Canadian Association of Gastroenterology Clinical Practice Guideline for the Management of Luminal Crohn's Disease.

BACKGROUND & AIMS: Crohn's disease (CD) is a lifelong illness with substantial morbidity, although new therapies and treatment paradigms have been developed. We provide guidance for treatment of ambulatory patients with mild to severe active luminal CD. METHODS: We performed a systematic review to identify published studies of the management of CD. The quality of evidence and strength of recommendations were rated according to the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. Statements were developed through an iterative online platform and then finalized and voted on by a group of specialists. RESULTS: The consensus includes 41 statements focused on 6 main drug classes: antibiotics, 5-aminosalicylate, corticosteroids, immunosuppressants, biologic therapies, and other therapies. The group suggested against the use of antibiotics or 5-aminosalicylate as induction or maintenance therapies. Corticosteroid therapies (including budesonide) can be used as induction, but not maintenance therapies. Among immunosuppressants, thiopurines should not be used for induction, but can be used for maintenance therapy for selected low-risk patients. Parenteral methotrexate was proposed for induction and maintenance therapy in patients with corticosteroid-dependent CD. Biologic agents, including tumor necrosis factor antagonists, vedolizumab, and ustekinumab, were recommended for patients failed by conventional induction therapies and as maintenance therapy. The consensus group was unable to clearly define the role of concomitant immunosuppressant therapies in initiation of treatment with a biologic agent. CONCLUSIONS: Optimal management of CD requires careful patient assessment, acknowledgement of patient preferences, evidence-based use of existing therapies, and thorough assessment to define treatment success.

Medical Summary Template for the Transfer of Patients with Inflammatory Bowel Disease from Pediatric to Adult Care.

BACKGROUND: The transfer of information is a key aspect of the transition of adolescent patients with inflammatory bowel disease (IBD) from pediatric to adult care. This is typically accomplished through the use of a consultation letter with a medical summary of the patient being transferred. To improve the quality and completeness of information included in a transfer letter, we developed a standardized medical summary template by integrating the feedback of adult and pediatric health care providers. METHODS: To develop the letter template, we purposively sampled gastroenterologists or nurse practitioners caring for patients with IBD in four Canadian cities and invited them to take part in focus group discussions. Using a semi-structured approach, we explored the items deemed essential for inclusion in a transfer summary. Using the conventional content analysis framework, the focus group discussions were inductively coded to identify areas of priority for inclusion in the template. RESULTS: Four focus groups were conducted, comprising 17 health care providers of 30 invited (56.7% participation). The resulting medical summary template included the following major headings: patient/disease characteristics, therapeutics history (including medications and surgeries), clinical history and current status, noteworthy investigations, history of complications (including hospitalizations), family history, immunization history and psychosocial history. The template also addressed health system process factors (i.e., urgency of transfer, mode of delivery and confidentiality) to ensure a seamless transfer to adult care. CONCLUSIONS: The standardized medical summary template should be used by pediatric providers to ensure that essential patient information and disease characteristics are sent to an adult provider.

Prospective evaluation of anti-tumor necrosis factor therapy guided by magnetic resonance imaging for Crohn's perineal fistulas.

OBJECTIVES: Anti-tumor necrosis factor (TNF) therapy heals Crohn's fistulas clinically, but the rate, extent, and duration to achieve fistula track healing are unknown. METHODS: We sought to monitor deep healing, as indicated by magnetic resonance imaging (MRI), and to use this to determine treatment duration. Clinical and MRI fistula healing (at 6, 12, and 18 months), Crohn's Disease Activity Index (CDAI), Perianal Crohn's Disease Activity Index (PDAI), and the Inflammatory Bowel Disease Questionnaire were prospectively assessed. RESULTS: Thirty-four consecutive patients with perineal fistulas were treated with infliximab (19), adalimumab (7; all infliximab failures) and thalidomide (8). Median follow-up was 110 weeks (range, 74-161). Baseline MRI: 38% >or=2 tracks, 21% anolabial/rectovaginal. At latest follow-up, clinical fistula 'response' and 'closure' were seen in 50 and 46% of antibody-treated patients, respectively. All patients stopped thalidomide early due to side effects. Of 26 antibody-treated patients, at 6 (n=25), 12 (n=25), and 18 (n=20) months, respectively, MRI showed complete healing (20, 28, and 30%, respectively), improvement (68, 72, and 65%), no change (12, 0, and 0%) or worsening (0, 0, and 5%). MRI healing at 6 months (n=5) persisted at 12 and 18 months, including in two patients who stopped treatment at 6 months. Fistula history length and complexity did not influence the outcome. The only surgical intervention was seton insertion in one patient. The PDAI and CDAI scores decreased, and quality of life improved significantly at last follow-up. CONCLUSIONS: MRI fistula resolution was variable and slower than clinical healing. Prolonged treatment is often required for internal track resolution. Preliminary data suggest once MRI healing has occurred fistulas remain healed, while remaining on, or stopping anti-TNFalpha therapy. The use of a second antibody is clinically valuable.

Canadian Association of Gastroenterology Clinical Practice Guideline for the Management of Luminal Crohn's Disease.

BACKGROUND & AIMS: Crohn's disease (CD) is a lifelong illness with substantial morbidity, although new therapies and treatment paradigms have been developed. We provide guidance for treatment of ambulatory patients with mild to severe active luminal CD. METHODS: We performed a systematic review to identify published studies of the management of CD. The quality of evidence and strength of recommendations were rated according to the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. Statements were developed through an iterative online platform and then finalized and voted on by a group of specialists. RESULTS: The consensus includes 41 statements focused on 6 main drug classes: antibiotics, 5-aminosalicylate, corticosteroids, immunosuppressants, biologic therapies, and other therapies. The group suggested against the use of antibiotics or 5-aminosalicylate as induction or maintenance therapies. Corticosteroid therapies (including budesonide) can be used as induction, but not maintenance therapies. Among immunosuppressants, thiopurines should not be used for induction, but can be used for maintenance therapy for selected low-risk patients. Parenteral methotrexate was proposed for induction and maintenance therapy in patients with corticosteroid-dependent CD. Biologic agents, including tumor necrosis factor antagonists, vedolizumab, and ustekinumab, were recommended for patients failed by conventional induction therapies and as maintenance therapy. The consensus group was unable to clearly define the role of concomitant immunosuppressant therapies in initiation of treatment with a biologic agent. CONCLUSIONS: Optimal management of CD requires careful patient assessment, acknowledgement of patient preferences, evidence-based use of existing therapies, and thorough assessment to define treatment success.

Clinical Practice Guideline for the Medical Management of Perianal Fistulizing Crohn's Disease: The Toronto Consensus.

Background: Fistulas occur in about 25% of patients with Crohn's disease (CD) and can be difficult to treat. The aim of this consensus was to provide guidance for the management of patients with perianal fistulizing CD. Methods: A systematic literature search identified studies on the management of fistulizing CD. The quality of evidence and strength of recommendations were rated according to the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. Statements were developed through an iterative online platform using a modified Delphi process, then finalized, and voted on by a group of specialists. Results: The quality of evidence for treatment of fistulizing CD was generally of very low quality, and because of the scarcity of good randomized controlled trials (RCTs), these consensus statements generally provide conditional suggestions (5 of 7 statements). Imaging and surgical consultations were recommended in the initial assessment of patients with active fistulizing CD, particularly those with complicated disease. Antibiotic therapy is useful for initial symptom control. Antitumor necrosis factor (anti-TNF) therapy was recommended to induce symptomatic response, and continued use was suggested to achieve and maintain complete remission. The use of concomitant immunosuppressant therapies may be useful to optimize pharmacokinetic parameters when initiating anti-TNF therapy. When there has been an inadequate symptomatic response to medical management strategies, surgical therapy may provide effective fistula healing for some patients. Conclusions: Optimal management of perianal fistulizing CD requires a collaborative effort between gastroenterologists and surgeons and may include the evidence-based use of existing therapies, as well as surgical assessments and interventions when needed. 10.1093/ibd/izy247_video1izy247.video15978518763001.

Dynamics of the mucosa-associated flora in ulcerative colitis patients during remission and clinical relapse.

The colonic mucosa-associated flora (MAF) in patients with active ulcerative colitis (UC) (n = 13) was investigated by examining 16S rRNA gene signatures during remission and relapse against levels for controls (n = 5). Baseline reduction, temporal instability, and decrease of bacterial richness toward relapse were observed for UC patients, whereas the MAF for controls was stable over time.

Clinical Practice Guideline for the Medical Management of Perianal Fistulizing Crohn's Disease: The Toronto Consensus.

BACKGROUND: Fistulas occur in about 25% of patients with Crohn's disease (CD) and can be difficult to treat. The aim of this consensus was to provide guidance for the management of patients with perianal fistulizing CD. METHODS: A systematic literature search identified studies on the management of fistulizing CD. The quality of evidence and strength of recommendations were rated according to the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. Statements were developed through an iterative online platform using a modified Delphi process, then finalized, and voted on by a group of specialists. RESULTS: The quality of evidence for treatment of fistulizing CD was generally of very low quality, and because of the scarcity of good randomized controlled trials (RCTs), these consensus statements generally provide conditional suggestions (5 of 7 statements). Imaging and surgical consultations were recommended in the initial assessment of patients with active fistulizing CD, particularly those with complicated disease. Antibiotic therapy is useful for initial symptom control. Antitumor necrosis factor (anti-TNF) therapy was recommended to induce symptomatic response, and continued use was suggested to achieve and maintain complete remission. The use of concomitant immunosuppressant therapies may be useful to optimize pharmacokinetic parameters when initiating anti-TNF therapy. When there has been an inadequate symptomatic response to medical management strategies, surgical therapy may provide effective fistula healing for some patients. CONCLUSIONS: Optimal management of perianal fistulizing CD requires a collaborative effort between gastroenterologists and surgeons and may include the evidence-based use of existing therapies, as well as surgical assessments and interventions when needed.

Topical tacrolimus in the treatment of perianal Crohn's disease: exploratory randomized controlled trial.

BACKGROUND: The aim of this study is to evaluate the efficacy of topical tacrolimus in treating perianal Crohn's disease. METHODS: Nineteen patients, stratified into 7 with ulcerating, and 12 with fistulizing, perianal Crohn's disease were randomized to topical tacrolimus 1 mg/g (1 g ointment twice a day [bid]) or placebo for 12 weeks. Sixteen patients had been on, or were currently taking, azathioprine/6-MP, and 6 had received infliximab. The primary outcome in ulcerating disease was global improvement in perianal/anal lesions, as assessed by the attending physician; for fistulas, it was reduction of > or =50% of actively draining fistulas on 2 consecutive visits. Blood tacrolimus levels and adverse events were assessed. RESULTS: Three of 4 patients treated with topical tacrolimus for ulcerating disease improved compared with none of 3 in the placebo group. Complete healing was not achieved. In fistulizing disease, topical tacrolimus was not beneficial. Two tacrolimus-treated patients developed perianal abscesses, 1 after improvement in fistula drainage. Adverse events were otherwise infrequent and mild. Whole blood tacrolimus levels were detectable in only 2 patients and were low. CONCLUSIONS: These preliminary data suggest that topical tacrolimus is effective and safe in the treatment of perianal or anal ulcerating Crohn's disease. This therapy is unlikely to be beneficial in fistulizing perianal Crohn's disease, although a larger study is required to confirm this.

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.

Defining quality indicators for best-practice management of inflammatory bowel disease in Canada.

BACKGROUND: There is a paucity of published data regarding the quality of care of inflammatory bowel disease (IBD) in Canada. Clinical quality indicators are quantitative end points used to guide, monitor and improve the quality of patient care. In Canada, where universal health care can vary significantly among provinces, quality indicators can be used to identify potential gaps in the delivery of IBD care and standardize the approach to interprovincial management. METHODS: The Emerging Practice in IBD Collaborative (EPIC) group generated a shortlist of IBD quality indicators based on a comprehensive literature review. An iterative voting process was used to select quality indicators to take forward. In a face-to-face meeting with the EPIC group, available evidence to support each quality indicator was presented by the EPIC member aligned to it, followed by group discussion to agree on the wording of the statements. The selected quality indicators were then ratified in a final vote by all EPIC members. RESULTS: Eleven quality indicators for the management of IBD within the single-payer health care system of Canada were developed. These focus on accurate diagnosis, appropriate and timely management, disease monitoring, and prevention or treatment of complications of IBD or its therapy. CONCLUSIONS: These quality indicators are measurable, reflective of the evidence base and expert opinion, and define a standard of care that is at least a minimum that should be expected for IBD management in Canada. The next steps for the EPIC group involve conducting research to assess current practice across Canada as it pertains to these quality indicators and to measure the impact of each of these indicators on patient outcomes.

Long-term MRI-guided combined anti-TNF-α and thiopurine therapy for Crohn's perianal fistulas.

BACKGROUND: Anti-tumor necrosis factor (TNF) therapy heals many Crohn's disease (CD) anal fistulas clinically but the rate, extent, and durability of deep tissue healing and factors influencing long-term outcome are unknown. METHODS: Consecutive patients with CD-related perianal (anal, rectovaginal, anolabial) fistulas treated with infliximab or adalimumab were monitored prospectively both clinically and radiologically using magnetic resonance imaging (MRI). RESULTS: Forty-one consecutive patients with CD-related perianal fistulas were treated with infliximab (n = 32) or adalimumab (n = 9; following infliximab failure) in combination with a thiopurine (unless intolerant). Fifty-eight percent of all patients, comprising 66% and 43% of infliximab and adalimumab-treated patients, respectively, demonstrated remission or response at 3 years. Thirty-three percent of infliximab treated patients maintained clinical remission at 3 years. Radiological healing lagged behind clinical remission by a median of 12 months. The likelihood of clinical remission at any time was five times greater in patients who had early clinical response within 6 weeks than those without. A higher number of fistula tracts was associated with reduced clinical remission. All patients who achieved radiological healing maintained healing on infliximab treatment, while only 43% maintained healing after cessation of anti-TNF therapy. CONCLUSIONS: Combination anti-TNF and thiopurine therapy provides sustained benefit in patients with perianal CD fistula. Early clinical response is associated with subsequent clinical remission. Radiological healing is slower than clinical healing. Radiologically healed fistula tracts maintain healing on infliximab but can recur after cessation of therapy.

Immunosuppressive effects via human intestinal dendritic cells of probiotic bacteria and steroids in the treatment of acute ulcerative colitis.

BACKGROUND: In ulcerative colitis (UC) gut bacteria drive inflammation. Bacterial recognition and T-cell responses are shaped by intestinal dendritic cells (DCs); therapeutic effects of probiotic bacteria may relate to modulation of intestinal DC. The probiotic mixture, VSL#3, increases interleukin (IL)-10 and downregulates IL-12p40 production by DC in vitro. We evaluated in vivo effects of oral VSL#3 and steroids on colonic DC in patients with acute UC. METHODS: Rectal biopsies were obtained from patients with active UC before and after treatment with VSL#3, corticosteroids, or placebo, and from healthy controls. Myeloid colonic DC were studied from freshly isolated lamina propria cells using multicolor flow cytometry. Surface expression of activation markers, CD40, CD86, pattern recognition receptors, Toll-like receptor (TLR)-2 and TLR-4 were assessed. Changed function was measured from ongoing intracellular IL-10, IL-12p40, IL-6, and IL-13 production. RESULTS: Acute UC colonic myeloid DC were producing more IL-10 and IL-12p40 than control DC (P = 0.01). In VSL#3-treated patients DC TLR-2 expression decreased (P < 0.05), IL-10 production increased and IL-12p40 production decreased (P < 0.005); 10/14 patients on VSL#3 showed a clinical response. Corticosteroids also resulted in increased IL-10 and reduced IL-12p40 production by DC. Conversely, in patients on placebo, TLR-2 expression and intensity of staining for IL-12p40 and IL-6 increased (all P < 0.05); 5/14 patients on placebo showed a clinical response (P = NS). CONCLUSIONS: Despite small numbers of human colonic DC available, we showed that treatment of UC patients with probiotic VSL#3 and corticosteroids induced "favorable" intestinal DC function in vivo, increasing regulatory cytokines and lowering proinflammatory cytokines and TLR expression. These effects may contribute to therapeutic benefit.