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Background: Thiopurine‐related adverse events such as leukopenia, liver dysfunction and pancreatitis are associated with variants in the NUDT15 gene. Loss‐of‐function (low or no enzyme activity) alleles are more common in Asian and Hispanic populations. The prevalence of these variants in the Australian inflammatory bowel disease (IBD) population has not yet been reported. Aim: To evaluate the presence of NUDT15 loss‐of‐function alleles *2,*3,*9 in the Australian IBD population. Methods: The NUDT15 screening cohort included 423 IBD patients from Brisbane, Australia. Study patients were recruited by: (i) retrospective review of clinical charts for thiopurine‐related severe adverse events; (ii) pathology data (white blood cell (WBC) and neutrophil counts). NUDT15 genotyping was performed using polymerase chain reaction (PCR)‐high‐resolution melt (HRM), TaqMan genotyping and Sanger sequencing. Results: NUDT15 mutation R139C (allele *3) was identified in 8 of 423 (1.9%) IBD patients. Seven of eight patients were R139C heterozygous (C/T) and one patient was R139C homozygous (T/T). One of the C/T group and the T/T patient developed thiopurine‐induced myelosuppression (TIM) within 60 days of dosing. One patient in the C/T group developed TIM after 60 days of thiopurine dosing. The remaining five patients in the C/T group did not show TIM; however, other thiopurine‐related events could not be ruled out and therefore careful monitoring over a long period is recommended. Conclusions: This is the first study to report the frequency of NUDT15 haplotypes *2,*3,*9 in an Australian IBD population. The most common variant detected was the R139C mutation. PCR and Sanger sequencing are efficient and cost‐effective approaches for NUDT15 genotyping. [ABSTRACT FROM AUTHOR]

Aim: Previous research has shown that individuals with inflammatory bowel disease avoid specific food items, such as fibre rich foods, in order to manage symptoms. Dietary fibre and the traditional Mediterranean diet are both associated with reduced mucosal and systemic inflammation, gut barrier integrity, and microbiota diversity. There is limited data on the diet composition of individuals with inflammatory bowel disease. The aim of this study was to evaluate how it compares to the traditional Mediterranean diet and national dietary guidelines. Methods: Outpatients with inflammatory bowel disease were recruited to the study between February and August 2019. Demographic and medical information was obtained for consenting participants. All participants completed a dietary assessment of usual intake (24‐h diet recall and 17‐point ready reckoner) from which a Mediterranean diet adherence score was calculated. Dietary intake of core food groups was compared to the recommended number of serves outlined in the Australian Guide to Healthy Eating. Results: 100 participants were recruited. The mean Mediterranean diet adherence score was 5.1 ± 1.3 (maximum 14 points), 4% of participants scored ≥9 (commonly agreed criteria for Mediterranean diet adherence). Participants also consumed considerably less grains and vegetables than national dietary guidelines recommendations. Conclusions: The diet of outpatients with inflammatory bowel disease did not align with Mediterranean diet characteristics. Participants consumed significantly less grains and vegetables than national guidelines, suggesting a low fibre intake. These findings suggest that dietary interventions focusing on improving the diet of individuals with inflammatory bowel disease to align with Mediterranean diet characteristics are warranted. [ABSTRACT FROM AUTHOR]

Background: Inflammatory bowel disease (IBD) patients living in regional or remote Queensland are often disadvantaged by limited access to IBD specialist care. Telehealth clinics could potentially address this disparity and improve patient outcomes. Aim: We report the impact of the Royal Brisbane and Women's Hospital (RBWH) IBD telehealth clinics from March 2011 to December 2017, including patient satisfaction and healthcare activity. Methods: Patient satisfaction surveys were collected prospectively between March 2011 and March 2012. Healthcare activity was assessed through occasions of service (OOS), number of enrolled patients on biologics and IBD related admissions to RBWH. Results: Overall, 3764 OOS were completed including 576 new patient and 3188 follow‐up visits. Mean age at first telehealth visit was 44 years (range: 16–87 years). The IBD telehealth clinics were well accepted with 99% of the first 153 patients surveyed choosing to continue with telehealth and 94% rated the telehealth experience as very good or excellent. The net number of patients under active review increased from 125 patients in 2011 to 345 patients in 2017. Enrolled patients on biologics also increased from 9 patients in 2011 to 63 patients in 2017. There was an initial dip in annual IBD related admissions to RBWH in 2011 but these have progressively increased over time although the average length of inpatient stay annually has remained stable. Conclusion: The RBWH IBD telehealth clinics have shown that telemedicine is well received and can be used successfully to deliver IBD specialist care to patients living in regional or remote areas. [ABSTRACT FROM AUTHOR]

There is growing recognition that the composition of the gut microbiota influences behaviour, including responses to threat. The cognitive‐interoceptive appraisal of threat‐related stimuli relies on dynamic neural computations between the anterior insular (AIC) and the dorsal anterior cingulate (dACC) cortices. If, to what extent, and how microbial consortia influence the activity of this cortical threat processing circuitry is unclear. We addressed this question by combining a threat processing task, neuroimaging, 16S rRNA profiling and computational modelling in healthy participants. Results showed interactions between high‐level ecological indices with threat‐related AIC‐dACC neural dynamics. At finer taxonomic resolutions, the abundance of Ruminococcus was differentially linked to connectivity between, and activity within the AIC and dACC during threat updating. Functional inference analysis provides a strong rationale to motivate future investigations of microbiota‐derived metabolites in the observed relationship with threat‐related brain processes. [ABSTRACT FROM AUTHOR]

Background: Functional gut disorders (FGD) are common. Diagnosis is symptom based, although symptoms may be indistinguishable from inflammatory bowel disease. As a result of this, investigations are common, diagnostic yield is low. A streamlined novel model of care may reduce costly investigations. Aim: To compare a new model of care for patients with low‐risk gastrointestinal symptoms to a matched historical cohort. Methods: Data were prospectively collected over 12 months. General practitioner referrals for low‐risk abdominal symptoms were triaged to a new multidisciplinary clinic structure utilising intestinal ultrasound. Outcomes were compared to the historical model in the preceding 12 months. Duration of care (time from referral to discharge), number of contact episodes and investigations ordered were reviewed. Results: Thirty‐seven patients meeting strict inclusion criteria completed their care. Compared with the historical cohort, colonoscopies reduced from 0.7 to 0.05 per patient (P < 0.0001). Gastroenterology consults reduced from 1.5 to 1.2 (P = 0.303) and dietitian review increased from 0.8 to 1.5 (P < 0.0001). Total contact episodes reduced from 3.2 to 1.8 (P < 0.0001). Duration of care reduced from a median of 252 days to 130 days (interquartile ranges (IQR) 287 and 69, respectively; P < 0.0001). Time from first consultation to discharge reduced from 125 to 42 days (IQR 188 and 63; P < 0.0001). Conclusion: This multidisciplinary approach to care of low‐risk abdominal symptoms significantly reduced contact episodes, time in care and invasive investigations. It decreased costly gastroenterology consultation and increased allied health exposure. It demonstrates improved health service outcomes. [ABSTRACT FROM AUTHOR]

Background and Aims: Many patients presenting with an acute severe ulcerative colitis to a regional hospital are transferred to a metropolitan hospital for specialised care. This study aimed to evaluate the outcomes and characteristics of these patients. Method: A retrospective observational cohort study was conducted to examine the 30‐day colectomy rate using prospectively collected data on 69 consecutive index cases of acute severe ulcerative colitis transferred from regional hospitals to our metropolitan hospital meeting Truelove and Witts criteria. Those that avoided colectomy were followed out to 1 year to examine outcomes. Results: The 30‐day colectomy rate was 46.4% (32/69) in regional transfer patients. Rescue therapy was administered to 65% (45/69) of patients after transfer to our metropolitan hospital. Colectomy was avoided in 55% of these patients at 30 days. Colectomy free status was maintained in 78% (29/39) of these patients. Mortality was 0% at 30 days and 1 year. Conclusion: Over 50% of the patients failing therapy in a regional centre and requiring transfer avoided short term colectomy with co‐ordinated referral for rescue therapy in a tertiary metropolitan inflammatory bowel disease unit. These patients would have ultimately required colectomy in their regional hospital without intervention. [ABSTRACT FROM AUTHOR]

Summary: Background: Delays in Crohn's disease (CD) diagnosis are positively associated with ileal location and an increased risk of complications. Aim: To develop a simple risk assessment tool to enable primary care physicians to recognise potential ileal CD earlier, shortening the delay to specialist investigation Methods: Three cohorts were acquired for this study. Cohort 1 included 61 patients retrospectively identified with ileal CD between 2000 and 2010 and 78 matched controls drawn from a cohort referred for investigation of abdominal symptoms. Cohort 2 included 42 individuals diagnosed with ileal CD and 57 controls identified prospectively. Cohort 3 included an additional 84 individuals with ileal CD and 495 without CD referred for colonoscopy. Clinical symptoms and serological biomarkers were acquired and used to develop a risk prediction algorithm. The algorithm was trained independently on each of the three cohorts and tested on the latter two cohorts. Results: Altered bowel habit with abdominal pain combined with derangements in white cell count (WCC), albumin and platelet counts were important features in predicting ileal CD (AUC = 0.92, 95% CI = 0.89‐0.92). This was validated in cohorts 2 (AUC = 0.96, 95% CI = 0.95‐0.98) and 3 (AUC = 0.94, 95% CI = 0.92‐0.96). C‐reactive protein was independently associated with ileal CD but non‐signficant in a multivariate model. Conclusion: A web‐based risk stratification tool for ileal CD has been developed from objective and symptom‐based criteria. This tool enables primary care physicians to more confidently request urgent specialist assessment for patients identified as at high risk for ileal CD. [ABSTRACT FROM AUTHOR]

Background: Colonoscopy is the gold standard in the diagnosis of significant bowel disease (SBD), including colorectal cancer, high‐risk adenoma and inflammatory bowel disease. As the demand for colonoscopy services is placing significant pressure on hospital resources, new solutions are needed to manage patients more efficiently and effectively. Aim: We investigated the impact of using a risk assessment tool (RAT) to improve selection of patients for colonoscopy procedures to detect SBD. Methods: A hybrid simulation model was constructed to replicate the current patient triage bookings and waiting times in a large metropolitan hospital. The model used data on 327 patients who were retrospectively assessed for risk of SBD. Risk assessment incorporated blood and faecal immunochemical test results, gender and age in addition to patient symptoms. The model was calibrated over 12 months to current outcomes and was compared with the RAT and a third scenario where low‐risk patients did not proceed to a colonoscopy. One‐way sensitivity analyses were undertaken. Results: Using the RAT was expected to shorten waiting times by 153 days for moderately‐urgent patients and 138 days for non‐urgent patients. If low‐risk patients did not proceed to colonoscopy, waiting times were expected to reduce for patients with SBD by 17 days producing cost‐savings of AU$373 824 through avoided colonoscopies. Conclusions: A hybrid model that combines patient‐level characteristics with hospital‐level resource constraints can demonstrate improved efficiency in a hospital clinic. Further research on risk assessment is required to improve quality patient care and reduce low‐value service delivery. [ABSTRACT FROM AUTHOR]

Abstract: Background and Aim: Acute severe ulcerative colitis (ASUC) is a medical emergency requiring prompt therapeutic intervention. Although infliximab has been used as salvage therapy for over 15 years, clinical predictors of treatment success are lacking. We performed a retrospective analysis to identify factors that predict colectomy and may guide dose intensification. Methods: Fifty‐four hospitalized patients received infliximab for ASUC at seven Australian centers (April 2014–May 2015). Follow‐up was over 12 months. The data were primarily analyzed for predictors of colectomy. Accelerated (AI) versus standard (SI) infliximab induction strategies were also compared. Results: Of 54 patients identified, the overall colectomy rate was 15.38% (8/52) at 3 months and 26.92% (14/52) at 12 months. 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. Conclusions: The 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. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Okabayashi et al papers. To view these articles, visit https://doi.org/10.1111/apt.16865 and https://doi.org/10.1111/apt.16925 [ABSTRACT FROM AUTHOR]

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% vs 55%, ≥ 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. [ABSTRACT FROM AUTHOR]

Background and Aim The etiology of Crohn's disease ( CD) implicates both genetic and environmental factors. Smoking behavior is one environmental risk factor to play a role in the development of CD. The study aimed to assess the contribution of the interleukin 23 receptor ( IL23 R) in determining disease susceptibility in two independent cohorts of CD, and to investigate the interactions between IL23 R variants, smoking behavior, and CD-associated genes, NOD2 and ATG16 L1. Methods Ten IL23 R single-nucleotide polymorphisms ( SNPs) were genotyped in 675 CD cases, and 1255 controls from Brisbane, Australia (dataset 1). Six of these SNPs were genotyped in 318 CD cases and 533 controls from Canterbury, New Zealand (dataset 2). Case-control analysis of genotype and allele frequencies, and haplotype analysis for all SNPs was conducted. Results We demonstrate a strong increased CD risk for smokers in both datasets (odds ratio 3.77, 95% confidence interval 2.88-4.94), and an additive interaction between IL23 R SNPs and cigarette smoking. Ileal involvement was a consistent marker of strong SNP- CD association ( P ≤ 0.001), while the lowest minor allele frequencies for location were found in those with colonic CD ( L2). Three haplotype blocks were identified across the 10 IL23 R SNPs conferring different risk of CD. Haplotypes conferred no further risk of CD when compared with single SNP analyses. Conclusion IL23 R gene variants determine CD susceptibility in the Australian and New Zealand population, particularly ileal CD. A strong additive interaction exists between IL23 R SNPs and smoking behavior resulting in a dramatic increase in disease risk depending upon specific genetic background. [ABSTRACT FROM AUTHOR]

Aims AMG 181 pharmacokinetics/pharmacodynamics ( PK/ PD), safety, tolerability and effects after single subcutaneous (s.c.) or intravenous (i.v.) administration were evaluated in a randomized, double-blind, placebo-controlled study. Methods Healthy male subjects ( n= 68) received a single dose of AMG 181 or placebo at 0.7, 2.1, 7, 21, 70 mg s.c. (or i.v.), 210 mg s.c. (or i.v.), 420 mg i.v. or placebo. Four ulcerative colitis ( UC) subjects ( n= 4, male : female 2:2) received 210 mg AMG 181 or placebo s.c. (3:1). AMG 181 concentration, anti- AMG 181-antibody ( ADA), α4β7 receptor occupancy ( RO), target cell counts, serum C-reactive protein, fecal biomarkers and Mayo score were measured. Subjects were followed 3-9 months after dose. Results Following s.c. dosing, AMG 181 was absorbed with a median tmax ranging between 2-10 days and a bioavailability between 82% and 99%. Cmax and AUC increased dose-proportionally and approximately dose-proportionally, respectively, within the 70-210 mg s.c. and 70-420 mg i.v. ranges. The linear β-phase t1/2 was 31 (range 20-48) days. Target-mediated disposition occurred at serum AMG 181 concentrations of less than 1 μg ml−1. The PD effect on α4β7 RO showed an E C50 of 0.01 μg ml−1. Lymphocytes, eosinophils, CD4+ T cells and subset counts were unchanged. AMG 181-treated UC subjects were in remission with mucosal healing at weeks 6, 12 and/or 28. The placebo-treated UC subject experienced colitis flare at week 6. No ADA or AMG 181 treatment-related serious adverse events were observed. Conclusions AMG 181 has PK/ PD, safety, and effect profiles suitable for further testing in subjects with inflammatory bowel diseases. [ABSTRACT FROM AUTHOR]

Head-to-head trials are typically either classified as non-inferiority, equivalence, or superiority studies. Superiority trials investigating biologics have been rare until recently.5 Initially commencing in rheumatology and dermatology, superiority trials now are being undertaken in patients with IBD. Such design features include robust and validated measures of disease activity, dosing, therapeutic-drug monitoring, concomitant IBD therapy, and effective strategies to achieve timely subject recruitment. [Extracted from the article]

LINKED CONTENT This article is linked to Khalili et al paper. To view this article, visit https://doi.org/10.1111/apt.15889 [ABSTRACT FROM AUTHOR]

Anti-tumor-necrosis-factor-alpha (anti-TNF-α) medications are effective in inflammatory bowel disease (IBD), but have an increased risk of tuberculosis (TB) and serious infections. The aim of this study was to examine the Australian/New Zealand experience of serious infections and TB in IBD patients receiving anti-TNF-α therapy from 1999-2009. Serious infections, defined as 'requiring hospital admission' and TB cases in patients receiving, or within 3 months following, anti-TNF-α therapy were analyzed across Australia and New Zealand. Patient demographics, IBD medications, duration of anti-TNF-α therapy, and infection details were collected. A total of 5562 IBD patients were managed across the centers. Of these, 489 (16.8%) Crohn's disease and 137 (5.2%) ulcerative colitis patients received anti-TNF-α therapy. There were three cases of latent TB that received prophylaxis prior to anti-TNF-α therapy. No cases of active TB were reported. Fourteen (2.2%) serious infections occurred. Seven occurred in patients receiving anti-TNF-α therapy for less than 6 months, including two cases of primary Varicella zoster (VZV), two cases of Pneumocystis jiroveci pneumonia, two cases of Staphylococcus aureus bacteremia, and one severe flu-like illness. Six patients were taking additional immunosuppressive medications. The other seven infections occurred after 6 months (mean 32.6 ± 24.3 months) and included one case of primary VZV, one flu-like illness, and five bacterial infections. All infections resolved with treatment. TB is a very rare complication of anti-TNF-α therapy in Australia and New Zealand. Serious infections are uncommon but early opportunistic infections with Pneumocystis jiroveci pneumonia suggest a need for vigilance in patients on multiple immunosuppressive medications. VZV vaccination prior to immunosuppressive therapy should be considered in VZV-naïve patients. [ABSTRACT FROM AUTHOR]

Background and Aim: New treatments for Crohn's disease are expensive and place economic strain upon health-care systems, and ‘value-for-money’ needs to be confirmed. This study aimed to correlate disease severity with health-related quality of life and with health-care resource use, to allow evaluation of the cost effectiveness of these treatments. Methods: A cross-sectional, non-interventional, pharmacoeconomics study was performed with patients completing questionnaires comprising demographic, disease and health-care utilization questions, together with the disease-specific Inflammatory Bowel Disease Questionnaire (IBDQ) and the Assessment of Quality of Life (AQoL) multi-attribute utility instrument. The Crohn's Disease Activity Index (CDAI) was used to assess disease severity. Results: 143 patients with a broad range of disease severity (CDAI 36–446, fistulae 23%) were recruited from referral centers. Stepwise regression analyses demonstrated a negative correlation between disease severity and both IBDQ and AQoL (both P < 0.0001). Age, gender and years since diagnosis did not impact upon either of the quality-of-life outcomes. Mean utility score for non-fistulizing patients with moderate–severe active disease (CDAI ≥ 220) was 0.45, mild disease (CDAI 150–219) was 0.68 and for remission (CDAI < 150) was 0.77. Health-care resource utilization increased with increasing CDAI ( P < 0.001), with hospital admissions being the largest component cost. Twenty-seven percent of patients (mean age 38 year) received a government benefit, 51% primarily due to their Crohn's disease. Conclusion: Crohn's disease severity correlates with poor quality of life. Utility scores determined will permit cost–utility analyses to be made in order to best allocate limited health resources. [ABSTRACT FROM AUTHOR]

Background and Aim: There is limited consensus on the major variables that determine bone integrity and bone loss in patients with Crohn's disease. Twin and family studies in the general population indicate that up to 85% of variance in bone mineral density is inherited. The aim was to determine the prevalence of bone loss and both molecular and clinical risk factors for bone loss in a large Crohn's disease population. Methods: This was a cross-sectional study of 304 patients with Crohn's disease attending the Inflammatory Bowel Disease unit at Royal Brisbane and Women's Hospital, Queensland. The results of bone density testing were ascertained directly and by a mailed questionnaire. Bone mineral density data were combined with clinical information and correlated with single nucleotide polymorphisms within the tumor necrosis factor-α ( TNF-α), interleukin-10, and NOD2/CARD15 genes. Results: Of 304 Crohn's disease patients, 101 had undergone previous bone density testing. Forty-five patients (45%) had been diagnosed with osteopenia and 18 (18%) were osteoporotic. After multivariate analysis, both the TNF-α GT haplotype and the −857 CC genotype showed strong associations with bone mineral density overall ( P = 0.003 and P = 0.002, respectively). Body mass index ( P = 0.01) and previous bowel resection in female patients ( P = 0.03) were predictive of a higher spine bone density, while body mass index ( P = 0.003) and the effect of years since first bowel resection ( P = 0.02) remained independent predictors of proximal femur bone mineral density. There were no other significant associations observed. Conclusions: This study has identified a novel protective association between a TNF-α haplotype and bone mineral density in Crohn's disease. It confirms the important influence of body mass index and intestinal resection on bone loss in this population. [ABSTRACT FROM AUTHOR]

LINKED CONTENT This article is linked to Kochhar et al paper. To view this article, visit https://doi.org/10.1111/apt.15721 [ABSTRACT FROM AUTHOR]

Background: Narcotic addiction can be a significant problem in inflammatory bowel disease (IBD). However, there are few published reports about this problem. Methods: All patients prescribed narcotics chronically in the absence of demonstrable organic pathology were identified on the computerized Brisbane IBD Research Group database (n = 332 patients with informative data as of 1 January 1999). Individual case records were reviewed with regard to clinical, psychiatric and social characteristics of these patients, and the prevalence of psychiatric disorders were compared with a control group of IBD patients. Results: Eleven patients were identified. Nine had complete datasets, eight with Crohn's disease (CD), of which six had previous stricturing ileal disease, and one patient had ulcerative colitis, making a prevalence of 2.7% of IBD patients and 5.1% of CD patients. A 67% prevalence of a psychiatric disorder in narcotic users was significantly greater than the 8% prevalence in the control group of IBD patients (odds ratio 22, 95% CI 3.24-177). Conclusions: A significant proportion of IBD patients without demonstrable organic pathology were chronic narcotic users. Psychiatric disorders are common in this subgroup, as with chronic functional abdominal pain syndromes. It is suggested that inappropriate narcotic use in IBD patients can be reduced by appreciating that narcotics are a temporary therapy only for IBD patients, and awareness of pre-existing social and psychiatric disorders, which not only impact on clinical presentation of pain, but also help define the subgroup of patients who are at risk of narcotic misuse. [ABSTRACT FROM AUTHOR]

Summary Background Aims Methods Results Conclusions An episode of acute ulcerative colitis (UC) represents an important watershed moment in a patient's disease course.To derive a personalised algorithm for identifying patients at high risk of corticosteroid non‐response from variables available at hospital presentation using a large prospectively collected acute UC patient database and machine learning‐based techniques.We analysed data from 682 consecutive presentations of acute UC. We used an Akaike information criterion‐based elastic net model to select variables based on the 419 earliest presentations of acute UC (1996–2017). We constructed two risk‐scoring algorithms, with and without utilising additional endoscopic variables, using logistic regression models. We validated these risk scores on separate cohorts of 181 (2018–2022) and 82 (2015–2022) acute UC presentations.The partial risk of rescue (ROR) score included the admission indices of oral corticosteroid treatment, bowel frequency ≥6/24 h, albumin, CRP ≥12 mg/mL and log10CRP. The full ROR score incorporates the same variables with the addition of the Mayo endoscopic subscore and disease extent. The AUCs in the main validation cohort were 0.76 (95% CI: 0.69–0.83) and 0.78 (95% CI: 0.71–0.85) for the partial and full ROR scores, respectively.These pragmatic personalised risk scores (available at www.severecolitis.com) have comparably strong performance characteristics and usability enabling the identification of individuals at high risk of corticosteroid non‐response before or after endoscopic assessment. The ROR scores have the potential to challenge conventional acute UC treatment paradigms by identifying patients who may benefit from early rescue therapy or participation in relevant clinical trials. [ABSTRACT FROM AUTHOR]

Objective: To examine the prevalence of perianal Crohn's disease (PCD) and the eligibility of PCD patients to access anti-tumour necrosis factor-alpha (anti-TNFalpha) treatment under current Australian Pharmaceutical Benefits Scheme (PBS) guidelines.Design, Setting and Participants: A retrospective study of patients with Crohn's disease (CD) and PCD attending four large adult inflammatory bowel disease (IBD) centres in Australia between January 2004 and May 2008. Patients for whom anti-TNFalpha therapy was clinically indicated were assessed to determine whether they satisfied PBS criteria for subsidised medication.Main Outcome Measures: Prevalence of CD and PCD in patients attending different IBD centres; eligibility of PCD patients for PBS-subsidised anti-TNFalpha medication.Results: Data were available on 3589 patients, representing about 6% of all patients with IBD in Australia. Of the 1815 patients with CD, 310 (17%) had PCD. Anti-TNFalpha therapy was deemed clinically indicated for 166 patients with PCD (54%), of whom 49 (30%) did not qualify for PBS-funded therapy.Conclusion: Thirty per cent of patients with clinically significant PCD currently do not have access to PBS-subsidised optimal medical treatment. We believe that PBS criteria should be extended to include this subgroup of IBD patients. [ABSTRACT FROM AUTHOR]

The article presents a study which determined the prevalence of Perianal Crohn's disease (PCD) in four Australian inflammatory bowel disease (IBD) centres and the number of patients that would qualify in receiving subsidised anti-tumour necrosis factor-alpha (Anti-TNFα) from the Pharmaceutical Benefits Scheme (PBS). Respondents included PCD patients attending IBD centres between January 2004 and May 2008. Results showed that 30% with significant PCD do not have access to PBS medical treatment.

Objective: Crohn's disease (CD) is characterised by inflammation, predominantly associated with ilea. To investigate the basis for this inflammation in patients with CD, we examined dendritic cells (DC) which are pivotal for maintenance of immunological tolerance in the gut. Methods: Ileal biopsies and blood DCs from CD patients and controls were examined by microscopy and flow cytometry for PD‐L1 and PD‐L2 expression, as PD‐L1 has been implicated in colitis but the contribution of PD‐L2 is less clear. In vitro studies, of blood samples from CD patients, were used to demonstrate a functional role for PD‐L2 in disease pathogenesis. Results: Quantitative microscopy of CD11c+DCs in inflamed and noninflamed ilea from CD patient showed > 75% loss of these cells from the villi, lamina propria and Peyer's patches compared with non‐CD controls. Given this loss of DCs from ilia of CD patients, we hypothesised DCs may have migrated to the blood as these patients can have extra‐intestinal symptoms. We thus examined blood DCs from CD patients by flow cytometry and found significant increases in PD‐L1 and PD‐L2 expression compared with control samples. Microscopy revealed an aggregated form of PD‐L2 expression, known to drive Th1 immunity, in CD patients but not in controls. In vitro functional studies with PD‐L2 blockade confirmed PD‐L2 contributes significantly to the secretion of pro‐inflammatory cytokines known to cause disease pathogenesis. Conclusion: Taken together, this study shows that PD‐L2 can influence the progression of CD and blockade of PD‐L2 may have therapeutic potential. [ABSTRACT FROM AUTHOR]

Aims: AMG 181 pharmacokinetics/pharmacodynamics (PK/PD), safety, tolerability and effects after single subcutaneous (s.c.) or intravenous (i.v.) administration were evaluated in a randomized, double-blind, placebo-controlled study., Methods: Healthy male subjects (n= 68) received a single dose of AMG 181 or placebo at 0.7, 2.1, 7, 21, 70 mg s.c. (or i.v.), 210 mg s.c. (or i.v.), 420 mg i.v. or placebo. Four ulcerative colitis (UC) subjects (n= 4, male : female 2:2) received 210 mg AMG 181 or placebo s.c. (3:1). AMG 181 concentration, anti-AMG 181-antibody (ADA), α4 β7 receptor occupancy (RO), target cell counts, serum C-reactive protein, fecal biomarkers and Mayo score were measured. Subjects were followed 3-9 months after dose., Results: Following s.c. dosing, AMG 181 was absorbed with a median tmax ranging between 2-10 days and a bioavailability between 82% and 99%. Cmax and AUC increased dose-proportionally and approximately dose-proportionally, respectively, within the 70-210 mg s.c. and 70-420 mg i.v. ranges. The linear β-phase t1/2 was 31 (range 20-48) days. Target-mediated disposition occurred at serum AMG 181 concentrations of less than 1 μg ml(-1) . The PD effect on α4 β7 RO showed an EC50 of 0.01 μg ml(-1) . Lymphocytes, eosinophils, CD4+ T cells and subset counts were unchanged. AMG 181-treated UC subjects were in remission with mucosal healing at weeks 6, 12 and/or 28. The placebo-treated UC subject experienced colitis flare at week 6. No ADA or AMG 181 treatment-related serious adverse events were observed., Conclusions: AMG 181 has PK/PD, safety, and effect profiles suitable for further testing in subjects with inflammatory bowel diseases., (© 2014 The British Pharmacological Society.)