Anthony Croft

Serious infections in patients with inflammatory bowel disease receiving anti‐tumor‐necrosis‐factor‐alpha therapy: An Australian and New Zealand experience

Background and Aim:  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.

Outcomes of salvage therapy for steroid-refractory acute severe ulcerative colitis: ciclosporin vs. infliximab

Up to 40% of patients who present with acute severe ulcerative colitis (UC) fail to make an adequate response to intravenous corticosteroids. Ciclosporin or infliximab are currently employed as salvage therapy in this clinical scenario.

Granulocyte-macrophage colony-stimulating factor autoantibodies: a marker of aggressive Crohn's disease.

Background: Neutralizing autoantibodies (Abs) against granulocyte–macrophage colony-stimulating factor (GM-CSF Ab) have been associated with stricturing ileal Crohns disease (CD) in a largely pediatric patient cohort (total 394, adult CD 57). The aim of this study was to examine this association in 2 independent predominantly adult inflammatory bowel disease patient cohorts. Methods: Serum samples from 742 subjects from the NIDDK IBD Genetics Consortium and 736 subjects from Australia were analyzed for GM-CSF Ab and genetic markers. We conducted multiple regression analysis with backward elimination to assess the contribution of GM-CSF Ab levels and established CD risk alleles and smoking on ileal disease location in the 477 combined CD subjects from both cohorts. We also determined associations of GM-CSF Ab levels with complications requiring surgical intervention in combined CD subjects in both cohorts. Results: Serum samples from patients with CD expressed significantly higher concentrations of GM-CSF Ab when compared with ulcerative colitis or controls in each cohort. Nonsmokers with ileal CD expressed significantly higher GM-CSF Ab concentrations in the Australian cohort (P = 0.002). Elevated GM-CSF Ab, ileal disease location, and disease duration more than 3 years were independently associated with stricturing/penetrating behavior and intestinal resection for CD. Conclusions: The expression of high GM-CSF Ab is a risk marker for aggressive CD behavior and complications including surgery. Modifying factors include environmental exposure to smoking and genetic risk markers.

Crohn's disease and smoking: Is it ever too late to quit?

BACKGROUND Smoking increases CD risk. The aim was to determine if smoking cessation at, prior to, or following, CD diagnosis affects medication use, disease phenotypic progression and/or surgery. METHODS Data on CD patients with disease for ≥5 yrs were collected retrospectively including the Montreal classification, smoking history, CD-related abdominal surgeries, family history, medication use and disease behaviour at diagnosis and the time when the disease behaviour changed. RESULTS 1115 patients were included across six sites (mean follow-up-16.6 yrs). More non-smokers were male (p=0.047) with A1 (p<0.0001), L4 (p=0.028) and perianal (p=0.03) disease. Non-smokers more frequently received anti-TNF agents (p=0.049). (p=0.017: OR 2.5 95%CI 1.18-5.16) and those who ceased smoking prior to diagnosis (p=0.045: OR 2.3 95%CI 1.02-5.21) progressed to complicated (B2/B3) disease as compared to those quitting at diagnosis. Patients with uncomplicated terminal ileal disease at diagnosis more frequently developed B2/B3 disease than isolated colonic CD (p<0.0001). B2/B3 disease was more frequent with perianal disease (p<0.0001) and if i.v. steroids (p=0.004) or immunosuppressants (p<0.0001) were used. 49.3% (558/1115) of patients required at least one intestinal surgery. More smokers had a 2nd surgical resection than patients who quit at, or before, the 1st resection and non-smokers (p=0.044: HR=1.39 95%CI 1.01-1.91). Patients smoking >3 cigarettes/day had an increased risk of developing B2/B3 disease (p=0.012: OR 3.8 95%CI 1.27-11.17). CONCLUSION Progression to B2/B3 disease and surgery is reduced by smoking cessation. All CD patients regardless of when they were diagnosed, or how many surgeries, should be strongly encouraged to cease smoking.

Inter-observer agreement for Crohn's disease sub-phenotypes using the Montreal Classification: How good are we? A multi-centre Australasian study

BACKGROUND Crohns disease (CD) exhibits significant clinical heterogeneity. Classification systems attempt to describe this; however, their utility and reliability depends on inter-observer agreement (IOA). We therefore sought to evaluate IOA using the Montreal Classification (MC). METHODS De-identified clinical records of 35 CD patients from 6 Australian IBD centres were presented to 13 expert practitioners from 8 Australia and New Zealand Inflammatory Bowel Disease Consortium (ANZIBDC) centres. Practitioners classified the cases using MC and forwarded data for central blinded analysis. IOA on smoking and medications was also tested. Kappa statistics, with pre-specified outcomes of κ>0.8 excellent; 0.61-0.8 good; 0.41-0.6 moderate and ≤0.4 poor, were used. RESULTS 97% of study cases had colonoscopy reports, however, only 31% had undergone a complete set of diagnostic investigations (colonoscopy, histology, SB imaging). At diagnosis, IOA was excellent for age, κ=0.84; good for disease location, κ=0.73; only moderate for upper GI disease (κ=0.57) and disease behaviour, κ=0.54; and good for the presence of perianal disease, κ=0.6. At last follow-up, IOA was good for location, κ=0.68; only moderate for upper GI disease (κ=0.43) and disease behaviour, κ=0.46; but excellent for the presence/absence of perianal disease, κ=0.88. IOA for immunosuppressant use ever and presence of stricture were both good (κ=0.79 and 0.64 respectively). CONCLUSION IOA using MC is generally good; however some areas are less consistent than others. Omissions and inaccuracies reduce the value of clinical data when comparing cohorts across different centres, and may impair the ability to translate genetic discoveries into clinical practice.

Surgical outcomes in steroid refractory acute severe ulcerative colitis: the impact of rescue therapy.

Aim  The advent of rescue medical therapy (cyclosporin or infliximab) and laparoscopic surgery has shifted the paradigm in managing steroid refractory acute severe ulcerative colitis (ASUC). We investigated prospectively the impact of rescue therapy on timing and postoperative complications of urgent colectomy and subsequent restorative surgery for steroid refractory ASUC.

Smoking behaviour modifies IL23r-associated disease risk in patients with Crohn's disease

The etiology of Crohns 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 (IL23R) in determining disease susceptibility in two independent cohorts of CD, and to investigate the interactions between IL23R variants, smoking behavior, and CD‐associated genes, NOD2 and ATG16L1.

Commentary: salvage medical therapy for acute severe colitis - ciclosporin or infliximab? Author's reply.

*Department of Gastroenterology, Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australia. Department of Gastroenterology, St Vincent’s Hospital, Sydney, NSW, Australia. The Australian E-Health Research Centre, Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australia. CSIRO Preventative Health Flagship, Parkville, Melbourne, Victoria, Australia. CSIRO Mathematics and Information Sciences, Macquarie University, Sydney, NSW, Australia. **IBD Group, Queensland Institute of Medical Research and University of Queensland School of Medicine, Herston Campus, Brisbane, Queensland, Australia. E-mail: anthony.croft@gmail.com

Letter: ciclosporin or infliximab in acute ulcerative colitis - still undecided; authors' reply

*Department of Gastroenterology, Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australia. Department of Gastroenterology, St Vincent’s Hospital, Sydney, NSW, Australia. The Australian E-Health Research Centre, Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australia. CSIRO Preventative Health Flagship, Parkville, Melbourne, Victoria, Australia. CSIRO Mathematics and Information Sciences, Macquarie University, Sydney, NSW, Australia. **IBD Group, Queensland Institute of Medical Research and University of Queensland School of Medicine, Herston Campus, Brisbane, Queensland, Australia. E-mail: anthony.croft@gmail.com