BACKGROUND:A laparoscopic ileocolic resection could lead to a better outcome to infliximab for ileocolic Crohn's disease. The aim of this study was to explore real world clinical outcomes in biologic-naïve patients with ileocolic Crohn's disease. RESEARCH DESIGN AND METHODS:All patients with ileocolic Crohn's disease treated at our institution between January 2011 and December 2018 with biologics or surgical resection were included. RESULTS:Overall, 222 patients were included, of which 149 (67%) underwent surgery before biologic therapy. Among these, 54 patients (36%) required post-operative biologic therapy. Seventy-three patients were treated with biologics first, of which 29 (40%) subsequently required a surgical resection (p = 0.60). There were 95 patients (43%) who were successfully treated with a surgery-first approach alone. Median follow-up was 73 months (0-406). Characteristics associated on multivariable analysis with change from surgery to biologics were: gender (female) (p = 0.010), presence of obstructive symptoms (p = 0.028), and smoking (p = 0.030). Characteristics associated with changing from biologics to surgery were: isolated terminal ileum disease (p = 0.001) and the presence of obstructive symptoms (p = 0.003). CONCLUSIONS:In our cohort, the risk of recurrent ileocolic Crohn's disease was similar whether patients were treated with a 'surgery first' or 'biologic first' approach.

We report a unique case of a 34-year-old man with ulcerative colitis, previously in complete remission with intravenous vedolizumab monotherapy, who developed an urticarial injection-site reaction on switching to a subcutaneous preparation and thereafter experienced a new hypersensitivity reaction on switch back to intravenous vedolizumab, necessitating complete discontinuation from this drug. This case highlights the need for vigilance on switching back to intravenous preparations of vedolizumab, in response to injection-site reactions with a subcutaneous preparation, even if the intravenous preparation had been previously well tolerated by the patient.

Background Current clinical guidelines recommend treating chronic hepatitis B virus (HBV) infection in a minority of cases, but there are relatively scarce data on evolution or progression of liver inflammation and fibrosis in cases of chronic HBV (CHB) that do not meet treatment criteria. We aimed to assess the impact of TDF on liver disease, and the risk of renal impairment in treated CHB patients in comparison to untreated patients. Methods We studied a longitudinal ethnically diverse CHB cohort in the UK attending out-patient clinics between 2005 and 2018. We examined TDF treatment (vs. untreated) as the main exposure, with HBV DNA viral load (VL), ALT, elastography scores and eGFR as the main outcomes, using paired tests and mixed effects model for longitudinal measurements. Additionally, decline of eGFR during follow-up was quantified within individuals by thresholds based on clinical guidelines. Baseline was defined as treatment initiation for TDF group and the beginning of clinical follow-up for untreated group respectively. Results We included 206 adults (60 on TDF, 146 untreated), with a median ± IQR follow-up duration of 3.3 ± 2.8 years. The TDF group was significantly older (median age 39 vs. 35 years, p = 0.004) and more likely to be male (63% vs. 47%, p = 0.04) compared to the untreated group. Baseline difference between TDF and untreated groups reflected treatment eligibility criteria. As expected, VL and ALT declined significantly over time in TDF-treated patients. Elastography scores normalised during treatment in the TDF group reflecting regression of inflammation and/or fibrosis. However, 6/81 (7.4%) of untreated patients had a progression of fibrosis stage from F0-F1 to F2 or F3. There was no evidence of difference in rates or incidence of renal impairment during follow-up in the TDF vs. untreated group. Conclusions Risk of liver inflammation and fibrosis may be raised in untreated patients compared to those receiving TDF, and TDF may benefit a larger percentage of the CHB population.

P107 Figure 1 Abstracts Gut 2021;70(Suppl 1):A1–A262 A97 on S etem er 4, 2021 by gest. P rocted by coright. http/gut.bm jcom / G t: frst pulished as 10.1136l-2020-bsgcam pu.183 on 21 Jauary 221. D ow nladed fom Results In total, 527 patients were enrolled on the registry; of whom, 54 were excluded due to incomplete information. Out of 473 patients [Collagenous colitis 328(69%), Lymphocytic colitis 127(27%), 18 unspecified (4%)] included in the analysis, 358(76%) were female, aged 20–96 (median 67) years. Watery diarrhoea (463, 98%) and abdominal pain (111, 23%) were predominant symptoms. Weight loss was noted in 115 (24%). Eight (2%) patients developed complications; 2 adverse drug reactions, 1 colorectal malignancy and 3 required surgical intervention for intractable symptoms related to MC. Variations were noted in the following areas: 1. Patient journey: Whilst 230(49%) were referred directly to Gastroenterology, 109(23%) were referred initially to Surgery– with subsequent referral to Gastroenterology following colonoscopy. This led to delay in therapy initiation in a proportion of patients. In one unit, average length of symptoms at diagnosis was 5.7 months, with an average length of 9.1 months to see Gastroenterology. 2. Medications: There was no evidence of medication review in 121(26%) patients. Reducing-dose Budesonide was the first line treatment in 205(43%). Though 174(37%) did not require initial medical therapy; of these 18(10%) required subsequent treatment with Budesonide. There are 4(1%) patients on biologics and 4(1%) patients on immunomodulators specifically for MC– all of which were treated with budesonide first line. 3. Follow-up: A majority, 337(71%) were followed-up in clinic, with 260(77%) later discharged. Relapse was noted in 118 (25%) patients. Conclusions Initial findings from the first MC Registry in the UK demonstrate variability in referral pathway, patient journey and management. Data suggests association with alarm features and significant complications. REFERENCE 1. Townsend T, Campbell F, O’Toole P, et al. Microscopic colitis: diagnosis and management. Frontline Gastroenterology 2019;10(4):388–93 P109 VEDOLIZUMAB IS AN EFFECTIVE TREATMENT FOR ANTIBIOTIC REFRACTORY CHRONIC POUCHITIS Sam Harrison*, Sara Cesano, Gareth-Rhys Jones, Philip Jenkinson, Alan Shand, Charlie Lees, Ian Arnott. University Of Edinburgh, Edinburgh, UK; Edinburgh IBD Unit – Western General Hospital, Edinburgh, UK 10.1136/gutjnl-2020-bsgcampus.184 Introduction Vedolizumab is a gut selective monoclonal antibody to a4b7 integrin that can successfully treat IBD, currently licenced for the treatment of Ulcerative colitis and Crohn’s disease. Chronic pouchitis is the most common complication arising following proctocolectomy, affecting 15–50% of patients after ileo-anal pouch formation. To date there is little data regarding the use of vedolizumab in pouchitis. We aim to evaluate the efficacy and safety of vedolizumab in the treatment of chronic antibiotic refractory pouchitis. Methods This was a retrospective study that took place in the Edinburgh IBD unit between July 2015 and September 2019. Patients were included in the study who had confirmed chronic pouchitis and had failed to respond to antibiotic therapy with at least 6 months of follow up. We assessed clinical disease activity by completing the Pouchitis Activity Score clinical sub-score. We also assessed blood tests including CRP, faecal calprotectin and inflammatory activity on pouch biopsy. In our statistical analysis continuous variables were assessed with paired samples t tests, whilst changes in frequencies were asses with chi-squared tests. Adverse events were recorded quantitively. Results A total of 13 patients were included in the study. 6 females, median age 50 years (IQR 44.5–62). All patients underwent colectomy for failure of medical therapy. Following vedolizumab treatment, 92% of patients experienced a reduction in Pouchitis Activity Score clinical sub-score, with median score falling from 10 at baseline to 2.5 at follow up (p= <0.0001, IQR= 8–12 at baseline, 0–5 at follow up). Median faecal calprotectin fell from 390mg/g to 197mg/g at 1 year (p=0.02, IQR= 340–644 at baseline, 60–283 at follow up). Active inflammation levels on pouch biopsy decreased in 71% of participants ( Baseline4 mild, 1 moderate, 2 severe. Follow up3 mild, 4 none. Chi p= 0.0008. No serious adverse events were reported and only 15% of patients reported mild adverse events (1 arthropathy, 1 rhinitis). Conclusions In our cohort, vedolizumab is an effective and safe treatment for chronic antibiotic refractory pouchitis and produces improvements in symptoms, biochemical tests and histological inflammation. Whilst larger studies are needed, this is a treatment option for those who have failed conventional medical therapy. P110 COST-EFFECTIVENESS OF A 17-GENE CLASSIFIER TO GUIDE TREATMENT CHOICE IN CROHN’S DISEASE IN THE UK Susan Griffin, Vanessa Buchanan, James C Lee, Eoin F McKinney, Paul Kinnon, Karen Hills. Predictimmune, Cambridge, UK; Department of Medicine, University of Cambridge, Cambridge, UK; Cogentia Healthcare Consulting, Cambridge, UK 10.1136/gutjnl-2020-bsgcampus.185 Introduction This study examines the cost-effectiveness of PredictSURE in guiding the early use of biologic therapy in newly diagnosed CD patients, at high-risk of requiring early and frequent treatment escalations in the UK. PredictSURE IBDTM is a 17-gene, whole blood-based qPCR-based classifier that predicts long-term outcome in IBD, enabling early personalised treatment strategies through the early use of biologics in high-risk patients. Methods A decision tree leading into a Markov state-transition model was constructed in MS Excel to compare two treatment approaches: 1) standard of care therapy following established Abstract P109 Figure 1 Abstracts A98 Gut 2021;70(Suppl 1):A1–A262 on S etem er 4, 2021 by gest. P rocted by coright. http/gut.bm jcom / G t: frst pulished as 10.1136l-2020-bsgcam pu.183 on 21 Jauary 221. D ow nladed fom

Introduction The management of ASC needs early characterisation of factors predictive of outcome to allow appropriate patient counselling and stratification for second-line therapy or surgery. Travis et al (1996) predicted colectomy rates during same admission on basis of Day 3 stool frequency and CRP. Dinesen et al (2010) suggested that the number of additional Truelove and Witts’ (TW) criteria (fever, tachycardia, anaemia or CRP elevation) on admission predict colectomy rates. Following this Corte et al (2015) shown that UCEIS at baseline predict adverse outcomes (need for rescue therapy, Colectomy and readmissions). We compared the predictive accuracy of TW criteria on admission with a validated endoscopic scoring system (UCEIS), and with accepted Day 3 criteria. Methods Cases of ASC were retrospectively evaluated. Number of TW criteria, UCEIS, inpatient medical therapy, same admission outcome and follow up were recorded. Pre-specified endpoints included rescue therapy, colectomy during same admission and colectomy within 1 year of follow up. Results Consecutive 131 admissions (117 patients) between 2015–9 were analysed. All satisfied modified TW definition of ASUC. Sixty-eight patients (58%) were female, index presentation 38 (29%),median age at presentation 40 years (16–76),median disease duration 1 year (1–43), median follow up 23 months (1–49).Seventy-one (54%) received rescue therapy (ciclosporin 35/71 and anti-TNF 36/71).Colectomy rates were 15% (19/131) during same admission and 26% (30/117) within 1 year of follow up. Outcomes were stratified according to UCEIS score and additional TW criteria on day 0(figure 1). UCEIS score > 6 predicted higher need for rescue therapy (Chi square, p = 0.01) but not colectomy during same admission (p=0.68) or within 1 year (p=0.41).In logistic regression analysis, UCEIS predicted rescue therapy (p=0.01) but not colectomy during same admission (p=0.68) or within 1 year(p=0.55); whereas day 0 TW criteria predicted need for rescue therapy (p=0.02),colectomy during admission (p=0.04) and within 1 year (p=0.03). D3 response predicted colectomy during same admission (p=0.001) and within 1 year(p=0.0002). Conclusion Endoscopic severity predicts use of rescue therapy but not colectomy rates (During same admission and at 1 year) whereas biological severity predicts use of rescue therapy, colectomy during same admission and at 1 year. Clinical criteria assessed by D3 response are the strongest predictors of colectomy on that admission or within 1 year.

Introduction Ustekinumab, a monoclonal human antibody to IL12/23, offers an alternative option for a cohort of patients with treatment refractory Crohn’s disease (CD). However, real world data for the effectiveness of ustekinumab in this challenging population is lacking. Here, we describe the outcomes of patients who have received ustekinumab at Oxford University Hospitals and Royal Berkshire Hospital NHS Foundation Trusts. Methods A retrospective multicentre study of all patients commenced on ustekinumab for active CD prior to January 2019. All patient records were reviewed up until June 2019. Harvey-Bradshaw Index (HBI), CRP and other biomarkers of disease activity (Faecal calprotectin, Hb, Plts, albumin & ferritin) were evaluated at baseline and at week 12. The primary outcome measures were clinical and biochemical response/remission at week 12, as defined by HBI and CRP respectively. Definitions: Clinical response-a decrease in HBI of ≥3 points; Clinical remission-HBI ≤3; Biochemical response-decrease in CRP ≥50%; Biochemical remission-CRP <5 mg/L. Secondary outcome measures included need for dose escalation, drug continuation and need for CD-related surgery. Results 68 patients were commenced on ustekinumab prior to January 2019. Median disease duration of 14.8 years (IQR 10–18), 43/68 (63%) had ileocolonic disease, 31/68 (46%) had perianal involvement. 65/68 (96%) had received ≥1 prior biologic while 49/68 (72%) had received ≥2 biologics. 66/68 (97%) underwent week 12 evaluation with HBI documented in 42/66 (62%) and CRP in all patients. At week 12, clinical remission was achieved in 26/42 (61%), and clinical response in an additional 8/42 (19%). Biochemical remission was achieved in 20/66 (31%) and biochemical response in an additional 9/66 (13%). Perianal disease, baseline albumin or CRP were not predictive of biochemical non-response, although a trend was observed for male sex. 21/68 (31%) received dose escalation to Q8W dosing, and 3/68 (4%) underwent IV re-induction. All patients receiving re-induction achieved clinical response at follow up. Median time to drug failure/cessation was 274d (IQR 115–377). Clinical improvement, as defined by reduction in PGA, was achieved in 43% at 1-year. Adverse events were observed in 10/68 (15%) including CD-related surgery (n=4), malignancy (n=1). Rates of AEs did not correlate with higher dosing. Conclusions Ustekinumab demonstrated both early clinical and biochemical efficacy in this complex real-world cohort, with no unexpected safety signals seen.

Aim Current clinical recommendations suggest treating chronic hepatitis B virus (HBV) infection in a minority of cases, but more data are needed to determine the benefits and risks of Tenofovir disoproxil fumarate (TDF) therapy. We aimed to assess the impact of TDF on liver disease, and the risk of nephrotoxicity. Method We studied a longitudinal UK chronic HBV (CHB) cohort attending out-patient clinics between 2005 and 2018, analysing data for 206 ethnically diverse adults (60 on TDF, 146 untreated), with median follow-up 3.3±2.8 years. Results Patients prescribed TDF were older (39 vs. 35 years, p=0.004) with a male excess (63% vs. 47%, p=0.04) compared to untreated patients. Reflecting treatment eligibility criteria, at baseline, treated patients were more likely to have elevated ALT (p<0.001), higher HBV DNA viral load (VL) (p<0.001), and higher elastography scores (p=0.002), but with no difference in renal function (p=0.6). In the TDF group, VL declined significantly between baseline and subsequent time points (all p<0.0001) with VL suppressed in 94% at three years, while in the untreated group viraemia was unchanged from baseline. In the TDF group, ALT and elastography scores normalised during treatment and by three years were equivalent to those in the untreated group. Progression of liver fibrosis did not occur in the TDF group but arose in 7.4% of untreated patients, although this difference was non-significant. There was no significant difference in renal impairment during follow-up between two groups. Conclusion TDF may have long-term benefits for a wider pool of the CHB population. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work has been supported by the National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) at Oxford and funded by the NIHR Health Informatics Collaborative (HIC). C.C reports funding from GlaxoSmithKline. E.B is supported by the Oxford NIHR Biomedical Research Centre and is an NIHR Senior Investigator. P.C.M is supported by a Wellcome intermediate fellowship (grant ref 110110/Z/15/Z). The views expressed in this article are those of the author and not necessarily those of the NHS, the NIHR, or the Department of Health. The authors would like to thank all the research nurses and research admin staff at the contributing site for their help in data collection and Gail Roadknight for her work supporting the NIHR HIC. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The research database for the NIHR HIC viral hepatitis theme was approved by South Central - Oxford C Research Ethics Committee (REF Number: 15/SC/0523). All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes No additional data are available.

Background: Tofacitinib is a partially selective Janus kinase inhibitor approved for the treatment of refractory moderate to severe ulcerative colitis [UC]. We sought to define the effectiveness and adverse effects of tofacitinib in a real-world cohort. Methods: We conducted a retrospective observational cohort study of 134 patients with UC [64% male; median age 37 years [range 16-81]; 83% of patients had previously received at least one biologic] treated with tofacitinib from October 2018 to October 2019 in four UK centres. Disease activity was assessed using the Simple Clinical Colitis Activity Index [SCCAl] or partial Mayo score [PMS], depending on study site. Response and remission were defined as a reduction in SCCAI or PMS of >= 3and SCCAI <= 2 or a PMS <= 1, respectively. Results: Overall, 74% (88/119; 95 confidence interval [CI] 65-81%] patients responded to tofacitinib at Week 8 and steroid-free remission was observed in 44% [47/108; 95% CI 3453%] patients at Week 26. Primary non-response was independently associated with younger age [p= 0.014] and higher C-reactive protein [CRP] levels at baseline [p = 0.004]. Only 23%[3/13] of patients who continued tofacitinib in the setting of primary non-response were in steroid-free remission at Week 26. Prior biologic exposure did not influence response or remission rates. Dose escalation, however, recaptured response in approximately half of patients who had lost response. Dyslipidaemia was observed in 20% [27/134; 95% CI 1428%] of patients, but adverse events necessitating drug withdrawal were uncommon and no venous thromboembolic events occurred. Conclusions: In this multicentre real-world cohort, tofacitinib was well tolerated and clinically effective in a treatment-refractory UC population.

### What’s new in the guidance Ulcerative colitis is a chronic inflammatory disease of the rectum and colon characterised by mucosal inflammation, resulting in symptoms of diarrhoea (both soft stool and an increased frequency of defecation), rectal bleeding, an urgent need to defecate, and abdominal pain. The condition usually affects the rectum and a variable extent of the colon proximal to the rectum. Inflammation of the rectum is referred to as proctitis, and inflammation of the rectum and sigmoid as proctosigmoiditis. Left sided colitis refers to disease involving the colon distal to the splenic flexure. Extensive colitis affects the colon proximal to the splenic flexure, and includes pan-colitis, where the whole colon is involved. The most widely used drugs for inducing remission in people with mild to moderate ulcerative colitis are aminosalicylates and corticosteroids. Choice of treatment depends on the extent of disease (proctitis, proctosigmoiditis, left sided colitis, extensive colitis), mechanism of action, route of administration, site and mechanism of drug release, dose, duration, cost of treatment, and patient preference. This article summarises recent recommendations from the update of the National Institute for Health and Care Excellence (NICE) guideline for the management of ulcerative colitis in children, young people, and adults.1 The update focuses on inducing remission in people with mild to moderate ulcerative colitis. All other areas of the guideline, such …

### What you need to know Crohn’s disease is a chronic inflammatory disease that mainly affects the gastrointestinal tract. Approximately 115 000 people are living with Crohn’s in the UK. There is no known cure, so the aim of medical treatment is to induce or maintain absence of symptoms (remission). If symptoms are refractory to medication, surgical resection may be required. Post-surgical recurrence is common, with approximately 20-40% of patients requiring reoperation within 10 years.12 This article summarises recent recommendations from the update of the National Institute for Health and Care Excellence (NICE) guideline for the management of Crohn’s disease in children, young people, and adults.3 The focus of this update is on maintaining remission in people with Crohn’s disease after surgery. It does not cover people who have had surgery and are not in remission—for example, people who have active disease at other sites. All other areas of the guideline, such as induction of remission and surgery, remain …

Advances in the diagnosis, monitoring, and treatment of hepatitis B virus (HBV) infection are urgently required if we are to meet international targets for elimination by the year 2030. Here we demonstrate how routine clinical data can be harnessed through an unbiased electronic pipeline, showcasing the significant potential for amassing large clinical data sets that can help to inform advances in patient care and provide insights that may help to inform new cure strategies. Our cohort from a large UK hospital includes adults from diverse ethnic groups that have previously been underrepresented in the literature. By tracking two protein biomarkers that are used to monitor chronic HBV infection, we provide new insights into the timelines of HBV clearance, both on and off treatment. These results contribute to improvements in individualized clinical care and may provide important clues into the immune events that underpin disease control.

Therapeutic Reviews aim to provide essential independent information for health professionals about drugs used in palliative and hospice care. Additional content is available via www.palliativedrugs.com. The series editors welcome feedback on the articles.

Crohn's disease (CD) is a chronic inflammatory condition of the gastrointestinal tract. Individuals with CD present with acute inflammatory exacerbations as well as acute and chronic complications. Management requires specialist input from gastroenterologists, colorectal surgeons, nurse specialists and pharmacists as well as general and primary care physicians to allow appropriate selection of treatment options including surgery and rapid assessment and treatment of those with acute exacerbations. Monitoring of the individual and their medication is crucial in preventing and recognising complications including those associated with treatment. This concise guideline focuses on recommendations from National Institute for Health and Care Excellence (NICE) Clinical Guideline 152 (CG152) considered of key importance for implementation.

ABSTRACT HBsAg and HBeAg have gained traction as biomarkers of control and clearance during monitoring of chronic hepatitis B virus infection (CHB). An improved understanding of the correlates of clearance of these proteins could help inform improvements in patient-stratified care and advance insights into the underlying mechanisms of disease control, thus underpinning new cure strategies. We collected electronic clinical data via an electronic pipeline supported by the National Institute for Health Research Health Informatics Collaborative (NIHR-HIC), adopting an unbiased approach to generating a robust longitudinal dataset for adults testing HBsAg-positive from a large UK teaching hospital over a six year period (2011-2016 inclusive). From 553 individuals with CHB, longitudinal data were available for 319, representing >107,000 weeks of clinical follow-up. Among these 319 individuals, 13 (4%) cleared HBsAg completely. HBsAg clearance rate was similar in individuals on NA therapy (n=4, median clearance time 150 weeks) vs those not on NA therapy (n=9, median clearance time 157 weeks). Those who cleared HBsAg were significantly older, and less likely to be on NA therapy compared to non-clearers (p=0.003 and p=0.001, respectively). Chinese ethnicity was associated with HBeAg positivity (p=0.025). HBeAg clearance occurred both on NA therapy (n=24, median time 49 weeks) and off NA therapy (n=19, median time 52 weeks). Improved insights into the dynamics of these biomarkers can underpin better prognostication and patient-stratified care. Our systematised approach to data collection paves the way for scaling up efforts to harness clinical data to address research questions and underpin improvements in clinical care provision. IMPORTANCE Advances in the diagnosis, monitoring and treatment of hepatitis B virus (HBV) infection are urgently required if we are to meet international targets for elimination by the year 2030. Here we demonstrate how routine clinical data can be harnessed through an unbiased electronic pipeline, showcasing the significant potential for amassing large clinical datasets that can help to inform advances in patient care, and provide clues that inform new cure strategies. Our cohort from a large UK hospital includes adults from diverse ethnic groups that have previously been under-represented in the literature. Tracking two protein biomarkers that are used to monitor chronic HBV infection, we provide new insights into the timelines of HBV clearance, both on and off treatment. These results contribute to improvements in individualised clinical care and may provide important clues into the immune events that underpin disease control.