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The cost of caring for patients with inflammatory bowel disease (IBD) continues to increase worldwide. The cause is not only a steady increase in the prevalence of Crohn's disease and ulcerative colitis in both developed and newly industrialised countries, but also the chronic nature of the diseases, the need for long-term, often expensive treatments, the use of more intensive disease monitoring strategies, and the effect of the diseases on economic productivity. This Commission draws together a wide range of expertise to discuss the current costs of IBD care, the drivers of increasing costs, and how to deliver affordable care for IBD in the future. The key conclusions are that (1) increases in health-care costs must be evaluated against improved disease management and reductions in indirect costs, and (2) that overarching systems for data interoperability, registries, and big data approaches must be established for continuous assessment of effectiveness, costs, and the cost-effectiveness of care. International collaborations should be sought out to evaluate novel models of care (eg, value-based health care, including integrated health care, and participatory health-care models), as well as to improve the education and training of clinicians, patients, and policy makers.

Introduction Crohn’s disease recurs after intestinal resection. This study evaluated accuracy of a new blood test, the Endoscopic Healing Index [EHI], in monitoring for disease recurrence. Methods Patients enrolled in the prospective POCER study [NCT00989560] underwent a postoperative colonoscopic assessment at 6 [2/3 of patients] and 18 months [all patients] following bowel resection, using the Rutgeerts score [recurrence ≥i2]. Serum was assessed at multiple time points for markers of endoscopic healing using the EHI, and paired with the Rutgeerts endoscopic score as the reference standard. Results A total of 131 patients provided 437 serum samples, which were paired with endoscopic assessments available in 94 patients [30 with recurrence] at 6 months and 107 patients [44 with recurrence] at 18 months. The median EHI at 6 months was significantly lower in patients in remission [Rutgeerts Conclusions The non-invasive multi-marker EHI has sufficient accuracy to be used to monitor for postoperative Crohn’s disease recurrence. A monitoring strategy that combines EHI with ileocolonoscopy, with or without faecal calprotectin, should now be prospectively tested.

Background: The combination of infliximab and immunosuppressant therapy is a standard management strategy for patients with Crohn's disease. Concerns regarding the implications of long-term combination therapy provided the rationale for a formal clinical trial of treatment de-escalation. Our aim was to compare the relapse rate and the time spent in remission over 2 years between patients continuing combination therapy and those stopping infliximab or immunosuppressant therapy. Methods: This multicentre, open-label, randomised controlled trial was performed in 64 hospitals in seven countries in Europe and Australia. Adult patients with Crohn's disease in steroid-free clinical remission for more than 6 months, on combination therapy of infliximab and immunosuppressant therapy for at least 8 months were randomly assigned (1:1:1) to either continue combination therapy (combination group), discontinue infliximab (infliximab withdrawal group), or discontinue immunosuppressant therapy (immunosuppressant withdrawal group). Randomisation was stratified according to disease duration before start of first anti-TNF treatment (≤2 or >2 years), failure of immunosuppressant therapy before start of infliximab, and presence of ulcers at baseline endoscopy. The patient number and group of each stratum were assigned by a central online randomisation website. Treatment was optimised or resumed in case of relapse in all groups. Participants, those assessing outcomes, and those analysing the data were not masked to group assignment. The coprimary endpoints were the relapse rate (superiority analysis) and time in remission over 2 years (non-inferiority analysis, non-inferiority margin 35 days). Analyses were done on an intention-to-treat basis. This study is registered with ClinicalTrials.gov, NCT02177071, and with EU Clinical Trials Register, EUDRACT 2014-002311-41. The trial was completed in April, 2021. Findings: Between Nov 2, 2015, and April 24, 2019, 254 patients were screened. Of these, 211 were randomised and 207 were included in the final analysis (n=67 in the combination group, n=71 in the infliximab withdrawal group, and n=69 in the immunosuppressant withdrawal group). 39 patients had a relapse (eight [12%] of 67 in the combination group, 25 [35%] of 71 in the infliximab withdrawal group, six [9%] of 69 in the immunosuppressant withdrawal group). 2-year relapse rates were 14% (95% CI 4–23) in the combination group, 36% (24–47) in the infliximab withdrawal group, and 10% (2–18) in the immunosuppressant withdrawal group (hazard ratio [HR] 3·45 [95% CI 1·56–7·69], p=0·003, for infliximab withdrawal vs combination, and 4·76 [1·92–11·11], p=0·0004, for infliximab withdrawal vs immunosuppressant withdrawal). Of 28 patients who had a relapse and were retreated or optimised according to protocol, remission was achieved in 25 patients (one of two in the combination group, 22 of 23 in the infliximab withdrawal group, and two of three in the immunosuppressant withdrawal group). The mean time spent in remission over 2 years was 698 days (95% CI 668–727) in the combination group, 684 days (651–717) in the infliximab withdrawal group, and 706 days (682–730) in the immunosuppressant withdrawal group. The difference in restricted mean survival time in remission was –14 days (95% CI –56 to 27) between the infliximab withdrawal group and the combination group and –22 days (–62 to 16) between the infliximab withdrawal group and the immunosuppressant withdrawal group. The 95% CIs contained the non-inferiority threshold (–35 days). We recorded 31 serious adverse events, in 20 patients, with no difference in frequency between groups. The most frequent serious adverse events were infections (four in the combination group, two in the infliximab withdrawal group, and one in the immunosuppressant withdrawal group) and Crohn's disease exacerbation (three in the combination group, four in the infliximab withdrawal group, and one in the immunosuppressant withdrawal group). No death nor malignancy was recorded. Interpretation: In patients with Crohn's disease in sustained steroid-free remission under combination therapy with infliximab and immunosuppressant therapy, withdrawal of infliximab should only be considered after careful assessment of risks and benefits for each patient, whereas withdrawal of immunosuppressant therapy could generally represent a preferable strategy when considering treatment de-escalation. Funding: European Union's Horizon 2020.

Background and Aims Currently used endoscopic items for the assessment of pouchitis and cuffitis have deficiencies in reliability and validation. We assessed the reliability and accuracy of new endoscopic items for pouchitis and of the Ulcerative Colitis Endoscopic Index of Severity [UCEIS] for cuffitis. Methods Three new endoscopic items were assessed and included in the Monash pouchitis endoscopic subscore: bleeding [absent/contact/spontaneous]; erosions [absent/ Results All three Monash endoscopic items had substantial intra-rater reliability with intraclass correlation coefficients [ICCs] >0.61 [95% CI >0.61], compared with only ulcers from the currently used PDAI endoscopic subscore, but inter-rater reliability was only substantial for ulceration and no better than those of the currently used endoscopic items. The Monash endoscopic subscore had a strong positive correlation with the reference standard global endoscopic lesion severity r = 0.80 [95% CI 0.80-0.80] and the reference standard PDAI endoscopic subscore r = 0.70 [95% CI 0.67–0.73], which was higher than the correlation observed for the currently used PDAI endoscopic subscore. The UCEIS had substantial intra-rater reliability, but only fair inter-rater reliability and poor diagnostic performance for cuffitis. Conclusions The Monash endoscopic items, and endoscopic subscore they generate, have enhanced overall performance compared with the currently used PDAI items and subscore. Further validation and responsiveness to change in disease state are indicated.

Background The presence and severity of endoscopic recurrence after Crohn's disease intestinal resection predicts subsequent disease course. The Rutgeerts postoperative endoscopic recurrence score is unvalidated but has proven prognostically useful in many clinical studies. This study aimed to investigate the association between specific early endoscopic findings and subsequent disease course. Methods In the setting of a randomized controlled trial (the POCER study), 85 patients underwent colonoscopy at 6 and 18 months after intestinal resection. Patients received 3 months of metronidazole, and high-risk patients received a thiopurine (or adalimumab if they were thiopurine intolerant). For endoscopic recurrence (Rutgeerts score ≥i2) at 6 months, patients stepped up to a thiopurine, fortnightly adalimumab with thiopurine, or weekly adalimumab. Central readers confirmed Rutgeerts, Simple Endoscopic Score for Crohn’s Disease, Crohn’s Disease Endoscopic Index of Severity scores, and 5 newly tested endoscopic parameters: anastomotic ulcer depth (superficial vs deep), number of ulcers (0, ≤2, >2), ulcer size (1-5 mm, ≥6 mm), circumferential extent of ulceration ( Results Of the 5 parameters, the combination of ulcer depth and circumference at the anastomosis at 6 months was associated with endoscopic recurrence at 18 months (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.03-2.50; P = 0.035) with an area under the receiver operating characteristic curve of 0.62 (95% CI, 0.5-0.75). The combination of these 2 parameters formed the basis of the POCER index (range, 0-4 with 0 denoting no ulcers and 4 denoting deep ulceration with >25% circumferential involvement). The new index had a strong correlation with the Rutgeerts score measured at the same time points: Spearmans’ r = .80 at 6 months and r = .77 at 18 months (P Conclusions The POCER postoperative index comprises 2 key endoscopic factors related to the anastomosis that are associated with subsequent disease progression. A higher score, comprising the adverse prognostic factors of deep or circumferentially extensive anastomotic ulceration, may help identify patients who require more intensive therapy.

Background There is considerable interest in improving the education and care of women with inflammatory bowel disease (IBD) to improve pregnancy outcomes. Despite increased awareness, not all women with IBD have access to pregnancy-related education and the quality of counseling is variable. We aimed to assess the effectiveness of a simple educational intervention for improving pregnancy-related knowledge and to evaluate the effect of education on patient outcomes including anxiety, depression, and quality of life in women with IBD. Methods This prospective study of women with IBD who were pregnant or planning a pregnancy evaluated the effectiveness of a single gastroenterologist-led educational intervention in improving pregnancy-related knowledge, measured using the Crohn’s and Colitis Pregnancy Knowledge score 1 month postintervention. Secondary outcomes included the effect on anxiety and depression, quality of life, medication adherence, and patient satisfaction. Results One hundred women with IBD were recruited. Fifty percent were pregnant at the time of the intervention. Baseline knowledge scores were similar independent of the patients’ pregnancy status or whether they had previously received counseling from their gastroenterologist. Median Crohn’s and Colitis Pregnancy Knowledge scores postintervention (n = 82) were higher than preintervention scores (14/17 vs 10/17; P < 0.001). In addition, 32% of patients had poor knowledge at baseline (score ≤7/17), compared to only 5% after the intervention (P < 0.001). There was a significant improvement in total anxiety and depression and quality of life scores postintervention. Medication adherence and patient satisfaction were excellent. Conclusions Uptake of this gastroenterologist-led educational intervention has the potential to improve pregnancy knowledge, promote medication adherence, and enhance quality of life for women with IBD globally.

BACKGROUND Vedolizumab (VDZ), a humanised monoclonal antibody that selectively inhibits alpha4-beta7 integrins is approved for use in adult moderate to severe ulcerative colitis (UC) patients. AIM To assess the efficacy and safety of VDZ in the real-world management of UC in a large multicenter cohort involving two countries and to identify predictors of achieving remission. METHODS A retrospective review of Australian and Oxford, United Kingdom data for UC patients. Clinical response at 3 mo, endoscopic remission at 6 mo and clinical remission at 3, 6 and 12 mo were assessed. Cox regression models and Kaplan Meier curves were performed to assess the time to remission, time to failure and the covariates influencing them. Safety outcomes were recorded. RESULTS Three hundred and three UC patients from 14 centres in Australia and United Kingdom, [60% n = 182, anti-TNF naïve] were included. The clinical response was 79% at 3 mo with more Australian patients achieving clinical response compared to Oxford (83% vs 70% P = 0.01). Clinical remission for all patients was 56%, 62% and 60% at 3, 6 and 12 mo respectively. Anti-TNF naive patients were more likely to achieve remission than exposed patients at all the time points (3 mo 66% vs 40% P < 0.001, 6 mo 73% vs 46% P < 0.001, 12 mo 66% vs 51% P = 0.03). More Australian patients achieved endoscopic remission at 6 mo compared to Oxford (69% vs 43% P = 0.01). On multi-variate analysis, anti-TNF naïve patients were 1.8 (95%CI: 1.3-2.3) times more likely to achieve remission than anti-TNF exposed (P < 0.001). 32 patients (11%) had colectomy by 12 mo. CONCLUSION VDZ was safe and effective with 60% of UC patients achieving clinical remission at 12 mo and prior anti-TNF exposure influenced this outcome.

BACKGROUND: Microbial factors are likely to be involved in the recurrence of Crohn’s disease (CD) after bowel resection. We investigated the luminal microbiota before and longitudinally after surgery, in relation to disease recurrence, using 16S metagenomic techniques. METHODS: In the prospective Post-Operative Crohn’s Endoscopic Recurrence (POCER) study, fecal samples were obtained before surgery and 6, 12, and 18 months after surgery from 130 CD patients. Endoscopy was undertaken to detect disease recurrence, defined as Rutgeerts score ≥i2, at 6 months in two-thirds of patients and all patients at 18 months after surgery. The V2 region of the 16S rRNA gene was sequenced using Illumina MiSeq. Cluster analysis was performed at family level, assessing microbiome community differences between patients with and without recurrence. RESULTS: Six microbial cluster groups were identified. The cluster associated with maintenance of remission was enriched for the Lachnospiraceae family [adjusted OR 0.47 (0.27–0.82), P = .007]. The OTU diversity of Lachnospiraceae within this cluster was significantly greater than in all other clusters. The cluster enriched for Enterobacteriaceae was associated with an increased risk of disease recurrence [adjusted OR 6.35 (1.24–32.44), P = .026]. OTU diversity of Enterobacteriaceae within this cluster was significantly greater than in other clusters. CONCLUSIONS: Luminal bacterial communities are associated with protection from, and the occurrence of, Crohn’s disease recurrence after surgery. Recurrence may relate to a higher abundance of facultatively anaerobic pathobionts from the Enterobacteriaceae family. The ecologic change of depleted Lachnospiraceae, a genus of butyrate-producing bacteria, may permit expansion of Enterobacteriaceae through luminal environmental perturbation.

BACKGROUND Virtual clinics represent a novel model of care in inflammatory bowel disease. Their effectiveness in promoting high quality use of biologic therapy and facilitating a treat-to-target approach is unknown. AIM To evaluate clinical and process-driven outcomes in a virtual clinic compared to standard outpatient care amongst patients receiving intensified anti-TNF therapy for secondary loss of response. METHODS We performed a retrospective multi-centre, parallel, observational cohort study of Crohn's disease patients receiving intensified anti-TNF therapy for secondary loss of response. Objective assessments of disease activity and anti-TNF trough levels at secondary loss of response and during subsequent 6-month semesters, were compared longitudinally between virtual clinic and standard outpatient care cohorts. The primary endpoint was treatment success, with appropriateness of dose intensification, tight disease monitoring and treatment de-escalation representing secondary outcomes. RESULTS Of 149 patients with similar baseline characteristics, 69 were managed via a virtual clinic and 80 via standard outpatient care. There were higher rates of treatment success in the virtual clinic cohort (60.9 vs 35.0%, P

Background The modified Rutgeerts’ score [RS] differentiates i2a—lesions confined to the anastomosis—and i2b—more than five aphthous ulcers in the neoterminal ileum with normal intervening mucosa, with or without anastomotic lesions—categories. Its relevance for the therapeutic management of Crohn’s disease [CD] patients after ileocolic resection is still debated. Our objective was to compare the postoperative recurrence risk in patients with an i2a or i2b score, using an individual patient data meta-analysis. Methods We conducted a systematic literature search until July 2020, to identify all relevant studies reporting the i2a/i2b status in the year following ileocolic resection and clinical and/or surgical postoperative CD recurrence in their follow-up. Individual patient-level data were obtained from the corresponding authors. The association between the modified RS and time-to-event was evaluated using a mixed Cox model with the centre as the random effect. Results Seven studies published between 2008 and 2019 were included, corresponding to 400 patients: 189 [47%] i2a and 211 [53%] i2b. Median [interquartile range, IQR] time from ileocolic resection to ileocolonoscopy was 6.2 [5.5, 7.9] months and median [IQR] follow-up time after ileocolonoscopy was 4.5 [2.9, 7.3] years. The risk of clinical postoperative recurrence at 1 and 3 years was 11% [6–15%], and 25% [18–32%] in the i2a group versus 9% [5–13%] and 33% [26–41%] in the i2b group [p = 0.63 and p = 0.12, respectively]. No significant difference was observed in terms of time to clinical postoperative recurrence [p = 0.16] or surgical postoperative recurrence [p = 0.87]. Results did not change after excluding patients having initiated an immunosuppressant or a biologic in the 3 months after endoscopy [remaining cohort, n = 361]. Conclusions In this individual patient data meta-analysis, no difference was observed between i2a and i2b subcategories with regards to clinical or surgical postoperative recurrence. As we wait for prospective trials, the same treatment strategy could be applied to all patients classified as i2 on the Rutgeerts score.

Background The lack of standardized methods for clinical trial design and disease activity assessment has contributed to an absence of approved medical therapies for the prevention of postoperative Crohn’s disease (CD). We developed recommendations for regulatory trial design for this indication and for endoscopic assessment of postoperative CD activity. Methods An international panel of 19 gastroenterologists was assembled. Modified Research and Development/University of California Los Angeles methodology was used to rate the appropriateness of 196 statements using a 9-point Likert scale in 2 rounds of voting. Results were reviewed and discussed between rounds. Results Inclusion of patients with a history of completely resected ileocolonic CD in regulatory clinical trials for the prevention of postoperative recurrence was appropriate. Given the absence of approved medical therapies, a placebo-controlled design with a primary end point of endoscopic remission at 52 weeks was appropriate for drug development for this indication; however, there was uncertainty regarding the appropriateness of a coprimary end point of symptomatic and endoscopic remission and the use of currently available patient-reported outcome measures. The modified Rutgeerts Score, endoscopic assessment of the anastomosis, and a minimum of 5cm of neoterminal ileum were also appropriate; although the appropriateness of other indices including the Simple Endoscopic Score for CD for endoscopic assessment of postoperative CD activity was uncertain. Conclusions A framework for regulatory trial design for the prevention of postoperative CD recurrence and endoscopic assessment of disease activity has been developed. Research to empirically validate end points for these trials is needed.

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.

Background and Aims In symptomatic patients with ileoanal pouches, pouchoscopy is needed for accurate diagnosis but is invasive. We aimed to assess the utility of non-invasive gastrointestinal ultrasound and faecal calprotectin in ileoanal pouch patients. Methods Patients with an ileoanal pouch were consecutively enrolled in this cross-sectional study from clinics in Victoria, Australia. The pouchitis disease activity index was used as a reference standard. Video-recorded pouchoscopies were reviewed by three gastroenterologists. Pouch, pre-pouch, and cuff biopsies were reviewed by a single pathologist. Ultrasound was performed by a single gastroenterologist transabdominally and transperineally. Faecal calprotectin was measured from morning stool samples. All examiners were blinded to patients’ clinical history. Results A total of 44 participants had a pouchoscopy, of whom 43 had a faecal calprotectin test and 42 had an ultrasound; 17 had pouchitis, 15 had pre-pouch ileitis, and 16 had cuffitis. Pouch wall thickness of Conclusions Faecal calprotectin and ultrasound are accurate and complementary tests to diagnose and localise inflammation of the ileoanal pouch. Prospective studies are needed to validate proposed sonographic indices and calprotectin levels.

Background and Aims Preliminary data regarding the effectiveness of tofacitinib in acute severe ulcerative colitis [ASUC] have been presented in two previous case series. We aimed to describe the novel use of high-dose tofacitinib immediately following non-response to infliximab in the setting of steroid-refractory ASUC. Methods Five patients who received high-dose tofacitinib 10 mg three times a day immediately following non-response to infliximab for steroid-refractory ASUC were identified at an Australian tertiary inflammatory bowel disease centre. Results Four of the five patients demonstrated clinical response to high-dose tofacitinib induction during their inpatient admission, with one patient requiring colectomy owing to a lack of clinical response. At 90 days, all four initial responders remained colectomy-free, with two patients achieving combined clinical and endoscopic remission. No adverse events directly attributable to high-dose tofacitinib were identified. Conclusions High-dose tofacitinib may have a role as salvage therapy in the setting of steroid-refractory ASUC. Prospective studies are required to determine the safety and efficacy of high-dose tofacitinib to determine whether it can be routinely recommended as primary or sequential salvage therapy in the setting of steroid-refractory ASUC.

Background and aim Chronic intestinal failure requiring home parenteral nutrition (HPN) is a disabling condition that is best facilitated by a multidisciplinary approach to care. Variation in care has been identified as a key barrier to achieving quality of care for patients on HPN and requires appropriate strategies to help standardize management. Method The Australasian Society for Parenteral and Enteral Nutrition (AuSPEN) assembled a multidisciplinary working group of 15 clinicians to develop a quality framework to assist with the standardization of HPN care in Australia. Obstacles to quality care specific to Australia were identified by consensus. Drafts of the framework documents were based on the available literature and refined by two Delphi rounds with the clinician work group, followed by a further two involving HPN consumers. The Oxford Centre for Evidence-Based Medicine Levels of Evidence was used to assess the strength of evidence underpinning each concept within the framework documents. Results Quality indicators, standards of care, and position statements have been developed to progress the delivery of quality care to HPN patients. Conclusion The quality framework proposed by AuSPEN is intended to provide a practical structure for clinical and organizational aspects of HPN service delivery to reduce variation in care and improve quality of care and represents the initial step towards development of a national model of care for HPN patients in Australia. While developed for implementation in Australia, the evidence-based framework also has relevance to the international HPN community.

Current recommendations concerning hepatitis C virus (HBV) reactivation are limited, with nearly all guidelines focused on its occurrence in patients with hematological malignancies or some solid tumors, who are treated with immunosuppressive therapies. Few of the guidelines address reactivation in patients receiving immunosuppression with organ transplants or treatment with any of the many immunosuppressive agents in use today for the treatment of multiple different diseases, or in patients receiving the direct-acting antivirals used in the treatment of hepatitis C virus (HCV). This article covers the immunology of HBV reactivation, mechanisms of viral clearance, and recommendations for screening and prophylaxis.

Background Decision support tools may facilitate shared decision-making and improve quality of care. Aim To assess the effectiveness of a decision support tool on improving quality of care in ulcerative colitis. Methods A prospective quality of care intervention was conducted at two Australian hospitals comparing out-patient-based ulcerative colitis care with, and without, a tablet-based decision support tool. This included questions on disease activity management; psychological well-being; and preventive care, with 13 process indicators relevant to each domain. Participants included adult out-patients with mild-to-moderate ulcerative colitis and their clinicians who were divided into two cohorts. The first cohort were followed up immediately after their clinical review to check whether their clinician had discussed the 13 process indicators during the consultation. The second cohort of patients used the decision support tool immediately prior to their consultation which then generated a suggested management plan for the patient and clinician to discuss during the consultation. Management between the 2 cohorts was compared to assess the effectiveness of the decision support tool in improving the primary outcome, defined as the proportion of quality process indicators used for ulcerative colitis care, with and without the decision support tool. Results Thirteen physicians and 100 patients participated. Fifty patients were managed without the decision support tool using standard care (median age 40; 44% male), and 50 patients used the decision support tool (median age 40; 46% male) over a 20-week period. Increase in the median use of process indicators overall was observed following use of the decision support tool (27% vs 100%; P < 0.001). Improvements were seen in psychological well-being management (30% vs 100%; P < 0.001), preventive care (16% vs 100%; P < 0.001) and process indicators related to disease activity management (50% vs 100%; P < 0.001). The decision support tool was found to be usable and acceptable. Shared decision-making was greater in the post-intervention group (mean decision conflict score of 18.0 vs 33.5; P = 0.002). Conclusions The decision support tool substantially improved the quality of the delivery of care. Decision support tools have the potential to minimise errors of omission via a standardised approach to care.

BackgroundInfliximab is an effective salvage therapy in acute severe ulcerative colitis; however, the optimal dosing strategy is unknown. We performed a systematic review and meta-analysis to examine the impact of infliximab dosage and intensification on colectomy-free survival in acute severe ulcerative colitis.MethodsStudies reporting outcomes of hospitalized steroid-refractory acute severe ulcerative colitis treated with infliximab salvage were identified. Infliximab use was categorized by dose, dose number, and schedule. The primary outcome was colectomy-free survival at 3 months. Pooled proportions and odds ratios with 95% confidence intervals were reported.ResultsForty-one cohorts (n = 2158 cases) were included. Overall colectomy-free survival with infliximab salvage was 79.7% (95% confidence interval [CI], 75.48% to 83.6%) at 3 months and 69.8% (95% CI, 65.7% to 73.7%) at 12 months. Colectomy-free survival at 3 months was superior with 5-mg/kg multiple (≥2) doses compared with single-dose induction (odds ratio [OR], 4.24; 95% CI, 2.44 to 7.36; P < 0.001). However, dose intensification with either high-dose or accelerated strategies was not significantly different to 5-mg/kg standard induction at 3 months (OR, 0.70; 95% CI, 0.39 to 1.27; P = 0.24) despite being utilized in patients with a significantly higher mean C-reactive protein and lower albumin levels.ConclusionsIn acute severe ulcerative colitis, multiple 5-mg/kg infliximab doses are superior to single-dose salvage. Dose-intensified induction outcomes were not significantly different compared to standard induction and were more often used in patients with increased disease severity, which may have confounded the results. This meta-analysis highlights the marked variability in the management of infliximab salvage therapy and the need for further studies to determine the optimal dose strategy.

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.

Azathioprine and mercaptopurine are considered safe during pregnancy. However, the pharmacokinetic effects of pregnancy on thiopurine metabolism are undefined.To characterise thiopurine metabolism in pregnancy and measure infant metabolite levels and outcomes.Women with IBD who were taking a thiopurine and pregnant or trying to conceive were recruited. Maternal thiopurine metabolites were measured pre-conception, in each trimester, at delivery and post-partum. Infant metabolite levels, full blood examination and liver function testing were performed at birth, and repeated until levels undetectable and haematological and biochemical abnormalities resolved.Forty patients were included with measurements on at least two occasions, and two with only mother-baby levels at delivery. The median maternal 6-TGN level dropped in the second trimester compared with post-partum (179.0 vs 323.5 pmol/8 × 106-TGN levels decrease and 6-MMP levels increase in the second trimester of pregnancy. Infants are exposed to thiopurine metabolites at low levels with clearance by 6 weeks and no anaemia. The cause of infant thrombocytosis and abnormal liver biochemistry in the absence of metabolites is unclear.

Background: The impact of pregnancy on levels of biologic agents in patients with IBD is undefined and time to elimination in vedolizumab-exposed infants is unknown. Aims: To determine the effect of pregnancy on infliximab, adalimumab and vedolizumab levels and to study infant vedolizumab clearance. Methods: In a prospective observational study, maternal drug levels were measured pre-conception, in each trimester, at delivery and postpartum. The association between drug levels and gestation in weeks was assessed using generalised estimating equation modelling. Infant vedolizumab levels were performed at birth (cord blood), 6 weeks and 3 months or until undetectable. Results: We included 50 IBD patients (23 on infliximab, 15 on adalimumab and 12 on vedolizumab) with at least two intrapartum observations, plus 5 patients on vedolizumab with only mother and baby samples at delivery. Modelling showed no change in adalimumab levels, an increase in infliximab levels of 0.16 (95% CI 0.08-0.24) µg/L/week (P < 0.001) and a decrease of 0.18 (95% CI: −0.33 to −0.02) µg/L/week (P = 0.03) for vedolizumab. In 17 mother-baby pairs, median infant vedolizumab levels at birth were lower than maternal levels (P < 0.05) with an infant:maternal ratio of 0.7 (IQR 0.5-0.9). Vedolizumab was undetectable between 15 and 16 weeks of age in all 12 infants completing follow-up testing. Conclusions: During pregnancy, adalimumab levels remain stable, while infliximab levels increase and vedolizumab levels decrease. However, the increments were small suggesting that intrapartum therapeutic drug monitoring and dose adjustment are not indicated. Unlike infliximab and adalimumab, infant vedolizumab levels are lower in cord blood than in mothers and appear to clear rapidly.

Nonadherence has been a key barrier to the efficacy of medical treatments in ulcerative colitis (UC). Engaging patients in their IBD care via shared decision-making (SDM) to facilitate self-management may improve adherence to therapy. Areas covered: This review aims to summarize the most recent trial evidence from 2012 to 2017 for mild-to-moderate UC in order to develop clinical algorithms that guide SDM to facilitate self-management. A structured literature search via multiple electronic databases was performed using the search terms 'ulcerative colitis,' 'treatment,' 'management,' 'medication,' 'maintenance,' 'remission,' '5-ASA,' and 'inflammatory bowel disease. Expert commentary: Novel formulations of existing oral and topical medications have expanded the treatment options available for the induction and maintenance therapy for mild-to-moderate UC. Daily dosing of 5-ASA therapy is equivalent to twice daily dosing. The combination therapies of oral plus topical 5-ASA therapy and 5-ASA plus corticosteroid therapy are more effective than monotherapy. Budesonide MMX now plays a role in the management of mild-to-moderate UC. This review collates the evidence on drug efficacy and safety, adherence and tolerability, and noninvasive monitoring of mild-to-moderate UC into SDM-orientated algorithms to facilitate self-management.

BACKGROUND The extent to which disease activity impacts patient-reported outcomes (PRO) is unclear. AIMS To examine the relationship between disease activity and PRO. METHODS Adult inflammatory bowel disease (IBD) patients attending a tertiary clinic from May to June 2015 were included. Assessment of disease activity (Simple Clinical Colitis Activity Index (SCCAI), Harvey Bradshaw Index (HBI)), IBD knowledge (CCKNOW), medication adherence (MMAS8), psychological distress (Hospital Anxiety and Depression Scale (HADS)), work productivity (WPAI) and quality of life (IBDQ) was performed to investigate any correlations between disease activity and PRO. RESULTS A total of 81 participants was included: 49% female, 57% Crohn disease (CD), 38% ulcerative colitis (UC) and 5% IBD-unclassified, with a median age of 34 years. At least mild levels of depression were present in 21 of 81 (26%) of patients; 37 of 81 (46%) expressed some level of anxiety. A moderate-to-strong correlation was found between disease activity and depression in UC (r = 0.84, P = 0.002) but not in CD (r = 0.53, P = 0.29). Disease activity correlated with: overall work impairment due to health (r = 0.85, P = 0.001), health-related impairment while working (r = 0.76, P = 0.02) and percentage of activity impaired due to health (r = 0.83, P = 0.002) in UC only. CONCLUSIONS Disease activity significantly affects mood and work productivity in patients with UC. Monitoring patients' ability to function and work, rather than minimising disease activity alone, should become a routine part of IBD care.

The rising burden of inflammatory bowel disease (IBD) has the potential to have a negative impact on the quality of care delivered to patients with IBD. Quality of care has been described by the World Health Organization as "the extent to which health care services provided to individuals and patient populations improve desired health outcomes." Variation in care has been identified as a key barrier to achieving quality of care in IBD. Assessment of quality of care attempts to minimize variation in care. Quality indicators have been developed in IBD as a minimum standard of care according to evidence-based guidelines. Models of care to achieve and maintain quality include integrated care, participatory care, and value-based health care. In this review, we outline current approaches to the assessment of quality of care in IBD and explore models of care currently being used to achieve and maintain quality.

BACKGROUND Electronic health (eHealth) decision support tools have the potential to: facilitate inflammatory bowel disease (IBD) self-management, reduce health care utilisation and alleviate the pressure on overburdened outpatient clinics. The purpose of this study was to explore the perspectives of key stakeholders on the potential use of a decision support tool for IBD patients. METHODS A qualitative study using focus group methodology was conducted at a tertiary IBD centre in Melbourne, Australia in February 2015. Key stakeholders, including physicians, nurses and patients, were included in the study. Two independent reviewers undertook inductive coding and generated themes. RESULTS In total, 31 participants were included in the study (including 16 males; 11 physicians; 6 nurses). An eHealth decision support tool was thought to be beneficial to facilitate IBD self-management. Four themes emerged: (i) Framework for the decision support tool - the tool should be an adjunct to current models of care and facilitate shared decision-making and patient engagement; (ii) Target population - stable patients with mild to moderate disease; (iii) Functionalities of the intervention - a web-based platform encompassing patient-reported outcomes, objective markers of disease and clinical algorithms based on international guidelines; and (iv) Design and Implementation - patients should be involved in the design. CONCLUSIONS eHealth interventions are thought to be an important strategy to facilitate self-management for patients with IBD. A multi-stage iterative approach should be adopted in the design and implementation process of eHealth interventions. Patient perspectives need to be sought prior to and throughout the development of an eHealth decision support tools for IBD.

Background and AimAcute severe ulcerative colitis (ASUC) is a medical emergency requiring prompt therapeutic intervention. Although infliximab has been used as salvage therapy for over 15years, clinical predictors of treatment success are lacking. We performed a retrospective analysis to identify factors that predict colectomy and may guide dose intensification.MethodsFifty-four hospitalized patients received infliximab for ASUC at seven Australian centers (April 2014-May 2015). Follow-up was over 12months. The data were primarily analyzed for predictors of colectomy. Accelerated (AI) versus standard (SI) infliximab induction strategies were also compared.ResultsOf 54 patients identified, the overall colectomy rate was 15.38% (8/52) at 3months and 26.92% (14/52) at 12months. Two patients were lost to follow-up. There was a numerically higher colectomy rate in those treated with AI compared with SI (P=0.3); however, those treated with AI had more severe biochemical disease. A C-reactive protein (CRP)/albumin ratio cut-off of 0.37 post-commencement of infliximab and before discharge was a significant predictor of colectomy with an area under receiver operating curve of 0.73. Pretreatment CRP and albumin levels were not predictive of colectomy. A Mayo Endoscopic Score of 2 had a 94% PPV for avoidance of colectomy following infliximab salvage.ConclusionsThe baseline Mayo Endoscopic Score and the CRP/albumin ratio following infliximab salvage are significant predictors of treatment response for ASUC and identify patients at high risk of colectomy. Whether this risk can be mitigated using infliximab dose intensification requires prospective evaluation before the CRP/albumin ratio can be integrated into ASUC management algorithms.

Anti-TNF prevents postoperative Crohn's disease recurrence in most patients but not all. This study aimed to define the relationship between adalimumab pharmacokinetics, maintenance of remission and recurrence.As part of a study of postoperative Crohn's disease management, some patients undergoing resection received prophylactic postoperative adalimumab. In these patients, serum and fecal adalimumab concentration and serum anti-adalimumab antibodies [AAAs] were measured at 6, 12 and 18 months postoperatively. Levels of Crohn's disease activity index [CDAI], C-reactive protein [CRP] and fecal calprotectin [FC] were assessed at 6 and 18 months postoperatively. Body mass index and smoking status were recorded. A colonoscopy was performed at 6 and/or 18 months.Fifty-two patients [32 on monotherapy and 20 on combination therapy with thiopurine] were studied. Adalimumab concentration did not differ significantly between patients in endoscopic remission vs recurrence [Rutgeerts ≥ i2] [9.98µg/mL vs 8.43 µg/mL, p = 0.387]. Patients on adalimumab monotherapy had a significantly lower adalimumab concentration [7.89 µg/mL] than patients on combination therapy [11.725 µg/mL] [p = 0.001], and were significantly more likely to have measurable AAA [31% vs 17%, p = 0.001]. Adalimumab concentrations were lower in patients with detectable AAA compared with those without [3.59 µg/mL vs 12.0 µg/mL, p0.001]. Adalimumab was not detected in fecal samples. Adalimumab serum concentrations were lower in obese patients compared with in non-obese patients [p = 0.046].Adalimumab concentration in patients treated with adalimumab to prevent symptomatic endoscopic recurrence postoperatively is, for most patients, well within the therapeutic window, and is not significantly lower in patients who develop recurrence compared with in those who remain in remission. Mechanisms of anti-TNF failure to prevent postoperative recurrence remain to be determined in these patients.

Background and Aims Data supporting the optimal maintenance drug therapy & strategy to monitor ongoing response following successful infliximab (IFX) induction, for acute severe ulcerative colitis (ASUC), are limited. We aimed to evaluate maintenance & monitoring strategies employed in patients post IFX induction therapy. Methods Patients in 6 Australian tertiary centres treated with IFX for steroid-refractory ASUC between April 2014 & May 2015 were identified via hospital IBD & pharmacy databases. Patients were followed-up for 1 year with clinical data over 12 months recorded. Analysis was limited to patient outcomes beyond 3 months. Results 41 patients were identified. 5/41 (12%) patients underwent colectomy within 3 months and 1 patient was lost to follow-up. 6/35 (17%) of the remaining patients progressed to colectomy by 12 months. Maintenance therapy Patients maintained on thiopurine monotherapy (14/35) vs. IFX/thiopurine therapy (15/35) were followed up. 2/15 (13%) patients who received combination maintenance therapy underwent a colectomy at 12 months, compared with 1/14 (7%) patients receiving thiopurine monotherapy (p=0.610). Monitoring during maintenance Post-discharge, thiopurine metabolites were monitored in 15/27 (56%); faecal calprotectin in 11/32 (34%); & serum IFX levels in 4/20 (20%). 20/32 (63%) patients had an endoscopic evaluation after IFX salvage with median time to 1st endoscopy of 109 days (IQR 113-230). Conclusion Following IFX induction therapy for ASUC, the uptake of maintenance therapy in this cohort & strategies to monitor ongoing response were variable. These data suggest that the optimal maintenance & monitoring strategy post IFX salvage therapy remains to be defined.

We read with interest the multicentre retrospective study by Irles-Depe et al1 reporting the impact of inflammatory bowel disease (IBD) on long-term outcomes after liver transplantation (LT) for primary sclerosing cholangitis (PSC). In their series PSC-IBD patients were found to have similar rates of death, recurrent PSC (rPSC) and malignancy as patients with isolated PSC. Moreover azathioprine (AZA) exposure was associated with increased mortality, an association which may have been due to an era effect.

Background and Aim: Disease recurs frequently after Crohn's disease resection. The role of serological antimicrobial antibodies in predicting recurrence or as a marker of recurrence has not been well defined. Methods: A total of 169 patients (523 samples) were prospectively studied, with testing peri‐operatively, and 6, 12 and 18 months postoperatively. Colonoscopy was performed at 18 months postoperatively. Serologic antibody presence (perinuclear anti‐neutrophil cytoplasmic antibody [pANCA], anti‐Saccharomyces cerevisiae antibodies [ASCA] IgA/IgG, anti‐OmpC, anti‐CBir1, anti‐A4‐Fla2, anti‐Fla‐X) and titer were tested. Quartile sum score (range 6–24), logistic regression analysis, and correlation with phenotype, smoking status, and endoscopic outcome were assessed. Results: Patients with ≥ 2 previous resections were more likely to be anti‐OmpC positive (94% vs55%, ≥ 2 vs < 2, P = 0.001). Recurrence at 18 months was associated with anti‐Fla‐X positivity at baseline (49% vs 29%; positive vs negative, P = 0.033) and 12 months (52% vs 31%, P = 0.04). Patients positive (n = 28) for all four antibacterial antibodies (anti‐CBir1, anti‐OmpC, anti‐A4‐Fla2, and anti‐Fla‐X) at baseline were more likely to experience recurrence at 18 months than patients negative (n = 32) for all four antibodies (82% vs 18%, P = 0.034; odds ratio 6.4, 95% confidence interval 1.16–34.9). The baseline quartile sum score for all six antimicrobial antibodies was higher in patients with severe recurrence (Rutgeert's i3‐i4) at 18 months, adjusted for clinical risk factors (odds ratio 1.16, 95% confidence interval 1.01–1.34, P = 0.039). Smoking affected antibody status. Conclusions: Anti‐Fla‐X and presence of all anti‐bacterial antibodies identifies patients at higher risk of early postoperative Crohn's disease recurrence. Serologic screening pre‐operatively may help identify patients at increased risk of recurrence.

Background: Although evidence-based guidelines have been developed for inflammatory bowel disease (IBD), the extent to which they are followed is unclear. The objective of this study was to review clinicians’ adherence to international IBD guidelines. Methods: Retrospective data collection of patients attending a tertiary Australian hospital IBD clinic over a 12-month period. Management practices were audited and compared to ECCO (European Crohn’s and Colitis Organization) guidelines. Results: Data from 288 patients were collected: 47% (136/288) male; mean age 43; 140/288 (49%) patients had ulcerative colitis (UC); 145/288 (50%) patients had Crohn’s disease (CD); 3/288 (1%) patients had IBD-unclassified (IBD-U). Patient care was undertaken by gastroenterologists, trainees and general practitioners. Disease Management: Overall adherence to disease management guidelines occurred in 204/288 (71%) of patient encounters. Discrepancies between guidelines and management were found in: 25/80 (31%) of patients with UC in remission receiving oral 5-aminosalicyclates (5-ASAs) as maintenance therapy, and; 46/110 (42%) of patients with small bowel and/or ileo-cecal CD receiving 5-ASA. Preventive Care: Adherence to ≥1 additional component of preventive care was observed in 73/288 (25%) of patient encounters: 12/133 (9%) on thiopurines underwent annual skin checks; 61/288 (21%) of patients with IBD underwent a bone scan; 46/288 (16%) patients were reminded to have their influenza vaccine. Psychological care: Assessment of psychological wellbeing was undertaken in only 16/288 (6%) of patients. Conclusions: There remains a gap between adherence to international guidelines and clinical practice. Standardizing practice using evidence-based clinical pathways may be a strategy towards improving the quality of IBD outpatient management.

We read the study by Roblin et al with interest.1 Given that prior antitumour necrosis factor (anti-TNF) monotherapy failure is frequently associated with antibody development to a second anti-TNF within 24 months,2 it is our practice, to (re)introduce immunomodulator cotherapy with the second anti-TNF to reduce immunogenicity and improve treatment persistence.3 4 Roblin et al ’s findings support this concept, reinforcing the value of thiopurine cotherapy to reduce immunogenicity with the second anti-TNF following immune-mediated failure of first-line anti-TNF monotherapy. Moreover, they demonstrated that combination therapy was less frequently associated with clinical relapse, clinical failure and pharmacokinetic failure (ie, undetectable anti-TNF trough levels with high antidrug antibodies) than anti-TNF monotherapy. These data also imply a longer (24 months) duration of combination therapy may be required for those at increased risk of immunogenicity than previously (6–12 months) suggested.5 In retrospect, perhaps continuing combination therapy ab initio, particularly for infliximab where combination …