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Background Diagnosis of monogenic disease is increasingly important for patient care and personalizing therapy. However, the current process is non-standardized, expensive, and time consuming. There is currently no accepted strategy to help identify disease-causing variants in monogenic inflammatory bowel disease (IBD). Aims To develop a prioritization strategy for monogenic IBD variant discovery through detailed analysis of a whole exome sequencing (WES) data set. Methods All consenting pediatric patients with IBD presenting to our tertiary care hospital during the study period were enrolled and underwent WES (n = 1005). Available family members also underwent WES. Variants were analyzed en mass using the GEMINI framework, and were further annotated using data from dbNSFP, CADD, and gnomAD. Known disease-causing variants (n = 36) were used as positive controls. Machine learning algorithms were optimized then compared to assist with identifying monogenic IBD case characteristics. Results Initial gene-level analysis identified 11 genes not previously linked to IBD that could potentially harbour IBD causing variants. Machine learning algorithms identified four primary variant characteristics (CADD score, dbNSFP score, relationship with a known immunodeficiency gene, and alternate allele frequency) and optimal threshold values for each were determined to assist with identifying monogenic IBD variants. Based on these characteristics, an automated variant prioritization pipeline was then created that filters and prioritizes variants from >100,000 variants per patient down to a mean of 15. This pipeline is available online for all to use. Conclusion Leveraging a large WES data set, we demonstrate a statistically rigorous strategy for prioritization of variants for monogenic IBD diagnosis.

The prevalence of inflammatory bowel diseases (IBD), Crohn’s disease and ulcerative colitis, in Canada, is over 0.75% in 2021. Many individuals with IBD are immunocompromised. Consequently, the World Health Organization’s declaration of a global pandemic uniquely impacted those with IBD. Crohn’s and Colitis Canada (CCC) formed the COVID-19 and IBD Taskforce to provide evidence-based guidance during the pandemic to individuals with IBD and their families. The Taskforce met regularly through the course of the pandemic, synthesizing available information on the impact of COVID-19 on IBD. At first, the information was extrapolated from expert consensus guidelines, but eventually, recommendations were adapted for an international registry of worldwide cases of COVID-19 in people with IBD. The task force launched a knowledge translation initiative consisting of a webinar series and online resources to communicate information directly to the IBD community. Taskforce recommendations were posted to CCC’s website and included guidance such as risk stratification, management of immunosuppressant medications, physical distancing, and mental health. A weekly webinar series communicated critical information directly to the IBD community. During the pandemic, traffic to CCC’s website increased with 484,755 unique views of the COVID-19 webpages and 126,187 views of the 23 webinars, including their video clips. CCC’s COVID-19 and IBD Taskforce provided critical guidance to the IBD community as the pandemic emerged, the nation underwent a lockdown, the economy reopened, and the second wave ensued. By integrating public health guidance through the unique prism of a vulnerable population, CCC’s knowledge translation platform informed and protected the IBD community.

Inflammatory bowel disease (IBD) is a disease that results from dysregulation of the immune system and frequently requires medications that can affect the immune response to infections; therefore, it was imperative to quickly understand the risk of coronavirus disease 2019 (COVID-19) infection on persons living with IBD and how that risk may be increased by commonly used IBD medications. The IBD research community in Canada and beyond quickly established collaborative efforts to better understand the specific risk posed by COVID-19 on persons with IBD. We learned that IBD itself was not a risk factor for death or serious complications of COVID-19, and that most commonly used drug classes (with the notable exception of corticosteroids) do not increase the risk of COVID-19-related adverse outcomes. The risk factors for serious complications and death from COVID-19 appear to be similar to those identified in the wider population; those being advanced age, having pre-existing heart or lung disease, and smoking. We recommend that persons with IBD do not alter their course of therapy to avoid complications of COVID-19, though the indiscriminate use of corticosteroids should be avoided. Persons with IBD should follow the same public health recommendations as the general population to reduce their personal risk of acquiring COVID-19.

The risk of hospitalization and death from Coronavirus disease-19 (COVID-19) increases with age. The extreme elderly have been particularly vulnerable, with those above the age of 80 having a case-fatality rate as high as 15%. Aging of the immune system can lead to impaired inflammatory responses where eradication of an organism such as Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV2) is inadequate but is exaggerated in such a way as to enhance pneumonia and acute respiratory distress syndrome. Frailty and comorbidity are both more common in the elderly, and these can enhance the morbidity and mortality from COVID-19. Studies from Northern California and Italy suggest that elderly persons with inflammatory bowel disease (IBD) were more likely to acquire SARS-CoV-2 infection than youths with IBD. While the specific impact of age-related comorbidity is less well established among people with IBD who acquire COVID-19, data from the Surveillance Epidemiology of Coronavirus Under Research Exclusion (SECURE-IBD) database reported that having two or more chronic illnesses was independently associated with developing severe COVID-19 among people with IBD. Despite having exaggerated auto-inflammatory responses, people with IBD do not appear to have an overall increased risk of developing severe COVID-19 than the general population. However, whether seniors with IBD do worse once they acquire COVID-19 compared with seniors without IBD is not known. The advent of telehealth care has posed an information technology challenge for many seniors with and without IBD. Most persons with IBD have expressed satisfaction with virtual IBD health care (phone or video-based visits). While the elderly may have less robust immune responses to vaccinations, learning from experiences with other vaccination programs, especially influenza, have shown that vaccinating seniors decreases both morbidity and mortality and, in turn, healthcare resources.

At the beginning of the coronavirus disease 2019 (COVID-19) pandemic, there were many unknowns: transmission vectors of the virus, appropriate intervention strategies and if being immunocompromised due to inflammatory bowel disease (IBD), for example, or medications put a person at increased risk for severe COVID-19. Imposing and relaxing of public health restrictions at different times and in different regions in Canada led to different epidemiologies of the virus in different provinces and territories. In order to understand the waxing and waning of waves of the COVID-19 pandemic, it is necessary to understand the effective reproductive number (Rt) and the countervailing forces that exert upward or downward pressure on the spread of the virus at a given point in time. As many regions in Canada deal with a third wave, the primary forces affecting the Rt of severe acute respiratory syndrome coronavirus 2 are variants of concern and the increasing vaccinations of Canadians leading to increased population-level immunity. Fortunately, for the IBD population, current research suggests that those with IBD are not at increased risk of contracting COVID-19, nor of having a more severe disease course when compared to the general population.

Coronavirus disease 2019 (COVID-19) in children with inflammatory bowel disease (IBD) typically results in a mild infection, similar to those without IBD. Children and adolescents have less severe manifestations of COVID-19 compared to older people, whether or not they have IBD. However, some IBD medications (in particular, corticosteroids) are associated with more severe COVID-19. During the first year of the global pandemic, more IBD care was provided with online technology, necessitated by efforts to reduce hospital and clinic visits. Additionally, non-endoscopic monitoring of inflammation has been required due to the cancellation of non-urgent procedures, resulting in longer endoscopy wait-times. In contrast, pregnant people (with and without IBD) who contract COVID-19 are at increased risk of severe manifestations, death and preterm delivery, making them a priority for severe acute respiratory syndrome coronavirus 2 protective measures and vaccination. Few studies have examined effect of COVID-19 on IBD-related disease activity in pregnant people with IBD. The pandemic has significantly affected the mental health and sense of well-being of children and their families, as well as pregnant people with IBD. These groups were much more likely to experience anxiety and depression compared with prior to the pandemic, even while concern has mostly abated regarding the effect of IBD medications and COVID-19 severity. Unfortunately, the availability of mental health care providers who specialize in people with IBD has not kept pace with the increasing demand.

The COVID-19 pandemic has ushered a globally focused vaccine development program that produced multiple successful vaccines within a year. Four SARS-CoV-2 vaccines have been approved for use in Canada, using two different technologies, all of which have shown excellent efficacy in reducing the rate of symptomatic COVID-19 infection and 100% efficacy in preventing death from COVID-19. People with inflammatory bowel disease (IBD), like many others with immune-mediated chronic diseases, were excluded from the pivotal trials of these vaccines, leading to early hesitancy by regulatory bodies to endorse administering the vaccines to these groups. However, recent data has shown that the adverse event rate to SARS-CoV-2 vaccine among people with IBD is similar to the general population. Early data has further shown that people with IBD are capable of mounting a robust immune response to SARS-CoV-2 vaccines, particularly following a second dose, whereas the response to the first dose is blunted in those receiving anti-TNF therapy or conventional immunosuppressants (azathioprine, 6-mercaptopurine, methotrexate). Based on these data and evidence from previous vaccine programs among people with IBD, multiple national and international expert panels have recommended that individuals with IBD receive complete vaccination against SARS-CoV-2 as soon as possible.

Jasbir Dhaliwal,1– 6 Meltem Tuna,1 Baiju R Shah,1,7,8 Sanjay Murthy,1,9,10 Emily Herrett,4 Anne M Griffiths,2,3 Eric I Benchimol1– 3,8 1ICES, Toronto, ON, Canada; 2SickKids Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, ON, Canada; 3Department of Paediatrics, University of Toronto, Toronto, ON, Canada; 4London School of Hygiene and Tropical Medicine, London, UK; 5Cincinnati Children’s Hospital Medical Center, Division of Gastroenterology, Hepatology and Nutrition, Cincinnati, OH, USA; 6Department of Pediatrics, University of Cincinnati, Cincinnati, OH, USA; 7Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON, Canada; 8Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada; 9The Ottawa Hospital IBD Centre, The Ottawa Hospital and Ottawa Hospital Research Institute, Ottawa, ON, Canada; 10Department of Medicine and School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON, CanadaCorrespondence: Jasbir DhaliwalPediatrics, University of Cincinnati, Cincinnati Children’s Hospital Medical Center, Division of Gastroenterology, Hepatology and Nutrition, Secondary Appointments in Division of Biomedical Informatics and James M Anderson Center for Health Systems Excellence, 3333 Burnet Avenue, Cincinnati, OH, 45229, USATel +15133789468Email Jasbir.dhaliwal@cchmc.orgBackground: Inflammatory bowel disease (IBD) is now a global disease with incidence increasing throughout Asia.Aim: To determine the incidence of IBD among South Asians and Chinese people residing in Ontario, Canada’s most populous province.Methods: All incident cases of IBD in children (1994– 2015) and adults (1999– 2015) were identified from population-based health administrative data. We classified South Asian and Chinese ethnicity using immigration records and surnames. We determined standardized incidence of IBD and adjusted incidence rate ratio (aIRR) in South Asians and Chinese compared to the general population.Results: Among 16,230,638 people living in Ontario, standardized incidence of IBD per 100,000 person-years was 24.7 (95% CI 24.4– 25.0), compared with 14.6 (95% CI 13.7– 15.5) in 982,472 South Asians and with 5.4 (95% CI 4.8– 5.9) in 764,397 Chinese. The risk of IBD in South Asians was comparable to the general population after adjusting for immigrant status and confounders (aIRR 1.03, 95% CI 0.96– 1.10). South Asians had a lower risk of Crohn’s disease (CD) (aIRR 0.66, 95% CI 0.60– 0.77), but a higher risk of ulcerative colitis (UC) (aIRR 1.47, 95% CI 1.34– 1.61). Chinese people had much lower rates of IBD (aIRR 0.24, 95% CI 0.20– 0.28), CD (aIRR 0.21, 95% CI 0.17– 0.26), and UC (aIRR 0.28, 95% CI 0.23– 0.25).Conclusion: Canadians of South Asian ethnicity had a similarly high risk of developing IBD compared to other Canadians, and a higher risk of developing UC, a finding distinct from the Chinese population. Our findings indicate the importance of genetic and environmental risk factors in people of Asian origin who live in the Western world.Keywords: inflammatory bowel disease, ulcerative colitis, Crohn’s disease, incidence, ethnicity, epidemiology, South Asian, Chinese

Background and Aims Age is a major prognostic factor for COVID-19 outcomes. The effect of inflammatory bowel disease [IBD] activity on COVID-19 is unclear. We examined the relationship between IBD activity and COVID-19 severity according to age. Methods We included IBD patients diagnosed with COVID-19, reported to SECURE-IBD between March 13, 2020 and August 3, 2021. Clinical IBD activity was measured by physician global assessment [PGA]. COVID-19-related outcomes were [1] intensive care unit [ICU] admission, ventilation or death, and [2] hospitalization. Using generalized estimating equations, we determined adjusted odds ratios [aOR, 95% confidence interval] for moderate and severe PGA vs clinical remission/mild PGA, controlling for demographics, medications and COVID-19 diagnosis period. We performed stratified analyses by age [≤50 vs >50 years]. Results Among 6078 patients, adverse COVID-19 outcomes were more common with active IBD: ICU/ventilation/death in 3.6% [175/4898] of remission/mild, 4.9% [45/920] of moderate and 8.8% [23/260] of severe [p < 0.001]; and hospitalization in 13% [649/4898] of remission/mild, 19% [178/920] of moderate and 38% [100/260] of severe [p < 0.001]. Stratified by decade, effect sizes were larger for younger patients. In patients ≤50 years, severe PGA was independently associated with ICU/ventilation/death (aOR 3.27 [1.15–9.30]) and hospitalization (aOR 4.62 [2.83–7.55]). In contrast, severe PGA was not independently associated with COVID-19 outcomes in those older than 50 years. Conclusions Clinically active IBD may be a risk factor for severe COVID-19, particularly in younger patients. IBD disease control, including through medication compliance, and strategies to mitigate the risk of COVID-19 infection amongst patients with active IBD [e.g. distancing, immunization] are key to limit adverse COVID-19 outcomes.

Inflammatory bowel diseases (IBDs), including Crohn's disease (CD) and ulcerative colitis, are chronic diseases of the gastrointestinal tract, with an unknown etiology, that affect over 6.8 million people worldwide. To characterize disease pathogenesis, proteomic and bioinformatic analyses were performed on colon biopsies collected during diagnostic endoscopy from 119 treatment-naïve pediatric patients, including from 78 IBD patients and 41 non-IBD patients who served as controls. Due to the presence of noninflamed and/or inflamed regions in IBD patients, up to two biopsies were obtained from IBD patients as compared to a single noninflamed biopsy from non-IBD pediatric control patients. Additional biopsies were obtained and analyzed from 33 of the IBD patients after IBD-directed therapeutic intervention for comparison of pre- and post-treatment proteomes. SuperSILAC was utilized to perform quantitative analysis of homogenized tissues, which were processed by filter-aided sample preparation. Hierarchical clustering and principal component analyses revealed proteomic patterns that distinguished inflamed from noninflamed tissues independent of therapy. Gene ontology revealed that proteins downregulated in inflammation are associated with metabolism, whereas upregulated proteins contribute to protein processing. A comparison of pre- and post-treatment proteomes from CD patients identified over 100 proteins that are significantly different between patients who responded and those who did not respond to therapy, including creatine kinase B and basigin.

Background and Aims Although venous thromboembolism [VTE] is a well-known complication of inflammatory bowel disease [IBD] in adults, limited data exist on the risk in children. We report the incidence of VTE among children with and without IBD. Methods We conducted a matched cohort study within a distributed network of population-based Canadian provincial health administrative databases. Children Results The 5-year incidence of VTE among 3593 children with IBD was 31.2 [95% CI 23.7–41.0] per 10 000 person-years [PY] compared to 0.8 [95% CI 0.4–1.7] per 10 000 PY among 16 289 children without IBD [unadjusted IRR 38.84, 95% CI 16.59–90.83; adjusted HR 22.91, 95% CI 11.50–45.63]. VTE was less common in Crohn’s disease than ulcerative colitis [unadjusted IRR 0.47, 95% CI 0.27–0.83; adjusted HR 0.52, 95% CI 0.29–0.94]. The findings were similar for deep vein thrombosis and pulmonary embolism when comparing children with and without IBD. Conclusions The risk of VTE is much higher in children with IBD than controls without IBD. While the absolute risk is low, we found a higher incidence rate than previously described in the pediatric literature. Conference Presentation: An abstract based on the data included in this paper was presented at Canadian Digestive Diseases Week [Montréal, Canada] in March 2020.

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.

Background Modern, specialised care for children with inflammatory bowel disease [IBD] may have resulted in changes in health services use. We report trends over time in health services utilisation and surgery for children with IBD and children without IBD. Methods Children aged Results IBD-specific hospitalisation rates decreased by 2.5% [95% CI 1.8–3.2%] annually, and all-cause hospitalisation rates in children without IBD decreased by 4.3% [95% CI 3.5–5.1%] annually. Intestinal resection risk in CD decreased by 6.0% [95% CI 4.6–7.3%] annually and colectomy risk in UC decreased by 3.0% [95% CI 0.7–5.2%] annually. In contrast, IBD-specific outpatient visit rates increased after 2005 by 4.0% [95% CI 3.1–4.9%] annually. Similar trends in outpatient visits were not observed in children without IBD. Conclusions Hospitalisations and surgeries decreased over time while outpatient visits increased after 2005. Decreasing hospitalisations were mirrored in children without IBD, likely resulting from a combination of changes in disease management and health system factors.

INTRODUCTION Environmental factors related to urbanization and industrialization are believed to be involved in inflammatory bowel disease (IBD) development, but no study has looked at the association between greenspace and IBD. METHODS We conducted a retrospective cohort study using linked population-based health administrative and environmental data sets. The study population comprised 2,715,318 mother-infant pairs from hospital births in Ontario, Canada, between April 1, 1991, and March 31, 2014. We measured the exposure to residential greenspace using the normalized difference vegetation index derived using remote-sensing methods. Average greenspace was estimated for the pregnancy and childhood periods. We used mixed-effects Cox proportional hazard models to assess potential associations between residential greenspace and the risk of developing IBD before 18 years while adjusting for covariates including sex, maternal IBD, rural/urban residence at birth, and neighborhood income. RESULTS There were 3,444 IBD diagnoses that occurred during follow-up. An increase in the interquartile range of residential greenspace during the childhood period was associated with a lower risk of developing pediatric-onset IBD (hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.74-0.81). This relationship was significant for both ulcerative colitis (HR 0.72 95% CI 0.67-0.78) and Crohn's disease (HR 0.81, 95% CI 0.76-0.87). There was a linear dose response across increasing quartiles of greenspace (P < 0.0001). No consistent association was detected between maternal intrapartum greenspace exposure and pediatric-onset IBD. DISCUSSION Higher exposure to residential greenspace during childhood was associated with a reduced risk of IBD, suggesting a novel avenue to prevent IBD in children.

Background and Aims Surgical treatment of inflammatory bowel disease (IBD) may impair female fertility. We conducted a systematic review to determine the risk of infertility and pregnancy outcomes in women with IBD who underwent surgery. Methods We identified studies evaluating the impact of IBD surgery on infertility and pregnancy outcomes. Risk ratios (RR) and 95% confidence intervals (CIs) were pooled when data were presented using contingency tables. Odds ratios (OR) were pooled when raw numbers were not provided. GRADE was used to evaluate the certainty of evidence. Results Sixteen observational studies were included, comparing women with and without surgery, open and laparoscopic surgery and before and after surgery. All studies were of low quality. The effect of surgery on infertility at 12 months (RR 5.45, 95% CI 0.41 to 72.57) was uncertain. Similarly, the fertility effects of laparoscopic versus open surgery method were unclear (RR 0.70, 95% CI 0.38 to 1.27). The impact of IBD surgery on pregnancy outcomes should be interpreted with caution. Surgery was associated with miscarriage (OR 2.03, 95% CI 1.14 to 3.60), use of assisted reproductive technologies (RR 25.09, 95% CI 1.56 to 403.76) and caesarean section (RR 2.23, 95% CI 1.00 to 4.95), but not with stillbirth (RR 1.96, 95% CI 0.42 to 9.18), preterm birth (RR 1.91, 95% CI 0.67 to 5.48), low birth weight (RR 0.61, 95% CI 0.08 to 4.83) or small for gestational age (RR 2.54, 95% CI 0.80 to 8.01). Conclusion The effect of surgical therapy for IBD on rates of female infertility and pregnancy-related outcomes was uncertain due to poor quality of existing literature.

Background Inflammatory bowel disease (IBD) is associated with a high risk of venous thromboembolism (VTE) during hospitalization. It is unclear if this association persists after discharge. We aimed to assess the incidence of postdischarge VTE in IBD patients and to determine if IBD is associated with increased VTE risk. Methods We performed a population-based cohort study between 2002 and 2016 using Ontario health administrative data sets. Hospitalized (≥72 hours) adults with IBD were stratified into nonsurgical and surgical cohorts and matched on propensity score to non-IBD controls. Time to postdischarge VTE was assessed by Kaplan-Meier methods, and VTE risk was assessed by Cox proportional hazard models. Results A total of 81,900 IBD discharges (62,848 nonsurgical and 19,052 surgical) were matched to non-IBD controls. The cumulative incidence of VTE at 12 months after discharge was 2.3% for nonsurgical IBD patients and 1.6% for surgical IBD patients. The incidence increased in the nonsurgical IBD cohort by 4% per year (incidence rate ratio, 1.04; 95% CI, 1.02–1.05). In our propensity score-matched analysis, the risk of VTE at 1-month postdischarge was greater in nonsurgical IBD patients (hazard ratio [HR], 1.72; 95% CI, 1.51–1.96) and surgical patients with ulcerative colitis (HR, 1.68; 95% CI, 1.16–2.45) but not surgical patients with Crohn’s disease. These trends persisted through 12 months. Conclusions Nonsurgical IBD patients and surgical patients with ulcerative colitis are 1.7-fold more likely to develop postdischarge VTE than non-IBD patients. These findings support the need for increased vigilance and consideration of thromboprophylaxis in this population.

OBJECTIVES The prevalence of inflammatory bowel disease (IBD) is increasing. The total direct costs of IBD have not been assessed on a population-wide level in the era of biologic therapy. DESIGN We identified all persons with IBD in Manitoba between 2005 and 2015, with each matched to 10 controls on age, sex, and area of residence. We enumerated all hospitalizations, outpatient visits and prescription medications including biologics, and their associated direct costs. Total and per capita annual IBD-attributable costs and health care utilization (HCU) were determined by taking the difference between the costs/HCU accrued by an IBD case and their controls. Generalized linear modeling was used to evaluate trends in direct costs and Poisson regression for trends in HCU. RESULTS The number of people with IBD in Manitoba increased from 6,323 to 7,603 between 2005 and 2015. The total per capita annual costs attributable to IBD rose from $3,354 in 2005 to $7,801 in 2015, primarily driven by an increase in per capita annual anti-tumor necrosis factor costs, which rose from $181 in 2005 to $5,270 in 2015. There was a significant decline in inpatient costs for CD ($99 ± 25/yr. P < 0.0001), but not for ulcerative colitis ($8 increase ±$18/yr, P = 0.63). DISCUSSION The direct health care costs attributable to IBD have more than doubled over the 10 years between 2005 and 2015, driven mostly by increasing expenditures on biological medications. IBD-attributable hospitalization costs have declined modestly over time for persons with CD, although no change was seen for patients with ulcerative colitis.

Background Canadian-born children of South Asian [SA] ethnicity develop inflammatory bowel disease [IBD] at similar rates to those among Caucasian children. We evaluated the variation in phenotypic spectrum of IBD in SA and Caucasian children in a national paediatric inception cohort of new-onset IBD. Methods Patients aged Results Of 1156 children enrolled over 2014 to 2019, 623 were Caucasian [98% and 88% parents Canadian born] and 114 SA [79% Canadian born, 87% parents SA born]. Fewer SAs have a first-degree relative with IBD, 6% vs 19% in Caucasians, p = 0.002. SAs present at a younger age, median age 11.4 years (interquartile range [IQR] 9.2–14.3) vs 13 years [IQR 10.9-15 years], p = 0.03 and more commonly with a UC/IBD-U [ulcerative colitis/IBD-unclassified] subtype [ratio of UC/IBD-U to CD 1.2:1 vs 1:1.8 for Caucasians, p Conclusions The phenotypic spectrum of new-onset IBD in SA children differs from that of Caucasian children, but treatment and clinical course are similar within phenotypic subgroups.

The SARS-CoV-2 pandemic has had a profound impact on inflammatory bowel disease (IBD) health care delivery. The implementation of necessary public health restrictions has restricted access to medications, procedures and surgeries throughout the pandemic, catalyzing widespread change in how IBD care is delivered. Rapid large-scale implementation of virtual care modalities has been shown to be feasible and acceptable for the majority of individuals with IBD and health care providers. The SARS-CoV-2 pandemic has exacerbated pre-existing barriers to accessing high-quality, multidisciplinary IBD care that addresses health care needs holistically. Continued implementation and evaluation of both synchronous and asynchronous eHealthcare modalities are required now and in the future in order to determine how best to incorporate these modalities into patient-centred, collaborative care models. Resources must be dedicated to studies that evaluate the feasibility, acceptability and effectiveness of eHealth-enhanced models of IBD care to improve efficiency and cost-effectiveness, while increasing quality of life for persons living with IBD. Crohn’s and Colitis Canada will continue to play a major leadership role in advocating for the health care delivery models that improve the quality of life for persons living with IBD.

Persons with inflammatory bowel disease (IBD) make up more than 0.75% of the Canadian population in 2021. Early in the COVID-19 pandemic, individuals with IBD, particularly those on immunosuppressive therapies, were concerned that their health status may place them at higher risk of contracting COVID-19 or experiencing more severe disease course if infected with SARS-CoV-2. In response, Crohn’s and Colitis Canada developed the COVID-19 and IBD Taskforce in March 2020 to rapidly synthesize the evolving knowledge of COVID-19 as relevant to Canadians with IBD. The Taskforce communicated expert information directly to the Canadian IBD community through online tools and a webinar series. In order to understand the full impact of COVID-19 on the IBD community, Crohn’s and Colitis Canada commissioned a policy report that was informed through a systematic literature review and synthesized across working groups along the following domains: Epidemiology, Children and Expectant Mothers with IBD, Seniors with IBD, Mental Health, Risk Factors and Medications, Vaccines, and Healthcare Delivery during the Pandemic and the Future Model of IBD Care. This report from Canadian physicians, researchers, and IBD community representatives highlights the physical, mental, and health systems impact of COVID-19 on the entire spectrum of the IBD community, including children, adolescents, adults, seniors, and pregnant people with IBD. This executive summary provides an overview of the crucial information from each of the chapters of the policy report, supplemented with additional information made available through Crohn’s and Colitis Canada’s webinar-based knowledge translation platform.

Background Most administrative studies of hospitalization in inflammatory bowel disease (IBD) use two definitions: IBD in any diagnostic position (IBD-ANY), and IBD as the most responsible diagnostic (IBD-MRD). There is a third less commonly used definition: total hospitalization; this definition captures all hospitalizations of prevalent IBD patients and therefore it can give a more realistic picture of the burden of IBD. Aims To compare differing definitions (total, IBD-ANY, and IBD-MRD) of hospitalizations. Methods A previously defined population-based IBD prevalent cohort for Alberta (n=30,698) was used to pull all hospital admissions from the Discharge Administrative Database (DAD; 2002–2015). Three hospitalization definitions were used: i. Total (all hospitalizations of prevalent cohort independent of presence of code for IBD); ii. IBD-ANY (code for IBD [K50.x; K51.x] contained in any diagnosis field); and, iii. IBD-MRD (most responsible diagnosis was IBD). Age- and sex- standardized rates (2015 Canadian population) were calculated using the prevalent population. Log-linear regression was performed to calculate Average Annual Percentage Change (AAPC) with associated 95% confidence intervals (CI) of each type of hospitalization. We assessed the top five most common most-responsible diagnosis codes for hospitalizations that were contained in the total hospitalizations but not an IBD-ANY hospitalization. Results From 2002 to 2015, 63.5% of IBD prevalent patients in AB had ≥1 hospitalization; 44.2% had ≥1 IBD-ANY hospitalization; 28.6% had ≥1 IBD-MRD hospitalization; and, 40.6% had a hospitalization that did not contain a code for IBD. All hospitalization rates decreased significantly over time. Of the top five most common most responsible diagnosis, contained in admissions that were not IBD-ANY, three were gastroenterological: i. K52.9 (non-infective gastroenteritis); ii. A09.9 (diarrhea and gastroenteritis of presumed infectious origin); and, iii. Z43.2 (attention to ileostomy). Conclusions Total hospitalizations is an important measure to report since accounting for all hospitalizations of IBD patients is necessary in order to allocate healthcare resources appropriately. To be able to ensure these patients receive the care they need we need to be able to accurately assess the true burden of IBD. Funding Agencies CIHR

The development of anti-tumour necrosis factor (TNF) therapies has transformed the care of patients with immune-mediated diseases such as inflammatory bowel disease (IBD), including ulcerative colitis and Crohn’s disease, psoriasis and inflammatory arthropathies, including rheumatoid arthritis and ankylosing spondylitis. For IBD patients, these biologic therapies are effective at inducing and maintaining remission (1), reducing the need for surgery (2) and improving quality of life (3). Although anti-TNF therapies are effective in several different immune-mediated disorders, individual biologics are not, necessarily, equally effective in all disorders suggesting that their actions may differ between disorders. For example, the paradox that anti-TNF drugs used to treat rheumatoid arthritis (RA) and psoriasis may yet cause joint pains and skin reactions in IBD patients, emphasizes our imperfect understanding of the mechanism of action of these biologic therapies and the need to evaluate treatment outcomes separately for different disorders. The main factors that limit the use of anti-TNF drugs are adverse events and cost. Anti-TNF therapy is associated with joint pains, dermatological disorders and transfusion reactions (4). Transfusion reactions are associated with the development of antibodies to anti-TNF agents and this may also be associated with reduced treatment efficacy (5). Anti-TNF agents are also associated with an increased risk of infection (6) and risk of lymphoma although these risks may be exacerbated, to a greater or lesser extent, by the concomitant use of azathioprine or other immunosuppressive agents (7). Anti-TNF therapies are also expensive costing up to $20,000 per year for each patient in Canada. Canada spent more on biologic therapies for all indications than on any other class of drug in 2018 accounting for 8.2% of the $33.7 billion spent on prescription medications (8). While the cost of these therapies is significant, the cost of having IBD is also expensive to society. It is estimated that the indirect cost of IBD was $1.29 billion in Canada in 2018 (9,10). Anti-TNF therapies can improve quality of life and productivity and, accounting for these societal costs, biologics may offer value for money (11). In the Canadian setting, health care is mainly funded centrally by the tax payer and the government, understandably, focuses on how biologic therapy may reduce health care costs. This is less clear cut with research using health administrative data failing to demonstrate any significant decrease in hospitalizations or surgical resections in the anti-TNF era compared to what would be expected if these drugs had not been introduced (12). Given this perspective, it is understandable that approaches to reducing the cost of these drugs are being explored. The emergence of biosimilars, also known as subsequent entry biologics have provided an opportunity for third party payers to reduce anti-TNF therapy drug costs. A biosimilar is a biological medical product that is similar to the original but manufactured by a different company once the patent for that product has expired. They are typically less expensive than the original product and therefore an obvious target in attempts to reduce biologic drug costs. Biosimilars are distinct from usual generic drugs, which are simple small molecules that are relatively straightforward to reproduce and manufacture on a large scale, and identical to the original drug. Biologic therapies are more complex proteins and require replication in living cells. The product is dependent on the type of genetically modified cell being used, the production process and purification techniques (13). The manufacturing process is considerably more expensive than standard small molecules and therefore costs of biosimilars are higher than generically produced drugs. Furthermore, the variation from the originator is greater than would normally be seen with generics. However, it is important to emphasize that even with the original manufacturer there is potential for variability between each manufacturing run due to the complexity of living organisms. The Federal Drug Agency has released documents regarding the approval process for biosimilars (14) that other regulatory authorities have largely adopted (15). Essentially biosimilars must show a high degree of similarity to the original product and have no clinically meaningful differences in safety, purity and potency (14). This is a reasonable definition in principle but the definitions of ‘high degree of similarity’ as well as ‘clinically meaningful differences in safety and potency’ need further clarification in clinical practice. The Canadian Association of Gastroenterology has previously published a position statement on biosimilars (16) but this was 6 years ago, and more data are now available. Crohn’s and Colitis Canada has published a position statement more recently (17) but the two organizations felt it was of value to release a joint position statement after a full literature review. Several positions statements have been released by various organizations (Table 1) but none has provided an explicit literature search, nor have they assessed the quality of evidence of a defined clinical question according to GRADE criteria (18). Table 1. Position statements reached by other groups on the use of biosimilars

Background & AimsWe aim to provide guidance for medical treatment of luminal Crohn’s disease in children.MethodsWe performed a systematic search of publication databases to identify studies of medical management of pediatric Crohn’s disease. Quality of evidence and strength of recommendations were rated according to the GRADE (Grading of Recommendation Assessment, Development, and Evaluation) approach. We developed statements through an iterative online platform and then finalized and voted on them.ResultsThe consensus includes 25 statements focused on medical treatment options. Consensus was not reached, and no recommendations were made, for 14 additional statements, largely due to lack of evidence. The group suggested corticosteroid therapies (including budesonide for mild to moderate disease). The group suggested exclusive enteral nutrition for induction therapy and biologic tumor necrosis factor antagonists for induction and maintenance therapy at diagnosis or at early stages of severe disease, and for patients failed by steroid and immunosuppressant induction therapies. The group recommended against the use of oral 5-aminosalicylate for induction or maintenance therapy in patients with moderate disease, and recommended against thiopurines for induction therapy, corticosteroids for maintenance therapy, and cannabis in any role. The group was unable to clearly define the role of concomitant immunosuppressants during initiation therapy with a biologic agent, although thiopurine combinations are not recommended for male patients. No consensus was reached on the role of aminosalicylates in treatment of patients with mild disease, antibiotics or vedolizumab for induction or maintenance therapy, or methotrexate for induction therapy. Patients in clinical remission who are receiving immunomodulators should be assessed for mucosal healing within 1 year of treatment initiation.ConclusionsEvidence-based medical treatment of Crohn’s disease in children is recommended, with thorough ongoing assessments to define treatment success.

Canada has one of the highest rates of inflammatory bowel disease (IBD) in the world, with 1 in 140 Canadians currently living with the disease. IBD occurs less often among individuals living in rural households. This protective effect is particularly pronounced in young children, and early-life exposure to the rural environment greatly reduces the risk. However, individuals living in rural areas who have IBD have decreased access to specialist gastroenterology care.

Background Anti–tumor necrosis factor (anti-TNF) drugs are highly effective in the treatment of moderate-to-severe Crohn’s disease (CD) and ulcerative colitis (UC), but they are very costly. Due to their effectiveness, they could potentially reduce future health care spending on other medical therapies, hospitalization, and surgery. The impact of downstream costs has not previously been quantified in a real-world population-based setting. Methods We used the University of Manitoba IBD Database to identify all persons in a Canadian province with CD or UC who received anti-TNF therapy between 2004 and 2016. All inpatient, outpatient, and drug costs were enumerated both in the year before anti-TNF initiation and for up to 5 years after anti-TNF initiation. Costs before and after anti-TNF initiation were compared, and multivariate linear regression analyses were performed to look for predictors of higher costs after anti-TNF initiation. Results A total of 928 people with IBD (676 CD, 252 UC) were included for analyses. The median cost of health care in the year before anti-TNF therapy was $4698 for CD vs $6364 for UC. The median cost rose to $39,749 and $49,327, respectively, in the year after anti-TNF initiation, and to $210,956 and $245,260 in the 5 years after initiation for continuous anti-TNF users. Inpatient and outpatient costs decreased in the year after anti-TNF initiation by 12% and 7%, respectively, when excluding the cost of anti-TNFs. Conclusions Direct health care expenditures markedly increase after anti-TNF initiation and continue to stay elevated over pre-initiation costs for up to 5 years, with only small reductions in the direct costs of non-drug-related health care.

Background The incidence of inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is increasing internationally, particularly in developing nations where rates were historically low. Previous reports of the incidence and prevalence of pediatric-onset IBD have identified a paucity of population-based studies. Aims We reviewed the global trends in incidence of pediatric IBD using evidence from population-based studies. Methods (PROSPERO CRD42019125193) We systematically reviewed studies indexed in MEDLINE, EMBASE, Airiti Library, and SciELO from 01/2010-02/2020 to identify population-based studies reporting the incidence of pediatric-onset IBD, CD, and UC. Included studies combined childhood and adolescent-onset IBD (onset Results Of 8096 abstracts screened, 74 studies described the incidence of IBD, CD, or UC in 33 countries (Figure panel A). The incidence of pediatric-onset IBD is highest in Northern Europe and North America, and lowest in Southern Europe, Asia, and the Middle East. This geographical distribution is similar in UC, while incidence of pediatric-onset CD is highest in North America and Northern Europe, followed by Australia. Trends in incidence over time, stratified by continent, are reported in Figure, panel B. Significantly increasing incidence of IBD, CD, and/or UC was reported in China, Bahrain, Canada, New Zealand, Australia, Singapore, Saudi Arabia, and most European countries. Very Early Onset (VEO) IBD significantly increased in Canada, however Saudi Arabia reported decreasing incidence of VEO-CD but stable incidence of VEO-UC. Conclusions Conclusion: Incidence of pediatric-onset IBD are highest in Northern Europe and North American and are increasing globally. There remains a paucity of studies from many parts of the world on the incidence pediatric IBD. Further research is needed to understand the pathogenesis of the rising incidence of pediatric IBD, including work to understand the genetic, environmental, immunological and microbiome alterations leading to the increasing rates in children. References: 1Benchimol, Fortinsky et al. Inflamm Bowel Dis 2011;17:423–39. Funding Agencies None

Background Paediatric data on the association between diagnostic delay and inflammatory bowel disease [IBD] complications are lacking. We aimed to determine the effect of diagnostic delay on stricturing/fistulising complications, surgery, and growth impairment in a large paediatric cohort, and to identify predictors of diagnostic delay. Methods We conducted a national, prospective, multicentre IBD inception cohort study including 1399 children. Diagnostic delay was defined as time from symptom onset to diagnosis >75th percentile. Multivariable proportional hazards [PH] regression was used to examine the association between diagnostic delay and stricturing/fistulising complications and surgery, and multivariable linear regression to examine the association between diagnostic delay and growth. Predictors of diagnostic delay were identified using Cox PH regression. Results Overall (64% Crohn’s disease [CD]; 36% ulcerative colitis/IBD unclassified [UC/IBD-U]; 57% male]), median time to diagnosis was 4.2 (interquartile range [IQR] 2.0–9.2) months. For the overall cohort, diagnostic delay was >9.2 months; in CD, >10.8 months and in UC/IBD-U, >6.6 months. In CD, diagnostic delay was associated with a 2.5-fold higher rate of strictures/internal fistulae (hazard ratio [HR] 2.53, 95% confidence interval [CI] 1.41–4.56). Every additional month of diagnostic delay was associated with a decrease in height-for-age z-score of 0.013 standard deviations [95% CI 0.005–0.021]. Associations persisted after adjusting for disease location and therapy. No independent association was observed between diagnostic delay and surgery in CD or UC/IBD-U. Diagnostic delay was more common in CD, particularly small bowel CD. Abdominal pain, including isolated abdominal pain in CD, was associated with diagnostic delay. Conclusions Diagnostic delay represents a risk factor for stricturing/internal fistulising complications and growth impairment in paediatric CD. Podcast This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast

Background There are currently no nationwide data on the epidemiology of inflammatory bowel diseases (IBD) in Israel. We aimed to determine the population-based epidemiological trends of IBD in the diverse Israeli population. Methods Health-administrative data were retrieved from all 4 Israeli health maintenance organizations, insuring 98% of the population, using validated identification algorithms. National trends were determined using Joinpoint regression analysis calculating annual percent change and average annual percent change (AAPC). Results By 2019, there were 46,074 patients with IBD in Israel, corresponding to a national prevalence of 519/100,000 (0.52%), of whom 54.1% had Crohn disease (CD) and 45.9% had ulcerative colitis (UC). The number of Jewish patients doubled from 18,701 in 2005 (354/100,000) to 38,950 (589/100,000) in 2018 (AAPC, +4.0%; P < 0.05), and the number of Arab patients increased 3-fold from 1096 (102.1/100,000) to 3534 (240.7/100,000; AAPC, +6.8%; P < 0.05) during the same years. However, the increase rate has gradually decelerated over time (annual percent change during 2005-2008, 2009-2014, and 2005-2018 was +6.7%, +4.2%, and +2.3%, respectively; P < 0.05). Pediatric prevalence increased from 37.4 to 52.2/100,000, with CD predominating in both Jews and Arabs. The incidence of CD remained stable (from 15.9/100,000 to 14.9/100,000) and the incidence of UC decreased (15.4/100,000 to 10.5/100,000 (AAPC, –3.2%; P < 0.001)). In contrast, pediatric incidence of CD increased from 7.3/100,000 to 8.3/100,000 (AAPC, +1.9%; P < 0.05) and that of UC increased from 2.6 to 4.4/100,000 (AAPC, +5.8%; P < 0.05). Conclusions The IBD prevalence rate in Israel is still increasing but gradually decelerating, probably due to the decreasing overall IBD incidence. Nonetheless, incidence rate in children is still increasing. Ongoing narrowing in the rates between Jews and Arabs over time may indicate shared environmental factors.

Introduction Corticosteroids are effective for inducing clinical remission in inflammatory bowel disease (IBD), but not for maintaining remission. Reducing corticosteroid use and dependence is an important treatment goal since their use is associated with adverse events. The extent to which the improvements in IBD therapy have led to less corticosteroid use in the modern era remains unclear. Methods We used the University of Manitoba Inflammatory Bowel Disease Epidemiologic Database to assess the cumulative annual dosing of corticosteroids on a per-patient basis for all persons with IBD in the province of Manitoba between 1997 and 2017. Joinpoint analysis was used to assess for trends in corticosteroid use and to look at variation in the trends over time. Results The mean annual exposure to corticosteroids decreased from 419 mg/yr (1997) to 169 mg/yr (2017) for Crohn's disease (CD) (annual decline: 3.8% per year, 95% confidence interval 3.1-4.6) and from 380 to 240 mg/yr in ulcerative colitis (UC) (annual decline: 2.5% per year, 95% confidence interval 2.1-2.8). In CD, there was an acceleration in the rate of decline after 2007 (pre-2007, 1.9% decline per year; after 2007, 5.7% per year); there was no corresponding acceleration in the rate of decline in UC. Discussion Corticosteroid use has decreased in both CD and UC over the past 2 decades, becoming more pronounced after 2007 in CD. Potential explanations include introduction and increasing penetrance of biologic therapy in CD and greater awareness of corticosteroid-related adverse events in IBD. Further work is required understand the drivers of persistent corticosteroid use in IBD and how this can be further reduced.

Background and Aims The combination of infliximab and azathioprine is more efficacious than either therapy alone for Crohn’s disease [CD] and ulcerative colitis [UC]. However, it is uncertain whether these benefits extend to real-world clinical practice and to other combinations of biologics and immunomodulators. Methods We collected health administrative data from four Canadian provinces representing 78 413 patients with inflammatory bowel disease [IBD] of whom 11 244 were prescribed anti-tumour necrosis factor [anti-TNF] agents. The outcome of interest was the first occurrence of treatment failure: an unplanned IBD-related hospitalization, IBD-related resective surgery, new/recurrent corticosteroid use or anti-TNF switch. Multivariable Cox proportional hazards modelling was used to assess the association between the outcome of interest and receiving combination therapy vs anti-TNF monotherapy. Multivariable regression models were used to assess the impact of choice of immunomodulator or biologic on reaching the composite outcome, and random effects generic inverse variance meta-analysis of deterministically linked data was used to pool the results from the four provinces to obtain aggregate estimates of effect. Results In comparison with anti-TNF monotherapy, combination therapy was associated with a significant decrease in treatment ineffectiveness for both CD and UC (CD: adjusted hazard ratio [aHR] 0.77, 95% confidence interval [CI] 0.66–0.90; UC: aHR 0.72, 95% CI 0.62–0.84). Combination therapy was equally effective for adalimumab and infliximab in CD. In UC azathioprine was superior to methotrexate as the immunomodulatory agent (aHR = 1.52 [95% CI 1.02–2.28]) but not CD (aHR = 1.22 [95% CI 0.96–1.54]). Conclusion In an analysis of a database of real-world patients with IBD, combination therapy decreased the likelihood of treatment failure in both CD and UC.

Background The incidence of very early onset inflammatory bowel disease (VEOIBD) is increasing, yet the phenotype and natural history of VEOIBD are not well described. Methods We performed a retrospective cohort study of patients diagnosed with VEOIBD (6 years of age and younger) between 2008 and 2013 at 25 North American centers. Eligible patients at each center were randomly selected for chart review. We abstracted data at diagnosis and at 1, 3, and 5 years after diagnosis. We compared the clinical features and outcomes with VEOIBD diagnosed younger than 3 years of age with children diagnosed with VEOIBD at age 3 to 6 years. Results The study population included 269 children (105 [39%] Crohn’s disease, 106 [39%] ulcerative colitis, and 58 [22%] IBD unclassified). The median age of diagnosis was 4.2 years (interquartile range 2.9–5.2). Most (94%) Crohn’s disease patients had inflammatory disease behavior (B1). Isolated colitis (L2) was the most common disease location (70% of children diagnosed younger than 3 years vs 43% of children diagnosed 3 years and older; P = 0.10). By the end of follow-up, stricturing/penetrating occurred in 7 (6.6%) children. The risk of any bowel surgery in Crohn’s disease was 3% by 1 year, 12% by 3 years, and 15% by 5 years and did not differ by age at diagnosis. Most ulcerative colitis patients had pancolitis (57% of children diagnosed younger than 3 years vs 45% of children diagnosed 3 years and older; P = 0.18). The risk of colectomy in ulcerative colitis/IBD unclassified was 0% by 1 year, 3% by 3 years, and 14% by 5 years and did not differ by age of diagnosis. Conclusions Very early onset inflammatory bowel disease has a distinct phenotype with predominantly colonic involvement and infrequent stricturing/penetrating disease. The cumulative risk of bowel surgery in children with VEOIBD was approximately 14%–15% by 5 years. These data can be used to provide anticipatory guidance in this emerging patient population.

Background Inflammatory bowel disease (IBD) increases the risk of venous thromboembolism (VTE) in patients of all ages but the risk of VTE among Canadian children with IBD has not previously been investigated. Aims Report the incidence of VTE and subtypes pulmonary embolism (PE) and deep vein thrombosis (DVT) in children with and without IBD. Methods Children diagnosed with IBD Results 3127 children with IBD (1826 CD; 1045 UC) were matched to 15,635 children without IBD. The cumulative incidence of VTE within 5 years of IBD diagnosis was 2.8 (95% CI 2.1–3.8) per 1000 PYs compared to 0.13 (95% CI 0.07–0.24) per 1000 PYs in children without IBD (Table). The 5-year cumulative incidences of VTE, DVT, and PE were significantly higher in children with IBD than in children without IBD (VTE: IRR 21.44, 95% CI 10.73–42.82; DVT: IRR 25.15, 95% CI 11.12–56.89; PE: IRR 4.01, 95% CI 1.22–13.18). Compared to UC patients, children with CD were at lower risk of VTE (IRR 0.53, 95% CI 0.29–0.96) and numerically, but not statistically, lower risk of DVT (IRR 0.59, 95% CI 0.30–1.14). Conclusions Although VTEs are relatively rare among children with IBD, these children are at much greater risk than children without IBD. Gastroenterologists caring for these patients should be cognizant of VTE risk and provide appropriate prophylaxis to those at high risk of VTE. Funding Agencies CCC

Background Health services use in inflammatory bowel disease (IBD) patients cost the Canadian healthcare system $1.3 billion per year, but recent changes to care in children with IBD may have altered trends in health services use. Characterization of these trends would aid health policy makers plan for the healthcare needs of IBD children. Aims To quantify time trends in IBD health services use in children and all-cause health services use in children with and without IBD using a population-based cohort. Methods Using the Ontario Crohn’s and Colitis Cohort, children Results IBD-specific hospitalization rates decreased by 2.5% (95%CI 1.8–3.2%) per year, but all-cause hospitalization rates in children without IBD decreased faster (APC, 95%CI: 4.3%, 3.5–5.1%, difference in rates p-value=0.0028). The hazard of intestinal resection for CD decreased by 6.0% (95%CI 4.6–7.3%) per year and the hazard of colectomy for UC decreased by 3.0% (95%CI 0.7–5.2%) per year. IBD-specific outpatient visit rates increased after 2005 by 4.0% (95%CI 3.1–4.9%) per year. Similar trends were not observed in children without IBD. Conclusions Decreasing hazards of intestinal resection and colectomy in children with IBD suggest changes in disease management, including more care being provided on an outpatient basis. Decreased hospitalization rates in IBD were mirrored by similar decreases in non-IBD children, indicating universal care changes. Understanding why these trends are occurring may help us better understand how to provide optimal care to children with IBD. Funding Agencies CIHRCanGIEC

Background Inflammatory bowel disease (IBD) is rising rapidly in Canadian children. These children require consistent high-quality specialized care to prevent long-term complications. Aims Evaluate variation in health services utilization and surgery rates across pediatric IBD centres in Ontario. Methods Incident cases of IBD Results Of 2584 IBD cases, 73.4% were treated in a pediatric IBD centre. Between-centre differences accounted for 0.18% (MHR 1.06) and 0.41% (MHR 1.09) of variation in hospitalizations and ED visits, respectively. Children treated at centres where a higher proportion of children were cared for by GIs were more likely to be hospitalized (HR 2.09, 95% CI 1.26–3.45). Children treated at centres with a longer mean diagnostic lag were also more likely to be hospitalized (HR 1.01, 95% CI 1.003–1.02). ED visits were not associated with the proportion of children cared for by gastroenterologists or diagnostic lag. Among 1529 CD cases, 14.1% required intestinal resection; 1.79% of variation in the risk of surgery resulted from between-centre differences (MHR 1.20). Surgery was less common among patients at centres where more children were cared for by GIs (HR 0.24, 95% CI 0.07–0.84) and with a longer mean diagnostic lag (HR 0.98, 95% CI 0.97–0.99). After adjusting for these, between-centre differences accounted for 0.005% (MHR 1.01) of variation in care. Minimal variation was observed among the 11.0% of 872 UC cases requiring colectomy, with 0.37% of variation due to between-centre differences (MOR 1.09). Colectomy risk was not associated with GI care or diagnostic lag. Conclusions Variation in ED visits, hospitalizations, and surgery among children with IBD is small; however, centre-level differences in GI specialist care use and time to diagnosis were associated with hospitalization and surgery. It is essential to understand between-centre differences to reduce variation and ensure high-quality care. Funding Agencies CCC

Background: High-income nations have the highest rates of inflammatory bowel disease (IBD). The incidence of pediatric-onset IBD is increasing faster than IBD diagnosed in older individuals. Previous epidemiological studies have shown that air pollution might be a risk factor for development of earlier-onset IBD, but results remain mixed. Objectives: The objective of this study was to evaluate the associations between maternal and early-life exposures to nitrogen dioxide (NO2), fine particulate matter (PM2.5), ozone (O3,) and oxidant capacity (Ox) and risk of pediatric-onset IBD diagnosis. Methods: We conducted a retrospective cohort study using linked population-based health administrative data. Singleton livebirths in Ontario, Canada between April 1st, 1991 and March 31st, 2014 were included. We investigated the association between weekly exposures during pregnancy and annual exposures from birth until the age of 18 years, and IBD diagnosed

The indirect cost of illness represents the portion of human capital that is foregone due to lost productivity of patients and their caregivers and out-of-pocket healthcare expenses borne directly by patients. Indirect costs among persons with inflammatory bowel diseases (IBD) may be substantial because disease onset occurs during the teens and 20s for most persons and is lifelong. Thus, most persons with IBD are affected during periods of study or employment. The literature on indirect health-related costs among persons with IBD is limited, particularly with regard to Canadian studies. The greatest burden of indirect costs in this population relates to absenteeism and presenteeism among working individuals and premature retirement. However, costs related to reduced professional development and personal achievement due to illness—as well as caregiver costs—are largely unknown. After being extrapolated from multiple sources, the total indirect health-related cost of IBD in Canada in 2018 is estimated to be $1.29 billion Canadian dollars. Notably, this may be a significant underestimate because costs relating to presenteeism, reduced achievement and caregiver burden could not be estimated and are excluded from this calculation. Highlights Indirect costs account for a major portion of total healthcare costs among persons with inflammatory bowel disease (IBD) and are higher than indirect costs among persons without IBD. Persons with IBD are more likely to require time off work (absenteeism) and have reduced productivity at work (presenteeism) due to illness as compared with persons without IBD. Premature retirement and long-term disability are major factors contributing to indirect costs among IBD patients. A substantial proportion of individuals with IBD pay out-of-pocket for complementary and alternative medicines. After being extrapolated from multiple sources, the total annual indirect cost of IBD in Canada is estimated to be $1.29 billion CAD in 2018, or $4781 CAD per person with IBD. Key Summary Points The total indirect economic burden of IBD in Canada is estimated to be $1.29 billion CAD in 2018, or roughly $4781 CAD per person with IBD. This estimate comprises lost wages related to sick days and disability, premature retirement and premature death, and out-of-pocket costs. Losses from presenteeism, reduced professional development and caregiver burden are not included due to insufficient data on the cost impact of these factors. In a meta-analysis of studies between 1994 and 2014, the annual indirect cost of absenteeism for IBD patients ranged from $515.67 USD (USA) to $14,727 USD (Germany) per patient per annum (pooled estimate $7189 USD), after adjusting for purchasing power disparity. A large US survey found that, on average, IBD patients incurred an extra 4.8 days off of work and $783 USD in excess lost wages annually compared with persons without IBD. A study based on US private insurance claims found that ulcerative colitis patients cost an additional $2164 per person per annum relating to disability days and medically related absenteeism. A prospective study from an IBD centre reported weekly indirect health-related costs of $1133 for IBD patients with active disease, $370.13 for IBD patients in remission, and $191.23 for persons without IBD relating to both presenteeism and absenteeism. In a survey of 744 IBD patients from Manitoba, reduced workplace productivity during the previous 14 days was reported in 37% of individuals, including a reduction of one to two days by 18% of patients, thre to nine days by 16% of patients, and on most days by 3% of patients. The estimated average lifetime lost wages due to premature retirement is $1,044,498 CAD per person with Crohn’s disease and $994,760 CAD per person with ulcerative colitis. Aggregated over all IBD retirees, this equates to roughly $629 million CAD in permanent lost wages annually due to premature retirement. The lifetime indirect cost associated with premature death among IBD patients is estimated to be $746,070 CAD per decedent, or roughly $33.6 million aggregated across all IBD decedents of working age. In a US study of caregivers of children, the average unadjusted annual work loss was 214 hours for caregivers of Crohn’s disease patients and 170 hours for caregivers of children without IBD, translating to an additional $1122 in lost productivity for caregivers of persons with Crohn's disease. Canadian studies have reported complementary and alternative medicines (CAMs) use in 56% to 74% of people with IBD. A US national survey study estimated annual per-person out of pocket costs of $1603 USD for Crohn’s disease patients and $1263 USD for ulcerative colitis patients, which were substantially higher than in persons without IBD. Gaps in Knowledge and Future Directions Canadian-specific data on indirect health-related costs of IBD is sparse across all domains of indirect costs. In particular, the rates of absenteeism, presenteeism and premature retirement among IBD patients living in Canada require further study to gauge more accurately the indirect health-related costs of IBD in Canada. Indirect costs relating to decreased professional development, caregiver burden and out-of-pocket purchases among IBD patients are largely unknown and require further study. Indirect costs incurred by Canadian children with IBD and their families or caregivers are largely unknown.

Approximately one in every 160 seniors live with IBD. Due to the fact that IBD has no known cure, and thus patients diagnosed at younger ages will carry their disease with them into their senior years, the number of senior IBD patients is rising significantly in Canada. Seniors with IBD present unique challenges for care. Patients with IBD will experience greater comorbid conditions resulting from their advancing age and longer disease duration. Risks associated with IBD-related surgeries and complications from other illnesses associated with age and their medications further complicate treatment options and may lead to higher healthcare utilization. Healthcare providers need to be prepared to work in multidisciplinary teams with other specialists in order to address the complexity and comorbidities of seniors with IBD. Highlights 1. Approximately one out of every 160 individuals over the age of 65 in Canada is living with IBD. 2. The rising prevalence of IBD in seniors results from new diagnoses and advancing age of previously diagnosed patients with IBD. 3. Patients with IBD will experience greater comorbid conditions resulting from their advancing age and longer disease duration. 4. As the IBD population ages, the proportion of seniors with IBD will increase in gastroenterology clinics. 5. The care of seniors with IBD brings unique challenges with respect to therapeutic decision-making. Key Summary Points 1. Approximately 0.6% of seniors in Canada live with IBD. 2. In Ontario, the prevalence of IBD among seniors increased by 5.2% per year, which outpaced the 3.9% per year rise observed in nonseniors. 3. Approximately 15% of IBD patients are newly diagnosed after the age of 65 years. 4. The incidence of IBD in seniors ranged from 16.5 to 18.9 per 100,000 in Canada. 5. In Ontario, the diagnosis of ulcerative colitis in seniors was double that of Crohn’s disease. 6. Clinical presentation of seniors with Crohn’s disease is unique with a higher likelihood to present with isolated colonic disease without fistulizing disease or extra-intestinal manifestations as compared with those diagnosed at a younger age. 7. Seniors with IBD are less likely to have outpatient visits relating to their IBD as compared with younger patients with IBD. 8. Among individuals diagnosed over the age of 65, the 10-year risk of intestinal surgery was 7% to 19% for ulcerative colitis and 31% for Crohn’s disease. 9. Seniors who undergo intestinal resections for their IBD have significantly higher postoperative complications and mortality as compared with younger IBD patients undergoing surgery. 10. The use of anti-TNF agents in seniors is lower for Crohn’s disease (4.0%) and ulcerative colitis (2.3%) as compared with younger individuals with IBD. However, the rate of use of biologics is increasing over time. 11. Therapeutic decision-making in seniors with IBD is challenging due to their comorbid conditions. 12. Seniors who use thiopurines have a higher risk of lymphoma (5.4 per 1000 person-years) as compared with IBD patients younger than 50 (0.37 per 1000 person-years) exposed to thiopurines. 13. Newer gut-selective α4β7 integrin inhibitors may be a safer choice for seniors due to potentially lower risk of infection and cancer. 14. Due to multiple comorbidities, seniors with IBD may struggle with polypharmacy that can lead to drug interactions and reduced medication adherence. 15. Persons between 65 and 79 of age with IBD on average cost the healthcare system $5298 per year, which is higher than age-matched controls. Gaps in Knowledge and Future Directions 1. Administrative healthcare databases are more likely to misclassify senior patients with IBD. Future research is necessary to improve the identification of senior patients with IBD in databases. 2. Gastroenterologists will need to contend with an older IBD population with greater comorbidities. Research focusing on defining the burden of comorbidities in senior IBD patients is needed for healthcare resource utilization planning. 3. The use of anti-TNF in senior patients is lower than in younger individuals with IBD. Future research should evaluate trends in using biologics in the senior population with the advent of newer biologics such as integrin and other cellular adhesion molecule inhibitors. 4. Polypharmacy is a challenge for senior IBD patients. Future research should focus on interventions to simplify drug regimens and administration for senior patients. 5. Senior individuals with IBD cost the healthcare system more than age-matched controls. However, research is necessary to establish the IBD-attributable cost to the healthcare system and the indirect cost to society.

Inflammatory bowel disease (IBD) has a substantial impact on quality of life. It causes considerable personal, emotional and social burdens. The impact of IBD on quality of life cannot readily be quantified as a cost; however, the impact places a significant burden on the patient and caregivers. Numerous studies have shown that health-related quality of life is impaired in patients living with IBD as compared with the general population. While disease activity and severity is an important driver of physical and mental health–related quality of life, patients may experience psychological distress even during clinical remission. Reduced quality of life can impact persons living with IBD as they pursue employment, family planning and personal milestones. Further, the impact of IBD extends to the patient influencing the quality of lives of those around them, including their caregivers. Improving quality of life requires a multidisciplinary approach that includes screening for and managing psychological distress. Adaptive coping mechanisms help manage illness perceptions and reduce psychosocial distress. Highlights Health-related quality of life (HRQOL) is an important measure of the global impact of IBD on a person’s physical, mental and emotional well-being. Persons living with IBD have significantly lower HRQOL compared with that of the general population. Inflammatory bowel disease often affects individuals as they pursue employment, family building and personal milestones. Inflammatory bowel disease affects the quality of life (QOL) of those afflicted and their caregivers. Access to multidisciplinary, collaborative, chronic disease models of care improves the HRQOL of people living with IBD. Key Summary Points Inflammatory bowel disease impairs HRQOL by inhibiting need fulfillment (i.e., self-esteem, relationships, nutrition, hygiene and security) and causing psychological distress. Inflammatory bowel disease impairs interpersonal relationships, life activities, social participation and mental well-being. Patient symptoms like diarrhea and abdominal pain reduce HRQOL. While disease severity is an important driver of physical and mental HRQOL, patients experience psychological distress even during clinical remission. Psychological distress impairs work productivity and disrupts social activities and relationships. Patients with IBD experience emotional distress relating to factors such as loss of bowel control, impairment of body image, fear of sexual inadequacy, social isolation, fear of dependency, concern about not reaching one’s full potential and fear of stigmatization. Families with children with IBD have impaired QOL as a collective—for example, parental stress from medical factors and child’s perceived stress. Patients’ perception of their illness affects their ability to adjust to a diagnosis of IBD. Adaptive coping mechanisms help manage illness perceptions and reduce psychosocial distress. Biologics are associated with improvement in long-term HRQOL in people with IBD. Patients with IBD should have access to multidisciplinary care, including mental health practitioners, to screen for and manage psychological distress. Gaps in Knowledge and Future Directions Patients with IBD experience emotional distress that reduces HRQOL. Clinical tools are necessary to identify the key factors causing psychological distress in patients with IBD. HRQOL is reduced in individuals with IBD and their families. Studies should evaluate the cumulative burden of IBD on HRQOL in patients with IBD and their caregivers. Patient self-perception of their IBD influences their HRQOL. Clinical studies of interventions that improve adaptive coping are needed to reduce psychosocial distress. Multidisciplinary care including a psychologist to screen for and manage psychosocial risk and psychological distress should be evaluated in IBD clinics.

Canada has among the highest incidence and prevalence of inflammatory bowel disease (IBD) in the world. After decades of rising incidence of IBD in Canada during the 20th Century, the prevalence of IBD in 2018 is 0.7% of the Canadian population. Forecasting models predict that prevalence of IBD will continue to rise to 1.0% of the population by 2030. In 2018, the number of Canadians living with IBD is approximately 270,000 and is predicted to rise to 403,000 Canadians in 2030. Inflammatory bowel disease affects all age groups with adolescents and young adults at highest risk of diagnosis. Canadians of all ethnicities are being diagnosed with IBD including known high-risk groups such as Ashkenazi Jews and offspring of South Asian immigrants who were previously thought to be low risk. Moreover, IBD has evolved into a global disease with rising incidence in newly industrialized countries in Asia and South America. The causes of IBD remain unsolved; however, the high rates of disease in Western countries and its emergence in newly industrialized countries suggest that environmental factors associated with urbanization, modernization, or Western diets may be pertinent to understanding the pathogenesis of the disease. Highlights 1. Canada continues to have among the highest prevalence of IBD in the world. 2. Today, approximately 270,000 Canadians live with IBD. By 2030 it is estimated that nearly 403,000 Canadians will have a diagnosis of IBD. 3. Inflammatory bowel disease has become a worldwide disease with increasing rates in Asia, Africa, and South America—continents where IBD was rarely diagnosed prior to 1990. 4. The causes of IBD are unknown, but the high rates of disease over the past 60 years in Western countries and the emergence of disease in developing countries suggest that factors associated with urbanization, modernization, or Western diets may be pertinent to understanding the pathogenesis of the disease. 5. Many of the leading hypotheses as to the causes of IBD tie in with alteration of the gut microbiome, the suite of organisms that reside in the bowel and maintain bowel health throughout life. Key Summary Points 1. The incidence (the number of new diagnoses annually) of IBD rose throughout the 20th century in Canada and then stabilized at the turn of the 21st century. 2. The prevalence (the total number of diagnosed persons in the population) of IBD in Canada is among the highest in the world. 3. Today, 270,000 (0.7%, or 7 in 1000) Canadians are estimated to live with IBD. By 2030, that number is expected to rise to 403,000 Canadians (1% or 1 in 100). 4. Inflammatory bowel disease can be diagnosed at any age. However, the age groups that are most likely to be diagnosed are adolescents and young adults from 20 to 30 years of age. 5. Inflammatory bowel disease in Canada affects the lives of Canadians of all ethnicities, including known high-risk groups such as Ashkenazi Jews, and those thought previously to be at low risk, such as first-generation offspring of South Asian immigrants. 6. Canadian health policy makers will need to prepare the Canadian health care system for the rising burden of IBD. 7. As newly industrialized countries in Asia, Africa, and South America are transitioning to a Westernized society, IBD has emerged and its incidence in these countries is rising rapidly. 8. The gut microbiome includes microorganisms that maintain digestive health. Thus, changes in the microbiome, which may change the immune system’s response to triggers, may be important in initiating and perpetuating IBD. 9. A number of factors can alter the gut microbiome and early childhood may be a particularly important time such that breastfeeding, early life diet, use of antibiotics, infections, and other environmental exposures may impact the gut microbiome in such a way that facilitates developing IBD. 10. Smoking is associated with an increased risk and worsening disease course of Crohn’s disease. Quitting smoking is associated with an increased risk of developing ulcerative colitis. Therefore, never initiating smoking can mitigate the risk for IBD. Educational programs aimed at those at-risk for IBD should emphasize the risk of starting to smoke tobacco. 11. Modifying exposure to environmental risk factors associated with the Westernization of society (e.g., Western diet and lifestyles) may provide an avenue for reducing the risk of IBD in Canada and worldwide. Gaps in Knowledge and Future Directions 1. While the incidence of IBD appears to be stabilizing in some regions in Canada, IBD may be occurring more frequently in certain populations such as in children, South Asians, Ashkenazi Jews, and immigrants. Future research should focus on the changing demographics of IBD in Canada. 2. The prevalence of IBD will rise steadily over the next decade. To enable better health care system planning and to respond adequately to the increasing burden of IBD, ongoing surveillance of the epidemiology and health services utilization of IBD in Canada is necessary. 3. Most studies have focused on the mortality associated with IBD. Future research is necessary to assess health-adjusted life expectancy and overall life expectancy for those living with IBD. 4. Analyses of resources, infrastructure, and personnel need to be modeled into the future in order to prepare our health care system for the rising burden of IBD. 5. Research on the interaction between genes, microbes, and our environment will inform our understanding of the pathogenesis of IBD, information necessary to prevent IBD in the future.

Canada has among the highest rates of childhood-onset IBD in the world. Over 7000 children and youth under 18 years old are living with IBD in Canada, and 600 to 650 children under 16 years old are diagnosed annually. While the peak age of onset of IBD is highest in the second and third decades of life, over the past two decades incidence has risen most rapidly in children under 5 years old. The treatment of children with IBD presents important challenges including therapeutic choices, risk of adverse events to medications, psychosocial impact on the child and family, increased cost of health care and the implications of the transition from pediatric to adult care. Despite the unique circumstances faced by children and their families, there is a lack of research to help understand the causes of the rising incidence and the best therapies for children with IBD. Scientific evidence—and specifically clinical trials of pharmaceuticals—are too often extrapolated from adult research. Health care providers must strive to understand the unique impact of childhood-onset IBD on patients and families, while researchers must expand work to address the important needs of this growing patient population. Highlights In 2018, there are over 7000 children and youth under 18 years old living with IBD in Canada, and 600 to 650 young children (under 16 years) diagnosed every year. The number of children in Canada living with IBD is growing rapidly, increasing 50% in the first decade of the 21st century. Inflammatory bowel disease is still rare in children younger than 5 years of age, but it is occurring in such young children more often than in the past. Children with IBD are different from adults. For example, delayed growth, extent of disease and difficulties encountered during adolescence are all unique to the pediatric experience. We must consider the psychosocial well-being of both children and their families, given that caring for a child with IBD can affect the global functioning of families. Treatment approaches in children sometimes differ from those in adults. However, to date, all effective therapies in adults have also been effective in children. There is great need for clinical trials of new therapies in children so that they have equal access to emerging treatments and optimal pediatric dosing can be established. Key Summary Points Rates of new diagnoses in children under 16 years old were increasing most rapidly in Ontario (increased 5.8% per year) and Quebec (increased 2.8% per year). Nova Scotia has the highest rate of pediatric IBD, with lower rates in Quebec and Ontario. However, even Ontario and Quebec have higher rates of pediatric IBD than most countries in the world. Inflammatory bowel disease is caused by the interaction between genes, environmental risk factors, the microbiome and the immune system. Since children experience shorter exposures and possibly fewer environmental risk factors, the interaction between these risk factors and genes may be stronger with childhood-onset IBD. The microbiome is mostly established in early childhood and is affected by a number of factors such as environment, diet, pregnancy/delivery factors and antibiotic use. Changing the microbiome to a healthier state may prevent the disease and may also be a novel therapeutic target to treat active inflammation in children with IBD. Children with IBD are different from adults. They are more likely to have extensive involvement of their intestines, especially in ulcerative colitis, and are at risk for growth impairment, osteoporosis, and psychosocial difficulties affecting their families. Children with IBD may incur more direct health costs for treatment of their IBD compared with adults. However, this is not universally true for all children because those who are very young at diagnosis (2 to 6 years old) may have milder disease or respond better to medications. This may result in decreased use of the health system, fewer hospitalizations and less risk of surgery than older children and adolescents. The choice of treatments for children with IBD may be different from that of adults. It is important to consider pediatric-specific disease considerations. Delayed growth, deficient bone development, psychosocial well-being of the child and family, disease extent, disease severity and risk of poor outcomes during transition from pediatric to adult health care are all important considerations when choosing the best treatment for children and adolescents. While the medications used are similar in children and adults with IBD, research to assess the effectiveness and safety of these medications in children (especially very young children) is sparse. Children with IBD may be more responsive to treatment than adults because they are more likely to have inflammatory (rather than stricturing) disease. Therefore, treating the inflammation earlier in the course of disease may prevent long-term complications such as strictures, obstruction, need for surgery and need for hospitalization. Some medications used in IBD have unique or more pronounced risks in children compared with adults. For example, chronic prednisone use is associated with growth impairment and stunting in children. Anti-TNF biologics are the only medications proven to improve growth in children with Crohn’s disease and should be considered early in the course of disease in patients with severe IBD or those with marked growth impairment at the time of diagnosis. Some medications are used differently, depending on the sex of the patient. For example, azathioprine (with or without biologics) is associated with hepatosplenic T cell lymphoma (and other forms of lymphoma) in adolescent and young adult males more often than females. Methotrexate is associated with birth defects in the growing fetus and therefore should be avoided in adolescent and adult women of child-bearing age who are not using two or more forms of birth control. A small group of children, typically presenting in the first two years of life, have single-gene mutations that cause an IBD-like bowel disease and also immune system dysfunction. These patients may not respond to traditional IBD medications and may require therapies such as bone marrow transplant. Canada is leading research efforts to investigate, diagnose and treat this small group of very vulnerable children. Inflammatory bowel disease (especially when it is active) can affect school attendance, social interactions, concentration and learning. Schools should be aware of the implications of IBD and make allowances for these factors in children with active inflammation and symptoms to optimize their chances of academic and social success. Gaps in Knowledge and Future Research Directions We have limited knowledge on what causes IBD in children and why rates are rising most rapidly in young children. We must better understand the interaction between genes, the environment, the immune system and the microbiome in order to better prevent and treat the disease. Treatment for infants with IBD-like illnesses and single-gene mutations is limited. Future research should work towards identifying these children and learning how best to treat them. There are few clinical trials for biologics in children, and most exclude very young children. Support for such trials is important to understand whether the treatments work, how they should optimally be given and whether they are safe for young children with IBD. Considering the effectiveness of dietary therapies for children with Crohn’s disease (exclusive enteral nutrition), we should work to understand how diet affects intestinal inflammation and the microbiome in order to better use dietary therapies to treat IBD. Health services researchers, health care providers and policy-makers should work together to understand why variation in the access to treatment and medical care of children with IBD exists. We must work together to improve the quality of care provided to these children and ensure they have the highest quality of care. Psychosocial implications of IBD in children and their families are of importance to long-term and overall well-being. Children with a chronic, incurable disease are at risk for mental illness associated with their disease. We should design interventions to improve the psychosocial status, mental health and quality of life of children with IBD and their families. While nonlive immunizations are safe for children with IBD, we must understand how to improve their effectiveness in children who are immunosuppressed. While the peak onset of IBD occurs in the second or third decades of life, the frequency of new diagnoses in younger children is rising rapidly. In Canada, the fastest growing group of newly diagnosed people with IBD are children aged under 5 years (termed ‘very early onset [VEO] IBD). These young children have not been included in clinical trials of new medications, resulting in a lack of scientific evidence of safety and effectiveness of treatments in this group, and clinical experience has shown that they do not respond to usual medications used for the majority of children with IBD. Providing children with IBD with high-quality care and social support also poses other challenges to care providers, families and the health system. This section will focus on the unique challenges facing Canadian children with IBD. A complete overview of the objectives, working committees and methodology of creating the report can be found in the supplemental file, Technical Document.

Eric I Benchimol,1–5 M Ellen Kuenzig,1,2,5 Charles N Bernstein,6,7 Geoffrey C Nguyen,5,8 Astrid Guttmann,5,9 Jennifer L Jones,10 Beth K Potter,4 Laura E Targownik,6,7 Christina A Catley,5 Zoann J Nugent,6,11 Divine Tanyingoh,12,13 Nassim Mojaverian,5 Fox E Underwood,12,13 Shabnaz Siddiq,1,2 Anthony R Otley,14 Alain Bitton,15 Matthew W Carroll,16 Jennifer C deBruyn,17 Trevor JB Dummer,18 Wael El-Matary,19 Anne M Griffiths,9 Kevan Jacobson,20,21 Desmond Leddin,10 Lisa M Lix,22 David R Mack,1–3 Sanjay K Murthy,4,23 Juan Nicolás Peña-Sánchez,24 Harminder Singh,6,7 Gilaad G Kaplan12,13 On behalf of the Canadian Gastro-Intestinal Epidemiology Consortium 1Children’s Hospital of Eastern Ontario IBD Centre, Division of Gastroenterology, Hepatology and Nutrition, Children’s Hospital of Eastern Ontario, Ottawa, Canada; 2Children’s Hospital of Eastern Ontario Research Institute, Ottawa, Canada; 3Department of Pediatrics, University of Ottawa, Ottawa, Canada; 4School of Epidemiology and Public Health, University of Ottawa, Ottawa, Canada; 5ICES, Toronto, Canada; 6University of Manitoba IBD Clinical and Research Centre, University of Manitoba, Winnipeg, Canada; 7Department of Internal Medicine, University of Manitoba, Winnipeg, Canada; 8Department of Medicine, Mount Sinai Hospital Centre for Inflammatory Bowel Disease, University of Toronto, Toronto, Canada; 9Department of Paediatrics, University of Toronto, Toronto, Canada; 10Department of Medicine, Dalhousie University, Halifax, Canada; 11CancerCare Manitoba, Winnipeg, Canada; 12Department of Medicine, University of Calgary, Calgary, Alberta, Canada; 13Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada; 14Department of Pediatrics, Dalhousie University, Halifax, Canada; 15Division of Gastroenterology, McGill University Health Centre, Montreal, Canada; 16Division of Pediatric Gastroenterology and Nutrition, Department of Pediatrics, University of Alberta, Edmonton, Canada; 17Division of Gastroenterology, Department of Pediatrics, University of Calgary, Calgary, Canada; 18School of Population and Public Health, University of British Columbia, British Columbia, Canada; 19Department of Pediatrics, University of Manitoba, Winnipeg, Canada; 20Department of Pediatrics, The University of British Columbia, British Columbia, Canada; 21Child and Family Research Institute, The University of British Columbia, British Columbia, Canada; 22Department of Community Health Sciences, University of Manitoba, Winnipeg, Canada; 23The Ottawa Hospital IBD Centre, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada; 24Department of Community Health and Epidemiology, University of Saskatchewan, Saskatoon, Canada Background and aims: Canada’s large geographic area and low population density pose challenges in access to specialized health care for remote and rural residents. We compared health services use, surgical rate, and specialist gastroenterologist care in rural and urban inflammatory bowel disease (IBD) patients in Canada.Methods: We used validated algorithms that were applied to population-based health administrative data to identify all people living with the following three Canadian provinces: Alberta, Manitoba, and Ontario (ON). We compared rural residents with urban residents for time to diagnosis, hospitalizations, outpatient visits, emergency department (ED) use, surgical rate, and gastroenterologist care. Multivariable regression compared the outcomes in rural/urban patients, controlling for confounders. Provincial results were meta-analyzed using random-effects models to produce overall estimates.Results: A total of 36,656 urban and 5,223 rural residents with incident IBD were included. Outpatient physician visit rate was similar in rural and urban patients. IBD-specific and IBD-related hospitalization rates were higher in rural patients (incidence rate ratio [IRR] 1.17, 95% CI 1.02–1.34, and IRR 1.27, 95% CI 1.04–1.56, respectively). The rate of ED visits in ON were similarly elevated for rural patients (IRR 1.53, 95% CI 1.42–1.65, and IRR 1.33, 95% CI 1.25–1.40). There were no differences in surgical rates or prediagnosis lag time between rural and urban patients. Rural patients had fewer IBD-specific gastroenterologist visits (IRR 0.79, 95% CI 0.73–0.84) and a smaller proportion of their IBD-specific care was provided by gastroenterologists (28.3% vs 55.2%, P65years (33.0% vs 59.2%, P

M Ellen Kuenzig,1–3 Mohsen Sadatsafavi,4 J Antonio Aviña-Zubieta,5 Rebecca M Burne,6 Michal Abrahamowicz,6,7 Marie-Eve Beauchamp,7 Gilaad G Kaplan,8–11,* Eric I Benchimol1–3,12,13,* 1Children’s Hospital of Eastern Ontario (CHEO) Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology and Nutrition, Children’s Hospital of Eastern Ontario, Ottawa, ON, Canada; 2Health Information Technology Program, CHEO Research Institute, Ottawa, ON, Canada; 3Institute for Clinical Evaluative Sciences, Ottawa, ON, Canada; 4Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada; 5Arthritis Research Canada, Division of Rheumatology, University of British Columbia, Vancouver, BC, Canada; 6Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada; 7Centre for Health Outcomes Research (CORE), Research Institute of the McGill University Health Centre, Montreal, QC, Canada; 8Department of Medicine, University of Calgary, Calgary, AB, Canada; 9Department of Community Health Sciences, University of Calgary, Calgary, AB, Canada; 10O’Brien Institute for Public Health, University of Calgary, Calgary, AB, Canada; 11Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada; 12Department of Pediatrics, University of Ottawa; Ottawa, ON, Canada; 13School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON, Canada *These authors contributed equally to this work Purpose: Growing evidence suggests asthma and Crohn’s disease commonly cooccur. However, the impact of asthma on the prognosis of Crohn’s disease is unknown. The aim of our study was to assess the effect of asthma on the need for intestinal resection in patients with Crohn’s disease while adjusting for smoking status, imputed from a smaller, secondary data set. Patients and methods: Using health administrative data from a universally funded healthcare plan in Alberta, Canada, we conducted a cohort study to assess the effect of asthma on the need for surgery in patients with Crohn’s disease diagnosed between 2002 and 2008 (N=2,113). Validated algorithms were used to identify incident cases of Crohn’s disease, cooccurring asthma, and intestinal resection. The association between asthma and intestinal resection was estimated using multivariable Cox proportional hazards regression. Smoking status was imputed using a novel method using martingale residuals, derived from a data set of 485 patients enrolled in the Alberta Inflammatory Bowel Disease Consortium (2007 to 2014) who completed environmental questionnaires. All analyses were adjusted for age, sex, rural/urban status, and mean neighborhood income quintile. Results: Asthma did not increase the risk of surgery in the health administrative data when not adjusting for smoking status (HR 1.03, 95% CI 0.81 to 1.29). The association remained nonsignificant after imputing smoking status in the health administrative data (HR 1.03, 95% CI 0.81 to 1.29). Conclusion: Although asthma is associated with an increased risk of Crohn’s disease, co-occurring asthma is not associated with the risk of surgery in these patients. This null association persisted after adjusting for smoking status. This study described a novel method to adjust for confounding (smoking status) in time-to-event analyses, even when the confounding variable is unmeasured in health administrative data. Keywords: Crohn’s disease, asthma, surgery, unmeasured confounding, health administrative data

Mira Y Friedman,1,2 Maya Leventer-Roberts,3 Joseph Rosenblum,4 Nir Zigman,4 Iris Goren,4 Vered Mourad,4 Natan Lederman,5 Nurit Cohen,5 Eran Matz,6 Doron Z Dushnitzky,6 Nirit Borovsky,6 Moshe B Hoshen,3 Gili Focht,1 Malka Avitzour,1 Yael Shachar,1 Yehuda Chowers,7 Rami Eliakim,8 Shomron Ben-Horin,8 Shmuel Odes,9 Doron Schwartz,9 Iris Dotan,10 Eran Israeli,11 Zohar Levi,10 Eric I Benchimol,12–14 Ran D Balicer,3 Dan Turner1 On behalf of the Israeli IBD Research Nucleus (IIRN) 1The Juliet Keidan Institute of Pediatric Gastroenterology and Nutrition, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel; 2Braun School of Public and Community Medicine, The Hebrew University– Hadassah Medical Center, Jerusalem, Israel; 3Clalit Research Institute, Chief’s Office, Clalit Health Services, Tel Aviv, Israel; 4Maccabi Healthcare Services, Tel Aviv, Israel; 5Meuhedet Health Services, Tel Aviv, Israel; 6Leumit Health Services, Tel Aviv, Israel; 7Department of Gastroenterology, Rambam Health Care Campus, Bruce Rappaport School of Medicine, Technion Israel Institute of Technology, Haifa, Israel; 8Department of Gastroenterology, Chaim Sheba Medical Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; 9Department of Gastroenterology and Hepatology, Soroka Medical Center, Ben-Gurion University of the Negev, Beer Sheva, Israel; 10Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel; 11Institute of Gastroenterology and Liver Diseases, Hadassah Medical Center, Hebrew University, Jerusalem, Israel; 12CHEO Inflammatory Bowel Disease Centre, Children’s Hospital of Eastern Ontario, Ottawa, ON, Canada; 13Department of Pediatrics and School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, ON, Canada; 14Institute for Clinical Evaluative Sciences, Ottawa, ON, Canada Background: Before embarking on administrative research, validated case ascertainment algorithms must be developed. We aimed at developing algorithms for identifying inflammatory bowel disease (IBD) patients, date of disease onset, and IBD type (Crohn’s disease [CD] vs ulcerative colitis [UC]) in the databases of the four Israeli Health Maintenance Organizations (HMOs) covering 98% of the population. Methods: Algorithms were developed on 5,131 IBD patients and 2,072 controls, following independent chart review (60% CD and 39% UC). We reviewed 942 different combinations of clinical parameters aided by mathematical modeling. The algorithms were validated on an independent cohort of 160,000 random subjects. Results: The combination of the following variables achieved the highest diagnostic accuracy: IBD-related codes, alone if more than five to six codes or combined with purchases of IBD-related medications (at least three purchases or ≥3 months from the first to last purchase) (sensitivity 89%, specificity 99%, positive predictive value [PPV] 92%, negative predictive value [NPV] 99%). A look-back period of 2–5 years (depending on the HMO) without IBD-related codes or medications best determined the date of diagnosis (sensitivity 83%, specificity 68%, PPV 82%, NPV 70%). IBD type was determined by the majority of CD/UC codes of the three recent contacts or the most recent when less than three contacts were recorded (sensitivity 92%, specificity 97%, PPV 97%, NPV 92%). Applying these algorithms, a total of 38,291 IBD patients were residing in Israel, corresponding to a prevalence rate of 459/100,000 (0.46%). Conclusion: The application of the validated algorithms to Israel’s administrative databases will now create a large and accurate ongoing population-based cohort of IBD patients for future administrative studies. Keywords: inflammatory bowel diseases, Crohn’s disease, ulcerative colitis, search algorithms, validation, case ascertainment, Israel, administrative database research

Background Budesonide is an oral glucocorticoid designed for the treatment of inflammatory bowel disease (IBD) that may reduce systemic adverse events (AEs). This review examined the efficacy and safety of budesonide for the induction and maintenance of clinical remission in Crohn’s disease (CD). Methods MEDLINE, EMBASE, other electronic databases, reference lists and conference proceedings were searched to November 2017 to identify randomized controlled trials of budesonide. Outcomes were the induction and maintenance of remission at eight weeks and one year, respectively, as well as corticosteroid-related AEs and abnormal adrenocorticotropic hormone (ACTH) tests. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were estimated using random effects models. Results Thirteen induction and 10 maintenance trials were included. Budesonide 9 mg/day was more effective than placebo (RR 1.93; 95% CI, 1.37–2.73; GRADE: moderate) but less effective than conventional steroids (RR 0.85; 95% CI, 0.75–0.97; GRADE: moderate) to induce remission. Corticosteroid-related AEs occurred less often with induction doses of budesonide than steroids (RR 0.64; 95% CI, 0.54–0.76; GRADE: moderate); budesonide did not increase AEs relative to placebo (RR 0.97; 95% CI, 0.76–1.23; GRADE: moderate). Budesonide 6 mg/day was not different from placebo for maintaining remission (RR 1.13; 95% CI, 0.94–1.35; GRADE: moderate). Both induction (GRADE: low for 3 mg/day, moderate for 9 mg/day) and maintenance budesonide treatment (GRADE: very low for 3 mg/day, low for 6 mg/day) increased the risk of an abnormal ACTH test compared with placebo, but less than conventional steroids (GRADE: very low for both induction and maintenance). Conclusion For induction of clinical remission, budesonide was more effective than placebo, but less effective than conventional steroids. Budesonide was not effective for the maintenance of remission. Budesonide was safer than conventional steroids, but the long-term effects on the adrenal axis and bone health remain unknown.

BACKGROUND: Incidence of Inflammatory Bowel Disease (IBD)—Crohn’s Disease (CD) and ulcerative colitis (UC)—is decreasing in some provinces, but increasing in pediatrics. Even with this decrease in incidence, prevalence will continue to rise until incidence equals to mortality. Decision makers require accurate data on the current and future burden of IBD for resource planning to ensure IBD patients receive proper care. AIMS: 1. Assess current and forecast future IBD incidence trends; 2. determine IBD mortality rates; and, 3. use mortality to calculate the threshold that incidence must approximate to stabilize prevalence. METHODS: Using population-based data from Alberta, annual incidence (per 100,000 persons) is calculated from 2010 to 2015, stratified by pediatric (

The incidence and prevalence of childhood-onset inflammatory bowel diseases (IBD), including subtypes Crohn's disease and ulcerative colitis, have risen dramatically in recent years, and have emerged globally as important pediatric chronic diseases. Therefore, health care providers are more frequently encountering very young children with IBD, a chronic and incurable condition requiring life-long therapy. These children are living long lives with IBD and therefore knowledge of long-term outcomes is increasingly important to better counsel families and determine the best course of treatment. This review summarizes the current knowledge and literature surrounding long-term outcomes of pediatric IBD, with emphasis on the following areas: need for surgery due to complicated disease behavior, risk of disease remission and recurrence, mental health and psychosocial well-being, educational outcomes, linear growth impairment, cancer risk, and mortality. In addition, we review recent research about predicting negative long-term outcomes in children with IBD.