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Background and Aims: Children with very early onset inflammatory bowel disease (VEO-IBD) are uniquely at risk of inadequate infliximab (IFX) exposure. We studied the association between standard body weight (BW)-based and body surface area (BSA)-based dosing strategies and outcomes. Methods: We identified VEO-IBD patients treated with IFX before 9 years at a single center. Patients were separated into those that received a BSA-based dose (200 mg/m2) and standard BW dosing (5 mg/kg). IFX drug levels, dose intensification, time on steroids, and long-term outcomes were compared. Receiver operator characteristic curves determined the optimal BW- and BSA-based dose to achieve a trough ≥10 µg/ml at dose 4 (IFX#4). Results: Forty-three children with VEO-IBD were identified. Receiver operator characteristic curves demonstrated optimal BW- and BSA-based doses to achieve IFX trough ≥10 µg/ml at IFX#4 were 7.5 mg/kg and 180mg/m2. Children were classified to standard BW dosing (22/43) and BSA dosing (10/43). IFX#4 trough was significantly higher in those who received BSA dosing (BSA 18.6 µg/ml [interquartile range 10.8-28.1] vs BW 5.1 µg/ml [interquartile range 2.6-10.7], P = .04). BSA dosing was more likely to achieve a target drug level >10 µg/ml at IFX#4 (BSA 70% vs BW 18%, P = .02). BW dosing was associated with a greater likelihood of dose escalation (BW 82% vs BSA 30%, P < .01) and a shorter time to first escalation. BSA dosing was associated with shorter time spent on steroids (P = .02). Conclusion: Young children require higher IFX dosing to achieve adequate drug exposure. Our data support the use of a BSA-based dose of 200 mg/m2 or, if a BW-based approach is used, 7.5 mg/kg. BSA dosing allows the use of a consistent dose over the age and weight spectrum.
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BACKGROUND: The incidence of pediatric-onset inflammatory bowel disease (IBD) and the costs of caring for individuals with IBD are both increasing. We calculated the direct healthcare costs of pediatric IBD in the first year after diagnosis and developed a model to predict children who would have high costs (top 25th percentile). METHODS: Using data from the Canadian Children IBD Network inception cohort (≤16 years of age, diagnosed between 2013 and 2019) deterministically linked to health administrative data from Ontario, Canada, we estimated direct healthcare and medication costs accrued between 31 and 365 days after diagnosis. Candidate predictors included age at diagnosis, sex, rural/urban residence location, distance to pediatric center, neighborhood income quintile, IBD type, initial therapy, disease activity, diagnostic delay, health services utilization or surgery around diagnosis, regular primary care provider, and receipt of mental health care. Logistic regression with stepwise elimination was used for model building; 5-fold nested cross-validation optimized and improved model accuracy while limiting overfitting. RESULTS: The mean cost among 487 children with IBD was CA$15â 168 ± 15â 305. Initial treatment (anti-tumor necrosis factor therapy, aminosalicylates, or systemic steroids), having a mental health care encounter, undergoing surgery, emergency department visit at diagnosis, sex, and age were predictors of increased costs, while having a regular primary care provider was a predictor of decreased costs. The C-statistic for our model was 0.71. CONCLUSIONS: The cost of caring for children with IBD in the first year after diagnosis is immense and can be predicted based on characteristics at diagnosis. Efforts that mitigate rising costs without compromising quality of care are needed.
Cost of caring for children with IBD is highCA$15â 168 between 31 and 365 days from diagnosis in 487 Canadian children. Predictors of high costs included anti-tumor necrosis factor therapy and mental health care, with lower costs in those with a primary-care provider.
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INTRODUCTION: To study digestive system cancer risks in individuals with inflammatory bowel diseases (IBDs) in the biologic era. METHODS: We used population-level administrative and cancer registry data from Ontario, Canada, (1994-2020) to compare people with IBD to matched controls (1:10 by sex and birth year) on trends in age-sex standardized cancer incidence and risk ratios of incident cancers and cancer-related deaths. RESULTS: Among 110,919 people with IBD and 1,109,190 controls, colorectal cancer incidence (per 100,000 person-years) declined similarly in people with ulcerative colitis (average annual percentage change [AAPC] -1.81; 95% confidence interval [CI] -2.48 to -1.156) and controls (AAPC -2.79; 95% CI -3.44 to -2.14), while small bowel cancer incidence rose faster in those with Crohn's disease (AAPC 9.68; 95% CI 2.51-17.3) than controls (AAPC 3.64; 95% CI 1.52-5.80). Extraintestinal digestive cancer incidence rose faster in people with IBD (AAPC 3.27; 95% CI 1.83-4.73) than controls (AAPC -1.87; 95% CI -2.33 to -1.42), particularly for liver (IBD AAPC 8.48; 95% CI 4.11-13.1) and bile duct (IBD AAPC 7.22; 95% CI 3.74-10.8) cancers. Beyond 2010, the incidences (and respective mortality rates) of colorectal (1.60; 95% CI 1.46-1.75), small bowel (4.10; 95% CI 3.37-4.99), bile duct (2.33; 95% CI 1.96-2.77), and pancreatic (1.19; 95% CI 1.00-1.40) cancers were higher in people with IBD. DISCUSSION: Cancer incidence is declining for colorectal cancer and rising for other digestive cancers in people with IBD. Incidence and mortality remain higher in people with IBD than controls for colorectal, small bowel, bile duct, and pancreatic cancers.
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BACKGROUND: Patients with inflammatory bowel disease (IBD) exhibit considerable interindividual variability in medication response, highlighting the need for precision medicine approaches to optimize and tailor treatment. Pharmacogenetics (PGx) offers the ability to individualize dosing by examining genetic factors underlying the metabolism of medications such as thiopurines. Pharmacogenetic testing can identify individuals who may be at risk for thiopurine dose-dependent adverse reactions including myelosuppression. We aimed to evaluate PGx variation in genes supported by clinical guidelines that inform dosing of thiopurines and characterize differences in the distribution of actionable PGx variation among diverse ancestral groups. METHODS: Pharmacogenetic variation in TPMT and NUDT15 was captured by genome-wide genotyping of 1083 pediatric IBD patients from a diverse Canadian cohort. Genetic ancestry was inferred using principal component analysis. The proportion of PGx variation and associated metabolizer status phenotypes was compared across 5 genetic ancestral groups within the cohort (Admixed American, African, East Asian, European, and South Asian) and to prior global estimates from corresponding populations. RESULTS: Collectively, 11% of the cohort was categorized as intermediate or poor metabolizers of thiopurines, which would warrant a significant dose reduction or selection of alternate therapy. Clinically actionable variation in TPMT was more prevalent in participants of European and Admixed American/Latino ancestry (8.7% and 7.5%, respectively), whereas variation in NUDT15 was more prevalent in participants of East Asian and Admixed American/Latino ancestry (16% and 15% respectively). CONCLUSIONS: These findings demonstrate the considerable interpopulation variability in PGx variation underlying thiopurine metabolism, which should be factored into testing diverse patient populations.
In a large, pediatric inflammatory bowel disease cohort comprised of 5 genetic ancestry groups, we evaluated the distribution of loss-of-function pharmacogenetic variants in TPMT and NUDT15 and predicted phenotypes (impact on thiopurine metabolism).
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Clinicians, researchers, regulators, and other decision-makers increasingly rely on evidence from real-world data (RWD), including data routinely accumulating in health and administrative databases. RWD studies often rely on algorithms to operationalize variable definitions. An algorithm is a combination of codes or concepts used to identify persons with a specific health condition or characteristic. Establishing the validity of algorithms is a prerequisite for generating valid study findings that can ultimately inform evidence-based health care. This paper aims to systematize terminology, methods, and practical considerations relevant to the conduct of validation studies of RWD-based algorithms. We discuss measures of algorithm accuracy; gold/reference standard; study size; prioritizing accuracy measures; algorithm portability; and implication for interpretation. Information bias is common in epidemiologic studies, underscoring the importance of transparency in decisions regarding choice and prioritizing measures of algorithm validity. The validity of an algorithm should be judged in the context of a data source, and one size does not fit all. Prioritizing validity measures within a given data source depends on the role of a given variable in the analysis (eligibility criterion, exposure, outcome or covariate). Validation work should be part of routine maintenance of RWD sources.
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BACKGROUND AND AIMS: There is an incomplete understanding of the full safety profiles of repeated COVID-19 vaccinations in patients with inflammatory bowel disease (IBD). Among individuals with IBD, we assessed whether COVID-19 vaccines were associated with serious adverse events of special interest (AESI) and health care utilization [all-cause hospitalizations, Emergency Department (ED) visits, gastroenterology visits, IBD-related visits]. METHODS: Using comprehensive administrative health data from Ontario, Canada, adults with IBD who received at least one COVID-19 vaccine from December 2020-January 2022 were included. Self-controlled case series analyses were conducted to evaluate the relative incidence rates of AESI and health care utilization outcomes across post-vaccination risk and control periods. RESULTS: Among 88,407 IBD patients, 99.7% received mRNA vaccines and 75.9% received ≥ 3 doses. Relative to control periods, we did not detect an increase in AESI. IBD patients had fewer all-cause hospitalizations during post-vaccination risk periods. Patients experienced more all-cause ED visits after dose 2 [Relative Incidence (RI):1.08(95%CI:1.04-1.12)] but fewer visits after doses 3 [RI:0.85 (95%CI:0.81-0.90)] and 4 [RI:0.73 (95%CI:0.57-0.92)]. There was no increase in gastroenterologist visits or IBD-related health care utilization post-vaccination. There were fewer IBD-related hospitalizations after dose 1 [RI:0.84 (95%CI:0.72-0.98)] and 3 [RI:0.63 (95%CI:0.52-0.76)], fewer IBD-related ED visits after dose 3 [RI:0.81 (95%CI:0.71-0.91)] and 4 [RI:0.55 (95%CI:0.32-0.96)], and fewer outpatient visits after dose 2 [RI:0.91 (95%CI:0.90-0.93)] and 3 [RI:0.87 (95%CI:0.86-0.89)]. CONCLUSION: This population-based study did not detect increased AESI, all-cause or IBD-related health care utilization following COVID-19 vaccination, suggesting a lack of association between vaccination and increased disease activity.
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Vacunas contra la COVID-19 , COVID-19 , Hospitalización , Enfermedades Inflamatorias del Intestino , Aceptación de la Atención de Salud , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , COVID-19/prevención & control , COVID-19/epidemiología , Vacunas contra la COVID-19/efectos adversos , Servicio de Urgencia en Hospital/estadística & datos numéricos , Hospitalización/estadística & datos numéricos , Incidencia , Ontario/epidemiología , Aceptación de la Atención de Salud/estadística & datos numéricos , SARS-CoV-2 , Vacunación/estadística & datos numéricos , Vacunación/efectos adversosRESUMEN
OBJECTIVE: To explore the mental health experiences of adolescents and young adults (AYA) with inflammatory bowel disease (IBD) enrolled in a randomized controlled trial evaluating the impact of a multimodal transition intervention. STUDY DESIGN: Virtual semistructured interviews were held with 21 AYA aged 16 through 18 years with IBD. Guided by qualitative description, interviews were digitally recorded, transcribed verbatim, and analyzed using an inductive approach to reflexive thematic analysis. RESULTS: Three themes were generated from the data: (1) a continuum of integration between IBD and personal identity in adolescence and young adulthood; (2) manifestations of the mind-gut connection among AYA with IBD; and (3) hopes and priorities for addressing mental health in IBD care. CONCLUSIONS: AYA with IBD endorsed the criticality of incorporating mental health discussions into routine care during the transition to adult care, given the co-occurrence of psychosocial stressors throughout this period. A series of factors promoting and hindering the integration of IBD into one's identity were identified and could be explored in clinical encounters.
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OBJECTIVES: It is unclear if use of cesarean delivery in people with inflammatory bowel disease (IBD) is guideline-concordant. We compared the odds of cesarean delivery among primiparous individuals with IBD versus without, overall, and by disease characteristics, as well as time to subsequent delivery. METHODS: Retrospective matched population-based cohort study between 1 April 1994 and 31 March 2020. Primiparous individuals aged 15-55 years with IBD were matched to those without IBD on age, year, hospital, and number of newborns delivered. Primary outcome was cesarean delivery versus vaginal delivery. Multivariable conditional logistic regression analyses were performed to estimate the odds of cesarean delivery among individuals with and without IBD as a binary exposure, and a categorical exposure based on IBD-related indications for cesarean delivery. Time to subsequent delivery was evaluated using a Cox proportional hazard model. RESULTS: We matched 7472 individuals with IBD to 37 360 individuals without (99.02% match rate). Individuals with IBD were categorised as having perianal (PA) disease (IBD-PA, n = 764, 10.2%), prior ileal pouch-anal anastomosis (n = 212, 2.8%), or IBD-Other (n = 6496, 86.9%). Cesarean delivery rates were 35.4% in the IBD group versus 30.4% in their controls (adjusted odds ratio 1.27; 95% CI 1.20-1.34). IBD-ileal pouch-anal anastomosis had a cesarean delivery rate of 66.5%, compared to 49.9% in IBD-PA and 32.7% in IBD-Other. There was no significant difference in the rate of subsequent delivery in those with and without IBD (adjusted hazard ratio 1.03; 95% CI 1-1.07). CONCLUSIONS: The higher risk of cesarean delivery in people with IBD reflects guideline-concordant use. Individuals with and without IBD were equally likely to have a subsequent delivery with similar timing.
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Cesárea , Enfermedades Inflamatorias del Intestino , Humanos , Femenino , Cesárea/estadística & datos numéricos , Adulto , Embarazo , Estudios Retrospectivos , Enfermedades Inflamatorias del Intestino/epidemiología , Enfermedades Inflamatorias del Intestino/cirugía , Adulto Joven , Adolescente , Persona de Mediana Edad , Complicaciones del Embarazo/epidemiología , Estudios de Cohortes , Factores de RiesgoRESUMEN
OBJECTIVES: Health administrative data can be used to improve the health of people who inject drugs by informing public health surveillance and program planning, monitoring, and evaluation. However, methodological gaps in the use of these data persist due to challenges in accurately identifying injection drug use (IDU) at the population level. In this study, we validated case-ascertainment algorithms for identifying people who inject drugs using health administrative data in Ontario, Canada. STUDY DESIGN AND SETTING: Data from cohorts of people with recent (past 12 months) IDU, including those participating in community-based research studies or seeking drug treatment, were linked to health administrative data in Ontario from 1992 to 2020. We assessed the validity of algorithms to identify IDU over varying look-back periods (ie, all years of data [1992 onwards] or within the past 1-5 years), including inpatient and outpatient physician billing claims for drug use, emergency department (ED) visits or hospitalizations for drug use or injection-related infections, and opioid agonist treatment (OAT). RESULTS: Algorithms were validated using data from 15,241 people with recent IDU (918 in community cohorts and 14,323 seeking drug treatment). An algorithm consisting of ≥1 physician visit, ED visit, or hospitalization for drug use, or OAT record could effectively identify IDU history (91.6% sensitivity and 94.2% specificity) and recent IDU (using 3-year look back: 80.4% sensitivity, 99% specificity) among community cohorts. Algorithms were generally more sensitive among people who inject drugs seeking drug treatment. CONCLUSION: Validated algorithms using health administrative data performed well in identifying people who inject drugs. Despite their high sensitivity and specificity, the positive predictive value of these algorithms will vary depending on the underlying prevalence of IDU in the population in which they are applied.
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Algoritmos , Abuso de Sustancias por Vía Intravenosa , Humanos , Ontario/epidemiología , Abuso de Sustancias por Vía Intravenosa/epidemiología , Masculino , Femenino , Adulto , Persona de Mediana EdadRESUMEN
BACKGROUND: Patterns of health services utilization among children with inflammatory bowel disease (IBD) are important to understand as the number of children with IBD continues to increase. We compared health services utilization and surgery among children diagnosed <10 years of age (Paris classification: A1a) and between 10 and <16 years of age (A1b). METHODS: Incident cases of IBD diagnosed <16 years of age were identified using validated algorithms from deterministically linked health administrative data in 5 Canadian provinces (Alberta, Manitoba, Nova Scotia, Ontario, Quebec) to conduct a retrospective cohort study. We compared the frequency of IBD-specific outpatient visits, emergency department visits, and hospitalizations across age groups (A1a vs A1b [reference]) using negative binomial regression. The risk of surgery was compared across age groups using Cox proportional hazards models. Models were adjusted for sex, rural/urban residence location, and mean neighborhood income quintile. Province-specific estimates were pooled using random-effects meta-analysis. RESULTS: Among the 1165 (65.7% Crohn's) children with IBD included in our study, there were no age differences in the frequency of hospitalizations (rate ratio [RR], 0.88; 95% confidence interval [CI], 0.74-1.06) or outpatient visits (RR, 0.95; 95% CI, 0.78-1.16). A1a children had fewer emergency department visits (RR, 0.70; 95% CI, 0.50-0.97) and were less likely to require a Crohn's-related surgery (hazard ratio, 0.49; 95% CI, 0.26-0.92). The risk of colectomy was similar among children with ulcerative colitis in both age groups (hazard ratio, 0.71; 95% CI, 0.49-1.01). CONCLUSIONS: Patterns of health services utilization are generally similar when comparing children diagnosed across age groups.
Among 1165 children with inflammatory bowel disease, health services utilization was similar for children diagnosed <10 years of age and those diagnosed ≥10 years of age, except younger children had fewer emergency department visits and Crohn's diseaserelated surgeries.
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Purpose: The incidence of childhood-onset inflammatory bowel disease (IBD) is rising. We described variation in health services utilization and need for surgery among children with IBD between six and 60 months following IBD diagnosis across Canadian pediatric centers and evaluated the associations between care provided at diagnosis at each center and the variation in these outcomes. Patients and Methods: Using population-based deterministically-linked health administrative data from four Canadian provinces (Alberta, Manitoba, Nova Scotia, Ontario) we identified children diagnosed with IBD <16 years of age using validated algorithms. Children were assigned to a pediatric center of care using a hierarchical approach based on where they received their initial care. Outcomes included IBD-related hospitalizations, emergency department (ED) visits, and IBD-related abdominal surgery occurring between 6 and sixty months after diagnosis. Mixed-effects meta-analysis was used to pool results and examine the association between center-level care provision and outcomes. Results: We identified 3784 incident cases of pediatric IBD, of whom 2937 (77.6%) were treated at pediatric centers. Almost a third (31.4%) of children had ≥1 IBD-related hospitalization and there were 0.66 hospitalizations per person during follow-up. More than half (55.8%) of children had ≥1 ED visit and there were 1.64 ED visits per person. Between-center heterogeneity was high for both outcomes; centers where more children visited the ED at diagnosis had more IBD-related hospitalizations and more ED visits during follow-up. Between-center heterogeneity was high for intestinal resection in Crohn's disease but not colectomy in ulcerative colitis. Conclusion: There is variation in health services utilization among children with IBD and risk of undergoing intestinal resection in those with Crohn's disease, but not colectomy among children with ulcerative colitis, across Canadian pediatric tertiary-care centers. Improvements in clinical care pathways are needed to ensure all children have equitable and timely access to high quality care.
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INTRODUCTION: Canada has a high burden of inflammatory bowel disease (IBD). Historical trends of IBD incidence and prevalence were analyzed to forecast the Canadian burden over the next decade. METHODS: Population-based surveillance cohorts in 8 provinces derived from health administrative data assessed the national incidence (2007-2014) and prevalence (2002-2014) of IBD. Autoregressive integrated moving average models were used to forecast incidence and prevalence, stratified by age, with 95% prediction intervals (PI), to 2035. The average annual percentage change (AAPC) with 95% confidence interval (CI) was calculated for the forecasted incidence and prevalence. RESULTS: The national incidence of IBD is estimated to be 29.9 per 100,000 (95% PI 28.3-31.5) in 2023. With a stable AAPC of 0.36% (95% CI -0.05 to 0.72), the incidence of IBD is forecasted to be 31.2 per 100,000 (95% PI 28.1-34.3) in 2035. The incidence in pediatric patients (younger than 18 years) is increasing (AAPC 1.27%; 95% CI 0.82-1.67), but it is stable in adults (AAPC 0.26%; 95% CI -0.42 to 0.82). The prevalence of IBD in Canada was 843 per 100,000 (95% PI 716-735) in 2023 and is expected to steadily climb (AAPC 2.43%; 95% CI 2.32-2.54) to 1,098 per 100,000 (95% PI 1,068-1,127) by 2035. The highest prevalence is in seniors with IBD (1,174 per 100,000 in 2023; AAPC 2.78%; 95% CI 2.75-2.81). DISCUSSION: Over the next decade, the Canadian health care systems will contend with the juxtaposition of rising incidence of pediatric IBD and a rising prevalence of overall IBD driven by the aging population.
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Predicción , Enfermedades Inflamatorias del Intestino , Humanos , Incidencia , Prevalencia , Canadá/epidemiología , Adolescente , Adulto , Femenino , Enfermedades Inflamatorias del Intestino/epidemiología , Masculino , Persona de Mediana Edad , Adulto Joven , Niño , Anciano , Distribución por Edad , PreescolarAsunto(s)
Enfermedades Inflamatorias del Intestino , Enfermedades Inflamatorias del Intestino/epidemiología , Enfermedades Inflamatorias del Intestino/prevención & control , Incidencia , América del Norte/epidemiología , Oceanía/epidemiología , Europa (Continente)/epidemiología , Atención a la SaludRESUMEN
AIM: To assess contemporary outcomes in children with acute severe ulcerative colitis [ASUC] at initial presentation. METHODS: Between April 2014 and January 2019, children aged <17 years, with new onset ASUC (Paediatric Ulcerative Colitis Activity Index [PUCAI ≥65) were prospectively followed in a Canadian inception cohort study. 16S rRNA amplicon sequencing captured microbial composition of baseline faecal samples. Primary endpoint was corticosteroid-free clinical remission with intact colon at 1 year [PUCAI <10, no steroids ≥4 weeks]. RESULTS: Of 379 children with new onset UC/IBD-unclassified, 105 [28%] presented with ASUC (42% male; median [interquartile range; [IQR]) age 14 [11-16] years; extensive colitis in all). Compared with mild UC, gut microbiome of ASUC patients had lower α-diversity, decreased beneficial anaerobes, and increased aerobes; 54 [51%] children were steroid-refractory and given infliximab [87% intensified regimen]. Corticosteroid-free remission at 1 year was achieved by 62 [61%] ASUC cohort (by 34 [63%] steroid-refractory patients, all on biologics; by 28 [55%] steroid responders,13 [25%] on 5- aminosalicylic acid [5-ASA], 5 [10%] on thiopurines, 10 [20%] on biologics). By 1 year, 78 [74%] escalated to infliximab including 24 [47%] steroid-responders failed by 5-ASA and/or thiopurines. In multivariable analysis, clinical predictors for commencing infliximab included hypoalbuminaemia, greater PUCAI, higher age, and male sex. Over 18 months, repeat corticosteroid course[s] and repeat hospitalisation were less likely among steroid-refractory versus -responsive but -dependent patients (adjusted odds ratio [aOR] 0.71 [95% CI 0.57-0.89] and 0.54 [95% CI 0.45-0.66], respectively). CONCLUSION: The majority of children presenting with ASUC escalate therapy to biologics. Predictors of need for advanced therapy may guide selection of optimal maintenance therapy.
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Productos Biológicos , Colitis Ulcerosa , Humanos , Niño , Masculino , Femenino , Infliximab/uso terapéutico , Estudios de Cohortes , Estudios Prospectivos , ARN Ribosómico 16S , Canadá , Colitis Ulcerosa/diagnóstico , Colitis Ulcerosa/tratamiento farmacológico , Mesalamina/uso terapéutico , Corticoesteroides/uso terapéutico , Esteroides/uso terapéutico , Productos Biológicos/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND: This study compared real-world effectiveness between adalimumab (ADA) and infliximab (IFX) in children with Crohn's disease (CD). METHODS: Children enrolled into the prospective Canadian Children Inflammatory Bowel Disease Network (CIDsCaNN) National Inception Cohort between 2014 and 2020 who commenced ADA or IFX as first anti-tumor necrosis factor (antiTNF) agent for luminal CD were included. Multivariate logistic regression modelled the propensity of commencing ADA; propensity score matching was used to match IFX-treated children to ADA-treated children. The primary outcome at one year was steroid-free clinical remission (SFCR). Secondary outcomes at one year were I) combined SFCR and c-reactive protein (CRP) remission; II) treatment intensification; and III) antiTNF durability. Odds ratios (aOR) and hazard ratio (aHR) adjusted for concomitant immunomodulator use with 95% confidence interval (CI) are reported. RESULTS: In the propensity score matched cohort of 147 ADA-treated and 147 IFX-treated children, 92 (63%) ADA- and 87 (59%) IFX-treated children achieved SFCR at one year (aOR: 1.4, 95% CI 0.9-2.4); 75 of 140 (54%) ADA- and 85 of 144 (59%) IFX-treated children achieved combined SFCR and CRP remission (aOR: 1.0, 95% CI 0.6-1.6). ADA-treated children less frequently underwent treatment intensification (21 [14%]) compared to IFX-treated children (69 [47%]) (P<0.0001). Discontinuation of antiTNF occurred in 18 (12%) ADA-treated and 15 (10%) IFX-treated children (aHR: 1.2, 95% CI 0.6-2.2). CONCLUSION: Children with Crohn's disease achieved favourable outcomes at one year with either ADA or IFX as first antiTNF agents. Those receiving IFX did not have significantly superior outcomes compared to clinically similar children receiving ADA.
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Importance: Immune-mediated inflammatory diseases (IMIDs) and COVID-19 are independently associated with venous thromboembolisms (VTEs). Objective: To determine if individuals with IMIDs are at higher risk of VTE following COVID-19 infection compared with individuals without IMIDs. Design, Setting, and Participants: Population-based matched cohort study using multiple deterministically linked health administrative databases from Ontario, Canada, and including patients testing positive for COVID-19 between January 1, 2020, and December 30, 2021, and followed up until March 31, 2022. Individuals with IMIDs (n = 28â¯440) who tested positive for COVID-19 were matched with up to 5 individuals without an IMID (n = 126â¯437) who tested positive for COVID-19. Matching was based on year of birth, sex, neighborhood income, and rural/urban residence. Data analysis was performed from August 6, 2022, to August 21, 2023. Exposure: Diagnosis of an IMID, identified using algorithms based on diagnostic codes, procedures, and specialist visits. Main Outcome and Measure: The main outcome was estimated age- and sex-standardized incidence of VTE. Proportional cause-specific hazard models compared the risk of VTE in people with and without IMIDs. Death was a competing risk. Models adjusted for history of VTE, 2 or more doses of a COVID-19 vaccine 14 or more days prior to COVID-19 diagnosis, and the Charlson Comorbidity Index. Routinely collected health data were used, so the hypothesis tested was formulated after data collection but prior to being granted access to data. Results: The study included 28â¯440 individuals (16â¯741 [58.9%] female; 11â¯699 [41.1%] male) with an IMID diagnosed prior to first COVID-19 diagnosis, with a mean (SD) age of 52.1 (18.8) years at COVID-19 diagnosis. These individuals were matched to 126â¯437 controls without IMIDs. The incidence of VTE within 6 months of COVID-19 diagnosis among 28â¯440 individuals with an IMID was 2.64 (95% CI, 2.23-3.10) per 100â¯000 person-days compared with 2.18 (95% CI, 1.99-2.38) per 100â¯000 person-days among 126â¯437 matched individuals without IMIDs. The VTE risk was not statistically significantly different among those with vs without IMIDs (adjusted hazard ratio, 1.12; 95% CI, 0.95-1.32). Conclusions and Relevance: In this retrospective population-based cohort study of individuals with IMIDs following COVID-19, individuals with IMIDs did not have a higher risk of VTE compared with individuals without an IMID. These data provide reassurance to clinicians caring for individuals with IMIDs and COVID-19.
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COVID-19 , Tromboembolia Venosa , Humanos , Masculino , Femenino , Persona de Mediana Edad , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/etiología , Estudios Retrospectivos , Estudios de Cohortes , Factores de Riesgo , Vacunas contra la COVID-19 , Prueba de COVID-19 , Agentes Inmunomoduladores , COVID-19/complicaciones , COVID-19/epidemiología , Ontario/epidemiologíaRESUMEN
Inflammatory bowel disease (IBD), consisting of Crohn's disease and ulcerative colitis, is recognized across the world, though Canada has among the highest burdens of IBD in the world. The Canadian Gastro-Intestinal Epidemiology Consortium (CanGIEC) led a six-province study that demonstrated the compounding prevalence of IBD in Canada from 400 per 100,000 in 2002 to 636 per 100,000 in 2014. The prevalence in 2023 is estimated at 825 per 100,000, meaning that over 320,000 people in Canada are living with IBD. Prevalence is forecasted to rise by 2.44% per year such that 1.1% of the population, 470,000 Canadians, will live with IBD by 2035. The overall incidence of IBD in 2023 is 30 per 100,000 person-years, indicating that over 11,000 Canadians will be newly diagnosed with IBD in 2023. Incidence is forecasted to rise by 0.58% per year up to 32.1 per 100,000 by 2035. The rising incidence of IBD is propelled by pediatric-onset IBD, which is rising by 1.23% per year from 15.6 per 100,000 in 2023 to 18.0 per 100,000 in 2035. In contrast, incidence rates among adults and seniors are relatively stable. Understanding the determinates of IBD has expanded through prospective cohort studies such as the Crohn's and Colitis Canada Genetic, Environmental, Microbial (CCC-GEM) project. Consensus recommendations towards diet, lifestyle, behavioural and environmental modifications have been proposed by international organizations with the goal of optimizing disease control and ultimately preventing the development of IBD. Despite these efforts, Canadian healthcare systems will need to prepare for the rising number of people living with IBD.
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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.
RESUMEN
The COVID-19 pandemic had a monumental impact on the inflammatory bowel disease (IBD) community. At the beginning of the pandemic, knowledge on the effect of SARS-CoV-2 on IBD was lacking, especially in those with medication-suppressed immune systems. Throughout the pandemic, scientific literature exponentially expanded, resulting in clinical guidance and vaccine recommendations for individuals with IBD. Crohn's and Colitis Canada established the COVID-19 and IBD Taskforce to process and communicate rapidly transforming knowledge into guidance for individuals with IBD and their caregivers, healthcare providers, and policy makers. Recommendations at the onset of the pandemic were based on conjecture from experience of prior viruses, with a precautionary principle in mind. We now know that the risk of acquiring COVID-19 in those with IBD is the same as the general population. As with healthy populations, advanced age and comorbidities increase the risk for severe COVID-19. Individuals with IBD who are actively flaring and/or who require high doses of prednisone are susceptible to severe COVID-19 outcomes. Consequently, sustaining maintenance therapies (e.g., biologics) is recommended. A three-dose mRNA COVID-19 vaccine regimen in those with IBD produces a robust antibody response with a similar adverse event profile as the general population. Breakthrough infections following vaccine have been observed, particularly as the virus continues to evolve, which supports receiving a bivalent vaccine booster. Limited data exist on the impact of IBD and its therapies on long-term outcomes following COVID-19. Ongoing research is necessary to address new concerns manifesting in those with IBD throughout the evolving pandemic.
RESUMEN
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.