Assessment of dietary intake and its inflammatory potential in persons with pediatric-onset multiple sclerosis.

OBJECTIVE: To compare diet and the modified dietary inflammatory index (mDII) between individuals with pediatric-onset multiple sclerosis (PoMS), monophasic acquired demyelinating syndromes (monoADS), and controls. METHODS: The association between diet, mDII, and disease status was examined in 131 individuals with PoMS/monoADS/controls (38/45/48) using logistic regression. RESULTS: The associations between diet and PoMS were modest, reaching significance for whole grain intake (adjusted odds ratio, aOR=0.964, 95 % confidence intervals, CI:0.934-0.995) but not mDII (aOR=1.20, 95 %CI:0.995-1.46) versus controls. No findings for monoADS reached significance versus controls. CONCLUSIONS: Individuals with PoMS, but not monoADS, had lower dietary whole grain intake than controls.

The 2023 Impact of Inflammatory Bowel Disease in Canada: Direct Health System and Medication Costs.

Healthcare utilization among people living with inflammatory bowel disease (IBD) in Canada has shifted from inpatient management to outpatient management; fewer people with IBD are admitted to hospitals or undergo surgery, but outpatient visits have become more frequent. Although the frequency of emergency department (ED) visits among adults and seniors with IBD decreased, the frequency of ED visits among children with IBD increased. Additionally, there is variation in the utilization of IBD health services within and between provinces and across ethnocultural and sociodemographic groups. For example, First Nations individuals with IBD are more likely to be hospitalized than the general IBD population. South Asian children with Crohn's disease are hospitalized more often than their Caucasian peers at diagnosis, but not during follow-up. Immigrants to Canada who develop IBD have higher health services utilization, but a lower risk of surgery compared to individuals born in Canada. The total direct healthcare costs of IBD, including the cost of hospitalizations, ED visits, outpatient visits, endoscopy, cross-sectional imaging, and medications are rising rapidly. The direct health system and medication costs of IBD in Canada are estimated to be $3.33 billion in 2023, potentially ranging from $2.19 billion to $4.47 billion. This is an increase from an estimated $1.28 billion in 2018, likely due to sharp increases in the use of biologic therapy over the past two decades. In 2017, 50% of total direct healthcare costs can be attributed to biologic therapies; the proportion of total direct healthcare costs attributed to biologic therapies today is likely even greater.

The 2023 Impact of Inflammatory Bowel Disease in Canada: Indirect (Individual and Societal) and Direct Out-of-Pocket Costs.

People living with inflammatory bowel disease (IBD) and their caregivers are faced with indirect and out-of-pocket costs that they would not otherwise experience. These costs impact one's ability to contribute to the economy to their fullest potential. The indirect costs of IBD in Canada are estimated to be at least $1.51 billion in 2023 and include costs associated with lost productivity resulting from a combination of missed work (absenteeism), decreased workplace productivity (presenteeism), unemployment, premature mortality, and caregiving costs. Unemployment is the largest contributor to indirect costs ($1.14 billion), followed by costs of absenteeism and presenteeism ($285 million). Caregiving costs for children with IBD are estimated to be nearly $58 million. Canadians with IBD also pay $536 million every year for care that is not covered by universal or supplemental private health insurance; this includes allied healthcare (e.g., care provided by psychologists), medication, and other supportive therapy. Combined, the indirect and out-of-pocket costs of IBD in Canada are estimated at more than $2 billion CAD in 2023. This is substantially higher than the estimate of $1.29 billion in Crohn's and Colitis Canada's 2018 Impact of IBD report with differences attributable to a combination of rising prevalence, inflation, and the addition of presenteeism and caregiving costs to the total indirect costs.

Assessment of differential item functioning of the PHQ-9, HADS-D and PROMIS-depression scales in persons with and without multiple sclerosis.

OBJECTIVE: We tested for the presence of differential item functioning (DIF) in commonly used measures of depressive symptoms, in people with multiple sclerosis (MS) versus people with a psychiatric disorder without MS. METHODS: Participants included individuals with MS, or with a lifetime history of a depressive or anxiety disorder (Dep/Anx) but no immune-mediated inflammatory disease. Participants completed the Patient Health Questionnaire (PHQ-9), Hospital Anxiety and Depression Scale (HADS), and the Patient Reported Outcome Measurement Information System (PROMIS)-Depression. We assessed unidimensionality of the measures using factor analysis. We evaluated DIF using logistic regression, with and without adjustment for age, gender and body mass index (BMI). RESULTS: We included 555 participants (MS: 252, Dep/Anx: 303). Factor analysis showed that each depression symptom measure had acceptable evidence of unidimensionality. In unadjusted analyses comparing the MS versus Dep/Anx groups we identified multiple items with evidence of DIF, but few items showed DIF effects that were large enough to be clinically meaningful. We observed non-uniform DIF for one PHQ-9 item, and three HADS-D items. We also observed DIF with respect to gender (one HADS-D item), and BMI (one PHQ-9 item). For the MS versus Dep/Anx groups, we no longer observed DIF post-adjustment for age, gender and BMI. On unadjusted and adjusted analyses, we did not observe DIF for any PROMIS-D item. CONCLUSION: Our findings suggest that DIF exists for the PHQ-9 and HADS-D with respect to gender and BMI in clinical samples that include people with MS whereas DIF was not observed for the PROMIS-Depression scale.

The cost of inflammatory bowel disease in high-income settings: a Lancet Gastroenterology & Hepatology Commission.

The cost of caring for patients with inflammatory bowel disease (IBD) continues to increase worldwide. The cause is not only a steady increase in the prevalence of Crohn's disease and ulcerative colitis in both developed and newly industrialised countries, but also the chronic nature of the diseases, the need for long-term, often expensive treatments, the use of more intensive disease monitoring strategies, and the effect of the diseases on economic productivity. This Commission draws together a wide range of expertise to discuss the current costs of IBD care, the drivers of increasing costs, and how to deliver affordable care for IBD in the future. The key conclusions are that (1) increases in health-care costs must be evaluated against improved disease management and reductions in indirect costs, and (2) that overarching systems for data interoperability, registries, and big data approaches must be established for continuous assessment of effectiveness, costs, and the cost-effectiveness of care. International collaborations should be sought out to evaluate novel models of care (eg, value-based health care, including integrated health care, and participatory health-care models), as well as to improve the education and training of clinicians, patients, and policy makers.

Indirect and Out-of-Pocket Disease-associated Costs in Pediatric Inflammatory Bowel Disease: A Cross-sectional Analysis.

OBJECTIVES: Data on pediatric inflammatory bowel disease (IBD)-associated indirect and out-of-pocket (OOP) costs are limited. We aimed to estimate indirect (lost work hours and productivity) and OOP pediatric IBD-associated costs in Canada. METHODS: In a nation-wide cross-sectional analysis, caregivers of children with IBD were invited to complete a questionnaire on lost work hours and OOP costs related to IBD in the 4 weeks prior to the survey. Participants were reinvited to periodically answer the same questionnaire every 3-9 months for 2 years. Lost productivity was calculated using the Human Capital method. Costs were reported in 2018 inflation-adjusted Canadian dollars. Predictors of high cost users (top 25%) were examined using binary logistic regression. RESULTS: Consecutive 243 (82 incident cases) of 262 (92.7%) approached participants completed the first survey with a total of 450 surveys longitudinally completed over 2 years. The median annual indirect cost per patient was $5966 (IQR $1809-$12,676), with $5721 (IQR $1366-$11,545) for Crohn's disease (CD) and $7007 (IQR $2428-$14,057) for ulcerative colitis (UC) ( P = 0.11). The annual median per patient OOP costs were $4550 with $4550 for CD and $5038 for UC ( P = 0.53). Longer travel distance to clinic was associated with higher OOP costs (odds ratio = 4.55; P < 0.0001; 95% confidence interval: 1.99-10.40). CONCLUSIONS: Indirect and OOP IBD-associated costs are substantial and more likely to affect families living in remote communities.

IBD Disability Index Is Associated With Both Direct and Indirect Costs of Inflammatory Bowel Disease.

INTRODUCTION: We aimed to determine both direct (medical) and indirect (lost wages) costs of IBD and the association between the degree of IBD-related disability and extent of IBD-related costs. METHODS: Persons age 18-65 from the population-based University of Manitoba IBD Research Registry completed a survey including the IBD Disability Index (IBDDI) and questions related to employment, missed work (absenteeism), and reduced productivity at work (presenteeism). Administrative health data including surgeries, hospitalizations, physician claims, and prescriptions were linked to the survey and assessed. To calculate annual wage loss, number of days of missed work was multiplied by the average wage in Manitoba for the given occupation per Statistics Canada. Costs were adjusted to 2016-17 Canadian dollars. Using descriptive and regression analysis, we explored the association between IBDDI and annual direct and indirect costs associated with IBD. RESULTS: Average annual medical costs rose from $1918 among those with IBDDI 0-4 to $9,993 among those with IBDDI 80-86. Average annual cost of lost work rose from $0 among those with IBDDI 0-4 to $30,101 among those with IBDDI 80-86. Using linear regression, each additional unit of IBDDI was associated with an increase of $77 in annual medical cost (95% CI, $52-102; P < .001) and an increase of $341 in annual cost of lost wages (95% CI, $288-395; P < .001). CONCLUSIONS: Costs related to IBD are significantly associated with the degree of IBD-related disability. Among the approximate 30% of the IBD population with IBDDI scores ≥40, the indirect costs of absenteeism and presenteeism accounts for ~75% of the total IBD-related costs.

Costs related to IBD (both direct and indirect) are significantly associated with the degree of IBD-related disability. Among the approximately 30% of the IBD population with IBDDI scores ≥40, the indirect costs of absenteeism and presenteeism accounts for ~75% of the total IBD-related costs.

Trends in paediatric inflammatory bowel disease-attributable direct costs: a population-based analysis.

BACKGROUND: In addition to its morbidities, inflammatory bowel disease (IBD) has a major financial burden on patients and healthcare systems. However, there is a paucity of evidence on IBD-attributable costs in children. AIMS: To determine the trends of IBD-attributable direct costs over time using a population-based analysis. METHODS: Data were extracted from Manitoba Health Provider Claims and other population registry datasets from 1995 to 2017. Children with IBD were matched by age, sex and location with children without IBD. IBD-attributable direct costs were calculated using utilization counts from the administrative data and cost estimates from different sources. Inpatient hospitalisation and outpatient procedure costs were estimated using the resource intensity weight (RIW) that is attached to each record in the data. Costs were expressed in Canadian dollars. RESULTS: We included 733 (428 with Crohn's disease) prevalent cases who were diagnosed with IBD before the age of 18 years and were followed for 2450 person-years. A matched control group of 6763 persons who were followed for 21 558 person-years was included. The median annual costs of physician services billed per patient increased from $381 (IQR 215-1064) in 1995 to $936 (IQR 579-1932) in 2017 (P < 0.001). The annual medication costs per patient increased from a median of $270 in 1995 to $7944 in 2017 (P < 0.0001). The median annual direct cost per patient was $1810 in 2004 as compared to $14 791 (P < 0.0001) in 2017. CONCLUSIONS: Over two decades, there was a significant increase in the paediatric IBD-attributable direct costs mainly driven by medication costs.

COVID-19 Pandemic: Which IBD Patients Need to Be Scoped-Who Gets Scoped Now, Who Can Wait, and how to Resume to Normal.

Endoscopy is an essential component in the management of inflammatory bowel disease [IBD]. There is a risk of SARS-CoV-2 transmission during endoscopic procedures. The International Organization for the study of IBD [IOIBD] has developed 11 position statements, based on an online survey, that focus on how to prioritise endoscopies in IBD patients during the COVID-19 pandemic, alternative modes for disease monitoring, and ways to triage the high number of postponed endoscopies after the pandemic. We propose to pre-screen patients for suspected or confirmed COVID-19 and test for SARS-CoV-2 before endoscopy if available. High priority endoscopies during pandemic include acute gastrointestinal bleed, acute severe ulcerative colitis, new IBD diagnosis, cholangitis in primary sclerosing cholangitis, and partial bowel obstruction. Alternative modes of monitoring using clinical symptoms, serum inflammatory markers, and faecal calprotectin should be considered during the pandemic. Prioritising access to endoscopy in the post-pandemic period should be guided by control of COVID-19 in the local community and availability of manpower and personal protective equipment. Endoscopy should be considered within 3 months after the pandemic for patients with a past history of dysplasia and endoscopic resection for dysplastic lesion. Endoscopy should be considered 3-6 months after the pandemic for assessment of postoperative recurrence or new biologic initiation. Endoscopy can be postponed until after 6 months of pandemic for routine IBD surveillance and assessment of mucosal healing.

Assessment of Inter-Laboratory Variation in the Characterization and Analysis of the Mucosal Microbiota in Crohn's Disease and Ulcerative Colitis.

BACKGROUND: In studies evaluating the microbiome, numerous factors can contribute to technical variability. These factors include DNA extraction methodology, sequencing protocols, and data analysis strategies. We sought to evaluate the impact these factors have on the results obtained when the sequence data are independently generated and analyzed by different laboratories. METHODS: To evaluate the effect of technical variability, we used human intestinal biopsy samples resected from individuals diagnosed with an inflammatory bowel disease (IBD), including Crohn's disease (n = 12) and ulcerative colitis (n = 10), and those without IBD (n = 10). Matched samples from each participant were sent to three laboratories and studied using independent protocols for DNA extraction, library preparation, targeted-amplicon sequencing of a 16S rRNA gene hypervariable region, and processing of sequence data. We looked at two measures of interest - Bray-Curtis PERMANOVA R 2 values and log2 fold-change estimates of the 25 most-abundant taxa - to assess variation in the results produced by each laboratory, as well the relative contribution to variation from the different extraction, sequencing, and analysis steps used to generate these measures. RESULTS: The R 2 values and estimated differential abundance associated with diagnosis were consistent across datasets that used different DNA extraction and sequencing protocols, and within datasets that pooled samples from multiple protocols; however, variability in bioinformatic processing of sequence data led to changes in R 2 values and inconsistencies in taxonomic assignment and abundance estimates. CONCLUSION: Although the contribution of DNA extraction and sequencing methods to variability were observable, we find that results can be robust to the various extraction and sequencing approaches used in our study. Differences in data processing methods have a larger impact on results, making comparison among studies less reliable and the combined analysis of bioinformatically processed samples nearly impossible. Our results highlight the importance of making raw sequence data available to facilitate combined and comparative analyses of published studies using common data processing protocols. Study methodologies should provide detailed data processing methods for validation, interpretability, reproducibility, and comparability.

Cost-effectiveness analysis of a fecal microbiota transplant center for treating recurrent C.difficile infection.

OBJECTIVE: We assessed the cost-effectiveness of establishing a fecal microbial transplant (FMT) unit in Canada for the treatment of recurrent CDI. DESIGN: We performed a cost-effectiveness analysis to determine the number of patients with recurrent CDI needed to treat (NNT) annually to make establishing a FMT unit cost-effective. We compared treating patients for their second recurrence of CDI with FMT in a jurisdiction with a FMT unit, compared to being treated with antibiotics; then sent to a medical center with FMT available for the third recurrence. We used a willingness to pay threshold of $50,000 per quality-adjusted-life-year gained. RESULTS: The minimum annual NNT was 15 for FMT via colonoscopy, 17 for FMT via capsule, and 44 for FMT via enema compared with vancomycin, and 16, 18, and 47 compared with fidaxomicin, respectively. A medical center's minimum catchment area when establishing a FMT unit would have to be 56,849 if using FMT via colonoscopy, or 64,429 if using capsules. CONCLUSION: We report the minimum number of patients requiring treatment annually with FMT to achieve cost-effectiveness, when including start-up and ongoing costs. FMT is cost-effective in Canada in populations with a sufficient number of eligible patients, ranging from 15 to 47 depending on the FMT modality used. This is crucial for medical jurisdictions making decisions about establishing a FMT unit for the treatment of recurrent CDI. The cost-effectiveness can be generalized in other countries.

The Cost of Use of the Emergency Department by Persons With Inflammatory Bowel Disease Living in a Canadian Health Region: A Retrospective Population-Based Study.

BACKGROUND: We aimed to determine the costs of emergency department (ED) attendance by persons with inflammatory bowel disease (IBD) not admitted to hospital from the ED. METHODS: This was a population-based administrative database study linking the University of Manitoba IBD Epidemiology Database with the Winnipeg Regional Health Authority (WRHA) ED Information Service database. We identified persons with IBD who presented to the ED and were not admitted between January 1, 2009 and March 31, 2012. We then applied costs in Canadian dollars for these visits including an average ED visit cost plus 26% for overhead (total = $508), an average estimated cost of laboratory investigations ($50), and costs for each of radiographic imaging, lower endoscopy and consultation with an internist/gastroenterologist or a surgeon. We tallied the costs of each unique ED presentation. We determined average costs for visits associated with specific consultations or investigations. RESULTS: One thousand six hundred and eighty-two persons with IBD (4,853 individual visits) attended the ED and did not get hospitalized. The average cost per ED visit by a person with IBD who did not get hospitalized was $650. This resulted in a total expenditure of $3,152,227 on these persons for their ED attendance or $969,916 per year. The visits with the highest mean costs were those associated with an abdominal computerized tomography scan ($979), those associated with surgical consultation ($1019), and those associated with an internist/gastroenterologist consultation ($942). CONCLUSION: Better strategies for management of acute issues for persons with IBD that can reduce the use of an ED are needed and can be considerably cost saving.

Longitudinal Trends in the Direct Costs and Health Care Utilization Ascribable to Inflammatory Bowel Disease in the Biologic Era: Results From a Canadian Population-Based Analysis.

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.

Introduction of anti-TNF therapy has not yielded expected declines in hospitalisation and intestinal resection rates in inflammatory bowel diseases: a population-based interrupted time series study.

OBJECTIVES: To better understand the real-world impact of biologic therapy in persons with Crohn's disease (CD) and ulcerative colitis (UC), we evaluated the effect of marketplace introduction of infliximab on the population rates of hospitalisations and surgeries and public payer drug costs. DESIGN: We used health administrative data to study adult persons with CD and UC living in Ontario, Canada between 1995 and 2012. We used an interrupted time series design with segmented regression analysis to evaluate the impact of infliximab introduction on the rates of IBD-related hospitalisations, intestinal resections and public payer drug costs over 10 years among patients with CD and 5 years among patients with UC, allowing for a 1-year transition. RESULTS: Relative to what would have been expected in the absence of infliximab, marketplace introduction of infliximab did not produce significant declines in the rates of CD-related hospitalisations (OR at the last observation quarter 1.06, 95% CI 0.811 to 1.39) or intestinal resections (OR 1.10, 95% CI 0.810 to 1.50), or in the rates of UC-related hospitalisations (OR 1.22, 95% CI 1.07 to 1.39) or colectomies (OR 0.933, 95% CI 0.54 to 1.61). The findings were similar among infliximab users, except that hospitalisation rates declined substantially among UC patients following marketplace introduction of infliximab (OR 0.515, 95% CI 0.342 to 0.777). There was a threefold rise over expected trends in public payer drug cost among patients with CD following infliximab introduction (OR 2.98,95% CI 2.29 to 3.86), suggesting robust market penetration in this group, but no significant change among patients with UC (OR 1.06, 95% CI 0.955 to 1.18). CONCLUSIONS: Marketplace introduction of infliximab has not yielded anticipated reductions in the population rates of IBD-related hospitalisations or intestinal resections, despite robust market penetration among patients with CD. Misguided use of infliximab in CD patients and underuse of infliximab in UC patients may largely explain our study findings.

Direct cost of health care for individuals with community associated Clostridium difficile infections: A population-based cohort study.

BACKGROUND: Even though the incidence of community-acquired Clostridium difficile infection (CDI) is reported to be increasing, few studies have reported on the healthcare costs of community-acquired CDI. We estimated cost of care for individuals with community-associated CDI and compared with that for matched controls without CDI in the time period of six months before to one year after CDI. METHODS: All individuals in the province of Manitoba, diagnosed with CDI between July 2005 and March 2015 were matched up to 4 individuals without CDI. Health care utilization and direct costs resulting from hospitalizations, physician reimbursement claims and prescriptions were determined from the population based provincial databases. Quantile regressions were performed to determine predictors of cost of individuals with community associated CDI. RESULTS: Of all CDIs, 30-40% in each period of the study had community-associated CDI; of which 12% were recurrent CDIs. The incremental median and 90th percentile cost of care for individuals with community-associated CDI was $800 and $16,000 respectively in the six months after CDI diagnosis. After adjustment for age, co-morbidities, sex, socioeconomic status and magnitude of health care utilization prior to CDI, the median incremental cost for recurrent CDI was $1,812 and that for a subsequent episode of CDI was $3,139 compared to those with a single community-associated CDI episode. The median cost for a prescription of Vancomycin was $316 (IQR 209-489). CONCLUSIONS: Health care costs of an episode of community-associated CDI have been much more than the cost of antibiotic treatment. Our study provides population-based data for formal cost effectiveness analysis for use of newer treatments for community-associated CDI.

Inflammatory bowel disease patient profiles are related to specific information needs: A nationwide survey.

BACKGROUND: Inflammatory bowel diseases (IBD) is a heterogenous, lifelong disease, with an unpredictable and potentially progressive course, that may impose negative psychosocial impact on patients. While informed patients with chronic illness have improved adherence and outcomes, previous research showed that the majority of IBD patients receive insufficient information regarding their disease. The large heterogeneity of IBD and the wide range of information topics makes a one-size fits all knowledge resource overwhelming and cumbersome. We hypothesized that different patient profiles may have different and specific information needs, the identification of which will allow building personalized computer-based information resources in the future. AIM: To evaluate the scope of disease-related knowledge among IBD patients and determine whether different patient profiles drive unique information needs. METHODS: We conducted a nationwide survey addressing hospital-based IBD clinics. A Total of 571 patients completed a 28-item questionnaire, rating the amount of information received at time of diagnosis and the importance of information, as perceived by participants, for a newly diagnosed patient, and for the participants themselves, at current time. We performed an exploratory factor analysis of the crude responses aiming to create a number of representative knowledge domains (factors), and analyzed the responses of a set of 15 real-life patient profiles generated by the study team. RESULTS: Participants gave low ratings for the amount of information received at disease onset (averaging 0.9/5) and high ratings for importance, both for the newly diagnosed patients (mean 4.2/5) and for the participants themselves at current time (mean 3.5/5). Factor analysis grouped responses into six information-domains. The responses of selected profiles, compared with the rest of the participants, yielded significant associations (defined as a difference in rating of > 0.5 points with a P < 0.05). Patients with active disease showed a higher interest in work-disability, stress-coping, and therapy-complications. Patients newly diagnosed at age > 50, and patients with long-standing disease (> 10 years) showed less interest in work-disability. Patients in remission with mesalamine or no therapy showed less interest in all domains except for nutrition and long-term complications. CONCLUSION: We demonstrate unmet patient information needs. Analysis of various patient profiles revealed associations with specific information topics, paving the way for building patient-tailored information resources.

The Impact of Inflammatory Bowel Disease in Canada 2018: Indirect Costs of IBD Care.

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.