Live Rotavirus Vaccination Appears Low-risk in Infants Born to Mothers With Inflammatory Bowel Disease on Biologics.

BACKGROUND & AIMS: Biologic therapies in the context of inflammatory bowel disease and pregnancy lead to improved maternal and fetal outcomes. Placental transfer results in detectable drug concentrations in infants. Rotavirus infection results in diarrheal related hospitalizations; however, the live oral vaccine is not currently recommended in biologic exposed infants. The aim of this study was to assess the effect of maternal biologic therapies on the infant immune system and safety of live rotavirus vaccination in biologic-exposed infants. METHODS: Biologic-exposed infants underwent standardized clinical assessments, drug concentration, and immune function testing (complete blood count, differential, immunoglobulin levels, extended B-cell and T-cell subset enumeration, Recent Thymic Emigrants, regulatory T-cell numbers, mitogen stimulation assays, and review of T-cell Receptor Excision Circles in the newborn screen). Rotavirus vaccine-specific adverse effects following immunizations up to 42 days post the last dose of the vaccine series were recorded. RESULTS: There were 57 infants born to 52 mothers with inflammatory bowel disease exposed to infliximab (n = 21), adalimumab (n = 19), vedolizumab (n = 10), and ustekinumab (n = 7) in the third trimester for a median of 39 weeks (interquartile range, 38-39 weeks) at delivery. Immunologic assessments validated for age were normal in all infants despite median infliximab concentrations of 6.1 ug/mL (range, 0.4-28.8 ug/mL), adalimumab concentrations of 1.7 ug/mL (range, 0.7-7.9 ug/mL), ustekinumab concentrations of 0.6 ug/mL (range, 0-1.1), and undetectable for vedolizumab at 10.7 weeks (interquartile range, 9.4-12.4) of age. The live oral rotavirus vaccine series was provided to 50 infants with the first dose given at a median of 13 weeks of age. No adverse effects following immunization were reported. CONCLUSION: Immune function testing was normal, and administration of live rotavirus vaccination appeared low-risk in biologic-exposed infants irrespective of circulating drug levels.

A Novel Decision Aid Improves Quality of Reproductive Decision-Making and Pregnancy Knowledge for Women with Inflammatory Bowel Disease.

BACKGROUND: Women with inflammatory bowel disease (IBD) with poor IBD-specific reproductive knowledge experience more childlessness and fear of IBD medications in pregnancy. The Pregnancy in IBD Decision Aid (PIDA), developed by an international multidisciplinary team, offers personalized online decision support regarding pregnancy in IBD. AIMS: Assess the impact of PIDA on quality of reproductive decision-making and pregnancy-related knowledge among preconception (PC) and pregnant patients with IBD, and evaluate acceptability to patients and clinicians. METHODS: PC and pregnant patients with IBD aged 18-45 completed questionnaires pre- and post-PIDA to assess quality of decision-making (Decisional Conflict Scale (DCS); Decision Self-Efficacy Scale (DSES) and IBD-in-pregnancy knowledge (Crohn's and Colitis Pregnancy Knowledge Score (CCPKnow)). Paired t test assessed for differences pre- and post-PIDA. Patients and clinicians completed acceptability surveys. RESULTS: DCS and DSES were completed by 74 patients (42 Crohn's disease, 32 ulcerative colitis); 41 PC and 33 pregnant. DCS improved significantly post-PIDA in PC patients regarding pregnancy planning (t(40) = 4.83, p < 0.0001, Cohen's dz = 0.75) and in pregnant patients regarding medication management (t(32) = 2.37, p = 0.0242, dz = 0.41). DSES for PC patients improved significantly post-PIDA (t(40) = -3.56, p = 0.001, dz = -0.56). CCPKnow improved significantly post-PIDA in PC (t(42) = 4.93, p < 0.0001, dz = -0.75) and pregnant patients (t(32) = 5.1, p < 0.0001, dz = -0.89). PIDA was deemed optimal for length, readability, and content amount and considered highly useful by patients (n = 73) and clinicians (n = 14). CONCLUSIONS: Patients using PIDA developed an improved quality of reproductive decision-making and IBD-in-pregnancy knowledge. PIDA is an accessible tool that can empower women with IBD to make values-congruent, evidence-based decisions regarding pregnancy and may reduce voluntary childlessness.

Shared decision making in pregnancy in inflammatory bowel disease: design of a patient orientated decision aid.

BACKGROUND: Research has indicated a lack of disease-specific reproductive knowledge among patients with Inflammatory Bowel Disease (IBD) and this has been associated with increased "voluntary childlessness". Furthermore, a lack of knowledge may contribute to inappropriate medication changes during or after pregnancy. Decision aids have been shown to support decision making in pregnancy as well as in multiple other chronic diseases. A published decision aid for pregnancy in IBD has not been identified, despite the benefit of pre-conception counselling and patient desire for a decision support tool. This study aimed to develop and test the feasibility of a decision aid encompassing reproductive decisions in the setting of IBD. METHODS: The International Patient Decision Aid Standards were implemented in the development of the Pregnancy in IBD Decision Aid (PIDA). A multi-disciplinary steering committee was formed. Patient and clinician focus groups were conducted to explore themes of importance in the reproductive decision-making processes in IBD. A PIDA prototype was designed; patient interviews were conducted to obtain further insight into patient perspectives and to test the prototype for feasibility. RESULTS: Issues considered of importance to patients and clinicians encountering decisions regarding pregnancy in the setting of IBD included fertility, conception timing, inheritance, medications, infant health, impact of surgery, contraception, nutrition and breastfeeding. Emphasis was placed on the provision of preconception counselling early in the disease course. Decisions relating to conception and medications were chosen as the current focus of PIDA, however content inclusion was broad to support use across preconception, pregnancy and post-partum phases. Favourable and constructive user feedback was received. CONCLUSIONS: The novel development of a decision aid for use in pregnancy and IBD was supported by initial user testing.

A Randomized Trial Comparing High Definition Colonoscopy Alone With High Definition Dye Spraying and Electronic Virtual Chromoendoscopy for Detection of Colonic Neoplastic Lesions During IBD Surveillance Colonoscopy.

OBJECTIVES: Dye spraying chromoendoscopy (DCE) is recommended for the detection of colonic neoplastic lesions in inflammatory bowel disease (IBD). The majority of neoplastic lesions are visible endoscopically and therefore targeted biopsies are appropriate for surveillance colonoscopy. To compare three different techniques for surveillance colonoscopy to detect colonic neoplastic lesions in IBD patients: high definition (HD), (DCE), or virtual chromoendoscopy (VCE) using iSCAN image enhanced colonoscopy. METHODS: A randomized non-inferiority trial was conducted to determine the detection rates of neoplastic lesions in IBD patients with longstanding colitis. Patients with inactive disease were enrolled into three arms of the study. Endoscopic neoplastic lesions were classified by the Paris classification and Kudo pit pattern, then histologically classified by the Vienna classification. RESULTS: A total of 270 patients (55% men; age range 20-77 years, median age 49 years) were assessed by HD (n=90), VCE (n=90), or DCE (n=90). Neoplastic lesion detection rates in the VCE arm was non-inferior to the DCE arm. HD was non-inferior to either DCE or VCE for detection of all neoplastic lesions. In the lesions detected, location at right colon and the Kudo pit pattern were predictive of neoplastic lesions (OR 6.52 (1.98-22.5 and OR 21.50 (8.65-60.10), respectively). CONCLUSIONS: In this randomized trial, VCE or HD-WLE is not inferior to dye spraying colonoscopy for detection of colonic neoplastic lesions during surveillance colonoscopy. In fact, in this study HD-WLE alone was sufficient for detection of dysplasia, adenocarcinoma or all neoplastic lesions.

The Toronto Consensus Statements for the Management of Inflammatory Bowel Disease in Pregnancy.

BACKGROUND & AIMS: The management of inflammatory bowel disease (IBD) poses a particular challenge during pregnancy because the health of both the mother and the fetus must be considered. METHODS: A systematic literature search identified studies on the management of IBD during pregnancy. The quality of evidence and strength of recommendations were rated using the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. RESULTS: Consensus was reached on 29 of the 30 recommendations considered. Preconception counseling and access to specialist care are paramount in optimizing disease management. In general, women on 5-ASA, thiopurine, or anti-tumor necrosis factor (TNF) monotherapy for maintenance should continue therapy throughout pregnancy. Discontinuation of anti-TNF therapy or switching from combination therapy to monotherapy may be considered in very select low-risk patients. Women who have a mild to moderate disease flare while on optimized 5-ASA or thiopurine therapy should be managed with systemic corticosteroid or anti-TNF therapy, and those with a corticosteroid-resistant flare should start anti-TNF therapy. Endoscopy or urgent surgery should not be delayed during pregnancy if indicated. Decisions regarding cesarean delivery should be based on obstetric considerations and not the diagnosis of IBD alone, with the exception of women with active perianal Crohn's disease. With the exception of methotrexate, the use of medications for IBD should not influence the decision to breast-feed and vice versa. Live vaccinations are not recommended within the first 6 months of life in the offspring of women who were on anti-TNF therapy during pregnancy. CONCLUSIONS: Optimal management of IBD before and during pregnancy is essential to achieving favorable maternal and neonatal outcomes.

Targeted Biopsies Identify Larger Proportions of Patients With Colonic Neoplasia Undergoing High-Definition Colonoscopy, Dye Chromoendoscopy, or Electronic Virtual Chromoendoscopy.

BACKGROUND & AIMS: It is unclear what are the best and most appropriate endoscopic procedures for detecting colonic neoplasia in patients with long-term colonic inflammatory bowel disease (IBD). Dye chromoendoscopy (DCE) is the standard used in IBD surveillance colonoscopies. However, studies are needed to determine the optimal endoscopic technique for detecting dysplastic lesions. We investigated current practices used in surveillance colonoscopies by IBD gastroenterologists at a single tertiary center. We also determined the rate of neoplasia detection among different surveillance endoscopic techniques in an analysis of random or targeted biopsies. METHODS: We collected data on 454 patients with IBD (54.5% male; mean age, 50 y; mean disease duration, 14.5 y; 55.9% with ulcerative colitis, 42.7% with Crohn's disease, and 1.3% with indeterminate colitis) who underwent surveillance colonoscopy from April 2011 through March 2014 at the University of Calgary in Canada. Subjects were examined using white-light standard-definition endoscopy (WLE), high-definition (HD) colonoscopy, virtual electronic chromoendoscopy (VCE), or DCE; random or targeted biopsy specimens were collected. Endoscopic and histologic descriptions with suspected neoplasia were recorded. Rates of neoplasia detection by the different endoscopic procedures were compared using chi-square analysis. RESULTS: Of the patients analyzed, 27.7% had WLE endoscopy with random collection of biopsy specimens, 27.3% had HD colonoscopy with random collection of biopsy specimens, 14.1% had VCE with random collection of biopsy specimens, 0.9% had DCE with random collection of biopsy specimens, 12.8% had HD colonoscopy with collection of targeted biopsy specimens, 11.9% had VCE with collection of targeted biopsy specimens, and 5.3% had DCE with collection of targeted biopsy specimens. Neoplastic lesions were detected in 8.2% of the procedures performed in the random biopsy group (95% confidence interval, 5.6-11.7) and 19.1% of procedures in the targeted biopsy group (95% confidence interval, 13.4-26.5) (P < .001). Neoplasias were detected in similar proportions of patients by HD colonoscopy, VCE, or DCE, with targeted biopsy collection. CONCLUSIONS: In a large cohort of IBD patients undergoing surveillance colonoscopy, targeted biopsies identified greater proportions of subjects with neoplasia than random biopsies. Targeted collection of biopsy specimens appears to be sufficient for detecting colonic neoplasia in patients undergoing HD colonoscopy, DCE, or VCE, but not WLE.

Postoperative Mortality Among Patients With Inflammatory Bowel Diseases: A Systematic Review and Meta-analysis of Population-Based Studies.

BACKGROUND & AIMS: There have been varying reports of mortality after intestinal resection for the inflammatory bowel diseases (IBDs). We performed a systematic review and meta-analysis of population-based studies to determine postoperative mortality after intestinal resection in patients with IBD. METHODS: We searched Medline, EMBASE, and PubMed, from 1990 through 2015, to identify 18 articles and 3 abstracts reporting postoperative mortality among patients with IBD. The studies included 67,057 patients with ulcerative colitis (UC) and 75,971 patients with Crohn's disease (CD), from 15 countries. Mortality estimates stratified by emergent and elective surgeries were pooled separately for CD and UC using a random-effects model. To assess changes over time, the start year of the study was included as a continuous variable in a meta-regression model. RESULTS: In patients with UC, postoperative mortality was significantly lower among patients who underwent elective (0.7%; 95% confidence interval [CI], 0.6%-0.9%) vs emergent surgery (5.3%; 95% CI, 3.8%-7.4%). In patients with CD, postoperative mortality was significantly lower among patients who underwent elective (0.6%; 95% CI, 0.2%-1.7%) vs emergent surgery (3.6%; 95% CI, 1.8%-6.9%). Postoperative mortality did not differ for elective (P = .78) or emergent (P = .31) surgeries when patients with UC were compared with patients with CD. Postoperative mortality decreased significantly over time for patients with CD (P < .05) but not UC (P = .21). CONCLUSIONS: Based on a systematic review and meta-analysis, postoperative mortality was high after emergent, but not elective, intestinal resection in patients with UC or CD. Optimization of management strategies and more effective therapies are necessary to avoid emergent surgeries.

Funding a smoking cessation program for Crohn's disease: an economic evaluation.

OBJECTIVES: Patients with Crohn's disease (CD) who smoke are at a higher risk of flaring and requiring surgery. Cost-effectiveness studies of funding smoking cessation programs are lacking. Thus, we performed a cost-utility analysis of funding smoking cessation programs for CD. METHODS: A cost-utility analysis was performed comparing five smoking cessation strategies: No Program, Counseling, Nicotine Replacement Therapy (NRT), NRT+Counseling, and Varenicline. The time horizon for the Markov model was 5 years. The health states included medical remission (azathioprine or antitumor necrosis factor (anti-TNF), dose escalation of an anti-TNF, second anti-TNF, surgery, and death. Probabilities were taken from peer-reviewed literature, and costs (CAN$) for surgery, medications, and smoking cessation programs were estimated locally. The primary outcome was the cost per quality-adjusted life year (QALY) gained associated with each smoking cessation strategy. Threshold, three-way sensitivity, probabilistic sensitivity analysis (PSA), and budget impact analysis (BIA) were carried out. RESULTS: All strategies dominated No Program. Strategies from most to least cost effective were as follows: Varenicline (cost: $55,614, QALY: 3.70), NRT+Counseling (cost: $58,878, QALY: 3.69), NRT (cost: $59,540, QALY: 3.69), Counseling (cost: $61,029, QALY: 3.68), and No Program (cost: $63,601, QALY: 3.67). Three-way sensitivity analysis demonstrated that No Program was only more cost effective when every strategy's cost exceeded approximately 10 times their estimated costs. The PSA showed that No Program was the most cost-effective <1% of the time. The BIA showed that any strategy saved the health-care system money over No Program. CONCLUSIONS: Health-care systems should consider funding smoking cessation programs for CD, as they improve health outcomes and reduce costs.

The Fundamentals of Inflammatory Bowel Disease Management in Pregnancy: A Practical Review for the Gastroenterologist.

This narrative review explores the management of Inflammatory Bowel Disease (IBD) during pregnancy, emphasizing its unique challenges to maternal and fetal health, particularly within the Canadian Gastroenterology setting. Seven key principles are highlighted: 1) Preconception counselling, aiming for steroid-free remission confirmed by objective markers, should be routine for female IBD patients. 2) Medication safety, with an eye to future pregnancies, should be addressed upon initiation. Methotrexate and small molecules are contraindicated during pregnancy, while most 5-ASA therapies, biologics, and thiopurines can be continued throughout pregnancy and breastfeeding. Steroids, though not without risks, can be utilized if necessary. 3) Routine monitoring during remission should include serum biomarkers and fecal calprotectin each trimester. 4) Routine endoscopy and imaging are not required, but if indicated, lower GI endoscopy, ultrasound, and unenhanced MRI can be used. Computed tomography and gadolinium enhanced MRI should be avoided. 5) Caesarean section is advised for patients with previous ileal pouch surgeries or active perianal disease, but other patients should follow obstetric indications for delivery. 6) Postpartum period may see more active disease, requiring continued monitoring. Breastfeeding is encouraged, and routine childhood vaccinations are advised, but live vaccinations in the first 6 months warrant detailed review. 7) Complex IBD patients may benefit from a multidisciplinary approach with robust communication between gastroenterologists and obstetricians.