Vedolizumab for the Treatment of Chronic Pouchitis.

BACKGROUND: Approximately half the patients with ulcerative colitis who undergo restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) will subsequently have pouchitis, and among those patients, one fifth will have chronic pouchitis. METHODS: We conducted a phase 4, double-blind, randomized trial to evaluate vedolizumab in adult patients in whom chronic pouchitis had developed after undergoing IPAA for ulcerative colitis. Patients were assigned (in a 1:1 ratio) to receive vedolizumab intravenously at a dose of 300 mg or placebo on day 1 and at weeks 2, 6, 14, 22, and 30. All the patients received concomitant ciprofloxacin from weeks 1 to 4. The primary end point was modified Pouchitis Disease Activity Index (mPDAI)-defined remission (an mPDAI score of ≤4 and a reduction from baseline of ≥2 points in the mPDAI total score; scores range from 0 to 12, with higher scores indicating more severe pouchitis) at week 14. The mPDAI is based on clinical symptoms and endoscopic findings. Other efficacy end points included mPDAI-defined remission at week 34, mPDAI-defined response (a reduction from baseline of ≥2 points in the mPDAI score) at weeks 14 and 34, and PDAI-defined remission (a PDAI score of ≤6 and a reduction from baseline of ≥3 points; scores range from 0 to 18, with higher scores indicating more severe pouchitis) at weeks 14 and 34. The PDAI is based on clinical symptoms, endoscopic findings, and histologic findings. RESULTS: Among the 102 patients who underwent randomization, the incidence of mPDAI-defined remission at week 14 was 31% (16 of 51 patients) with vedolizumab and 10% (5 of 51 patients) with placebo (difference, 21 percentage points; 95% confidence interval [CI], 5 to 38; P = 0.01). Differences in favor of vedolizumab over placebo were also seen with respect to mPDAI-defined remission at week 34 (difference, 17 percentage points; 95% CI, 0 to 35), mPDAI-defined response at week 14 (difference, 30 percentage points; 95% CI, 8 to 48) and at week 34 (difference, 22 percentage points; 95% CI, 2 to 40), and PDAI-defined remission at week 14 (difference, 25 percentage points; 95% CI, 8 to 41) and at week 34 (difference, 19 percentage points; 95% CI, 2 to 37). Serious adverse events occurred in 3 of 51 patients (6%) in the vedolizumab group and in 4 of 51 patients (8%) in the placebo group. CONCLUSIONS: Treatment with vedolizumab was more effective than placebo in inducing remission in patients who had chronic pouchitis after undergoing IPAA for ulcerative colitis. (Funded by Takeda; EARNEST ClinicalTrials.gov number, NCT02790138; EudraCT number, 2015-003472-78.).

Treatment Algorithm for Chronic Idiopathic Constipation and Constipation-Predominant Irritable Bowel Syndrome Derived from a Canadian National Survey and Needs Assessment on Choices of Therapeutic Agents.

Background. Chronic idiopathic constipation (CIC) and constipation-predominant irritable bowel syndrome (IBS-C) are common functional lower gastrointestinal disorders that impair patients' quality of life. In a national survey, we aimed to evaluate (1) Canadian physician practice patterns in the utilization of therapeutic agents listed in the new ACG and AGA guidelines; (2) physicians satisfaction with these agents for their CIC and IBS-C patients; and (3) the usefulness of these new guidelines in their clinical practice. Methods. A 9-item questionnaire was sent to 350 Canadian specialists to evaluate their clinical practice for the management of CIC and IBS-C. Results. The response rate to the survey was 16% (n = 55). Almost all (96%) respondents followed a standard, stepwise approach for management while they believed that only 24% of referring physicians followed the same approach. Respondents found guanylyl cyclase C (GCC) agonist most satisfying when treating their patients. Among the 69% of respondents who were aware of published guidelines, only 50% found them helpful in prioritizing treatment choices and 69% of respondents indicated that a treatment algorithm, applicable to Canadian practice, would be valuable. Conclusion. Based on this needs assessment, a treatment algorithm was developed to provide clinical guidance in the management of IBS-C and CIC in Canada.

Site-Specific Immunomodulator: A Novel Treatment for Crohn's Disease.

We investigated the mechanism of action, safety, and efficacy of the Site-Specific Immunomodulator (SSI) QBECO, a novel immunotherapy for Crohn's disease (CD). Using human monocytic THP-1 cells, we demonstrate that SSI QBECO (derived from the common colon bacteria E. coli) activates macrophages to an M1 phenotype (associated with enhanced capacity to eliminate bacteria and activate innate immune responses). We assessed SSI QBECO in a compassionate use protocol of ten adult patients with active CD. Patients with moderate to severe clinical symptoms receiving conventional CD treatments and/or complementary therapies were included, except patients receiving anti-TNF medications. SSI QBECO was self-administered subcutaneously every second day, for a minimum of 2.5 months and a maximum of 11 months. All 10 patients reported improvement of symptoms while on the SSI QBECO treatment. Seven patients reported full resolution of clinical symptoms during a course of SSI QBECO of at least three months. Three patients have experienced ongoing sustained clinical remission after discontinuing all medications, including SSI treatment. The longest case of clinical remission is still ongoing (>4 years). No serious severe adverse clinical events were reported. Collectively, we conclude that treatment with the immunoactive SSI QBECO was well tolerated and effective for treatment of Crohn's disease in this case series.

A randomized controlled trial assessing the effect of prescribed patient position changes during colonoscope withdrawal on adenoma detection.

BACKGROUND: High-quality colonoscope withdrawal technique is associated with a higher adenoma detection rate. Position change is routinely used in barium enema and CT colonography to facilitate adequate distension of the colon and promote movement of fluid from the segment of the colon being assessed. OBJECTIVE: To determine whether prescribed position changes during colonoscope withdrawal affect the adenoma detection rate compared with the usual care per endoscopist. DESIGN: Prospective, randomized, controlled trial. SETTING: Tertiary-care, university-affiliated hospital. PATIENTS: Patients referred for outpatient colonoscopy between July 2011 and July 2012 were evaluated for eligibility. Inclusion criteria were outpatient status and age ≥40 years. Exclusion criteria were (1) complete colonoscopy within 1 year before the procedure, (2) inability to provide informed consent, (3) incomplete colonoscopy to the cecum, (4) previous bowel resection, (5) inflammatory bowel disease, (6) colonic polyposis syndrome, (7) inadequate bowel preparation, and (8) musculoskeletal disorder or other mobility issues limiting effective patient position changes during colonoscopy. INTERVENTIONS: Prescribed position changes during colonoscope withdrawal. MAIN OUTCOME MEASUREMENTS: Polyp detection rate (PDR) and adenoma detection rate (ADR). RESULTS: A total of 776 patients were enrolled, with 388 in the dynamic group. There was no difference in PDR (odds ratio [OR] 0.99; P = .93) or ADR (OR 1.17; P = .28). Colonoscope withdrawal time was longer in the dynamic group (median time 466.5 vs 422.5 seconds; P < .0001). LIMITATIONS: Single-center study. Indication for procedure not controlled. Lack of standardized bowel preparation and blinding. CONCLUSION: Prescribed position changes during colonoscope withdrawal do not affect polyp/adenoma detection compared with the usual practice when the baseline ADR is above the recommended standard. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT01395173.).

A survey of perceptions and practices of complementary alternative medicine among Canadian gastroenterologists.

BACKGROUND: Despite a high prevalence of complementary alternative medicine (CAM) use among inflammatory bowel disease (IBD) patients, there is a dearth of information about the attitudes and perceptions of CAM among the gastroenterologists who treat these patients. OBJECTIVE: To characterize the beliefs, perceptions and practices of gastroenterologists toward CAM use in patients with IBD. METHODS: A web-based survey was sent to member gastroenterologists of the Canadian Association of Gastroenterology. The survey included multiple-choice and Likert scale questions that queried physician knowledge and perceptions of CAM and their willingness to discuss CAM with patients. RESULTS: Fifty-three per cent of respondents considered themselves to be IBD subspecialists. The majority (86%) of gastroenterologists reported that less than one-half of their patient population had mentioned the use of CAM. Only 8% of physicians reported initiating a conversation about CAM in the majority of their patient encounters. Approximately one-half (51%) of respondents were comfortable with discussing CAM with their patients, with lack of knowledge being cited as the most common reason for discomfort with the topic. Most gastroenterologists (79%) reported no formal education in CAM. While there was uncertainty as to whether CAM interfered with conventional medications, most gastroenterologists believed it could be effective as an adjunct treatment. CONCLUSION: Our findings demonstrate that gastroenterologists were hesitant to initiate discussions about CAM with patients. Nearly one-half were uncomfortable or only somewhat comfortable with the topic, and most may benefit from CAM educational programs. Interestingly, most respondents appeared to be receptive to CAM as adjunct therapy alongside conventional IBD treatment.

The risks of post-operative complications following pre-operative infliximab therapy for Crohn's disease in patients undergoing abdominal surgery: a systematic review and meta-analysis.

BACKGROUND: Infliximab is an anti-TNF alpha blocker frequently utilized in the management of moderate to severe Crohn's Disease. The immunosuppressive effects of infliximab may increase the risk for post-operative complications among Crohn's Disease patients undergoing abdominal surgery. We conducted a systematic review and meta-analysis of studies comparing the rates of post-operative complications among Crohn's disease patients treated with Infliximab therapy versus alternative therapies. METHODS: We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and searched 4 electronic databases along with major conference abstract databases from inception of database until November, 2012. English-language articles and abstracts evaluating post-operative complications among Crohn's disease patients were considered eligible. We applied meta-analysis with random effects model to calculate the overall odds ratio for total major complications as well as several secondary outcomes. RESULTS: Data were extracted from six studies including 1159 patients among whom 413 complications were identified. The most common complications were wound infections, anastomotic leak and sepsis. There was no significant difference in the major complication rate (OR=1.59[95% CI: 0.89-2.86]; p=0.15), minor complication rate (OR=1.80 [CI: 0.87-3.71]; p=0.11), reoperation rate (OR=1.33 [CI: 0.55-3.20]; p=0.52) or 30 day mortality rate (OR=3.74 [CI: 0.56-25.16]; p=0.13) between the Infliximab and control groups. CONCLUSIONS: This meta analysis provides some evidence that infliximab may be safe to continue in the pre-operative period without increasing the risk of post-operative complications for Crohn's disease patients undergoing abdominal surgery.

Rates of new or missed colorectal cancers after colonoscopy and their risk factors: a population-based analysis.

BACKGROUND & AIMS: The rate of new or missed colorectal cancer (CRC) after colonoscopy and their risk factors in usual practice are unknown. Our objective was to evaluate the rate and risk factors in a population-based study. METHODS: We analyzed data from the Canadian Institute for Health Information, the Ontario Health Insurance Program, and Ontario Cancer Registry for all patients (> or =20 years of age) with a new diagnosis of right-sided, transverse, splenic flexure/descending, rectal or sigmoid CRC in Ontario from April 1, 1997 to March 31, 2002, who had a colonoscopy within the 3 years before their diagnosis. Patients with new or missed cancers were those whose most recent colonoscopy was 6 to 36 months before diagnosis. We examined characteristics that might be risk factors for new or missed CRC. RESULTS: We identified a diagnosis of CRC in 3288 (right sided), 777 (transverse), 710 (splenic flexure/descending), and 7712 (rectal or sigmoid) patients. The rates of new or missed cancers were 5.9%, 5.5%, 2.1%, and 2.3%, respectively. Independent risk factors for these cancers in men and women were older age; diverticular disease; right-sided or transverse CRC; colonoscopy by an internist or family physician; and colonoscopy in an office. CONCLUSIONS: Because having an office colonoscopy and certain patient, procedure, and physician characteristics are independent risk factors for new or missed CRC, physicians must inform patients of the small risk (2% to 6%) of these cancers after colonoscopy. The influence of type of physician and setting on the accuracy of colonoscopy, potentially modifiable risk factors, warrants further study.

Prospective evaluation of screening colonoscopy: who is being screened?

BACKGROUND: Universal access to medical procedures is deemed an advantage of the Canadian health care system. The purposes of this prospective study were to determine the degree to which the practice of colon cancer screening by colonoscopy differed among socioeconomic classes and to assess adherence to screening guidelines. METHODS: Consecutive patients scheduled to undergo colonoscopy at a single center between August 2000 and August 2002 completed a questionnaire that determined patient characteristics and indications for the procedure. The patients were divided into two groups: screening patients, defined as individuals who indicated they were undergoing colonoscopy for screening purposes and were asymptomatic, and a control group, which comprised patients undergoing colonoscopy because of symptoms. Statistical analysis was performed to determine if patients in the screening group had different characteristics with respect to socioeconomic class, compared with the control group. RESULTS: A total of 1088 patients completed the questionnaire: 707 (65%) had colonoscopy because of symptoms, compared with 381 (35%) who underwent a screening examination. Mean age and marital status were similar in both groups. Of all colonoscopy procedures, there was a significantly greater proportion of men undergoing colonoscopy for screening purposes: 199 (52.2%) vs. 294 (41.6%) in the symptomatic group ( p = 0.001). Based on the Cochran-Armitage test, patients in the screening group had significantly higher education levels ( p = 0.004) and household incomes ( p = 0.001). CONCLUSIONS: Income and education level, two indices of socioeconomic status, are statistically significantly higher in patients undergoing screening colonoscopy compared with those having colonoscopy for any other reason.