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Background and Aims:The incidence of paediatric-onset inflammatory bowel disease (PIBD) continues to rise globally. We aimed to determine whether mode of delivery, gestational age at birth, or type of infant feeding contribute to the development of PIBD in a nationwide cohort of Scottish children.Methods:All children born in Scotland between 1981-2017 were identified using linked health administrative data to determine mode of delivery, gestational age at birth, and type of infant feeding. PIBD cases were defined as onset of Crohn’s disease (CD), ulcerative colitis (UC) or IBD-unclassified (IBDU) before age 16 years. Validation was performed within an entire Scottish health board (16% of total population) via individual case-note verification. Hazard ratios (HR) were calculated for each exposure using Cox proportional hazards models.Results:A study population of 2,013,851 children was identified including 1,721 PIBD cases. Validation of 261 PIBD patients coded as CD and/or UC identified 242 (93%) as true positive. Children delivered vaginally did not have an altered risk of developing PIBD compared to those delivered by caesarean section; adjusted HR 0.95 [95% CI 0.84-1.08] (p=0.46). Compared to children born at term (≥37 weeks), children born prematurely did not have an altered risk of developing PIBD; 24-31 weeks gestation HR 0.99 [95% CI 0.57-1.71] (p=0.97); 32-36 weeks gestation HR 0.96 (95% CI 0.76-1.20] (p=0.71). Compared to children exclusively breast fed at age 6 weeks, children exclusively formula fed did not have an altered risk of developing PIBD; adjusted HR 0.97 [95% CI 0.81-1.15] (p=0.69).Conclusions:This population-based study demonstrates no association between mode of delivery, gestational age, or exclusive formula feeding at 6 weeks and the development of PIBD.

BACKGROUND AND AIMS: The progressive nature of Crohn's disease is highly variable and hard to predict. In addition, symptoms correlate poorly with mucosal inflammation. There is therefore an urgent need to better characterize the heterogeneity of disease trajectories in Crohn's disease by utilizing objective markers of inflammation. We aimed to better understand this heterogeneity by clustering Crohn's disease patients with similar longitudinal fecal calprotectin profiles.METHODS: We performed a retrospective cohort study at the Edinburgh IBD Unit, a tertiary referral center, and used latent class mixed models to cluster Crohn's disease subjects using fecal calprotectin observed within five years of diagnosis. Information criteria, alluvial plots, and cluster trajectories were used to decide the optimal number of clusters. Chi-squared, Fisher's exact test, and ANOVA were used to test for associations with variables commonly assessed at diagnosis.RESULTS: Our study cohort comprised of 365 patients with newly diagnosed Crohn's disease and 2856 fecal calprotectin measurements taken within five years of diagnosis (median 7 per subject). Four distinct clusters were identified by characteristic calprotectin profiles: a cluster with consistently high fecal calprotectin and three clusters characterized by different downward longitudinal trends. Cluster membership was significantly associated with smoking (p = 0.015), upper gastrointestinal involvement (p < 0.001), and early biologic therapy (p < 0.001).CONCLUSIONS: Our analysis demonstrates a novel approach to characterizing the heterogeneity of Crohn's disease by using fecal calprotectin. The group profiles do not simply reflect different treatment regimens and do not mirror classical disease progression endpoints.

Contains fulltext : 291530.pdf (Publisher’s version ) (Open Access) BACKGROUND: Switching from originator infliximab (IFX) to biosimilar IFX is effective and safe. However, data on multiple switching are scarce. The Edinburgh inflammatory bowel disease (IBD) unit has undertaken three switch programmes: (1) Remicade to CT-P13 (2016), (2) CT-P13 to SB2 (2020), and (3) SB2 to CT-P13 (2021). OBJECTIVE: The primary endpoint of this study was to assess CT-P13 persistence following switch from SB2. Secondary endpoints included persistence stratified by the number of biosimilar switches (single, double and triple), effectiveness and safety. METHODS: We performed a prospective, observational, cohort study. All adult IBD patients on IFX biosimilar SB2 underwent an elective switch to CT-P13. Patients were reviewed in a virtual biologic clinic with protocol driven collection of clinical disease activity, C-reactive protein (CRP), faecal calprotectin (FC), IFX trough/antibody levels, and drug survival. RESULTS: 297 patients (CD n = 196 [66%], ulcerative colitis/inflammatory bowel disease unclassified n = 101, [34%]) were switched (followed-up: 7.5 months [6.8-8.1]). This was the third, second and first IFX switch for 67/297 (22.5%), 138/297 (46.5%) and 92/297 (31%) of the cohort respectively. 90.6% of patients remained on IFX during follow-up. The number of switches was not independently associated with IFX persistence after adjusting for confounders. Clinical (p = 0.77), biochemical (CRP ≤5 mg/ml; p = 0.75) and faecal biomarker (FC

The UNITI trial reports efficacy of ustekinumab (UST) dose intensification in Crohn's disease (CD) from 12- to 8-weekly, but not 4-weekly. We aimed 1) to assess the cumulative incidence of UST dose intensification to 4- or 6-weekly, 2) to identify factors associated with dose intensification, and 3) to assess the effectiveness of this strategy.We performed a retrospective, observational cohort study in NHS Lothian including all UST treated CD patients (2015-2020).163 CD patients were treated with UST (median follow-up: 20.3 months [13.4-38.4]), of whom 55 (33.7%) underwent dose intensification to 4-weekly (n = 50, 30.7%) or 6-weekly (n = 5, 3.1%). After 1 year 29.9% were dose intensified. Prior exposure to both anti-TNF and vedolizumab (HR 9.5; 1.3-70.9), and concomitant steroid use at UST start (HR 1.8; 1.0-3.1) were associated with dose intensification. Following dose intensification, 62.6% patients (29/55) remained on UST beyond 1 year. Corticosteroid-free clinical remission was achieved in 27% at week 16 and 29.6% at last follow-up.One third of CD patients treated with UST underwent dose intensification to a 4- or 6-weekly interval within the first year. Patients who failed both anti-TNF and vedolizumab, or required steroids at initiation were more likely to dose intensify.

Background and AimsThe progressive nature of Crohn’s disease is highly variable and hard to predict. In addition, symptoms correlate poorly with mucosal inflammation. There is therefore an urgent need to better characterise the heterogeneity of disease trajectories in Crohn’s disease by utilising objective markers of inflammation. We aimed to better understand this heterogeneity by clustering Crohn’s disease patients with similar longitudinal faecal calprotectin profiles.MethodsLatent class mixed models were used to model faecal calprotectin trajectories within five years of diagnosis and to cluster subjects. Information criteria, alluvial plots, and cluster trajectories were used to decide the optimal number of clusters. Chi-squared, Fisher’s exact test, and ANOVA were used to test for associations with variables commonly assessed at diagnosis.ResultsOur study cohort comprised of 365 patients with newly diagnosed Crohn’s disease and 2856 faecal calprotectin measurements taken within five years of diagnosis (median 7 per subject). Four distinct clusters were identified by characteristic calprotectin profiles: a cluster with consistently high faecal calprotectin and three clusters characterised by different downward longitudinal trends. Cluster membership was significantly associated with smoking (p= 0.015), upper gastrointestinal involvement (p <0.001), and early biologic therapy (p <0.001).ConclusionsOur analysis demonstrates a novel approach to characterising the heterogeneity of Crohn’s disease by using faecal calprotectin. The group profiles do not simply reflect different treatment regimes and do not mirror classical disease progression endpoints. We believe these profiles represent an entirely new way of classifying disease behaviour in Crohn’s disease.

BACKGROUND AND AIM Ustekinumab is a monoclonal antibody that targets interleukin-12/23. In Scotland, it was approved for the treatment of moderate to severe Crohn's disease in 2017. The objective of this study was to establish the real-world effectiveness and safety of ustekinumab in the treatment of Crohn's disease. METHODS We conducted a retrospective study of patients receiving ustekinumab across eight Scottish National Health Service health boards between 2017 and 2019. Inclusion criteria included a diagnosis of Crohn's disease with symptoms attributed to active disease plus objective signs of inflammation at baseline (C-reactive protein ≥ 5 mg/L or fecal calprotectin ≥ 250 μg/g or inflammation on endoscopy/magnetic resonance imaging) and completion of induction plus at least one clinical follow-up at 8 weeks. Kaplan-Meier survival analysis was used to establish 12-month cumulative rates of clinical remission, mucosal healing, deep remission, and perianal fistula response. Rates of serious adverse events were described quantitatively. RESULTS Our cohort consisted of 216 patients (female sex, 37.9%; median age, 39.0 years, interquartile range [IQR] 28.8-51.8 years; disease duration, 9.9 years, IQR 6.0-16.5 years; prior biologic, 98.6%) with a median follow-up of 35.0 weeks (IQR 17.4-52.0 weeks). Twelve-month cumulative rates of clinical remission, mucosal healing, and deep remission (clinical remission plus mucosal healing) were 32.0%, 32.7%, and 19.3%, respectively. In patients with active perianal disease (n = 37), the 12-month cumulative perianal response rate was 53.1%. The serious adverse event rate was 13.6 per 100 patient-years of follow-up. CONCLUSION Ustekinumab is a safe and effective treatment for the treatment of complex Crohn's disease.

Aim Biological treatment is effective in maintaining remission in ulcerative colitis (UC), although the effect on colectomy rates remains unclear. In the UK the use of antitumour necrosis factor and anti-α4β7 treatments for maintenance therapy in UC was restricted until 2015. The aim of this study was to describe the impact that this change in the prescribing of biologicals had on colectomy rates for UC. Method All patients (adult and paediatric) with a diagnosis of UC who received maintenance biological treatment and/or underwent a colectomy in Lothian, Scotland between 2005 and 2018 were identified. Linear and segmental regression analyses were used to identify the annual percentage change (APC) and temporal trends (statistical joinpoints) in biological prescription and colectomy rates. Results Rates of initiation of maintenance biological therapy increased from 0.05 per 100 UC patients in 2005 to 1.26 in 2018 (p p p = 0.019). Conclusion The use of maintenance biological therapy increased sharply following the change in guidance. This has been paralleled by a significant reduction in the rates of colectomy over the same time period.

Background and Aims Multiple adalimumab [ADA] biosimilars are now approved for use in inflammatory bowel disease [IBD]; however, effectiveness and safety data remain scarce. We aimed to investigate long-term outcomes of the ADA biosimilar SB5 in IBD patients following a switch from the ADA originator [SB5-switch cohort] or after start of SB5 [SB5-start cohort]. Methods We performed an observational cohort study in a tertiary IBD referral centre. All IBD patients treated with Humira underwent an elective switch to SB5. We identified all these patients in a biological prescription database that prospectively registered all ADA start and stop dates including brand names. Data on IBD phenotype, C-reactive protein [CRP], drug persistence, ADA drug and antibody levels, and faecal calprotectin were collected. Results In total, 481 patients were treated with SB5, 256 in the SB5-switch cohort (median follow-up: 13.7 months [IQR 8.6–15.2]) and 225 in the SB5-start cohort [median follow-up: 8.3 months [4.2–12.8]). Of the SB5-switch cohort, 70.8% remained on SB5 beyond 1 year; 90/256 discontinued SB5, mainly due to adverse events [46/90] or secondary loss of response [37/90]. In the SB5-start cohort, 81/225 discontinued SB5, resulting in SB5-drug persistence of 60.3% beyond 1 year. No differences in clinical remission [p = 0.53], CRP [p = 0.80], faecal calprotectin [p = 0.40] and ADA trough levels [p = 0.55] were found between baseline, week 26 and week 52 following switch. Injection site pain was the most frequently reported adverse event. Conclusion Switching from ADA originator to SB5 appeared effective and safe in this study with over 12 months of follow-up.

Background Intravenous (IV) steroids remain the first-line treatment for patients with acute ulcerative colitis (UC). However, 30% of patients do not respond to steroids, requiring second-line therapy and/or surgery. There are no existing indices that allow physicians to predict steroid nonresponse at admission. We aimed to determine if admission biochemical and endoscopic values could predict response to IV steroids. Methods All admissions for acute UC (ICD-10 K51) between November 1, 2011, and October 31, 2016 were identified. Case note review confirmed diagnosis; clinical, endoscopic, and laboratory data were collected. Steroid response was defined as discharge home with no further therapy for active UC. Nonresponse was defined as requirement for second-line therapy or surgery. Univariate and binary logistic regression analyses were employed to identify factors associated with steroid nonresponse. Results Two hundred and thirty-five acute UC admissions were identified, comprising both acute severe and acute nonsevere UC; 155 of the 235 patients (66.0%) responded to steroids. Admission C-reactive protein (CRP) (P = 0.009, odds ratio [OR] 1.006), albumin (P < 0.001, OR 0.894) and endoscopic severity (P < 0.001, OR 3.166) differed significantly between responders and nonresponders. A simple UC severity score (area under the curve [AUC] 0.754, P < 0.001) was derived from these variables; 78.1% (25 of 32) of patients with concurrent CRP ≥50 mg/L, albumin ≤30 g/L, and increased endoscopic severity (severe on physician’s global assessment) (maximum score = 3) did not respond to IV steroids (positive predictive value [PPV] 78.1%, negative predictive value [NPV] 87.1%). Conclusions More than three quarters of patients scoring 3 (albumin ≤30 g/L, CRP ≥50 mg/L, and increased endoscopic severity) did not respond to IV steroids. This combination of parameters (ACE) identifies on admission a high-risk population who may benefit from earlier second-line medical treatment or surgical intervention.

Objective Limited data are available regarding the relationship between anti-tumor necrosis factor (TNF) drug/antibody levels and perianal fistula outcomes in Crohn's disease. The aims of this study were to assess the relationship between maintenance anti-TNF levels and perianal fistula outcomes. Methods This was a retrospective cross-sectional study of patients receiving maintenance adalimumab or infliximab therapy (minimum 24 weeks) for the treatment of Crohn's disease with associated perianal fistulas, who had anti-TNF drug/antibody levels (trough for infliximab) measured within 4 weeks of clinical assessment. The primary outcome was the association of anti-TNF levels with perianal fistula healing defined as the absence of drainage. The secondary outcome was the association of anti-TNF levels with complete perianal fistula closure. Results A total of 64 patients (adalimumab, n = 35; infliximab, n = 29) were included. Patients with fistula healing had higher levels of anti-TNF vs. those without fistula healing (adalimumab: 12.6 vs. 2.7 μg/mL, P 6.8 μg/mL and >9.8 μg/mL for fistula healing and closure, respectively. For infliximab, receiver operator characteristic analysis identified an optimum trough level of >7.1 μg/mL for both fistula healing and closure. Conclusion Higher maintenance anti-TNF levels are associated with perianal fistula healing and closure in Crohn's disease.

Background Treatment of inflammatory bowel diseases (IBD) is associated with multiple side effects, such as malignancies and infections, that may be more common in the elderly population. The aim of this study was to compare the safety and efficacy of vedolizumab (VDZ) in young and elderly patients. Methods This is a binational, multicentre, retrospective, case–control study consisting of patients from multiple centres in Israel and from Edinburgh, UK. IBD patients in whom VDZ treatment was initiated during 2015–2019, and were followed for at least 14 weeks, were included in the study according to their age groups: ≤40 years or ≥60 years. Patients were matched for disease duration, classification and severity. Results We recruited 144 patients (82 CD and 62 UC) to the elderly cohort and 140 patients (83 CD and 57 UC) to the young cohort. The respective average age was 70.2 ± 7.3 years and 29.6 ± 5.7 years. Elderly patients had significantly more cardiovascular, metabolic and respiratory co-morbidities and had less prior exposure to anti-TNF agents compared with the young cohort (CD: 51% vs. 88%, p < 0.001; UC: 47% vs. 70%, p = 0.03). Clinical and endoscopic responses were comparable between the groups at Weeks 14 and 52 among elderly and young (Week 52 remission: CD: 40% vs. 35%, p = 0.7; UC: 48% vs. 51%, p = 0.84) (Figure 1). However, the use of more than one anti-TNF agent was an independent predictor of poor response and remission rates to VDZ at all time points among the elderly (OR 0.13; 95% CI 0.03–0.69). A total of 49 adverse events were documented, 23 (16%) in the young cohort and 26 (18%) in the elderly cohort (p = 0.5). Overall there were significantly more infections in the elderly cohort (3 (2%) vs. 17 (12%), p = 0.002) and included nasopharyngeal, urinary, skin and Clostridium difficile infections. None of them was fatal but one patient stopped treatment due to urinary sepsis. There were significantly more non-specific adverse events such as headache and myalgia in the young cohort (8% vs. 2%, p = 0.03). Six patients (4%) in the young cohort required drug discontinuation due to adverse events compared with 4 patients (3%) in the elderly cohort (p = 0.5). The reasons for discontinuation were similar between the groups. Conclusion VDZ is equally effective in elderly and young IBD patients. This study shows an increased risk of overall infections in the elderly cohort, it is unclear whether these are related to VDZ treatment or the age and background diseases of these patients. In elderly patients, the use of VDZ before anti-TNF therapy may improve response and remission rates.

ObjectiveTo establish the relationship between trough vedolizumab levels and outcomes during maintenance therapy.DesignCross-sectional service evaluation was performed on patients with inflammatory bowel disease (IBD) receiving maintenance vedolizumab therapy (minimum of 12 weeks following induction). Prior to infusion, data on clinical activity (Harvey-Bradshaw Index or partial Mayo score), trough C-reactive protein (CRP)/vedolizumab levels and faecal calprotectin were collected. Endoscopic data (±8 weeks from vedolizumab level testing) were obtained by review of medical records. Vedolizumab levels were processed using the Immundiagnostik monitor ELISA.SettingThe Edinburgh IBD Unit, Western General Hospital (tertiary IBD referral centre).PatientsSeventy-three patients (30 ulcerative colitis and 43 Crohn’s disease) were identified who fulfilled inclusion criteria and had vedolizumab levels matched with clinical activity scores, CRP and faecal calprotectin. Of these, 40 patients also had matched endoscopic data.Main outcome measuresThe association of trough vedolizumab levels with clinical remission (Harvey-Bradshaw Index ResultsThe median trough vedolizumab levels were similar between patients in and not in clinical remission (10.6 vs 9.9 µg/mL, p=0.54); biologic remission (10.6 vs 9.8 µg/mL, p=0.35) and endoscopic remission (8.1 vs 10.2 µg/mL, p=0.21). Quartile analysis revealed no significant increase in the proportion of patients in clinical remission, biologic remission or endoscopic remission with increasing trough vedolizumab levels (pConclusionsIn this cohort, trough vedolizumab levels were not associated with clinical, biological or endoscopic outcomes during maintenance therapy.

ObjectiveIBD prevalence is estimated to be rising, but no detailed, recent UK data are available. The last reported prevalence estimate in the UK was 0.40% in 2003. We aimed to establish the current, and project future, prevalence in Lothian, Scotland.DesignWe conducted an all-age multiparameter search strategy using inpatient IBD international classification of disease (ICD-10) coding (K50/51)(1997–2018), IBD pathology coding (1990–2018), primary and secondary care prescribing data (2009–2018) and a paediatric registry, (1997–2018) to identify ‘possible’ IBD cases up to 31/08/2018. Diagnoses were manually confirmed through electronic health record review as per Lennard-Jones/Porto criteria. Autoregressive integrated moving average (ARIMA) regression was applied to forecast prevalence to 01/08/2028.ResultsIn total, 24 601 possible IBD cases were identified of which 10 499 were true positives. The point prevalence for IBD in Lothian on 31/08/2018 was 784/100 000 (UC 432/100 000, Crohn’s disease 284/100 000 and IBD unclassified (IBDU) 68/100 000). Capture–recapture methods identified an additional 427 ‘missed’ cases (95% CI 383 to 477) resulting in a ‘true’ prevalence of 832/100 000 (95% CI 827 to 837).Prevalence increased by 4.3% per year between 2008 and 2018 (95% CI +3.7 to +4.9%, p80 years of age.ConclusionsWe report a rigorously validated IBD cohort with all-age point prevalence on 31/08/2018 of 1 in 125, one of the highest worldwide.

Background and aimsEvidence on the outcomes of tofacitinib therapy in real world ulcerative colitis (UC) patients is needed, as a number of these patients would not match the inclusion criteria for clinical trials. We have therefore summarised data derived from observational, real-world evidence (RWE) studies on the effectiveness and safety of tofacitinib in moderate to severe ulcerative colitis (UC) patients.MethodsWe searched the PubMed, EMBASE, Scopus, Web of Science and Cochrane databases for observational studies on the use of tofacitinib in UC patients, published between 30/05/2018 and 24/01/2021. Pooled induction (8-14 weeks) and maintenance (16-26 weeks) clinical response and remission rates were calculated, as well as the proportion of reported adverse events using random effects models.ResultsNine studies were included, comprising 830 patients, of which 81% were previously treated with anti-TNF and 57% with vedolizumab. Induction of clinical response and remission were achieved in 51% (95% CI 41-60%) and 37% (26-45%) of patients, after a median follow-up of 8 weeks. At the end of a median follow-up of 24 weeks, maintenance of clinical response and remission were met in 40% (31-50%) and 29% (23-36%) of patients, respectively. Thirty-two percent of the patients had at least one adverse event, the most commonly reported being mild infection (13%) and worsening of UC, requiring colectomy (13%). A third of the patients (35%) discontinued tofacitinib, most frequently due to primary non-response (51%).ConclusionsTofacitinib is a safe and effective therapy in real-world UC patients, as previously reported by clinical trials.WHAT YOU NEED TO KNOWBackgroundTofacitinib is the first Janus kinase inhibitor (JAKi) approved for the treatment of moderate to severe ulcerative colitis (UC). Real-world data is needed to understand clinical effectiveness of new therapies.FindingsClinical response rates were consistent with those reported by OCTAVE Induction trials, showing clinical efficacy similar in real-world and controlled clinical trial cohorts. There were no major safety concerns reported.Implications for patient careThe results of this meta-analysis confirm the effectiveness and acceptable safety profile of tofacitinib in a real-world, highly refractory UC population, and further support its use in clinical practice.

Introduction Ustekinumab (UST) is an anti-IL12/23 biologic licensed for the treatment of moderate to severe Crohn’s disease (CD). The aims of this study were to establish the long-term real-world effectiveness and safety of UST for the treatment of CD in a large UK cohort. Methods This was a multicentre retrospective cohort study including 8 NHS health-boards in Scotland. Patients treated with UST between Nov 2015 and Jun 2019 were identified. Inclusion criteria included: a diagnosis of CD; active symptoms attributed to CD with objective evidence of mucosal inflammation (CRP >5 mg/L or faecal calprotectin ≥250 µg/g or inflammation on endoscopy/MRI); completion of standard induction; week 8 review ± further follow up. Clinical assessments were performed based on physician global assessment (response was defined as ≥50% reduction in CD-related symptoms and remission defined as complete resolution of all CD-related symptoms). Mucosal healing was defined as absence of ulceration/erosions on ileo-colonoscopy or no inflammation on MRI if ileo-colonoscopy was not possible (eg. B2 disease). Deep remission was defined as clinical remission plus mucosal healing. Perianal response was determined by follow up MRI (reduction in enhancement, closure or fibrosis of tract compared to baseline MRI). Rates of serious adverse events (discontinuation of UST, hospitalisation or death) during follow up were described quantitively. Results A total of 216 patients (57.9% female; median age 39.0 years, IQR 28.8–51.8; median disease duration 9.9 years, IQR 6.0–16.5) with a median follow up of 35.0 weeks (IQR 17.4–52.0) were included. The majority of patients had ileo-colonic disease (L1, 19.9%; L2, 23.1%; L3, 56.9%) and an inflammatory phenotype (B1, 43.1%; B2, 41.2%; B3, 15.7%). A total of 98.6% of patients had previously been exposed to a biologic and 55.1% had undergone previous surgery. Seventy-one percent of patients received 8-weekly maintenance dosing, whilst 25.5% and 40.7% of patients were also receiving an immunomodulator and/or steroids at initiation, respectively. At week 8, clinical response and remission rates were 45.4% and 6.0%, respectively. Twelve-month cumulative rates of clinical remission, mucosal healing (n=123) and deep remission (n=123) were 32.0%, 32.7% and 19.3%, respectively (figure 1). In patients with active perianal disease at initiation (n=37), 12-month cumulative rates of perianal response were 53.1%. During 140 patient years of follow up (PYF), 19 patients experienced a serious adverse event (13.6 per 100 PYF). Conclusions We have shown in a large real-world cohort of complex, treatment refractory CD patients that UST is a safe and effective treatment option

Introduction This study evaluated corticosteroid and antibiotic prescribing during the first 12 months of first-line biologic therapy in patients with ulcerative colitis (UC) initiated on vedolizumab (VDZ) compared with patients initiated on anti-tumour necrosis factor-α (anti-TNF) agents. Methods A multicentre, retrospective observational study was conducted in six United Kingdom secondary care centres. Eligible consenting patients were aged ≥18 years at initiation, without primary fistulising disease or acute severe disease. Patients were matched for age, gender, Montreal classification of disease extent and steroid use at initiation. Results The study included 56 patients initiated on VDZ and 56 patients initiated on anti-TNF (table 1). During the overall 12 month post-initiation observation period, patients initiated on VDZ and anti-TNF were prescribed a median of 1.0 (interquartile range [IQR] 0.0–4.8) and 2.0 (IQR 0.0–7.8; Mann-Whitney U test P=0.16) courses of corticosteroids, respectively. During the post-initiation maintenance period (week 14 to month 12), 37% (95% confidence interval [CI] 24%–49%; n=52) of patients initiated on VDZ and 57% (95%CI 44%–70%; n=53; χ2P=0.039) of patients initiated on anti-TNF received at least one course of corticosteroids. During the overall 12 month post-initiation observation period, patients initiated on VDZ and anti-TNF were prescribed a median of 0 (range 0–4) and 0 (range 0–2; Mann-Whitney U test P=0.42) courses of antibiotics, respectively. During the post-initiation maintenance period, 11% (95%CI 3%–19%; n=56) of patients initiated on VDZ and 16% (95%CI 6%–26%; n=56; χ2 P=0.41) of patients initiated on anti-TNF received at least one course of antibiotics. Conclusions During the post-initiation maintenance period of first-line biologic therapy in patients with UC, patients initiated on VDZ were significantly less likely to be prescribed corticosteroids than matched patients initiated on anti-TNF agents. Numerically less patients on VDZ received antibiotics, however this did not reach significance.

Background The use of biologic therapy for Crohn’s disease [CD] continues to evolve, however, the effect of this on the requirement for surgery remains unclear. We assessed changes in biologic prescription and surgery over time in a population-based cohort. Methods We performed a retrospective cohort study of all 1753 patients diagnosed with CD in Lothian, Scotland, between January 1, 2000 and December 31, 2017, reviewing the electronic health record of each patient to identify all CD-related surgery and biologic prescription. Cumulative probability and hazard ratios for surgery and biologic prescription from diagnosis were calculated and compared using the log-rank test and Cox regression analysis stratified by year of diagnosis into cohorts. Results The 5-year cumulative risk of surgery was 20.4% in cohort 1 [2000–2004],18.3% in cohort 2 [2005–2008], 14.7% in cohort 3 [2009–2013], and 13.0% in cohort 4 [2014–2017] p Conclusions The increased and earlier use of biologic therapy in CD patients corresponded with a decreasing requirement for surgery over time within our cohort. This could mean that adopting a top-down or accelerated step-up treatment strategy may be effective at reducing the requirement for surgery in newly diagnosed CD.

Ustekinumab is effective in Crohn's disease. However, a substantial proportion of patients will not respond or lose response to ustekinumab. The current evidence to support the effectiveness of dose-optimisation for ustekinumab nonresponse is limited., info:eu-repo/semantics/published

BACKGROUND AND AIMS Magnetic resonance enterography [MRE] is the gold standard for assessing ileal inflammation in Crohn's disease [CD]. The aim of the present study was to correlate faecal calprotectin [FC] to MRE via a simple score in an exclusive ileal cohort with long-term follow-up for association with time to surgery or biologic therapy. METHODS In total, 150 MRE studies with matched FC [±30 days] were identified from the Edinburgh FC Register [2008-12; n = 18138]. Scans were re-read blinded to clinical data, independently, by two expert gastrointestinal radiologists, to generate a simple MRE score [range 0-10] from assessment of the worst intestinal segment plus total disease extent. RESULTS In total, 119 MRE scans were evaluated from 104 patients with ileal CD [L1 or L3 with panproctocolectomy]. Receiver operating characteristic analysis showed an area under the curve of 0.77 [0.67-0.87, p 1, with an optimal cut-off of 145 μg/g for severe inflammation on MRE with 69.3% [57.6-79.5] sensitivity and 71.4% [53.7-85.4] specificity. Long-term follow-up over a median [interquartile range] of 2086 days [1786-2353] revealed FC ≥ 145 μg/g was associated with reduced biologic-free survival until 3 years following MRE, whereas MRE score [severe vs absent] was associated with reduced surgery- and biologic-free survival throughout follow-up. Backwards stepwise logistic regression revealed that length of ileal disease (odds ratio [OR] 3.8, 1.1-13.2, p = 0.034) and increased bowel wall thickness at MRE [OR 4.2, 1.6-10.7, p < 0.0001] or female sex [OR 5.2, 1.5-18.7, p = 0.011] increased the risk of biologic use or surgery, respectively. CONCLUSIONS FC correlates well with MRE assessment of ileal CD with MRE parameters associated with long-term biologic- and surgery-free remission.

Background Multiple adalimumab (ADA) biosimilars, including SB5 (Imraldi) and ABP 501 (Amgevita), are now approved for use in IBD. Data about biosimilar ADA in IBD remain scarce. We therefore aimed to investigate long-term outcomes of the biosimilar SB5 in IBD patients following a switch from the ADA originator (Humira) or after start of SB5 as their first ADA-therapy. Methods We performed a retrospective cohort study in a tertiary IBD referral centre. All IBD patients treated with Humira underwent an elective switch to SB5 regardless of IBD phenotype, disease activity and ADA dosing. All patients were reviewed regularly in the virtual biologics clinic with protocol driven collection of clinical disease activity, blood tests, TDM and faecal calprotectin. We identified all patients on SB5 in a biologic prescription database that prospectively registered all ADA by brand name and start and stop dates. Results 441 patients were treated with SB5, including 234 who switched from Humira to SB5 (CD=209, 89.3%; median IBD duration 10 years, IQR 6-16) and 207 who started on SB5 as their first ADA-therapy (CD=162, 78.3%; median IBD duration 6 years, IQR 1-16.8). 107/234 (45.7%) patients who switched to SB5 used infliximab before ADA. These patients were treated for a median of 32 months (IQR 17-57) with Humira prior to switching. At Humira – SB5 switch, 60.1% (140/234) received 40mg ADA every other week and 39.1% (91/234) once weekly. The median duration of follow up was 13 months (IQR 8-14). At week 26 and week 52, 194/231 (84.1%) and 148/215 (70.3%) patients remained on SB5, respectively (Figure 1). 81/234 patients (35.0%) discontinued SB5, mostly due to adverse events (n=40/81) or secondary loss of response (n=35/81). Pain at the injection site was the most frequently reported adverse event (n=31); all these patients switched to Amgevita. 30/31 patients with a double biosimilar continued Amgevita until the end of follow up (median 30 months), resulting in 172/215 (81.3%) patients that remained on ADA at week 52 (Figure 1). Proportions of patients in biochemical remission and clinical remission were similar at baseline, week 26 and week 52 following switch (Figure 2). Median ADA trough levels were similar before (10.2 ug/ml, IQR 7.4-13.5) and after switch 10.3 (IQR 7.4-13.1). 17/234 (7.3%) patients developed antibodies during SB5 treatment. Conclusion Switching from Humira to SB5 appeared effective and safe in this study with over 12 months of follow up. The most common adverse event was injection site pain; these patients were successfully moved on to Amgevita providing the first data about a double biosimilar switch. Over the 24 months of this biosimilar ADA program substantial cost savings were effected.

Background There is an established disconnect between intestinal inflammation and symptoms in patients with IBD. Faecal calprotectin (FCAL) is an excellent surrogate for mucosal healing and we have good data to support treat to target approaches based on FCAL. However, there is relatively little data analysing how well FCAL correlates with a fuller breakdown of a patient’s symptoms. We were interested to explore the impact of ongoing intestinal inflammation as measured by FCAL in patients reported to be in clinical remission. Methods The PREdiCCt study (https://www.predicct.co.uk) is the largest prospective study of the causes of IBD flare. 2629 patients in clinical remission were recruited from 48 UK sites and followed for 2 years. 1946 (74%) patients completed the baseline questionnaires. We present here the results of the baseline questionnaire analysis of IBD symptoms (IBD Control questionnaire). Eight of the question items generate a summary score (IBDControl-8) ranging from 0 (worst control) to 16 (best control). This questionnaire also includes a visual analogue scale (VAS) for disease control ranging from 0 (worst control) to 100 (best control). These data were matched to a contemporaneous FCAL measurements, taken at study entry. Results IBD Control-8 results are available in 1,919 patients [male=840, CD=985 UC/IBDU=934, age 45.8±15.5 (mean±SD in years)]). Median FCAL values were 46 mcg/g (IQR 20–150) for the overall cohort, 50 mcg/g (IQR 20–156) for CD and 39 mcg/g (IQR 20–143) for UC. UC patients reported better disease control compared to CD patients (p There was a negative correlation between baseline FCAL values and (p Conclusion This is the first detailed symptom examination of clinical versus deep remission. We show how residual gut inflammation in patients in clinical remission affects meaningful patient reported outcomes measures including waking at night. UC and male patients reported better disease control compared to CD and female patients.

Background Faecal calprotectin (FC) demonstrates an excellent correlation with endoscopic inflammation. In addition, a treatment-decision algorithm for Crohn’s disease (CD) incorporating FC outperforms and improves 12-month mucosal healing compared with a strategy based on symptoms alone. The aim of this study was to determine whether normalisation of FC ( Methods This was a retrospective cohort study performed at a tertiary IBD centre. All incident cases of CD diagnosed between 2005 and 2017 were identified. Patients with an FC measurement of >250 μg/g at diagnosis who also had at least 1 follow-up FC measured within the first 12-months of diagnosis and >12 months of follow-up were included. The primary endpoint was a composite of progression in Montreal disease behaviour (B1 to B2/3 or B2 to B3 or new perianal disease), surgery or hospitalisation. Results A total of 375 patients were included with a median follow-up of 5.3 years (IQR 3.1–7.4). Normalisation of FC ( Conclusion Normalisation of FC by 12-months of diagnosis is associated with a reduced risk of disease progression in CD. Our data provide strong support for implementation of treat-to-target strategies earlier than previously tested in Crohn’s disease. The immediate implication for healthcare providers and patients is that by ensuring resolution of mucosal inflammation - measured by proxy with faecal calprotectin, and regardless of other variables - within 1 year of diagnosis has a dramatic effect on disease course.

Background Patients with inflammatory bowel disease (IBD) experience substantial impairment in health-related quality of life (HRQoL), therefore HRQoL endpoints are considered important measures of treatment outcome. OCTAVO evaluated the effects of vedolizumab on HRQoL, work productivity and patient concerns in IBD patients in the UK and Ireland. Methods OCTAVO is an ongoing multicentre, observational study to evaluate the impact of vedolizumab on two cohorts. Cohort 1 examined the impact of vedolizumab on concomitant medications compared with anti-TNFs in biologic naïve patients with ulcerative colitis (UC). Cohort 2 was non-comparative and observed changes in patient reported outcomes (PROs) in patients with UC and Crohn’s disease (CD) prescribed vedolizumab at any point in the treatment pathway. PROs are assessed by Short Inflammatory Bowel Disease Questionnaire (SIBDQ), IBD-Control-8 (IBD-C-8), Work Productivity and Activity Impairment (WAPI) and Rating Form of IBD Patient Concerns (RFIPC). PROs are collected prospectively at baseline, Week 14, 6 months and 12 months post-initiation via online questionnaires. The results of an interim analysis of Week 14 PROs for patients aged ≥18 years newly initiated on vedolizumab enrolled across 7 hospital sites in Cohort 2 are reported here. Results Sixty-one patients (21 CD, 40 UC; 51% male) were recruited, with a median age of 39.0 (IQR 32.0–55.0); and median disease duration of 9.6 years (IQR 1.7–17.2) for CD and 5.6 years (IQR 1.3–17.4) for UC. Mean total SIBDQ scores at Week 14 were: 45.2 for CD; 50.0 for UC. Scores increased by 8.5 points in CD patients and 10.2 points in UC patients in the first 14 weeks of the study. Similarly, improvements in IBD-C-8, WPAI-UC/CD sub-scores and RFIPC were observed in both CD and UC (Table 1). Conclusion Vedolizumab treatment was associated with meaningful improvements in PROs at Week 14. Improvements were seen across all measures (SIBDQ, IBD-C-8, WPAI-CD/UC and RFIPC) and were similar between CD and UC. Further investigation of vedolizumab on PROs in the real world is required to assess impact in the longer-term, the full analysis of OCTAVO at months 6 and 12 will help to provide this.

Background Ustekinumab (UST) is an effective agent for induction and maintenance of response and remission in Crohn’s disease (CD). In addition to randomised controlled trials, an abundance of real-world evidence is available as well, suggesting that a substantial proportion of patients will not respond or lose response to UST therapy. To date, there is very little evidence to support the effectiveness of dose-optimisation strategy to manage primary or secondary non-response to ustekinumab. Methods This was a multicentre retrospective cohort study. The protocol was reviewed and approved by the Clinical Committee of ECCO. We included active (HBI≥5; CDAI ≥220) CD patients that received a standard-dose IV induction and at least one SC UST dose of 90 mg. Patients with ostomy were excluded. All patients received dose escalation by either shortening the interval between the doses to q4/6 weeks, intravenous reinduction or a combination of intravenous and subcutaneous escalation. The primary aim of the study was a clinical response (defined as Δ HBI≥3 or Δ CDAI ≥ 70 points) at week 16 after dose escalation. Clinical remission was defined as HBI Results Of 140 patients, 83 (59.3%) were females, median age at treatment onset 36 (26–50) years, median duration of disease 9 (5–18) years from 21 centres in 13 countries (12 Europe, 1 Canada) were included. The patients were dose-escalated after a median treatment duration of 30 (20–45) weeks. Thirty-four (24,3%) were previously escalated from q12 to q8 maintenance regimen. Eighty-nine (63.5%) of the patients were escalated from q8 to q4 regimen, 20 (14.3%) – from q8 to q6, 15 (10.7%) received intravenous reinduction and 16 (11.4%) – a combination of intravenous reinduction and subcutaneous dose interval shortening. At week 16 from escalation, 83 (59.3%) responded to treatment, of them 21 (15%) were in clinical remission. Thirty-three (23.6%) of the patients were on systemic corticosteroids upon escalation; 7/33 (21.2%) achieved corticosteroid-free remission at week 16. One hundred and nine patients (77.8%) continued treatment beyond week 16. Follow-up data beyond week 16 were available for 75/150 (53.6%) of the patients (median duration of follow-up: 35 (32–54) weeks) from dose escalation. At the last follow-up, 53/75 (70.7%) continued to respond to treatment, including 42 (56%) in clinical remission; 25/75 (33%) discontinued treatment at last follow-up. Conclusion This large multicentre retrospective study demonstrates that intensification of ustekinumab maintenance dosage may be effective in up to 60% of the patients. This strategy should be considered in patients that are non-responsive to q8 ustekinumab maintenance dosing.

Limited data are available regarding the relationship between anti-tumor necrosis factor (TNF) drug/antibody levels and perianal fistula outcomes in Crohn's disease. The aims of this study were to assess the relationship between maintenance anti-TNF levels and perianal fistula outcomes.This was a retrospective cross-sectional study of patients receiving maintenance adalimumab or infliximab therapy (minimum 24 weeks) for the treatment of Crohn's disease with associated perianal fistulas, who had anti-TNF drug/antibody levels (trough for infliximab) measured within 4 weeks of clinical assessment. The primary outcome was the association of anti-TNF levels with perianal fistula healing defined as the absence of drainage. The secondary outcome was the association of anti-TNF levels with complete perianal fistula closure.A total of 64 patients (adalimumab, n = 35; infliximab, n = 29) were included. Patients with fistula healing had higher levels of anti-TNF vs. those without fistula healing (adalimumab: 12.6 vs. 2.7 μg/mL, P0.01; infliximab: 8.1 vs. 3.2 μg/mL, P0.01). Patients with fistula closure also had significantly higher anti-TNF levels vs. those without fistula closure (adalimumab: 14.8 vs. 5.7 μg/mL, P0.01; infliximab: 8.2 vs. 3.2 μg/mL, P0.01). For adalimumab, receiver operator characteristic analysis identified an optimum level of6.8 μg/mL and9.8 μg/mL for fistula healing and closure, respectively. For infliximab, receiver operator characteristic analysis identified an optimum trough level of7.1 μg/mL for both fistula healing and closure.Higher maintenance anti-TNF levels are associated with perianal fistula healing and closure in Crohn's disease.

Background A recent systematic review reports an overall prevalence for IBD of 0.3% in Western countries1 but there are no UK estimates since 2003. We aimed to report current all-age prevalence, healthcare usage and forecast 2028 caseload, for IBD in Lothian. Methods We conducted an extensive capture-recapture search strategy, manually confirming all diagnoses through electronic patient record (EPR) review, to provide point prevalence estimates for Lothian, Scotland (Population 889,450). Patients were identified from inpatient IBD codes (K50/51/52), IBD pathology codes, IBD biologic prescriptions, primary care mesalazine prescriptions, an existing calprotectin database and a paediatric IBD registry to identify ‘possible’ IBD cases to 31/08/18. Eight IBD physicians then manually screened the EPR for all possible cases to identify true cases as per Lennard-Jones/Porto criteria. Prevalence was calculated using postcode, date of diagnosis/death and population estimates from National Records Scotland. We then assessed our IBD cohort for attendance at secondary care, IBD-related admission, IBD-drug usage and projected 2028 Lothian IBD prevalence using auto-regressive integrated moving average (ARIMA) modelling. Results 24,188 possible IBD case records were manually reviewed to exclude non-IBD cases, leaving 10,866 true positives (figure 1A). The point prevalence of IBD in Lothian on 31/8/18 was 0.78% (figure 1A). 43.8% of prevalent cases attended out-patient clinic over the preceding 3 years which was inversely correlated with increasing age (Mean age 46.7±0.3 in follow up versus 54.9±0.3 not in follow up, p ARIMA modelling projects a point prevalence on 01/08/28 of 0.99% (0.94–1.04%) affecting 1.6% (1.5–1.7%) of the >50s who will account for 59% of prevalent IBD. Conclusions The prevalence of IBD in the UK is 0.78% (1 in 125 individuals). This is much higher than previously reported, and will continue to rise due to compound prevalence, reaching >1.0% by the end of 2028. Reference Siew Ng, et al. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. Lancet 2018;390:pp2769–2778.

Background & Aims Vedolizumab is an anti-a4b7 monoclonal antibody that is licensed for the treatment of moderate to severe Crohn’s disease and ulcerative colitis. The aims of this study were to establish the real-world effectiveness and safety of vedolizumab for the treatment of inflammatory bowel disease. Methods This was a retrospective study involving seven NHS health boards in Scotland between June 2015 and November 2017. Inclusion criteria included: a diagnosis of ulcerative colitis or Crohn’s disease with objective evidence of active inflammation at baseline (Harvey–Bradshaw Index[HBI] ≥5/Partial Mayo ≥2 plus C-reactive protein [CRP] >5 mg/L or faecal calprotectin ≥250 µg/g or inflammation on endoscopy/magnetic resonance imaging [MRI]); completion of induction; and at least one clinical follow-up by 12 months. Kaplan–Meier survival analysis was used to establish 12-month cumulative rates of clinical remission, mucosal healing, and deep remission [clinical remission plus mucosal healing]. Rates of serious adverse events were described quantitatively. Results Our cohort consisted of 180 patients with ulcerative colitis and 260 with Crohn’s disease. Combined median follow-up was 52 weeks (interquartile range [IQR] 26–52 weeks). In ulcerative colitis, 12-month cumulative rates of clinical remission, mucosal healing, and deep remission were 57.4%, 47.3%, and 38.5%, respectively. In Crohn’s disease, 12-month cumulative rates of clinical remission, mucosal healing, and deep remission were 58.4%, 38.9%, and 28.3% respectively. The serious adverse event rate was 15.6 per 100 patient-years of follow-up. Conclusions Vedolizumab is a safe and effective treatment for achieving both clinical remission and mucosal healing in ulcerative colitis and Crohn’s disease.

Background Patient reported outcomes are important endpoints in IBD management, but patient perceptions of the causes of disease flare are unknown and thus may reveal novel areas for future study. Methods The PREdiCCt study (https://www.predicct.co.uk) is the largest prospective study of the causes of IBD flare. 2629 patients in clinical remission were recruited from 48 UK sites and followed for 2 years with detailed assessment of environmental and dietary factors via monthly questionnaires. 1946 (74%) patients completed the baseline questionnaires. We present here the results of the baseline questionnaire analysis of patient perceptions of disease flare, derived from a list of 17 putative causes from the literature and their own experience via free text input. Results In total 1,946 IBD patients [male=852, CD=1000; UC/IBDU=946, age 45.8±15.5 (mean±SD in years)] gave their opinion about factors initiating a flare. The commonest causes reported were stress (n=1359, 69.8%), dietary changes (n=911, 46.8%), alcohol use (n=385, 19.8%), sleep disturbances (n=331, 17%) and that their medication stopped working (n=308, 15.8%) (Figure 1). CD participants were more likely to identify dietary changes (50% vs 43%, p Conclusion Stress, dietary changes and alcohol use were identified as the main causes of flare by patients with dietary changes more frequently reported in CD (especially those with small bowel involvement). The impact of environmental and dietary factors in the development of flare is being further investigated with ongoing longitudinal data collection in the PREdiCCt Study.

Switching from Remicade to CT-P13 allows for significant cost savings and has been shown to be non-inferior to continued therapy with Remicade for the treatment of Crohn’s disease. The aim of this work was to prospectively evaluate clinical outcomes in a cohort of patients with Crohn’s disease switching from Remicade to CT-P13. A prospective service evaluation was performed. The Harvey-Bradshaw index, CRP, faecal calprotectin and serum for infliximab/antibody levels were collected prior to patients' final Remicade infusion and at 6 and 12 months after switching to CT-P13 as part of routine clinical care. All adverse events during follow-up were also recorded. One hundred and ten patients on Remicade switched to CT-P13. No significant difference was observed between the Harvey-Bradshaw Index (p = 0.07), CRP (p = 0.13), faecal calprotectin (p = 0.25) or trough infliximab levels (p = 0.47) comparing before and at 6 and 12 months after the switch to CT-P13. Seven patients developed new infliximab antibodies after switching from Remicade to CT-P13. The majority of patients remained on CT-P13 at 12 months (84.5%) and the rate of adverse events and serious adverse events was 53.8 and 13.5 per 100 patient-years of follow-up, respectively. Switching to CT-P13 resulted in a cost saving of approximately 46.4%. The transition to CT-P13 from Remicade for the treatment of Crohn’s disease is safe and has no negative effect on clinical outcomes at 12 months.

Adalimumab is an established treatment for Crohn's disease. Limited data are available regarding the relationship between adalimumab drug levels and serum/fecal markers of gut inflammation. We therefore aimed to characterize the relationship between adalimumab levels and biologic remission during maintenance therapy.A single-center prospective cross-sectional study was undertaken on Crohn's disease patients who had received adalimumab therapy for a minimum of 12 weeks after induction. Data on clinical activity (Harvey-Bradshaw Index), C-reactive protein (CRP), adalimumab drug and antibody levels, and fecal calprotectin were collected. Biologic remission was defined as a CRP5 mg/L and fecal calprotectin250 µg/g. Adalimumab drug and antibody levels were processed using the Immundiagnostik monitor enzyme-linked immunosorbent assay.One hundred fifty-two patients had drug and antibody samples matched with CRP and fecal calprotectin. Patients in biologic remission had significantly higher adalimumab levels compared with others (12.0 µg/mL vs 8.0 µg/mL, P0.0001). Receiver operating characteristic curve analysis demonstrated an optimal adalimumab level of8.5 µg/mL (sensitivity, 82.2%; specificity, 55.7%; likelihood ratio, 1.9) for predicting biologic remission. Multivariable logistic regression revealed that adalimumab levels8.5 µg/mL were independently associated with biologic remission (odds ratio, 5.27; 95% confidence interval, 2.43-11.44; P0.0001).Higher adalimumab levels are associated with biologic remission. An optimal level of8.5 µg/mL was identified.

Introduction Acute Severe Ulcerative Colitis (ASUC) affects 15% of patients with Ulcerative Colitis. The current standard of care is intravenous (IV) steroids, with ciclosporin or anti-TNF as second line medical therapy and urgent colectomy when medical therapy fails. Previous data from our centre reports 40% of those admitted with ASUC required colectomy. We aimed to determine predictors of outcome in patients admitted with acute UC. Methods Patients admitted to NHS Lothian hospitals between 1/11/13 and 31/10/16 requiring IV steroids for UC were identified using ICD10 discharge codes. Only the first admission for each patient during that period was included. Case record review verified the diagnosis and collected clinical variables including age, sex, disease activity (Mayo endoscopic severity score) and distribution, and treatments needed. Response to therapy was defined as discharge from hospital requiring no further anti-inflammatory treatment. Comparisons were made using Kruskal-Wallace or chi-squared analyses where appropriate. Results 173 patients were identified (62% male, median age 39.67 years (IQR 29.58–54.75)). 108/173 (63%) responded to IV steroids, 29/173 (17%) responded to second line medical therapy and 35/173 (20%) patients required colectomy. One patient died from complications of concurrent disease. Endoscopic assessment more closely reflected response to intravenous steroids than stool frequency. 96% of those with mild endoscopic disease responded to IV steroids, compared to 40% of those with severe endoscopic disease (p 6 stools/day (p=0.028). Endoscopy was performed on day 2 on average (IQR 1–3) (figure 1). Those requiring surgery had a shorter disease duration compared with those responding to IV steroids (median 0.13 years vs 1.5 years, p=0.09 Kruskal-Wallace). The median length of admission was 7.5 days (IQR 6–16) and surgery was performed on day 9 (IQR 8–12) on average. Age, sex, disease extent at diagnosis and smoking status were similar between groups. Conclusions 20% of patients admitted to hospital for IV steroid treatment for active UC required urgent colectomy during admission. Response to steroids was greater in those with less severe endoscopic disease with a clearer relationship between endoscopic severity and response than stool frequency on admission. Those requiring surgery were likely to have a shorter disease duration on admission. These data emphasise the need for a timely endoscopic assessment for all patients admitted with acute colitis.

Introduction Adalimumab (ADA) is a well-established treatment for Crohn’s disease (CD). Despite this limited data are available regarding the relationship of serum ADA levels, and antibodies to ADA (ATA) with clinical outcomes. Methods We performed a prospective cross-sectional study to investigate the association of serum ADA levels and ATA on clinical outcomes. Inclusion criteria were a diagnosis of CD and minimum of 12 weeks therapy. Patients were written to in advance of their next clinic visit and advised to omit their ADA dose if due within 72 hour from their appointment. Harvey Bradshaw Index (HBI), serum ADA levels/ATA, CRP and faecal calprotectin (FC) were simultaneously collected at clinic. Biochemical remission was defined as FC Results At the time of drug level testing, 259 patients were on ADA maintenance therapy. A total of 195 samples were available for analysis from 178 patients; matched HBI, FC and CRP were available for 171 patients. Median duration of ADA therapy was 2.4 years (IQR 1.2–4.3) with 37/178 (20.8%) patients receiving concomitant immunosuppression. Median ADA levels were higher in patients receiving weekly (n=55) (14.0 µg/ml, 8.0–17.4) vs. fortnightly dosing (n=123) (11.0 µg/ml, 7.0–14.5, p=0.0095). 29/178 (16.3%) patients were positive for ATA. A clear negative correlation was observed between ADA levels and ATA (Spearman’s r=−0.567, p 50 AU/ml, respectively (p 8.8 µg/ml was identified for predicting biochemical remission (82.7% sens, 55.6% spec, positive LR 1.86). ADA levels but not ATA independently predicted biochemical remission in a multivariate logistic regression model. Conclusions Higher ADA levels were independently associated with biochemical remission; levels of >8.8 µg/ml, higher than previously suggested, might be an appropriate target in the maintenance treatment of CD.