Karen I. Kroeker

Patients with IBD are exposed to high levels of ionizing radiation through CT scan diagnostic imaging: a five-year study.

Goals The objective of this study was to assess the total effective dose of ionizing radiation from abdominal diagnostic imaging in patients with inflammatory bowel disease (IBD) over a 5-year period. Background Radiation exposure from diagnostic imaging is becoming increasingly common in IBD patients, in part due the availability of computed tomography (CT). Increased risk of malignancy has been associated with radiation exposure. Study This is a retrospective chart review. A university-based gastroenterology database was searched for patients with a diagnosis of Crohns disease (CD) or ulcerative colitis (UC) seen between 2003 and 2008. The cumulative ionizing radiation exposure, expressed in milli-Sieverts (mSv), was then calculated from standard tables and by counting the number of abdominal imaging studies. Results Patients with CD had higher cumulative radiation exposure from diagnostic imaging than patients with UC (14.3±1.45 mSv/5-y period vs. 5.9±0.81 mSv/5-y period, P=0.00003). Three-quarters of the radiation exposure in both CD and UC was from CT scans. Thirty-four percent (127 of 373) of CD patients had CT scans, compared with just 20% (37 of 182) of UC patients. Importantly, 7% of CD patients were exposed to high levels of radiation (>50 mSv/5 y), in contrast to none of the UC patients. Conclusions Patients with IBD, and especially CD patients, undergo frequent diagnostic imaging and thus significant exposure to ionizing radiation. This radiation exposure reaches high levels in 7% of CD patients, mainly from CT scanning. Efforts should be made to minimize the radiation exposure from diagnostic imaging by reducing either the number of studies or radiation dose in modalities with ionizing radiation.

The incidence rate of colectomy for medically refractory ulcerative colitis has declined in parallel with increasing anti-TNF use: a time-trend study

Medical therapy is standard treatment for ulcerative colitis with colectomy reserved for medically refractory disease or malignancy. The introductions of ciclosporin in 1994 and anti‐TNF therapy in 2005 have extended medical management options.

Increased Epithelial Gaps in the Small Intestine Are Predictive of Hospitalization and Surgery in Patients With Inflammatory Bowel Disease

OBJECTIVES:Epithelial gaps resulting from intestinal cell extrusions can be visualized with confocal laser endomicroscopy (CLE) during colonoscopy and increased in normal-appearing terminal ileum of inflammatory bowel disease (IBD) patients. Cell-shedding events on CLE were found to be predictive of disease relapse. The aim of this study was to assess the prognostic value of epithelial gap densities for major clinical events (hospitalization or surgery) in follow-up.METHODS:We prospectively followed IBD patients undergoing colonoscopy with probe-based CLE (pCLE) for clinical events including symptom flares, medication changes, hospitalization, or surgery. Survival analysis methods were used to compare event times for the composite outcome of hospitalization or surgery using log-rank tests and Cox proportional hazards models. We also examined the relationship of gap density with IBD flares, need for anti-tumor necrosis factor therapy, disease duration, gender and endoscopic disease severity, and location.RESULTS:A total of 21 Crohns disease and 20 ulcerative colitis patients with a median follow-up of 14 (11–31) months were studied. Patients with elevated gap density were at significantly higher risk for hospitalization or surgery (log-rank test P=0.02). Gap density was a significant predictor for risk of major events, with a hazard ratio of 1.10 (95% confidence interval=1.01, 1.20) associated with each increase of 1% in gap density. Gap density was also correlated with IBD disease duration (Spearmans correlation coefficient rho=0.44, P=0.004), and was higher in male patients (9.0 vs. 3.6 gaps per 100 cells, P=0.038).CONCLUSIONS:Increased epithelial gaps in the small intestine as determined by pCLE are a predictor for future hospitalization or surgery in IBD patients.

Adult liver transplant survey: policies towards eligibility criteria in Canada and the United States 2007.

Goals: To assess the current practice patterns of liver transplant centres in Canada and the USA regarding transplant eligibility.

Clinical, endoscopic and radiographic outcomes with ustekinumab in medically‐refractory Crohn's disease: real world experience from a multicentre cohort

Ustekinumab is a monoclonal antibody targeting interleukins‐12 and ‐23, with efficacy in Crohns disease (CD) demonstrated in clinical trials.

Prevalence of Epstein–Barr Virus in a population of patients with inflammatory bowel disease: a prospective cohort study

The Epstein–Barr Virus (EBV) is truly prolific, with a prevalence of more than 90% in the adult human population. There are, however, little data available on the prevalence of EBV among patients with Inflammatory Bowel Disease (IBD), a population that is frequently immunosuppressed and thus at risk for severe, often fatal, primary infection.

Crohn's disease outpatients treated with adalimumab have an earlier secondary loss of response and requirement for dose escalation compared to infliximab: A real life cohort study☆

BACKGROUND The efficacy of anti-tumor necrosis factor alpha agents in maintaining remission in Crohns disease may wane over time, leading to secondary loss of response that can often be overcome with dose escalation. Comparison of secondary loss of response of adalimumab and infliximab during long-term treatment of CD in a real-life IBD clinic has not been previously evaluated. METHODS A retrospective cohort study was conducted evaluating outpatients with CD on a maintenance regimen with adalimumab or infliximab from 200 to 2013 and who experienced a secondary loss of response. All infliximab-treated patients were anti-TNF naïve. Adalimumab-treated patients were stratified by prior anti-TNF exposure. Kaplan-Meier analysis was conducted to compare time to loss of response. RESULTS 218 CD patients met inclusion criteria (117 infliximab, 101 adalimumab). Median follow-up duration was 170.0weeks for infliximab and 122.0weeks for adalimumab (p=0.61). The proportion of patients with secondary loss of response was similar for infliximab-treated - 51.3% (60/117) compared to adalimumab patients naïve to anti-TNF therapy - 60.5% (23/38) (p=0.32), and adalimumab patients with prior anti-TNF exposure - 65.1% (41/63) (p=0.08). Median time to secondary loss of response was longer for infliximab patients (99.3wk, IQR 55.7-168.5) compared to both adalimumab patients naïve to anti-TNF therapy (58.9wk, IQR 29.0-85.7) (p=0.03), and adalimumab patients with prior anti-TNF exposure (52.7wk, IQR 20.1-85.0) (p<0.001). CONCLUSIONS Over 50% of CD patients treated with infliximab and adalimumab develop secondary loss of response. Time to loss of response was shorter in patients treated with adalimumab compared to those treated with infliximab. Prior anti-TNF exposure further accelerated time to loss of response.

Outpatient Ulcerative Colitis Primary Anti-TNF Responders Receiving Adalimumab or Infliximab Maintenance Therapy Have Similar Rates of Secondary Loss of Response.

Goals: To compare the proportion of secondary loss of response to adalimumab and infliximab during maintenance treatment of ulcerative colitis (UC) after primary response to induction therapy. Background: The efficacy of anti-tumor necrosis factor-&agr; (TNF-&agr;) therapy used to maintain response in patients with UC after primary response to induction therapy wanes with time, resulting in secondary loss of response. Methods: A retrospective cohort study evaluating anti-TNF-naive UC outpatients who were primary responders to adalimumab and infliximab induction therapy and who advanced onto a maintenance regimen with the respective anti-TNF agent from 2003 to 2013 was conducted. The primary outcome was the proportion of patients in each treatment group that had secondary loss of response. The secondary outcome was time to secondary loss of response, analyzed by the Kaplan-Meier method analysis. Results: A total of 102 UC primary anti-TNF responders met inclusion criteria. Thirty-six patients (35.3%) were treated with adalimumab and 66 patients (64.7%) with infliximab. Mean follow-up was 139.0 weeks for adalimumab and 158.8 weeks for infliximab. A total of 21/36 (58.3%) adalimumab-treated patients and 39/66 (59.1%) infliximab-treated patients experienced a secondary loss of response during maintenance therapy. Mean time to secondary loss of response was similar for adalimumab (55.8 wk) and infliximab (59.4 wk) (P=0.82). Sex, extent of colitis, previous or concomitant azathioprine, and concurrent corticosteroids with anti-TNF induction were not associated with increased risk of secondary loss of response. Conclusions: In this real-life cohort of anti-TNF-naive primary responders with UC, the proportion of secondary loss of response and the time to secondary loss of response are similar for adalimumab and infliximab.

Crohn's disease genotypes of patients in remission vs relapses after infliximab discontinuation.

AIM To investigate genetic differences between Crohns disease (CD) patients with a sustained remission vs relapsers after discontinuing infliximab while in corticosteroid-free remission. METHODS Forty-eight CD patients received infliximab and were in full corticosteroid-free clinical remission but then discontinued infliximab for reasons other than a loss of response, were identified by review of an electronic database and charts. Infliximab-associated remission was defined as corticosteroid-free plus normalization of clinical disease activity [CD activity index (CDAI) < 150] during follow-up visits based on physician global assessments. A CD relapse (loss of infliximab-induced remission) was clinically defined as a physician visit for symptoms of disease activity (CDAI > 220) and a therapeutic intervention with CD medication(s), or a hospitalization with complications related to active CD. Genetic analyses were performed on samples from 14 patients (n = 6 who had a sustained long term remission after stopping infliximab, n = 8 who rapidly relapsed after stopping infliximab). Nucleotide-binding oligomerization domain 2 (NOD2)/caspase activation recruitment domain 15 (CARD15) polymorphisms (R702W, G908R and L1007fs) and the inflammatory bowel disease 5 (IBD5) polymorphisms (IGR2060a1 and IGR3081a1) were analyzed in each group. RESULTS Five single nucleotide polymorphisms of IBD5 and NOD2/CARD15 genes were successfully analyzed for all 14 subjects. There was no significant increase in frequency of the NOD2/CARD15 polymorphisms (R702W, G908R and L1007fs) and the IBD5 polymorphisms (IGR2060a1 and IGR3081a1) in either group of patients; those whose disease relapsed rapidly or those who remained in sustained long term remission following the discontinuation of infliximab. Nearly a third of patients in full clinical remission who stopped infliximab for reasons other than loss of response remained in sustained clinical remission, while two-thirds relapsed rapidly. There was a marked difference in the duration of clinical remission following discontinuance of infliximab between the two groups. The patients who lost remission did so after 1.0 years ± 0.6 years, while those still in remission were at the time of this study, 8.1 years ± 2.6 years post-discontinuation of infliximab, P < 0.001. The 8 patients who had lost remission after discontinuing infliximab had a mean number of 5 infusions (range 3-7), with a mean treatment time of 7.2 mo (range 1.5 mo-15 mo). The mean duration of time from the last infusion of infliximab to the time of loss of remission was 382 d (range 20 d-701 d). The 6 patients who remained in remission after discontinuing infliximab had a mean number of 6 infusions (range 3-12), with a mean treatment duration of 12 mo (range 3.6 mo-32 mo) (P = 0.45 relative to those who lost remission). CONCLUSION There are no IBD5 or NOD2/CARD15 mutations that predict which patients might have sustained remission and which will relapse rapidly after stopping infliximab.

Adalimumab for orbital myositis in a patient with Crohn’s disease who discontinued infliximab: a case report and review of the literature

BackgroundOrbital myositis is a rare extra-intestinal manifestation of inflammatory bowel disease. Seventeen cases of Crohn’s disease associated orbital myositis and 3 cases of ulcerative colitis associated orbital myositis have been reported in the published literature since 1970. We report the use of adalimumab (Abbott, Canada, Inc.) for orbital myositis in a patient with Crohn’s disease who discontinued infliximab (Janssen, Canada, Inc.) and review of the published literature.Case presentationA 35 year-old male with a 7-year history of Crohn’s disease was treated with an ileocolonic resection and re-anastomosis followed by infliximab which maintained full endoscopic and clinical remission for four years. After stopping the infliximab for infusion-related reactions he presented with 3-day history of severe right eye pain, pain with ocular movement, proptosis, and conjunctival injection. He had no intestinal symptoms and endoscopic assessment revealed no active luminal disease. CT of the orbit revealed an enlarged right medial rectus muscle with tendonous involvement and a diagnosis of orbital myositis was made. Treatment with 80 mg per day prednisone with tapering dose and adalimumab, induction and maintenance, resulted in rapid resolution of the orbital myositis and ocular symptoms with no recurrences on follow-up at 10 months.ConclusionsThe current case demonstrates a rare extraintestinal manifestation of Crohn’s disease, orbital myositis, and its temporal relationship to the discontinuance of infliximab therapy and its successful treatment, without recurrence with tapering prednisone and adalimumab.