Ustekinumab use in Crohn's disease: a Canadian tertiary care centre experience.

OBJECTIVES: Real world data regarding clinical response to ustekinumab in Crohn's disease is lacking. We report our experience of ustekinumab use using a novel subcutaneous (SC) induction strategy and aim to identify predictors of response. MATERIALS AND METHODS: A retrospective, observational study of compassionate ustekinumab use in Crohn's disease was conducted with the use of a standard or high dose SC induction protocol. Symptomatic response was assessed after 3 months (short-term), and if remaining on therapy, within 3-12 months (medium-term) and at least 12 months (long-term). Endoscopic or radiologic response was assessed when available. Survival analysis of time to failure (cessation of ustekinumab) and multivariate logistic regression to identify predictors of response were performed. RESULTS: Seventy-nine patients commenced ustekinumab, with six patients lost to follow-up and five asymptomatic at baseline. Symptomatic response was assessed in 68 patients; 56% (38) of patients had a short-term symptomatic response. Type of preceding anti-TNF response was the only significant predictor of short-term response, with primary non-response being a strong predictor. In the medium-term, symptomatic response occurred in 72% (30/42) of patients and endoscopic or radiologic response was achieved in 72% (26/36) of patients assessed. The median time to failure was 22 months. Maintenance dose escalation to 90 mg every 4 weeks was successful in three of 16 patients. CONCLUSIONS: Fifty-six percent of patients had short-term symptomatic response, with a history of primary non-response to prior anti-TNF therapy being a predictor of response. Dose escalation had only modest benefit.

Efficacy and safety of tenofovir disoproxil fumarate in pregnancy to prevent perinatal transmission of hepatitis B virus.

BACKGROUND & AIMS: Perinatal transmission of hepatitis B virus still occurs despite immunoprophylaxis in approximately 9% of children from highly viraemic mothers. Antiviral therapy in this setting has been suggested, however with limited evidence to direct agent choice. METHODS: We conducted a multi-centre, prospective, opt-in observational study of antiviral safety and efficacy in pregnant women with high viral load (>7 log IU/ml); lamivudine was used from 2007 to 2010 and tenofovir disoproxil fumarate (TDF) from late 2010. Outcomes of treated and untreated cohorts were compared. RESULTS: 120 women with 130 pregnancies used TDF (58), lamivudine (52 including four who switched due to TDF intolerance) and no therapy (20). 96% were HBeAg positive, with baseline viral load mean 7.8 log IU/ml (±0.72) and ALT median 25 U/L (18.75-33). Duration of antiviral theraphy before birth was mean 58 days (±19) TDF and 53 (±14) lamivudine. Viral load declined by 3.64 log IU/ml (±0.9) TDF and 2.81 log IU/ml (±1.33) lamivudine. Virologic failure (birth viral load >7 IU/ml) occurred in 3% and 18% respectively. Congenital abnormality rate and neonatal growth centiles were similar across cohorts. Perinatal transmission reduced significantly to 2% and 0% in TDF and lamivudine cohorts, compared with 20% in untreated. CONCLUSIONS: TDF in this setting is safe, effective and more potent than lamivudine. Antiviral therapy did not adversely impact obstetric or infant parameters. More TDF intolerance occurred than expected. Perinatal transmission was significantly reduced in antiviral therapy cohorts.

Medical Imaging in Small Bowel Crohn's Disease-Computer Tomography Enterography, Magnetic Resonance Enterography, and Ultrasound: "Which One Is the Best for What?".

BACKGROUND: Small bowel imaging in Crohn's disease (CD) is an important adjunct to endoscopy for the diagnosis, assessment of postoperative recurrence, and detection of complications. The best imaging modality for such indications though remains unclear. This systematic review aims to identify the imaging modality of choice considering the use of ultrasound (US), computed tomography enterography (CTE), and magnetic resonance enterography (MRE). METHODS: Databases were systematically searched for studies pertaining to the performance of US, CTE, and MRE, as compared with a predefined reference standard in the assessment of small bowel CD. RESULTS: Thirty-three studies, from a total of 1427 studies, were included in the final analysis. A comparable performance was demonstrated for MRE, CTE, and US for the diagnosis of small CD. Ultrasound was found to have the highest accuracy in the differentiation of inflammation and fibrosis. Postoperative recurrence detection was feasible with the use of MRE and US. All 3 modalities were shown to have a role in the detection of small bowel CD complications. The radiation exposure associated with CTE can be minimized by using lower radiation protocols. CONCLUSIONS: Ultrasound, CTE, and MRE all play an important role in the diagnosis and management of small bowel CD, with preference for a particular modality being influenced by specific indication, institution resources, and patient preference.

FOCUS: Future of fecal calprotectin utility study in inflammatory bowel disease.

AIM: To evaluate the perspective of gastroenterologists regarding the impact of fecal calprotectin (FC) on the management of patients with inflammatory bowel disease (IBD). METHODS: Patients with known IBD or symptoms suggestive of IBD for whom the physician identified that FC would be clinically useful were recruited. Physicians completed an online "pre survey" outlining their rationale for the test. After receipt of the test results, the physicians completed an online "post survey" to portray their perceived impact of the test result on patient management. Clinical outcomes for a subset of patients with follow-up data available beyond the completion of the "post survey" were collected and analyzed. RESULTS: Of 373 test kits distributed, 290 were returned, resulting in 279 fully completed surveys. One hundred and ninety patients were known to have IBD; 147 (77%) with Crohn's Disease, 43 (21%) Ulcerative Colitis and 5 (2%) IBD unclassified. Indications for FC testing included: 90 (32.2%) to differentiate a new diagnosis of IBD from Irritable Bowel Syndrome (IBS), 85 (30.5%) to distinguish symptoms of IBS from IBD in those known to have IBD and 104 (37.2%) as an objective measure of inflammation. FC levels resulted in a change in management 51.3% (143/279) of the time which included a significant reduction in the number of colonoscopies (118) performed (P < 0.001). Overall, 97.5% (272/279) of the time, the physicians found the test sufficiently useful that they would order it again in similar situations. Follow-up data was available for 172 patients with further support for the clinical utility of FC provided. CONCLUSION: The FC test effected a change in management 51.3% of the time and receipt of the result was associated with a reduction in the number of colonoscopies performed.

Patients with Ulcerative Colitis Are More Concerned About Complications of Their Disease than Side Effects of Medications.

BACKGROUND: Patients with ulcerative colitis (UC) are often fearful about medication side effects and how the disease will affect their future. Our aim was to better understand what aspects of UC, and UC management, are most concerning to patients, and how they would like to be informed about treatment options. METHODS: A Web-based survey was sent to UC patients throughout the United States and Australia. In addition to standard closed-response questions, audio clips were embedded in the survey and respondents showed their strength of agreement or disagreement using moment-to-moment affect-trace methodology. Standard quantitative analysis was used for the survey results, and cluster analysis was performed on the affect-trace responses. RESULTS: A total of 460 patients with UC (370 patients from the United States and 90 patients from Australia) responded to the survey. Of them, 53% of the respondents were women, with a mean age of 49 (range 19-81) years. Most patients (87%) wanted to share treatment decision making with their doctors. The majority, 98%, wanted more than just a basic understanding of their disease. Patients were most concerned about the risk of colorectal cancer (37%), and the possible need for an ileostomy (29%). Only 14% of patients indicated that side effects from medications were their biggest concern. On affect-trace analysis, the most divergence in opinion centered on the appropriate timing for colectomy. CONCLUSIONS: To facilitate informed treatment decisions for UC patients, in addition to reviewing the benefits and risks of medications, it is also important to discuss the best strategies for decreasing the risk of colectomy and colorectal cancer.