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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]

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]

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]

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]

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]