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There are now a growing number of licensed biological therapies for patients with Crohn’s disease. However, there can be significant costs associated with long-term maintenance treatment, as well as some concerns about potential side-effects. As a result, there has been increasing interest in elective biological treatment discontinuation in selected patients, after a sustained period of remission. Following discontinuation, in cases of relapse, evidence to date has suggested that remission may often be regained by re-treatment with the same biological agent. Therefore, a concept has emerged in which cycles of biological therapy might be used. If this treatment strategy were to be applied in a subgroup of patients at low risk of relapse, cycling might allow a substantial number of patients to have a lower, overall therapeutic burden—ensuring decreased exposure to biological therapy but still enabling appropriate disease control.Currently, there remains uncertainty about the benefit–risk balance for using cycles of biological treatment for patients with Crohn’s disease. Accordingly, an expert panel was convened by the European Crohn’s and Colitis Organisation [ECCO] to review the published literature and agree a series of consensus practice points. The panel aimed to provide evidence-based guidance on multiple aspects of biological treatment discontinuation and cycling, including the risk of relapse after elective treatment discontinuation, predictors of probable relapse or remission, safety, patient preferences, and pharmacoeconomic aspects. Crucially, discussions about biological treatment discontinuation and cycling should be individualized, to enable shared decision-making by patients with their clinicians.

Background: Despite proven efficacy of biologics in inflammatory bowel disease (IBD), many exhibit primary non-response or secondary loss of response and switch to subsequent biologic(s). Here, we identified early predictors of second- and/or third-line biologic persistence in IBD, in a real-world cohort of patients. Methods: A retrospective multicentre cohort study was conducted on patients receiving second- and/or third-line biologics for IBD from 2005–2021. Cox regression was applied to identify factors predictive of longer cumulative biologic persistence prior to treatment failure. Results: Of 179 patients who received ≥2 biologics, 159 (88.8%) received an anti-tumour necrosis factor (anti-TNF) first-line. There was a significantly increased likelihood of longer treatment persistence in recipients who received an anti-TNF first, versus those that received a non-anti-TNF agent first (p < 0.01). A diagnosis of CD (OR 7.1, 95% CI [2.3–21.7], p < 0.01), and endoscopic remission achieved on the first biologic (OR 10.4 [1.3–79.9], p = 0.03) were positive predictors of longer biologic persistence, whilst advancing age at IBD diagnosis (OR 0.97 [0.94–0.99], p = 0.04) and primary non-response to initial biologic (OR 0.3 [0.1–0.7], p < 0.01) were inversely associated with biologic persistence. Conclusions: These real-world data demonstrate multiple, simple to identify factors that offer the potential for early objectively assessed response to first-line biologic to predict future biologic persistence.

Background Preventive health measures reduce treatment and disease-related complications including infections, osteoporosis, and malignancies in patients with inflammatory bowel disease (IBD). Although guidelines and quality measures for IBD care highlight the importance of preventive care, their uptake remains variable. This systematic review evaluates interventions aimed at improving the rates of provision and uptake of preventive health measures, including vaccinations, bone density assessment, skin cancer screening, cervical cancer screening, and smoking cessation counseling. Methods We searched PubMed, MEDLINE, EMBASE, and CENTRAL for full text articles published until March 2021. Studies were included if they evaluated interventions to improve the provision or uptake of 1 or more preventive health measures in adult IBD patients and if they reported pre- and postintervention outcomes. Results In all, 4655 studies were screened, and a total of 17 studies were included, including 1 randomized controlled trial, 1 cluster-controlled trial, and 15 prospective interventional studies. A variety of interventions were effective in improving the rates of adherence to preventive health measures. The most common interventions targeted gastroenterologists, including education, electronic medical records tools, and audit feedback. Other interventions targeted patients, such as education, questionnaires, and offering vaccine administration at clinic visits. Few interventions involved IBD nurses or primary care physicians. Conclusions A range of interventions—targeted at gastroenterologists, patients, or both—were effective in improving the provision and uptake of preventive care. Future studies should involve randomized controlled trials evaluating multifaceted interventions that target barriers to adherence and involve IBD nurses and primary care physicians.

Background and Aim While the advent of biologic therapy has led to improved outcomes in perianal fistulizing Crohn's disease (pfCD), loss of response is common. Previous studies suggest that patients who achieve radiological healing (with healing of underlying tracts on magnetic resonance imaging [MRI]) have a longer duration of response. The aim of this study was to characterize MRI outcomes of pfCD at a specialist inflammatory bowel disease (IBD) unit and compare the long‐term clinical outcomes between patients achieving MRI and clinical healing. Methods A retrospective analysis of perianal fistulizing Crohn's patients treated at one specialist IBD unit was performed. Records were reviewed for patient demographics, disease history, clinical assessments, investigation results, and disease flares. Clinical remission was defined as closure of all baseline fistula openings. Radiological healing was defined as the absence of any T2‐hyperintense sinuses, tracts, or collections. The primary end‐point was rate of MRI healing. The secondary outcome was defined as flare‐free period (time between clinical or radiological healing and patients' first signs/symptoms requiring therapy escalation). Results A total of 93 patients were included, with a median follow‐up of 4.8 years (interquartile range, 2.4–6 years). Of 44 patients, 22 (50%) achieved clinical remission, while 15 of 93 (16%) achieved radiological healing. Of 22 patients, 10 (45%) with clinical remission had a subsequent disease flare (median time of 7 months) compared with 3 of 15 (20%) patients with MRI healing (median time of 3.6 years). Radiological healing was associated with a significantly longer flare‐free period (P = 0.01). Conclusion Radiological healing occurs less commonly but represents a deeper form of healing, associated with improved long‐term clinical outcomes., Patients with MRI healing have a significantly longer flare‐free period compared to those with only clinical healing (P = 0.005). This suggests that MRI healing is associated with improved clinical course compared to clinical remission, highlighting a potentially more sensitive and meaningful treatment target.

Background While immunosuppression poses a theoretical increase in the risk of COVID‐19, the nature of this relationship is yet to be ascertained. Aims To determine whether immunosuppressed patients are at higher risk of COVID‐19 to help inform the management of patients receiving immunosuppressant therapies during the pandemic. Methods We performed a random‐effects meta‐analysis of data from studies that reported on the prevalence of immunosuppression among patient cohorts with COVID‐19. Results Sixty full‐text publications were identified. In total, six individual studies were included in the final analysis, contributing a total of 10 049 patients with COVID‐19 disease. The prevalence of immunosuppressed patients among the study cohorts with COVID‐19 ranged from 0.126% to 1.357%. In the pooled cohort a total of 64/10 049 (0.637%) patients with COVID‐19 disease was immunosuppressed. Observed to expected ratios were used to compare the prevalence of immunosuppression in cohorts with confirmed COVID‐19 disease to the background prevalence of immunosuppression in the general community. The observed to expected ratio of immunosuppression among patients with COVID‐19 illness, relative to the general community, was 0.12 (95% confidence interval: 0.05–0.27). Conclusions Compared to the general population, immunosuppressed patients were not at significantly increased risk of COVID‐19 infection. This finding provides support for current expert consensus statements, which have recommended the continuation of immunosuppressant therapy in the absence of COVID‐19.

Multiple investigations are available to aid the diagnosis and monitoring of disease activity in inflammatory bowel disease (IBD). Fecal calprotectin (FC) is an established surrogate for intestinal inflammatory activity. Therapeutic drug monitoring (TDM) including thiopurine metabolites, anti-tumor necrosis factor (TNF) levels and antidrug antibody measurements are a step toward personalized medicine in IBD, but face access barriers. We aimed to assess test availability and barriers for these investigations in European practice.Five-hundred questionnaires were distributed to workshop participants at the 11th Congress of the European Crohn's and Colitis Organisation (ECCO). Access to FC, TDM for thiopurines and anti-tumor necrosis factor agents, as well as factors associated with usage and barriers to access were recorded.Responses were obtained from 195 attendees from 38 countries across a range of practices, healthcare settings and levels of experience. FC was available to 92.3% while access to anti-TNF (78.9%, P = 0.02 vs. thiopurine TDM, P = 0.0002 vs. FC) and thiopurine TDM (67.7%, P = 0.0001) were less widespread. Cost was a frequently cited barrier to test access or usage, with access having a significant West-East and North-South divide across all three investigations. The strongest independent predictor of access to all tests was healthcare spending per capita (P = 0.005 for FC; P 0.0001 for both TDM).FC, anti-TNF and thiopurine TDM are increasingly incorporated as part of routine practice in IBD care across Europe and have the potential to impact positively on patient care. However, access barriers remain of which we found test cost the most significant with the investment required to reduce these barriers.

Perianal fistulas are a common and debilitating manifestation of Crohn's disease. Since the advent of biological agents, patient outcomes appear to have improved. While rates of clinical response and remission are well characterized in literature, magnetic resonance imaging (MRI) outcomes remain less so. This is despite previous studies demonstrating the persistence of fistula tracts on MRI, in spite of clinical healing, suggesting radiological markers of improvement may be more accurate. The aims of this study were to systematically review the literature for all studies reporting on MRI outcomes following biological therapy and to compare rates of radiological healing to clinical remission. A search was performed according to the Preferred Reporting Items For Systematic Reviews and Meta‐Analysis (PRISMA) guidelines. Nine articles were included, with a total sample size of 259 patients. Of these 259 patients, 47% achieved clinical remission following induction therapy and 42% following a median of 52 weeks' maintenance therapy. Out of the 259 patients, 7% achieved radiological healing in the short term and 25% in the long term. The odds ratio of MRI versus clinical healing was 0.10 (95% confidence interval [CI], 0.02–0.39) and 0.43 (95% CI, 0.26–0.71), respectively, at those corresponding time points. MRI healing of perianal fistulizing Crohn's, while arguably a more accurate assessment of treatment response, is significantly less common than clinical remission. Heterogeneity exists in the definition of radiological and clinical response, leading to variation in reported rates. Further studies, directly comparing the long‐term outcomes of patients achieving clinical remission and MRI healing are required, to better inform the role of MRI follow up in clinical practice., Perianal fistulizing Crohn's remains a significant clinical challenge, with a high burden of disease and relative treatment resistance. Magnetic resonance imaging outcomes, while more accurate and objective, remain uncharacterised. This systematic review with meta‐analysis presents the current evidence regarding the radiological response to anti‐TNF alpha treatment.

Background Strictures are the commonest complication in Crohn’s disease. Surgery and endoscopic dilation are the main treatments; drug therapy has been considered contra-indicated. Given that most strictures have an inflammatory component we aimed to assess the efficacy of anti-inflammatory therapy, and to identify the optimal treatment. Methods In this randomised trial patients with symptomatic Crohn’s disease strictures and inflammation were assessed by imaging (MRI, colonoscopy, intestinal ultrasound) and for inflammation (faecal calprotectin and CRP). Symptoms were assessed using an Obstructive Symptom Score (OSS). Patients with short endoscopically-accessible strictures had a baseline endoscopic balloon dilation if indicated. Patients were then randomised 2:1 to high dose adalimumab induction (160mg weekly for 4 weeks) with 40mg fortnightly maintenance plus thiopurine, with therapy increased for ongoing inflammation at 4 and 8 months, versus standard dose adalimumab mono-therapy. At 12 months primary endpoint was improved OSS. Secondary outcomes: disease activity, treatment failure, stricture morphology, inflammation, psychological well-being, disability, and quality of life. MRI was assessed blindly. Results 52 patients were randomised to the intensive and 25 to the standard treatment arm. 27 of 52 (52%) intensive treatment patients dose escalated at 4 or 8 months. Improved OSS at 12 months occurred in 41 (79%) intensive treatment and 16 (64%) standard treatment arms (P=0.17). Treatment failure was less common in the intensive treatment arm (10%) versus the standard treatment arm (28%) (P=0·045). Faecal calprotectin normalised (25% on ultrasound was seen in 22/43 (51%) and 7/21 (33%) respectively (P=0.18). MRI complete stricture resolution was seen in 10/51 (20%) and 4/25 (16%) (P=0.7). At 12 month colonoscopy 22/48 (46%) v 9/25 (36%) strictures were passable (P=0.42). 12 month median drug levels were 13.2µg/ml and 6.6µg/ml respectively (P Conclusion Crohn’s disease strictures are responsive to drug therapy. A majority of patients experience symptom improvement and many have improved stricture morphology. Treat-to-target therapy intensification results in less treatment failure, less stricture-associated inflammation, and greater improvement in stricture morphology.

Strictures are the most common structural complication of Crohn's disease. Surgery and endoscopic balloon dilation are the main treatments; drug therapy has been considered contraindicated. Given that most strictures have an inflammatory component, we aimed to find out whether strictures are responsive to drug treatment and whether intensive drug therapy is more effective than standard drug therapy.This open-label, single-centre, randomised controlled trial was performed in one specialist inflammatory bowel disease centre in Australia. Patients aged 18 years or older with Crohn's disease were included. Eligible patients had a de novo or postoperative anastomotic intestinal stricture on MRI or ileocolonoscopy, symptoms consistent with chronic or subacute intestinal obstruction (postprandial abdominal pain in the presence of a confirmed stricture), and evidence of active intestinal inflammation. Patients were randomly assigned (2:1) to receive intensive high-dose adalimumab (160 mg adalimumab once per week for 4 weeks followed by 40 mg every 2 weeks, with escalation of dose at 4 months and 8 months if assessment of disease activity indicated active inflammation) plus thiopurine (initial dose of azathioprine 2·5 mg/kg or mercaptopurine 1·5 mg/kg, with dose adjustment based on thiopurine metabolite testing) or standard adalimumab monotherapy (160 mg at week 0, 80 mg at week 2, then 40 mg every 2 weeks) using stratified fixed block randomisation. Stratification factors were stricture dilation at study baseline colonoscopy and current biologic drug use. The primary endpoint was improvement (decrease) in the 14-day obstructive symptom score at 12 months by one or more points compared with baseline. This trial is registered with ClinicalTrials.gov, NCT03220841, and is completed.Between Sept 10, 2017, and Sept 6, 2019, 123 patients were screened and 77 randomly assigned to intensive adalimumab plus thiopurine treatment (n=52) or standard adalimumab treatment (n=25). At 12 months, improvement in obstructive symptom score was noted in 41 (79%) of 52 patients in the intensive treatment group and 16 (64%) of 25 in the standard treatment group (odds ratio [OR] 2·10 [95% CI 0·73-6·01]; p=0·17). Treatment failure occurred in five (10%) patients in the intensive treatment group versus seven (28%) in the standard treatment group (OR 0·27 [95% CI 0·08-0·97]; p=0·045); four patients in each group required stricture surgery (0·44 [0·10-1·92]; p=0·27). Crohn's Disease Activity Index was less than 150 in 36 (69%) patients in the intensive treatment group versus 15 (60%) in the standard treatment group (1·50 [0·56-4·05]; p=0·42). MRI at 12 months showed improvement using the stricture MaRIA score (≥25%) in 31 (61%) of 51 versus seven (28%) of 25 patients (3·99 [1·41-11·26]; p=0·0091). MRI complete stricture resolution was seen in ten (20%) versus four (16%) patients (1·28 [0·36 to 4·57]; p=0·70). Intestinal ultrasound at 12 months showed improvement (25%) in bowel wall thickness in 22 (51%) of 43 versus seven (33%) of 21 patients (2·10 [0·71 to 6·21]; p=0·18). Faecal calprotectin normalised in 32 (62%) versus 11 (44%) patients (2·04 [0·77-5·36]; p=0·15). Normalisation of CRP was seen in 32 (62%) versus 11 (44%) patients (2·04 [0·77-5·36]; p=0·15). Eight (15%) patients in the intensive treatment group and four (16%) in the standard treatment group reported serious adverse events. No deaths occurred during the study.Crohn's disease strictures are responsive to drug treatment. Most patients had improved symptoms and stricture morphology. Treat-to-target therapy intensification resulted in less treatment failure, a reduction in stricture-associated inflammation, and greater improvement in stricture morphology, although these differences were not significantly different from standard therapy.Australian National Health and Medical Research Council, Gastroenterological Society of Australia Ferring IBD Clinician Establishment Award, Australasian Gastro Intestinal Research Foundation, AbbVie, and the Spotlight Foundation.

Summary Background Obesity may affect efficacy and safety of biologic treatments for ulcerative colitis (UC). Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of UC. Aims To assess efficacy and safety of tofacitinib in patients with UC, by baseline body mass index (BMI). Methods This post hoc analysis evaluated patients with UC receiving placebo or tofacitinib from the 8‐week OCTAVE Induction 1 and 2 (NCT01465763, NCT01458951) and 52‐week OCTAVE Sustain (NCT01458574) studies. Patients were stratified by BMI at OCTAVE Induction 1 and 2 baseline (, At Week 8 of OCTAVE Induction 1 and 2 and Week 52 of OCTAVE Sustain, proportions of patients achieving a clinical response with 5 or 10 mg twice daily (b.d.) tofacitinib were generally similar across body mass index (BMI) subgroups.Among patients receiving tofacitinib 10 mg b.d. in OCTAVE Induction 1 and 2, serious infections were numerically greater in the BMI ≥30 subgroup (3.2%) vs other BMI subgroups (0.4%). Analyses were limited by small patient numbers in the BMI ≥30 subgroup.Conclusions: Efficacy and safety of tofacitinib were similar in patients with ulcerative colitis, regardless of baseline BMI.

Background and study aims Endoscopic mucosal resection (EMR) of large sessile or laterally spreading colonic lesions is a safe alternative to surgery. We assessed reductions in Surgical Resection (SR) rates and associated clinical and financial benefits following the introduction of an EMR service to a large regional center. Patients and methods Ongoing prospective intention-to-treat analysis of EMR was undertaken from time of service inception in 2009 to 2017. Retrospective data for SR of large sessile/laterally spreading colonic lesions were collected for the period 4 years before commencement of the EMR service (2005 – 2008) and 9 years after its introduction (2009 – 2017). Results From 2005 to 2008, 32 surgical procedures were performed for non-malignant colonic neoplasia (50 % male, median age 68 years, median Length of Stay (LoS) 10 days). Following the introduction of the EMR service, there was a 56 % reduction in the number of patients referred for surgery (32 surgical procedures, 47 % male, median age 70 years, median LoS 8.5 days). During this period, EMR was successfully performed in 183 patients with 216 lesions resected (60 % male, median age 68 years, median LoS 1 day). Compared to the SR group, the EMR cohort had a lower peri-procedural complication rate (7.7 % vs 54.7 %, P Conclusions The introduction of a dedicated EMR service into a large regional center as an alternative to SR can lead to a substantial decrease in unnecessary surgery with subsequent clinical and financial benefits.

BACKGROUND: Loss of response to anti-TNF agents is a common clinical problem. Dose escalation may be effective for reestablishing clinical response in Crohn's disease (CD). AIMS: To perform a systematic review assessing the efficacy of escalated maintenance anti-TNF therapy in CD. METHODS: EMBASE, MEDLINE, Web of Science, and CENTRAL databases were searched for English language publications through to April 25, 2021. Full-text articles evaluating escalated maintenance treatment (infliximab or adalimumab) in adult CD patients were included. RESULTS: A total of 4733 records were identified, and 68 articles met eligibility criteria. Rates of clinical response (33%-100%) and remission (15%-83%) after empiric dose escalation for loss of response to standard anti-TNF therapy were high but varied across studies. Dose intensification strategies (doubling the dose versus shortening the therapeutic interval) were similarly efficacious. Dose-escalated patients tended to have higher serum drug levels compared to those on standard dosing. An exposure-response relationship following dose escalation was found in a number of observational studies. Randomised controlled trials comparing therapeutic drug monitoring (TDM) to empiric treatment intensification have failed to reach their primary end-points. Strategies including Bayesian dashboard-dosing and early treatment escalation targeting biomarker normalisation were found to be associated with improved long-term outcomes. CONCLUSIONS: Empiric escalation of maintenance anti-TNF therapy can recapture clinical response in a majority of patients with secondary loss of response to standard maintenance doses. Proactive optimisation of maintenance dosing might prolong time to loss of response in some patients.

BACKGROUND & AIMS: Higher anti-tumor necrosis factor-α (TNF) drug levels are associated with improved clinical healing of Crohn's perianal fistulas. It is unclear whether this leads to improved healing on radiologic assessment. We aimed to evaluate the association between anti-TNF drug levels and radiologic outcomes in perianal fistulising Crohn's disease. METHODS: A cross-sectional retrospective multicenter study was undertaken. Patients with perianal fistulising Crohn's disease on maintenance infliximab or adalimumab, with drug levels within 6 months of perianal magnetic resonance imaging were included. Patients receiving dose changes or fistula surgery between drug level and imaging were excluded. Radiologic disease activity was scored using the Van Assche Index, with an inflammatory subscore calculated using indices: T2-weighted imaging hyperintensity, collections >3 mm diameter, rectal wall involvement. Primary endpoint was radiologic healing (inflammatory subscore ≤6). Secondary endpoint was radiologic remission (inflammatory subscore =0). RESULTS: Of 193 patients (infliximab, n = 117; adalimumab, n = 76), patients with radiologic healing had higher median drug levels compared with those with active disease (infliximab 6.0 vs 3.9 μg/mL; adalimumab 9.1 vs 6.2 μg/mL; both P < .05). Patients with radiologic remission also had higher median drug levels compared with those with active disease (infliximab 7.4 vs 3.9 μg/mL; P < .05; adalimumab 9.8 vs 6.2 μg/mL; P = .07). There was a significant incremental reduction in median inflammatory subscores with higher anti-TNF drug level tertiles. CONCLUSIONS: Higher anti-TNF drug levels were associated with improved radiologic outcomes on magnetic resonance imaging in perianal fistulising Crohn's disease, with an incremental improvement at higher drug level tertiles for both infliximab and adalimumab.

INTRODUCTION Few studies have investigated perianal fistula etiopathogenesis, and although the cryptoglandular theory is widely accepted in idiopathic cases, in Crohn's disease, it is thought to involve the interplay between microbiological, immunological and genetic factors. A pilot study was conducted to assess for metabolic variations in Crohn's perianal fistula tissue that might differ from that of idiopathic (cryptoglandular) perianal fistula tissue as a comparator. The goal was to identify any potential biomarkers of disease, which may improve the understanding of pathogenesis. AIMS AND METHODS Fistula tract biopsies were obtained from 30 patients with idiopathic perianal fistula and 20 patients with Crohn's anal fistula. Two different assays were used in an ultra-high-performance liquid chromatography system coupled with a mass spectrometric detector to achieve broad metabolome coverage. Univariate and multivariate statistical data analyses were used to identify differentiating metabolic features corresponding to the perianal fistula phenotype (i.e. Crohn's disease vs. idiopathic). RESULTS Significant orthogonal partial least squares discriminant analysis predictive models (validated with cross-validated-analysis of variance P value

BACKGROUND AND AIMS: Comorbidities, polypharmacy, malignancies, and infections complicate management of elderly patients with inflammatory bowel diseases (IBD). This study assessed gastroenterologists' preference in the prescription of medications or surgery to elderly patients with IBD, and the factors associated with their choices. METHODS: An international case-based survey was conducted that presented three cases of steroid-dependent ulcerative colitis assessing young-age versus elderly-age patients, with and without comorbidity. Physician characteristics and practice demographics were collected. Factors associated with selection of different choices of therapy were determined by logistic regression analysis. RESULTS: A total of 424 respondents from 41 countries were included. Vedolizumab (53.2%) and thiopurines (19.4%) were the top treatment preferences for moderate-to-severe ulcerative colitis (P

COVID-19 pneumonia is a global viral disease and has been classified as a pandemic by the World Health Organization. The coronavirus that causes it can remain in the stool of some infected patients for a short period, even after recovery from COVID-19 pneumonia. Studies have increasingly reported the involvement of other organs, including the gastrointestinal system, in addition to the respiratory system. Ulcerative colitis is an inflammatory bowel disease with an unknown cause. Emerging data suggest that the gas trointestinal system may be influenced by COVID-19 via the expression of angiotensin-converting enzyme-2 (ACE-2), but data on the association between COVID-19 and inflammatory bowel diseases, including ulcerative colitis, are lacking. In this report, we describe a case of ulcerative colitis diagnosed in a 50-year-old male patient who presented with complaints of bloody diarrhea and abdominal pain following the completion of treatment for COVID-19 pneumonia. It is possible for the novel coronavirus to trigger ulcerative colitis. Hence, patients presenting with gastrointestinal com plaints should also be evaluated for COVID-19.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: The primary objective of this systematic review of the literature is to assess the efficacy and safety of vedolizumab in the induction and maintenance of remission in Crohn's disease.

Background and Aims Anti-tumour necrosis factor [anti-TNF] therapy is indicated for treatment of moderate to severe inflammatory bowel disease [IBD], but has a primary non-response rate of around 30%. We aim to use metabonomic and metataxonomic profiling to identify predictive biomarkers of anti-TNF response in Crohn’s disease. Methods Patients with luminal Crohn’s disease, commencing anti-TNF therapy, were recruited with urine, faeces, and serum samples being collected at baseline and 3-monthly. Primary response was defined according to a combination of clinical and objective markers of inflammation. Samples were measured using three UPLC-MS assays: lipid, bile acid, and Hydrophillic Interaction Liquid Chromatography [HILIC] profiling with 16S rRNA gene sequencing of faeces. Results Samples were collected from 76 Crohn’s disease patients who were anti-TNF naïve and from 13 healthy controls. There were 11 responders, 37 non-responders, and 28 partial responders in anti-TNF-treated Crohn’s patients. Histidine and cysteine were identified as biomarkers of response from polar metabolite profiling [HILIC] of serum and urine. Lipid profiling of serum and faeces found phosphocholines, ceramides, sphingomyelins, and triglycerides, and bile acid profiling identified primary bile acids to be associated with non-response to anti-TNF therapy, with higher levels of phase 2 conjugates in non-responders. Receiver operating curves for treatment response demonstrated 0.94 +/ -0.10 [faecal lipid], 0.81 +/- 0.17 [faecal bile acid], and 0.74 +/- 0.15 [serum bile acid] predictive ability for anti-TNF response in Crohn’s disease. Conclusions This prospective, longitudinal cohort study of metabonomic and 16S rRNA gene sequencing analysis demonstrates that a range of metabolic biomarkers involving lipid, bile acid, and amino acid pathways may contribute to prediction of response to anti-TNF therapy in Crohn’s disease. Podcast This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast

Australia has one of the highest incidence rates of inflammatory bowel disease (IBD) in the world. Early diagnosis and treatment for IBD is critical. For Crohn disease, in particular, this may change the natural history of disease and reduce disability. Faecal calprotectin is a sensitive test that can be used by primary care physicians to assist in determining which patients with gastrointestinal symptoms may have IBD. This allows for prompt identification of patients who may benefit from endoscopy. Regular re-evaluation of disease status with strategies that can safely, readily and reliably detect the presence of inflammation with faecal biomarkers and imaging is important. To avoid the risks of cumulative radiation exposure, magnetic resonance imaging and/or intestinal ultrasound, rather than computed tomography scanning, should be performed when possible. Drug treatments for IBD now include five biological drugs listed by the Pharmaceutical Benefits Scheme: adalimumab, infliximab, golimumab, vedolizumab and ustekinumab. Such developments offer the possibility for improved disease control in selected patients.

IntroductionPerianal fistulising Crohn’s disease (pfCD) can be somewhat treatment refractory. Higher infliximab trough levels (TLIs) may improve fistula healing rates; however, it remains unclear whether escalating infliximab therapy to meet higher TLI targets using proactive, or routine, therapeutic drug monitoring (TDM) improves outcomes. This randomised controlled trial aimed to assess whether infliximab therapy targeting higher TLIs guided by proactive TDM improves outcomes compared with standard therapy.Methods and analysisPatients with active pfCD will be randomised 1:1 to either the proactive TDM arm or standard dosing arm and followed up for 54 weeks. Patients in the proactive TDM arm will have infliximab dosing optimised to target higher TLIs. The targets will be TLI ≥ 25 µg/mL at week 2, ≥ 20 µg/mL at week 6 and ≥ 10 µg/mL during maintenance therapy. The primary objective will be fistula healing at week 32. Secondary objectives will include fistula healing, fistula closure, radiological fistula healing, patient-reported outcomes and economic costs up to 54 weeks. Patients in the standard dosing arm will receive conventional infliximab dosing not guided by TLIs (5 mg/kg at weeks 0, 2 and 6, and 5 mg/kg 8 weekly thereafter). Patients aged 18–80 years with pfCD with single or multiple externally draining complex perianal fistulas who are relatively naïve to infliximab treatment will be included. Patients with diverting ileostomies or colostomies and pregnant or breast feeding will be excluded. Fifty-eight patients per arm will be required to detect a 25% difference in the primary outcome measure, with 138 patients needed to account for an estimated 6.1% primary non-response rate and 10% dropout rate.Ethics and disseminationResults will be presented in peer-reviewed journals and international conferences. Ethics approval has been granted by the South Western Sydney Local Health District Human Research Ethics Committee in Australia.Trial registration numberAustralian New Zealand Clinical Trials Registry (ACTRN12621000023853); Pre-results.

Background Medical therapies that suppress various pathways involved in inflammation comprise the mainstay of inflammatory bowel disease (IBD) treatment. Adverse events, including the development of serious infection and malignancy, have been associated with these therapies. This study evaluates the current evidence regarding serious adverse events associated with immunosuppressive agents in the IBD patient population. Methods A systematic search was conducted in September 2019 by combining three key research themes: inflammatory bowel disease, immunosuppression, and adverse events. For this systematic review, adverse events are defined as either the development or recurrence of malignancy or the development of serious infection necessitating hospital admission. Results There is a demonstrated association between thiopurine use and increased risk of both nonmelanoma skin cancer (NMSC) or lymphoma. The length of thiopurine exposure required to increase NMSC risk is, however, unclear. Of the papers reporting on exposure length and NMSC risk, the thiopurine exposure duration required to result in a statistically significant increase in NMSC risk varied from 6 months to 5 years. Among the studies retrieved, there is a lack of consensus on malignancy risk associated with the use of anti-TNF agents. From 5 studies on malignancy risk associated with the use of anti-TNF agents, one concluded that malignancy risk is increased while three concluded that risk is unchanged from baseline. The fifth study is inconclusive on any possible association. Confounding by past or concurrent thiopurine exposure remains an issue. There is a clear association between combination therapy with both thiopurines and anti-TNF agents and increased malignancy risk when compared with exposure to either thiopurine or anti-TNF therapy alone. Anti-integrin agents were not found to be associated with an increase in adverse effects when compared with placebo, while nil studies on ustekinumab were retrieved. Individual studies on infection risk do not consistently stratify infections according to severity, limiting any analysis. Conclusion An established association between thiopurine use and increased risk of both lymphoma or NMSC exists. However, the duration of thiopurine exposure necessary to increase NMSC risk is uncertain. There is a lack of consensus on whether anti-TNF agents increase malignancy risk due to confounding from past or concurrent thiopurine exposure. Combination therapy increases malignancy risk when compared with exposure to either thiopurine or anti-TNF therapy alone. Limited studies on the newer biologic therapies were retrieved. Finally, evidence which stratifies infections according to severity is lacking.

Background Maintenance anti-tumour necrosis factor-α (anti-TNFα) treatment for Crohn's disease is the standard of care for patients with an inadequate response to corticosteroids and immunomodulators. Aim To compare the efficacy and safety of infliximab and adalimumab in clinical practice and assess the value of concomitant immunomodulator therapy. Methods We performed an observational cohort study in consecutive patients with Crohn's disease qualifying for anti-TNFα treatment in Australia and New Zealand between 2007 and 2011. Demographic and clinical data were prospectively recorded to identify independent factors associated with induction and maintenance of response to infliximab or adalimumab, or to either anti-TNFα therapy. Results Three hundred and twenty-seven patients (183 infliximab, 144 adalimumab) successfully applied for treatment. Eighty-nine percent responded in all groups and median maintenance of response was similar for the two agents. Concomitant immunomodulator with infliximab, but not adalimumab, demonstrated a significantly longer response overall (P = 0.002), and significantly fewer disease and treatment-related complications (P = 0.017). Corticosteroids at baseline, and/or in the preceding 12 months, were associated with a 9–13 times greater risk of disease flare during maintenance treatment as compared to no corticosteroids (P < 0.0001). Maintenance of response was similar in the anti-TNF naive and anti-TNF experienced subgroups. Conclusions In this large, real-life study, we demonstrate infliximab and adalimumab to have similar response characteristics. However, infliximab requires concomitant immunomodulator to achieve optimal maintenance of response comparable to adalimumab monotherapy. The results of this study will assist clinicians in further optimising patient care in their day-to-day clinical practice.

Patients with inflammatory bowel disease [IBD] increasingly use alternative and complementary therapies, for which appropriate evidence is often lacking. It is estimated that up to half of all patients with IBD use various forms of complementary and alternative medicine during some point in their disease course. Considering the frequent use of such therapies, it is crucial that physicians and patients are informed about their efficacy and safety in order to provide guidance and evidence-based advice. Additionally, increasing evidence suggests that some psychotherapies and mind–body interventions may be beneficial in the management of IBD, but their best use remains a matter of research. Herein, we provide a comprehensive review of some of the most commonly used complementary, alternative and psychotherapy interventions in IBD.

Background & Aims: Little is known about the effects of endoscopic balloon dilation (EBD) for strictures of the upper gastrointestinal (UGI) tract in patients with Crohn's disease (CD). We performed a pooled analysis of the efficacy and safety of EBD for UGI CD-associated strictures. Methods: We searched Embase, Medline, and the Cochrane library, as well as bibliographies of relevant articles, for cohort studies of adults with CD and strictures of the stomach or duodenum (up to the ligament of Treitz) who underwent EBD through December 2016. We obtained data from 7 international referral centers on 94 patients who underwent 141 EBDs. We performed a patient-level meta-analysis of data from published and unpublished cohort studies to determine mechanical and clinical success. We performed a time-to-event analysis to assess symptom recurrence and need for redilation or surgery. The patients analyzed had strictures of the duodenum (n = 107), stomach (n = 30), or spanning both (n = 4). Results: The rate of technical success for EBD was 100%, with 87% short-term clinical efficacy; major complications arose from 2.9% of all procedures. During a median follow-up period of 23.1 months, 70.5% of patients had a recurrence of symptoms, 59.6% required redilation, and 30.8% required surgical intervention. Patients whose disease was located in the small bowel had a higher risk for symptom recurrence (hazard ratio [HR], 2.1; P = .003). Asian race (HR, 2.8; P < .001) and location of disease in the small bowel (HR, 1.9; P = .004) increased the need for redilation. Prestenotic dilation was a risk factor for needing surgery earlier (HR, 1.9; P = .001). Conclusions: In a meta-analysis, we found EBD for CD-associated strictures of the UGI to be an effective alternative to surgery, with a high rate of short-term technical and clinical success, moderate long-term efficacy, and an acceptable rate of complications.

A group of stakeholders met, under the aegis of the British Society of Gastroenterology, to discuss the current landscape of faecal microbiota transplantation (FMT) within the UK and beyond. The meeting covered a wide range of topics, ranging from the practical aspects of establishing an FMT service and regulatory issues relating to its delivery, to research implications and likely future directions. Case report and case series data supportive of the efficacy of FMT as treatment for recurrent/refractory Clostridium difficile infection (CDI) have slowly accumulated over many decades, but randomised trial data supporting its use for this indication were lacking until as recently as 2013.1 There are now a growing number of randomised studies/trials that have consistently demonstrated the much greater efficacy of FMT than that of vancomycin in inducing remission from recurrent/refractory CDI; success from a single FMT is quoted at ≥80%, and for two FMTs as ≥90%.1 FMT appears to be similarly as efficacious for this indication regardless of whether the transplant is delivered via the upper gastrointestinal (GI)1 or lower GI tract.2 ,3 Based on this clinical evidence (along with data supporting the cost effectiveness of FMT in comparison with other treatment strategies),4 FMT has now been accepted as an appropriate treatment option for recurrent/refractory CDI by the National Institute for Health and Care Excellence,5 Public Health England6 and European guidelines.7 There is increasing recognition that a distinctive pattern of alteration of the structure of the gut microbiota (or ‘dysbiosis’) appears to characterise a number of conditions, including inflammatory bowel disease and metabolic syndrome. Although it remains largely unclear as to whether these microbiota changes are a cause of these conditions, consequence or incidental, there is much interest as to whether manipulation of the gut microbiota might be a …

Background The inflammatory bowel disease (IBD) Disk is a tool that has been developed from the IBD Disability Index in order to objectively measure the degree of disability in patients suffering from IBD. It provides a visual representation of disability state, thereby increasing the ease of application in a clinical setting. Currently, it has not yet been validated in any population. Our primary aim was to hence validate the IBD Disk in a clinical setting. Methods 40 patients were recruited from an outpatient setting in a tertiary centre in Australia. All patients completed four surveys, the IBD Disk, the IBD Disability Index (IBD-DI), the Hospital Anxiety and Depression Score (HADS) and the Shortened IBD Questionnaire (SIBDQ). Nineteen of these patients then elaborated on their answers in a semi-structured narrative interview based on the IBD Disk. After a consultation with a gastroenterologist, the treating doctors were also asked to fill out an IBD Disk based on their own perceptions of the participant’s degree of disability. The IBD Disk was assessed for its internal consistency, construct validity and factor structure. The qualitative data were analysed and coded using NVIVO and then associated to IBD Disk scores. Results Of the patients recruited 48% were female, 30% had ulcerative colitis and 52% were in clinical remission. Average IBD Disk score was 40.75. Our results suggest the IBD Disk is an internally consistent tool for clinical use when assessing disability (Cronbach’s Α = 0.888). This is supported by statistically significant differences in IBD Disk scores between patients in clinical remission and patients with active disease (p = 0.002). There is also a good correlation between the Patient-Reported IBD Disk scores and the IBD-DI scores (r = 0.864), Doctor Perceived IBD Disk scores (r = 0.794) and the HADS Depression score (r = 0.759). IBD Disk scores also negatively correlated with the Shortened IBD Questionnaire (r = −0.864). Qualitative data also correlate well thematically with IBD Disk scores. These results suggest an appropriate system for grading disability status via the IBD Disk is: 0–24 = no disability; 25–49 = mild disability; 50–74 = moderate disability; and, 75–100 = severe disability. Conclusion This study supports the use of the IBD Disk as a reliable and valid self-reporting tool in clinical situations. There is strong internal consistency, construct validity, factor structure and qualitative thematic association. However, more data are needed to further validate the IBD Disk. Most significantly though, the IBD Disk is likely to become a valuable tool for the practical assessment of disability in patients with IBD in the near future.

Background Perianal fistulas remain a debilitating and clinically challenging manifestation of Crohn’s disease (CD), given their prevalence and relative treatment resistance. Since the advent of biologic therapy, particularly the anti-TNFα agents infliximab and adalimumab, patient outcomes have improved. Serum trough levels have been associated with mucosal healing in luminal CD. However, the relationship between trough drug levels and healing of perianal fistulas remains less clear, with few studies assessing this cohort, and clinical healing typically defined as the primary endpoint. The aim of this study was to assess the relationship between radiological healing of perianal fistulising Crohn’s Disease (pfCD) on MRI, and serum trough drug levels, in patients treated with anti-TNFα therapy. Methods In this multi-centre, retrospective cross-sectional study, patients with pfCD who had trough levels measured within 6 months of a pelvic MRI were included. We collected patient demographics, infliximab and adalimumab trough levels, the presence or absence of anti-drug antibodies, concomitant steroid or antibiotic therapy, and Van Assche scores on MRI. The primary outcome, radiological response, was defined as a Van Assche score of 7 or less, while no response was defined as a score of greater than 7. Results A total of 99 patients were included (65 on infliximab, 34 on adalimumab). For patients receiving infliximab, the median drug levels for responders (n = 22) compared with non-responders (n = 43) were 5.5 mg/ml vs. 3.9 mg/ml respectively (p = 0.16). For patients receiving adalimumab, the median drug levels for responders (n = 14) compared with non-responders (n = 20) were 6.3 mg/ml vs. 3.1 mg/ml respectively (p = 0.09). On ROC curve analysis, the AUC for the association between radiological response and infliximab levels was 0.61, while for adalimumab it was 0.67. On quartile analysis, there appeared to be an increased response for increase in infliximab trough level quartile, with the exception of the highest quartile, however this association was not statistically significant (OR 1.36, 95% CI 0.85–2.16, p = 0.20). In comparison, the quartile analysis of adalimumab trough level and response demonstrated an exposure-response relationship (OR 2.24, 95% CI 1.11–4.52, p = 0.02). Conclusion Trough infliximab and adalimumab levels in patients who achieved radiological response were not significantly higher compared with those who did not, however quartiles analyses demonstrated trends toward an exposure-response relationship, in particular for adalimumab. The association between trough levels and radiological response could be further characterised with a larger, and ideally longitudinal, study.

Background The reasons why fistulas originate have been explained in idiopathic cases, with the cryptoglandular theory being widely accepted; however, in Crohn ́s disease, it is thought to involve interplay between microbiological, immunological and genetic factors. It remains unclear why fistulas persist. Novel investigative tools in systems biology are improving our understanding of pathogenesis, and one such tool is metabonomic profiling, whereby spectrometry is used to assess metabolic responses of complex systems in health and disease. These changes are mapped using analytical and statistical techniques. To the best our knowledge, these methodologies have not been applied to aid understanding of the pathogenesis of Crohn’s perianal fistula persistence. Methods Fistula tissue biopsy was obtained from the fistula tract of 30 patients with idiopathic perianal fistula and 20 patients with Crohn ́s anal fistula. Two analytical platforms were attempted to achieve broad metabolome coverage. Univariate (student t-test) and multivariate statistical data analyses were performed. From the latter principle component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA), models were built to find metabolites that could predict tissue samples from patients with either Crohn’s or idiopathic anal fistula. Metabolite putative identification was conducted by matching accurate mass:charge ratio (m/z) measurements of detected chromatographic features to theoretical value from in-house databases and on-line databases and previous publications. Results Significant OPLS-DA predictive models (validated with CV-ANOVA p-value Conclusion Forty-one differentiating metabolites were discovered belonging to various classes of lipids, amino acids and nucleotides. Pathways involved included amino acid metabolism, phospholipid metabolism and glycerolipid metabolism amongst others. Further work in larger numbers is required to validate these findings as well as cross correlation with microbiome work to understand the impact of host gut interactions in the pathophysiology of Crohn’s and idiopathic perianal fistulas.

Background: Restorative proctocolectomy with ileal pouch-anal anastomosis is considered the procedure of choice in patients with ulcerative colitis refractory to medical therapy. Subsequent inflammation of the pouch is a common complication and in some cases pouchitis fails to respond to antibiotics, the mainstay of treatment. In such cases, corticosteroids, immunomodulatory or biologic treatments are options. However, our understanding of the efficacy of anti-tumour necrosis factor medications in both chronic pouchitis and Crohn’s-like inflammation are based on studies that include relatively small numbers of patients. Methods: This was an observational, retrospective, multi-centre study to assess the long-term effectiveness and safety of infliximab for inflammatory disorders related to the ileoanal pouch. The primary outcome was the development of infliximab failure defined by early failure to infliximab or secondary loss of response to infliximab. Results: Thirty-four patients met the inclusion criteria; 18/34 (53%) who were initiated on infliximab for inflammatory disorders of the pouch had infliximab failure, 3/34 (8%) had early failure, and 15/34 (44%) had secondary loss of response with a median follow-up of 280 days (range 3-47 months). In total, 24/34 (71%) avoided an ileostomy by switching to other medical therapies at a median follow-up of follow-up of 366 days (1-130 months). Conclusions: Initial infliximab therapy for pouch inflammatory conditions is associated with Infliximab failure in just over half of all patients. Despite a high failure rate, an ileostomy can be avoided in almost three quarters of patients at four years by using other medical therapies.

Background Restorative proctocolectomy is considered the procedure of choice in patients with UC refractory to medical therapy. Inflammation of the pouch is a common complication and in some cases fails to respond to antibiotics, the mainstay of treatment. In such cases, corticosteroid, immunomodulatory or biologic treatments are an option. However, our understanding of the effectiveness of IFX for both chronic pouchitis and Crohn’s-like inflammation are based on small studies. Methods This was an observational, retrospective, multi-centre study to assess the effectiveness IFX for inflammatory disorders related to the pouch. The primary outcome was the development IFX failure defined by primary non-response or secondary loss of response to IFX. Results 38 patients were included. 20/38 (53%) who were initiated on IFX for inflammatory disorders of the pouch had IFX failure, 4/38 (11%) had primary non-response, and 16/38 (42%) had secondary loss of response with a median follow-up of 265 days (range 82–2119). Of those that had IFX failure 10/20 (50%) avoided an ileostomy by switching to an alternative biologic. In total, 28/38 (74%) avoided an ileostomy, of these, 17/38 (45%) continued on their IFX after a median follow-up of 311 days (42–3968), 5/38 (13%) were changed to Adalimumab after a median follow-up of 498 days (1–1544), 4/38 (11%) were changed to Vedolizumab after a median follow-up of 569 (251–1138), 1 achieved histological remission and stopped all treatments at 251 days and 1 was maintained on methotrexate and multiple antibiotics after 3968 days. Conclusions After initial IFX therapy over half will fail first line IFX, of those that fail half can avoid an ileostomy by switching to an alternative biologic. Patients should be counselled about a high incidence of failure and alternatives should be considered.

Introduction Restorative proctocolectomy is considered the procedure of choice in patients with UC refractory to medical therapy. Inflammation of the pouch is a common complication and in some cases fails to respond to antibiotics, the mainstay of treatment. In such cases, corticosteroid, immunomodulatory or biologic treatments are an option. However, our understanding of the effectiveness of IFX for both chronic pouchitis and Crohn’s-like inflammation are based on small studies. Methods This was an observational, retrospective, multi-centre study to assess the effectiveness IFX for inflammatory disorders related to the pouch. The primary outcome was the development IFX failure defined by primary non-response or secondary loss of response to IFX. Result 38 patients were included. 20/38 (53%) who were initiated on IFX for inflammatory disorders of the pouch had IFX failure, 4/38 (11%) had primary non-response and 16/38 (42%) had secondary loss of response with a median follow-up of 265 days (range 82–2119). Of those that had IFX failure 10/20 (50%) avoided an ileostomy by switching to an alternative biologic. In total, 28/38 (74%) avoided an ileostomy, of these, 17/38 (45%) continued on their IFX after a median follow-up of 311 days (42–3968), 5/38 (13%) were changed to Adalimumab after a median follow-up of 498 days (1–1544), 4/38 (11%) were changed to Vedolizumab after a median follow-up of 569 (251–1138), 1 achieved histological remission and stopped all treatments at 251 days and 1 was maintained on methotrexate and multiple antibiotics after 3968 days. Conclusions After initial IFX therapy over half will fail first line IFX, of those that fail half can avoid an ileostomy by switching to an alternative biologic. Patients should be counselled about a high incidence of failure and alternatives should be considered.

Background The 'United Registries for Clinical Assessment and Research' [UR-CARE] database is an initiative of the European Crohn's and Colitis Organisation [ECCO] to facilitate daily patient care and research studies in inflammatory bowel disease [IBD]. Herein, we sought to validate the database by using fictional case histories of patients with IBD that were to be entered by observers of varying experience in IBD. Methods Nineteen observers entered five patient case histories into the database. After 6 weeks, all observers entered the same case histories again. For each case history, 20 key variables were selected to calculate the accuracy for each observer. We assumed that the database was such that ≥ 90% of the entered data would be correct. The overall proportion of correctly entered data was calculated using a beta-binomial regression model to account for inter-observer variation and compared to the expected level of validity. Re-test reliability was assessed using McNemar's test. Results For all case histories, the overall proportion of correctly entered items and their confidence intervals included the target of 90% (Case 1: 92% [88-94%]; Case 2: 87% [83-91%]; Case 3: 93% [90-95%]; Case 4: 97% [94-99%]; Case 5: 91% [87-93%]). These numbers did not differ significantly from those found 6 weeks later [NcNemar's test p > 0.05]. Conclusion The UR-CARE database appears to be feasible, valid and reliable as a tool and easy to use regardless of prior user experience and level of clinical IBD experience. UR-CARE has the potential to enhance future European collaborations regarding clinical research in IBD.

SummaryBackground Nonresponse and loss of response to anti-TNF therapies in Crohn's disease represent significant clinical problems for which clear management guidelines are lacking. Aim To review the incidence, mechanisms and predictors of primary nonresponse and secondary loss of response to formulate practical clinical algorithms to guide management. Methods Through a systematic literature review, 503 articles were identified which fit the inclusion criteria. Results Primary nonresponse to anti-TNF treatment affects 13–40% of patients. Secondary loss of response to anti-TNF occurs in 23–46% of patients when determined according to dose intensification, and 5–13% of patients when gauged by drug discontinuation rates. Recent evidence suggests that the mechanisms underlying primary nonresponse and secondary loss of response are multifactorial and include disease characteristics (phenotype, location, severity); drug (pharmacokinetic, pharmacodynamic or immunogenicity) and treatment strategy (dosing regimen) related factors. Clinical algorithms that employ therapeutic drug monitoring (using anti-TNF tough levels and anti-drug antibody levels) may be used to determine the underlying cause of primary nonresponse and secondary loss of response respectively and guide clinicians as to which patients are most likely to respond to anti-TNF therapy and help optimise drug therapy for those who are losing response to anti-TNF therapy. Conclusions Nonresponse or loss of response to anti-TNF occurs commonly in Crohn's disease. Clinical algorithms utilising therapeutic drug monitoring may establish the mechanisms for treatment failure and help guide the subsequent therapeutic approach.

Background and Aim We have previously found high incidence of inflammatory bowel disease (IBD) in Australia. A population-based registry was established to assess disease severity, frequency of complications, and prognostic factors. Methods Incident cases were prospectively identified over 4 years. Early disease severity was assessed according to need for hospitalization and resective surgery and medication use. Results We report on the early outcomes (median 18 months, range 12–60 months) for 252 patients comprising 146 with Crohn's disease (CD), 96 with ulcerative colitis (UC), and 10 IBD undifferentiated. Eighty-seven percent of CD patients had inflammatory disease at diagnosis, and this reduced to 73% at 5 years (n = 38). Immunomodulators were prescribed in 57% of CD patients and 19% with UC. A third of all CD patients were hospitalized, the majority (77%) in the first 12 months. Risk factors for hospitalization included penetrating, perianal, and ileocolonic disease (P