Tofacitinib as a Rescue Therapy for Ulcerative Colitis in Pregnancy.

Tofacitinib, a potentially teratogenic nonselective Janus Kinase inhibitor was used as salvage therapy for ulcerative colitis during pregnancy with corticosteroids, maintenance ustekinumab, and rectal 5-ASA therapy. Corticosteroid-free remission ensued, resulting in term delivery without congenital malformations and avoidance of colectomy.

Letting go of control: A qualitative descriptive study exploring parents' perspectives on their child's transition from pediatric to adult care for inflammatory bowel disease.

Parents of young adults with chronic disease are important stakeholders in their child's transition from pediatric to adult care. There remains a gap in characterizing the parent experience during transition. This study describes the experiences of 13 mothers of young adults with inflammatory bowel disease during their child's transition. Most parents expressed fear and sadness about their child transitioning. Themes relating to involvement in their child's adult care included: direct involvement (sub-themes: disease management; logistics of care); and indirect involvement. Reasons for involvement included themes of parent's feelings and child's circumstances. Themes of involvement were discussed in terms of previous research on parenting of children with chronic disease. We suggest that future efforts focus on improving empathy and understanding toward parents of transitioning children and providing resources on how they can best support their child during transition and transfer to adult care.

Normal Infant Immunologic Assessment and Uneventful Live Rotavirus Vaccination Despite Continuous Tofacitinib Exposure In Utero and During Breastfeeding.

Background: Janus kinase (JAK) inhibitors are effective for the treatment of inflammatory bowel disease (IBD). However, this class of medications is not recommended during pregnancy or breastfeeding based on animal data suggesting teratogenesis and recent reports of transmammary transfer after maternal ingestion, raising concerns for immune system development in babies exposed to these drugs. Methods: We present the case of a patient with IBD treated with a JAK inhibitor who decided to continue the medication throughout her pregnancy and during breastfeeding. This is the first reported case of a detailed immunologic profile in a baby exposed to tofacitinib in utero and during lactation. Results: A 30-year-old female with ulcerative colitis with previous exposure to vedolizumab and infliximab achieved complete remission with tofacitinib therapy. The patient became pregnant after 5 months of JAK inhibitor therapy and decided to continue tofacitinib during pregnancy and while breastfeeding. The patient delivered a healthy offspring with no congenital malformations, a normal detailed immunologic profile, and subsequent safe provision of the live oral rotavirus vaccine. Conclusions: This case highlights the importance of individualized counseling for patients of childbearing age who are candidates for JAK inhibition. Those who are pregnant or breastfeeding with refractory disease may have limited medical therapeutic options. Ongoing effective therapy for IBD resulted in complete disease remission in the mother and favorable outcomes in the infant. Further, an in-depth infant immunological assessment can lead to specific vaccination recommendations in exposed infants.

Recent Immigrants with Inflammatory Bowel Disease Have Significant Health-Care Utilization from Preconception to Postpartum: A Population Cohort Study.

BACKGROUND: Immigrants with inflammatory bowel disease (IBD) may have increased health-care utilization during pregnancy compared to non-immigrants, though this remains to be confirmed. We aimed to characterize this between these groups. METHODS: We accessed administrative databases to identify women (age 18-55) with IBD with a singleton pregnancy between 2003-2018. Immigration status was defined as recent (< 5 years of date of conception), remote (≥ 5 years since date of conception), and none. Differences in ambulatory, emergency department (ED), hospitalization, endoscopic, and prenatal visits during 12-months preconception, pregnancy and 12-months postpartum were characterized. Region of immigration origin was ascertained. Multivariable negative binomial regression was performed for adjusted incidence rate ratios (aIRR) with 95% confidence intervals (95% CI). RESULTS: 8880 pregnancies were included, 8304 in non-immigrants, 96 in recent immigrants, 480 in remote immigrants. Compared to non-immigrants, recent immigrants had the highest rates of IBD-specific ambulatory visits during preconception (aIRR 3.06, 95% CI, 1.93-4.85), pregnancy (aIRR 2.15, 95% CI, 1.35-3.42), and postpartum (aIRR 2.21, 1.37-3.57) and the greatest rates of endoscopy visits during preconception (aIRR 2.69, 95% CI, 1.64-4.41) and postpartum (aIRR 2.01, 95% CI, 1.09-3.70). There were no differences in ED and hospitalization visits between groups though those arriving from the Americas were the most likely to be hospitalized for any reason. All immigrants with IBD were less likely to have a first trimester prenatal visit. CONCLUSION: Recent immigrants were more likely to have IBD-specific ambulatory care but less likely to receive adequate prenatal care during pregnancy.

Thiopurine Exposure During Pregnancy is Not Associated With Anemia in Infants Born to Mothers With IBD.

Background: Thiopurines are commonly used to treat inflammatory bowel disease (IBD). Thiopurines are considered safe throughout pregnancy. However, a published study suggested the risk of neonatal anemia was increased if exposed to thiopurines in utero. This prospective cohort study aimed to determine if there is an increased risk of cytopenia among infants born to pregnant people with IBD, exposed or unexposed to thiopurines, compared to infants born to those without IBD. Methods: Pregnant IBD patients, with and without thiopurine exposure, and one cohort of control individuals were recruited over a 5-year period. Consenting individuals completed a questionnaire and infants had a complete blood cell count at the newborn heel prick. Anemia was defined as hemoglobin (Hb) < 140g/L. Descriptive statistics were used to characterize the study population. Fisher exact tests were used to examine differences in outcomes between groups, a P-value of < 0.05 was deemed significant. Results: Three cohorts were recruited: 19 IBD patients on thiopurines, 50 IBD patients not on thiopurines, and 37 controls (total of 106). Neonatal median Hb was not different with 177g/L (IQR 38g/L) for the IBD thiopurine group, 180.5g/L (IQR 40g/L) for the IBD non-thiopurine group, and 181g/L (IQR 37g/L) for the controls. Nineteen infants (18%) were cytopenic with 12 (11%) anemic, 6 (5.6%) thrombocytopenic, and 1 (0.94%) lymphopenic. Thiopurine exposure was only in one, mildly anemic, infant. Conclusions: These findings further support physicians and IBD patients contemplating pregnancy that current guidelines recommending thiopurine adherence do not lead to increased perinatal risk of anemia or cytopenia.

The 2023 Impact of Inflammatory Bowel Disease in Canada: The Influence of Sex and Gender on Canadians Living With Inflammatory Bowel Disease.

Sex (the physical and physiologic effects resulting from having specific combinations of sex chromosomes) and gender (sex-associated behaviours, expectations, identities, and roles) significantly affect the course of inflammatory bowel disease (IBD) and the experience of living with IBD. Sex-influenced physiologic states, like puberty, the menstrual cycle, pregnancy, and andropause/menopause may also impact and be impacted by IBD. While neither Crohn's disease nor ulcerative colitis is commonly considered sex-determined illnesses, the relative incidence of Crohn's disease and ulcerative colitis between males and females varies over the life cycle. In terms of gender, women tend to use healthcare resources at slightly higher rates than men and are more likely to have fragmented care. Women are more commonly prescribed opioid medications and are less likely than men to undergo colectomy. Women tend to report lower quality of life and have higher indirect costs due to higher rates of disability. Women are also more likely to take on caregiver roles for children with IBD. Women with IBD are more commonly burdened with adverse mental health concerns and having poor mental health has a more profound impact on women than men. Pregnant people with active IBD have higher rates of adverse outcomes in pregnancy, made worse in regions with poor access to IBD specialist care. The majority of individuals with IBD in Canada do not have access to a pregnancy-in-IBD specialist; access to this type of care has been shown to allay fears and increase knowledge among pregnant people with IBD.

Despite Increased Disease Activity, Women who Attended a Dedicated Inflammatory Bowel Disease and Pregnancy Clinic Had Infants With Higher Apgar Scores: A Population-Based Study.

BACKGROUND: Attendance at a subspecialty pregnancy clinic for women with inflammatory bowel disease (IBD) improves disease-specific pregnancy knowledge. We examined the impact of attendance at a dedicated IBD-pregnancy clinic on IBD and perinatal outcomes. METHODS: Using linked administrative databases in Alberta, Canada (2012-2019), we identified 1061 pregnant women with IBD who delivered singleton liveborn infants in-hospital who did (n = 314) and did not attend (n = 747) the clinic. Propensity score weighted multivariable log-binomial and multinomial logistic regression models were used to determine the risk of IBD and perinatal outcomes. RESULTS: The median number of clinic visits was 3 (Q1-Q3, 3-5), with 34.7% completing a preconception consultation. A greater proportion of women who attended lived near the clinic, were nulliparous, had a disease flare prior to pregnancy, and were on maintenance IBD medication (P < .05). Women who attended had increased risks of a disease flare during pregnancy (adjusted risk ratio [aRR], 2.02; 95% CI, 1.45-2.82), an IBD-related emergency department visit during pregnancy (aRR, 2.66; 95% CI, 1.92-3.68), and cesarean delivery (aRR, 1.78; 95% CI, 1.23-2.57). Despite this, clinic attendees had a decreased risk of delivering an infant with a low Apgar score at 1 minute (risk ratio [RR], 0.49; 95% CI, 0.32-0.76) and 5 minutes (RR, 0.32; 95% CI, 0.12-0.87). CONCLUSIONS: Women who attended a dedicated IBD-pregnancy clinic were more likely to have a disease flare prior to pregnancy, reflecting a more severe disease phenotype, but had similar perinatal outcomes and infants with better Apgar scores at birth. Our study suggests the value of these subspecialty clinics in providing enhanced IBD-specific prenatal care.

Immunological effects and safety of live rotavirus vaccination after antenatal exposure to immunomodulatory biologic agents: a prospective cohort study from the Canadian Immunization Research Network.

BACKGROUND: People with inflammatory or autoimmune diseases are recommended to continue immunomodulatory biologic agents throughout pregnancy. However, concerns regarding potential immunosuppression in infants exposed to biologic agents have led to recommendations to avoid live vaccines in the first 6-12 months of life. We aimed to examine whether live rotavirus vaccine could be administered safely to infants exposed to biologic agents, assessed in the Canadian Special Immunization Clinic (SIC) Network. METHODS: In this prospective cohort study, infants exposed to biologic agents in utero were referred to one of six SIC sites in Canada for rotavirus vaccination recommendations. Children with other contraindications to rotavirus vaccination or older than 15 weeks were excluded. Clinical and laboratory evaluations were conducted according to a standard clinical pathway. Data were collected for relevant medical history, pregnancy outcomes, biologic agent exposure history, physical examination, laboratory results of the child, SIC recommendations for rotavirus vaccination, rotavirus vaccine series completion, and adverse events after immunisation. After parental consent, deidentified data were transferred to a central database for analysis. Children recommended for rotavirus vaccination were followed up for 8 months after series initiation to ascertain severe and serious adverse events, including severe diarrhoea, vomiting, and intussusception. FINDINGS: Between May 1, 2017, and Dec 31, 2021, 202 infants were assessed and 191 eligible infants were enrolled (97 [51%] were female and 94 [49%] were male). When including those exposed to multiple agents, the most common biologic agents to which infants were exposed were infliximab (67 [35%] of 191), adalimumab (49 [26%]), ustekinumab (18 [9%]), and vedolizumab (17 [9%]). Biologic agent exposure continued into the third trimester for 178 (93%) infants. No clinically significant abnormalities in lymphocyte subsets, quantitative immunoglobulins, or mitogen responses were detected. After SIC assessment, rotavirus vaccination was recommended for 187 (98%) of 191 infants, all of whom were followed up. By end of follow-up on Aug 19, 2022, 168 (90%) infants had initiated rotavirus vaccination; 150 (80%) completed the series. No serious adverse events after immunisation were reported, but three (2%) infants required medical attention, one for vomiting and change in stools who was subsequently diagnosed with gastroesophageal reflux disease, one for rash on labia unrelated to vaccination, and one for vomiting and diarrhoea associated with a milk allergy. INTERPRETATION: Findings from this study suggest that lymphocyte subsets and the safety of live rotavirus vaccination are generally not affected by in-utero exposure to biologic agents. Rotavirus vaccination can be offered to infants exposed to anti-TNF agents in utero. FUNDING: Public Health Agency of Canada and Canadian Institutes of Health Research through the Canadian Immunization Research Network.

Differences in Healthcare Utilization in Women with and without Inflammatory Bowel Diseases During Preconception, Pregnancy and Postpartum: A Population-Based Cohort Study.

BACKGROUND AND AIMS: Compared to those without inflammatory bowel disease [IBD], women with IBD may have increased healthcare utilization during pregnancy and postpartum, though this remains to be confirmed. We aimed to characterize this healthcare use between these groups. METHODS: Administrative databases were accessed to identify women [aged 18-55 years] with and without IBD who had a live, singleton pregnancy between 2003 and 2018. Differences in emergency department [ED] visits, hospitalizations and prenatal care during 12 months preconception, pregnancy and 12 months postpartum were characterized. Multivariable negative binomial regression was performed to report incidence rate ratios [IRRs] with 95% confidence intervals [95% CIs]. Covariates included maternal age at conception, location of residence, socioeconomic status and maternal comorbidity. RESULTS: In total, 6163 women with IBD [9158 pregnancies] and 1091 013 women without IBD [1729 411 pregnancies] were included. Women with IBD were more likely to visit the ED [IRR 1.13, 95% CI 1.08-1.18] and be hospitalized [IRR 1.11, 95% CI 1.01-1.21] during pregnancy, and visit the ED [IRR 1.21, 95% CI 1.15-1.27] and be hospitalized [IRR 1.18, 95% CI 1.05-1.32] during postpartum. On unadjusted analysis, women with IBD were more likely to be hospitalized for venous thromboembolic events. There was no difference in healthcare use in preconception. Finally, women with IBD also had a greater number of prenatal visits during pregnancy and were more likely to receive a first-trimester prenatal visit. CONCLUSION: Women with IBD have increased healthcare utilization during pregnancy and postpartum. Efforts should be made to increase ambulatory care access during this period, which in turn may reduce this health-services utilization.

Transition Readiness in Youth with Inflammatory Bowel Disease.

OBJECTIVES: To examine readiness of adolescents and young adults (AYAs) with inflammatory bowel disease (IBD) to transition to adult care. STUDY DESIGN: A cross-sectional multicenter study evaluating transition readiness in individuals with IBD 16-19 years old prospectively recruited from 8 Canadian IBD centers using the validated ON Taking Responsibility for Adolescent to Adult Care (ON TRAC) questionnaire. Secondary aims included (1) screening for depression and anxiety using the 8-item Personal Health Questionnaire Depression Scale and The Screen for Child Anxiety Related Emotional Disorders questionnaires, respectively; (2) evaluating the association between depression and anxiety with readiness and disease activity; and (3) subjectively evaluating AYA readiness based on physician and parent assessments. RESULTS: In total, 186 participants (139 adolescent, 47 young adult) were enrolled, mean age 17.4 years (SD, 0.87). ON TRAC scores determined that 26.6% of AYAs at pediatric and 40.4% at adult centers reached the threshold of readiness. On multivariable linear regression analysis age was positively (P = .001) and disease remission negatively (P = .03) associated with ON TRAC scores. No statistically significant differences were determined across centers. A significant percentage of AYAs reported moderate-to-severe depression (21.7%) and generalized anxiety (36%); however, neither were significantly associated with ON TRAC scores. Notably, physician and parental assessment of AYA readiness correlated poorly with ON TRAC scores (⍴ = 0.11, ⍴ = 0.24, respectively). CONCLUSIONS: Assessment of transition readiness in AYAs with IBD highlighted that a large proportion do not have adequate knowledge or behavior skills needed for transition to adult care. This study infers that readiness assessment tools are essential during transition to identify deficits in knowledge and behavior skills that could be specifically targeted by the youth, caregivers, and multidisciplinary team.

Australian inflammatory bowel disease consensus statements for preconception, pregnancy and breast feeding.

OBJECTIVE: Because pregnancy outcomes tend to be worse in women with inflammatory bowel disease (IBD) than in those without, we aimed to update consensus statements that guide the clinical management of pregnancy in patients with IBD. DESIGN: A multidisciplinary working group was established to formulate these consensus statements. A modified RAND/UCLA appropriateness method was used, consisting of a literature review, online voting, discussion meeting and a second round of voting. The overall agreement among the delegates and appropriateness of the statement are reported. RESULTS: Agreement was reached for 38/39 statements which provide guidance on management of pregnancy in patients with IBD. Most medications can and should be continued throughout pregnancy, except for methotrexate, allopurinol and new small molecules, such as tofacitinib. Due to limited data, no conclusion was reached on the use of tioguanine during pregnancy. Achieving and maintaining IBD remission before conception and throughout pregnancy is crucial to optimise maternofetal outcomes. This requires a multidisciplinary approach to engage patients, allay anxieties and maximise adherence tomedication. Intestinal ultrasound can be used for disease monitoring during pregnancy, and flexible sigmoidoscopy or MRI where clinically necessary. CONCLUSION: These consensus statements provide up-to-date, comprehensive recommendations for the management of pregnancy in patients with IBD. This will enable a high standard of care for patients with IBD across all clinical settings.

Nutritional interventions in adult fibrostenotic Crohn's disease: A systematic review.

Background: Management of Crohn's disease (CD) using dietary interventions has become an area of increased research interest. There is a lack of specific research exploring if diet and nutrition interventions are beneficial in patients with strictures, as current dietary recommendations in fibrostenotic CD are often based on clinical judgment. The aim of this systematic review was to assess the impact of dietary interventions in fibrostenotic CD on medical and surgical outcomes. Methods: A systematic search of MEDLINE (Ovid), EMBASE (Ovid), CINAHL (EBSCO), and Cochrane Central Register of Controlled Trials (Ovid) was conducted. Studies reporting dietary interventions or nutritional factors in fibrostenotic CD were included. Outcomes for studies assessing dietary interventions such as enteral nutrition were evaluated as changes in (1) CD symptoms (CD Activity Index), (2) stricture parameters on diagnostic imaging, and (3) rates of surgical or medical intervention following dietary interventions. Results: Five studies were included in this review. Three studies assessed exclusive enteral nutrition (EEN), one evaluated total parenteral nutrition (TPN), and one studied a liquid diet. All included studies evaluated symptoms as an outcome, while diagnostic imaging parameters and surgical outcomes in the studies were either absent or too heterogeneous to appraise improvement post dietary intervention. Included EEN studies displayed similar efficacy, with approximately 60% of patients having symptom improvement. The included TPN study also reported 75% of patients with symptom improvement, while the liquid diet did not. Conclusion: Exclusive enteral nutrition and total parental nutrition may provide benefit for use as a dietary intervention for fibrostenotic CD. There remains a need for high-quality controlled trials which utilize standardized definitions of strictures.

Breastfeeding difficulties in the first 6 weeks postpartum among mothers with chronic conditions: a latent class analysis.

BACKGROUND: Breastfeeding difficulties frequently exacerbate one another and are common reasons for curtailed breastfeeding. Women with chronic conditions are at high risk of early breastfeeding cessation, yet limited evidence exists on the breastfeeding difficulties that co-occur in these mothers. The objective of this study was to explore clusters of breastfeeding difficulties experienced up to 6 weeks postpartum among mothers with chronic conditions and to examine associations between chronic condition types and breastfeeding difficulty clusters. METHODS: We analyzed 348 mothers with chronic conditions enrolled in a prospective, community-based pregnancy cohort study from Alberta, Canada. Data were collected through self-report questionnaires. We used latent class analysis to identify clusters of early breastfeeding difficulties and multinomial logistic regression to examine whether types of chronic conditions were associated with these clusters, adjusting for maternal and obstetric factors. RESULTS: We identified three clusters of breastfeeding difficulties. The "physiologically expected" cluster (51.1% of women) was characterized by leaking breasts and engorgement (reference outcome group); the "low milk production" cluster (15.4%) was discerned by low milk supply and infant weight concerns; and the "ineffective latch" cluster (33.5%) involved latch problems, sore nipples, and difficulty with positioning. Endocrine (adjusted relative risk ratio [RRR] 2.34, 95% CI 1.10-5.00), cardiovascular (adjusted RRR 2.75, 95% CI 1.01-7.81), and gastrointestinal (adjusted RRR 2.51, 95% CI 1.11-5.69) conditions were associated with the low milk production cluster, and gastrointestinal (adjusted RRR 2.44, 95% CI 1.25-4.77) conditions were additionally associated with the ineffective latch cluster. CONCLUSION: Half of women with chronic conditions experienced clusters of breastfeeding difficulties corresponding either to low milk production or to ineffective latch in the first 6 weeks postpartum. Associations with chronic condition types suggest that connections between lactation physiology and disease pathophysiology should be considered when providing breastfeeding support.

Innovative Care for Inflammatory Bowel Disease Patients during the COVID-19 Pandemic: Use of Bedside Intestinal Ultrasound to Optimize Management.

Background: The COVID-19 pandemic caused by SARS-CoV-2 has reduced access to endoscopy and imaging. Safe alternatives, available at the bedside, are needed for accurate, non-invasive strategies to evaluate disease activity. The aim of this study is to establish the impact of clinic-based bedside intestinal ultrasound (IUS) on decision making, reduction in reliance on endoscopy and short-term healthcare utilization. Methods: We conducted a prospective observational evaluation during the COVID-19 pandemic, of the impact of a regional comprehensive care pathway to manage IBD patients consecutively recruited with acute symptoms, or suspected new diagnosis of IBD. Clinic-based access to sigmoidoscopy and bedside intestinal ultrasound were evaluated, used to direct clinical care and avoid hospitalization or hospital-based endoscopy. Results: A total of 72 patients were seen between March 15 and June 30, 2020. Of these, 57% (41/72) were female, 64% had Crohn's disease (46/72) with 14% (10/72) presenting with symptoms requiring investigation, of which 5 new cases of IBD were identified (50%). Immediate access to ultrasound and sigmoidoscopy led to meaningful changes in management in 80.5% (58/72) of patients. Active inflammation was detected by IUS alone (72.5%, 29/40) or in combination with in-clinic sigmoidoscopy (78%, 18/23) or sigmoidoscopy alone (78% 7/9). Six patients were referred to colorectal surgery for urgent surgical intervention including two patients admitted directly. Conclusion: Implementation of IUS as part of a clinical care pathway during the COVID-19 pandemic is a useful strategy to enhance care delivery and improve clinical decisions, while sparing other important acute care resources.

Meta-analysis: Placebo rates in microscopic colitis randomised trials and applications for future drug development using a historical control arm.

BACKGROUND: Effective medical therapies for patients with microscopic colitis (MC) who fail budesonide are lacking. However, conducting randomised controlled trials (RCTs) in MC has been challenging due to small sample sizes. Understanding placebo responses can help inform more efficient future trials. AIMS: The aim of this study is to estimate clinical and histologic placebo response rates and to determine factors associated with placebo response in MC. METHODS: EMBASE, MEDLINE, and CENTRAL were searched until 7 January 2022, to identify placebo-controlled RCTs in adult patients with MC. Clinical and histologic response in the placebo arms were pooled using random-effects models. Stratified analyses based on disease- and trial-level characteristics, leave-one-out meta-analysis, and cumulative meta-analysis were performed. RESULTS: Twelve RCTs enrolling a total of 391 patients (placebo n = 163) with MC were included. Pooled clinical and histologic placebo response rates were 24.4% (95% CI: 12.4%-38.4%), I2  = 60.8%, p < 0.01, and 19.9% (95% CI: 5.3%-39.0%), I2  = 66.4%, p = 0.01 (tests for heterogeneity), respectively. Clinical response to placebo was numerically higher in patients with lymphocytic compared to collagenous colitis (39.9% vs. 19.8%, p = 0.08). Heterogeneity in clinical response to placebo was significantly reduced when the Miehlke 2014 RCT was excluded in the leave-one-out meta-analysis or when a more stringent secondary definition of response based on the Hjortswang criteria was applied. CONCLUSIONS: Approximately one-quarter of patients in MC trials respond to placebo, although with substantial heterogeneity, reflecting the need for standardised outcome definitions and study designs for MC. This analysis also serves to inform future MC trials that may consider incorporating an external, historical placebo control arm, rather than directly randomising patients to placebo.

Inflammatory Bowel Disease Among Canadian Children: Comparison Between Children of Non-European Descent and Children of European Descent.

BACKGROUND: Inflammatory bowel disease (IBD) phenotypes may differ between countries and ancestral groups. The study aim was to examine ancestry and subtype variations of children newly diagnosed with IBD. METHODS: Children newly diagnosed with IBD enrolled into the Canadian Children Inflammatory Bowel Disease Network inception cohort study were categorized into 8 ancestral groups. Prospectively collected data at diagnosis and follow-up were compared between ancestral groups. RESULTS: Among 1447 children (63.2% Crohn's disease, 30.7% ulcerative colitis), 67.8% were European, 9.4% were South Asian, 3.8% were West Central Asian and Middle Eastern, 2.3% were African, 2.2% were East/South East Asian, 2.0% were Caribbean/Latin/Central/South American, 9.9% were mixed, and 2.6% were other. Children of African descent with ulcerative colitis had an older age of diagnosis compared with children of European descent (median 15.6 years vs 13.3 years; P = .02). Children of European descent had a higher proportion of positive family history with IBD (19.3% vs 12.1%; P = .001) compared with children of non-European descent. Children of European descent also had a lower proportion of immigrants and children of immigrants compared with children of non-European descent (9.8% vs 35.9%; P < .0001; and 3.6% vs 27.2%; P < .0001, respectively) . CONCLUSIONS: Important differences exist between different ancestral groups in pediatric patients with IBD with regard to age of diagnosis, family history, and immigrant status. Our study adds to the knowledge of the impact of ancestry on IBD pathogenesis.

This study explores the ancestral and phenotypic variation of Canadian children newly diagnosed with inflammatory bowel disease. It identifies differences between children of European and non-European descent in phenotypes of inflammatory bowel disease, disease location and behavior, family history, and immigrant status.

Global Hospitalization Trends for Crohn's Disease and Ulcerative Colitis in the 21st Century: A Systematic Review With Temporal Analyses.

BACKGROUND & AIMS: The evolving epidemiologic patterns of inflammatory bowel disease (IBD) throughout the world, in conjunction with advances in therapeutic treatments, may influence hospitalization rates of IBD. We performed a systematic review with temporal analysis of hospitalization rates for IBD across the world in the 21st century. METHODS: We systematically reviewed Medline and Embase for population-based studies reporting hospitalization rates for IBD, Crohn's disease (CD), or ulcerative colitis (UC) in the 21st century. Log-linear models were used to calculate the average annual percentage change (AAPC) with associated 95% confidence intervals (95% CIs). Random-effects meta-analysis pooled country-level AAPCs. Data were stratified by the epidemiologic stage of a region: compounding prevalence (stage 3) in North America, Western Europe, and Oceania vs acceleration of incidence (stage 2) in Asia, Eastern Europe, and Latin America vs emergence (stage 1) in developing countries. RESULTS: Hospitalization rates for a primary diagnosis of IBD were stable in countries in stage 3 (AAPC, -0.13%; 95% CI, -0.72 to 0.97), CD (AAPC, 0.20%; 95% CI, -1.78 to 2.17), and UC (AAPC, 0.02%; 95% CI, -0.91 to 0.94). In contrast, hospitalization rates for a primary diagnosis were increasing in countries in stage 2 for IBD (AAPC, 4.44%; 95% CI, 2.75 to 6.14), CD (AAPC, 8.34%; 95% CI, 4.38 to 12.29), and UC (AAPC, 3.90; 95% CI, 1.29 to 6.52). No population-based studies were available for developing regions in stage 1 (emergence). CONCLUSIONS: Hospitalization rates for IBD are stabilizing in countries in stage 3, whereas newly industrialized countries in stage 2 have rapidly increasing hospitalization rates, contributing to an increasing burden on global health care systems.

Declining Corticosteroid Use for Inflammatory Bowel Disease Across Alberta: A Population-Based Cohort Study.

Background and Aims: Corticosteroid-free remission is a primary treatment goal in IBD which may be achieved with greater use of anti-TNF therapy. We defined temporal trends of corticosteroid use, anti-TNF use, hospitalization and surgery in a prevalent IBD cohort within the province of Alberta, Canada. Methods: Health administrative data were used to identify medication dispensing, hospitalizations and surgery in individuals with IBD from 2010 to 2015. Temporal trends were calculated using log-binomial regression for medications and log-linear models for hospitalizations and surgery rates. Analyses were stratified based on geographic location. Results: Of 28890 individuals with IBD, 50.3% had Crohn's disease. One in six individuals (15.45%) were dispensed a corticosteroid. Corticosteroid use decreased in both metropolitan areas (AAPC -20.08%, 95% CI: -21.78 to -18.04) and non-metropolitan areas (AAPC -18.14%, 95% CI: -20.78 to -18.04) with a similar pattern for corticosteroid dependence. Corticosteroid dependence was more prevalent in UC vs. CD (P < 0.05), and in the pediatric IBD cohort (13.45) compared to the adult (8.89) and elderly (7.54) cohorts (per 100 prevalent population, P < 0.001). The proportion of individuals dispensed an anti-TNF increased over the study period (AAPC 12.58%, 95% CI: 11.56 to 13.61). Significantly more non-metropolitan versus metropolitan residing individuals were hospitalized for any reason, for an IBD-related, or IBD-specific indication (all P < 0.001) though the proportion requiring IBD surgery was similar between groups. Conclusions: An increase in anti-TNF use corresponded to a decline in corticosteroid use and dependence in those with IBD. Inequities in IBD care still exist based on location and age.

Efficacy of Intravenous Ustekinumab Reinduction in Patients With Crohn's Disease With a Loss of Response.

Background/Aims: In patients receiving ustekinumab (UST) for treatment of Crohn's disease, there is no proven strategy to enhance or re-capture response. We assessed the utility of UST intravenous (IV) reinduction (~6 mg/kg) to achieve clinical, biochemical and endoscopic response or remission, in patients with partial or loss of response to UST maintenance therapy. Methods: A multicentre, retrospective cohort study was performed. Adults who received an IV reinduction dose of UST for either partial response or secondary loss of response to UST were assessed. The primary outcome was clinical remission off corticosteroids (Harvey Bradshaw Index <5), with biochemical response (defined as ≥ 50% decrease of CRP or FCP and/or endoscopic response (defined as a decrease in Simple Endoscopic Score-CD ≥ 50%). Secondary outcomes included clinical, biomarker and endoscopic response/remission, as well as safety. Results: Sixty-five patients (median age 38 years, 54.7% women) underwent IV UST reinduction between January 2017 and April 2019. Most patients (88.3%) were already on escalated maintenance dosing of UST 90 mg subcutaneous every 4 weeks. Clinical outcomes were assessed at a median of 14 weeks (IQR: 12-19) post-reinduction. The primary outcome of clinical remission off corticosteroids with biochemical and/or endoscopic response was achieved in 31.0% (n = 18). Pre-reinduction UST concentrations were ≥1 µg/mL in 88.6% (mean 3.2 ± 2.0 µg/mL). No serious adverse events were reported. Conclusions: UST IV reinduction can be effective in patients with Crohn's disease with partial or loss of response to UST maintenance therapy. Further studies evaluating this strategy are warranted.