phone call, the number of OPDs saved, and the costs incurred were calculated with the Specialist Medicine Informatics. The VIC was prospectively audited. Results 70 patients were commenced on immunosuppressant therapy during the 8 months observed. During this time, 35 virtual clinics were held, averaging 13 calls per clinic (total calls=464). The income generated by the VIC tariff (£30 per VIC) was £13,9200. This saved the CCG £39 904 if all patients had instead required face to face follow up. The VIC detected 28 patients with abnormal blood tests requiring dose adjustment (31.1%). The VIC detected 5 AZA shunters (5.6%) and identified 17 patients with drug related side effects requiring the cessation of therapy (18.9%). Conclusion The co-ordination of patients’ care through a weekly virtual immunosuppression clinic provides an efficient and effective forum for instigating therapy safely. The IBD service proactively works to delivery optimal care and reduce unnecessary outpatient appointments, whilst enhancing patient experience. Disclosure of Interest None Declared

Regulation of intestinal T-cell responses is crucial for immune homeostasis and prevention of inflammatory bowel disease (IBD). A vital cytokine in regulating intestinal T cells is transforming growth factor-β (TGFβ), which is secreted by cells as a latent complex that requires activation to function. However, how TGFβ activation is regulated in the human intestine, and how such pathways are altered in IBD is completely unknown. Here we show that a key activator of TGFβ, integrin αvβ8, is highly expressed on human intestinal dendritic cells (DCs), specifically on the CD1c + but not the CD141 + intestinal DC subset. Expression was significantly upregulated on intestinal DC from IBD patients, indicating that inflammatory signals may upregulate expression of this key TGFβ-activating molecule. Indeed, we found that the Toll-like receptor 4 ligand lipopolysaccharide upregulates integrin αvβ8 expression and TGFβ activation by human DC. We also show that DC expression of integrin αvβ8 enhanced induction of FOXP3 in CD4 + T cells, suggesting functional importance of integrin αvβ8 expression by human DC. These results show that microbial signals enhance the TGFβ-activating ability of human DC via regulation of integrin αvβ8 expression, and that intestinal inflammation may drive this pathway in patients with IBD.

Introduction The IBD Standards, the Royal College of Physicians national biologic audit, and the NICE IBD quality standard (QS81) all aim to help deliver high quality, safe and appropriate clinical care to IBD patients throughout the UK. In line with these recommendations, and to improve and standardise the care of our IBD patients on biologic therapies we began a weekly multi-disciplinary (physicians, IBD nurses, and pharmacist) virtual biologics clinic (VBC). Here, the response to therapy is monitored (clinical scoring, well-being, laboratory results), the scheduling of investigations are coordinated, and the review and writing of prescriptions undertaken. Methods We prospectively collected data from our VBC for 8 consecutive weeks. Changes to therapy on clinical grounds were noted, and the financial implications of these changes calculated. Calculations for IFX savings were based on an average dose of 300 mg per patient, plus infusion costs. The ordering of required investigations and the occurrence of adverse clinical events were recorded Results In 8 weeks, 360 patient reviews were performed relating to 327 patients (IFX = 207, ADA = 79, VEDO = 41). Therapy was adjusted in 41/327 patients (12.5%). 5 stopped biologic therapy, 19 switched drug, 10 reduced and 7 increased the frequency of therapy. Net saving was £10,928 at week 8 (>£65 K/annum). The coordinated prescribing of medication and pharmacy sign off improved the delivery of therapy and patient satisfaction. 23 colonoscopies, 9 MR scans, and 45 outpatient appointments to assess response to therapy at 3 or 12 months and clinical input were scheduled from the VBC. The ordering of anti-TNF drug and antibody levels solely through the VBC reduced any duplication of requests and ensured the review and actioning of results. 5 complications were highlighted (recurrent infections; 2 requiring surgery; cancer; severe IBD flare requiring hospitalisation). Conclusion The introduction of a multi-disciplinary VBC has altered the management of 41/327 patients (12.5%) based on clinical findings and the results of investigations. Significant financial savings (£65 K per annum), the streamlining of prescribing, and superior patient monitoring have helped to improve the quality and safety of care provided. With better monitoring, care, NICE compliance, and financial prudence, this will help to sustain or service and practices. Disclosure of Interest None Declared