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Epidemiology Publications // 2019

Coward S, Clement F, Benchimol EI, Bernstein CN, Avina-Zubieta JA, Bitton A, Carroll MW, Hazlewood G, Jacobson K, Jelinski S, Deardon R, Jones JL, Kuenzig ME, Leddin D, McBrien KA, Murthy SK, Nguyen GC, Otley AR, Panaccione R, Rezaie A, Rosenfeld G, Peña-Sánchez JN, Singh H, Targownik LE, Kaplan GG. Past and future burden of inflammatory bowel diseases based on modeling of population-based data. Gastroenterology 2019; 156:1345-1353.

 

Inflammatory bowel diseases exist worldwide, with high prevalence in North America. IBD is complex and costly, and its increasing prevalence places a greater stress on health care systems. In this study we aimed to determine the past current, and future prevalences of IBD in Canada. We used administrative health data from Alberta (2002-2015), British Columbia (1997-2014), Manitoba (1990-2013), Nova Scotia (1996-2009), Ontario (1999-2014), Quebec (2001-2008), and Saskatchewan (1998-2016). In 2018, the prevalence of IBD in Canada was estimated at 725 per 100,000 (95% PI 716-735) and the annual average percent change increase was nearly 3% per year. The prevalence in 2030 was forecasted to be 981 per 100,000 159 per 100,000 in children, 1118 per 100,000  in adults, and 1370 per 100,000 in the elderly. In 2018, 267,983 Canadians were estimated to be living with IBD, which was forecasted to increase to 402,853 by 2030.

 

Targownik LE, Benchimol E, Witt J, Bernstein CN, Singh H, Lix L, Tennakoon A, Zubieta AA, Coward S, Jones J, Kuenzig E, Murthy S, Nguyen G, Peña Sánchez JN, Kaplan GG. The effect of initiation of anti-TNF therapy on the subsequent direct healthcare costs of inflammatory bowel disease. Inflammatory Bowel Diseases 2019; in press.

Background: The prevalence of inflammatory bowel disease (IBD) is known to be increasing. The total direct costs of IBD have not been assessed on a population wide level in the era of biologic therapy. We identified all persons with IBD in Manitoba in the University of Manitoba Inflammatory Bowel Disease Epidemiology Database between January 2005 and December 2015, with each matched to 10 controls on age, sex, and geographic area of residence. Costs of all hospitalizations, outpatient physician-patient contacts and prescription medication use were enumerated for cases and controls. Total and per-capital annual costs attributable to IBD were determined by taking the difference between the costs accrued by an IBD case and their control. 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 pre capital annual anti-TNF drug (i.e. infliximab and adalimumab) costs, which rose from $181 in 2005 to  $5,270 in 2015.  There was a significant decline in inpatient costs for CD ($180±35/year. p=0.0006), but not for UC ($56±35/year, p=0.23), In summary, 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 (i.e. anti-TNF drugs). IBD-attributable hospitalization costs have declined modestly over time for persons with CD, though no change was seen for patients with UC.

 

Murthy SK, Begum J, Benchimol EI, Kaplan GG, Targownik LE, Singh H, Bernstein CN, McCurdy JD, Taljaard. Introduction of anti-TNF therapy has not yielded expected declines in hospitalization and intestinal resection rates in inflammatory bowel diseases: a population-based interrupted time series study. Gut 2019; in press.

 

We evaluated the effect of introduction of infliximab in Ontario on the population rates of major health events and direct costs in persons with IBD. We studied all adult patients with Crohn’s disease (CD) and ulcerative colitis (UC) living in Ontario, Canada between July 1, 1995 and March 31, 2012 using population-level health administrative data. Marketplace introduction of infliximab in CD did not have a significant immediate  or gradual impact on the rate of IBD-related hospitalizations, nor an immediate or gradual impact on the rate of intestinal resections. Marketplace introduction of infliximab in UC was not associated with an immediate effect but was associated with a gradual decrease in IBD-related hospitalization rates. There were no significant persistent effects of infliximab availability on colectomy rates among UC patients nor on the rates of non-IBD hospitalizations or other major abdomino-thoracic surgeries (control outcomes) among CD or UC patients. We concluded that robust market penetration of infliximab among CD patients has not resulted in a meaningful reduction in the population rates of IBD-related hospitalizations or intestinal resections. Despite the absence of UC-related colectomies there was a reduction in UC-related hospitalization rates. Since we know these drugs can have dramatic effects in a substantial number of patients we believe that the absence of an impact of infliximab on key outcomes likely relates to underuse of this agent in the target populations.

Nugent Z, Singh H, Targownik LE, Bernstein CN. Herpes Zoster infection and Herpes Zoster vaccination in a population based sample of persons with IBD: Is there still an unmet need? Inflammatory Bowel Disease 2019; 25:532-540.

In this study we aimed to report the rates of herpes zoster infection before and after the introduction of herpes zoster vaccine (HZVac) and to determine the rates of HZVac after it became available in Manitoba in 2009. We used the population-based University of Manitoba IBD Epidemiology Database to identify cases of IBD and controls (1984-2016) who were diagnosed with herpes zoster infection before and after 2009 and to determine the rate of HZVac in those older than age 50 years. Further, we explored predictors of receipt of HZVac among persons with IBD. Persons with IBD vs matched controls have higher rates of herpes zoster infection before diagnosis and postdiagnosis. Herpes zoster infection rates before 2009 per 1000 person-years were increased in persons with IBD (9.2) vs controls (7.2, P < 0.0001). Persons with IBD compared with controls were more likely to get HZVac (15.5 vs 12 per 1000 person-years). Persons newly diagnosed with IBD after 2009 and of higher socioeconomic status were more likely to get HZVac. Despite the introduction of HZVac, there was a steady rise in herpes zoster infection throughout the study period (annual percent change in infection rates of +0.54, P < 0.0001). The increased risk of herpes zoster infection in IBD may reflect an inherent risk associated with the disease or, in those already diagnosed, an increased risk secondary to the use of immunomodulating drugs. HZVac rates are very low, which may reflect physician and patient knowledge of the vaccine's availability and utility and the fact that it is not covered by the provincially provided health care plan.We must do better in encouraging patients with IBD, especially those using immunosuppressive drugs to get vaccinated against Herpes Zoster (shingles).

 

Bernstein CN, Burchill C, Targownik LE, Singh H, Roos LL. Events within the first year of life, but not the neonatal period, affect risk for later development of inflammatory bowel diseases. Gastroenterology 2019; in press.

We performed a population-based study to determine whether there was an increased risk of inflammatory bowel diseases (IBD) in persons with critical events at birth and within 1 year of age. We collected data from the University of Manitoba IBD Epidemiology Database, which contains records on all Manitobans diagnosed with IBD from 1984 through 2010 and matched controls. From 1970 individuals' records can be linked with those of their mothers, so we were able to identify siblings. All health care visits or hospitalizations during the neonatal and postnatal periods were available from 1970 through 2010. In previous studies using this data source we showed that development of IBD was not associated with being born by caesarean section (versus vaginal delivery) and was not associated with mothers’ having antenatal or perinatal infections. In this study we collected data on infections, gastrointestinal illnesses, failure to thrive, and hospital readmission in the first year of life and sociodemographic factors at birth. From 1979, data were available on gestational age, Apgar score, neonatal admission to the intensive care unit, and birth weight. We compared incident rate of infections, gastrointestinal illnesses, and failure to thrive between IBD cases and matched controls as well as between IBD cases and siblings. Data on 825 IBD cases and 5999 matched controls were available from 1979. Maternal diagnosis of IBD was the greatest risk factor for IBD in offspring (increased the risk for IBD development in offspring 4.5x). When we assessed neonatal events, only being in the highest vs lowest socioeconomic quintile increased risk for later development of IBD. For events within the first year of life, being in the highest socioeconomic quintile at birth and infections increased risk for developing IBD at any age. Infection in the first year of life was associated with diagnosis of IBD before age 10 years (by 3x)  and before age 20 years (by 1.5x) Risk for IBD was not affected by gastrointestinal infections, gastrointestinal disease, or abdominal pain in the first year of life. In a population-based study, we concluded that infection within the first year of life was associated with a diagnosis of IBD. This might be due to use of antibiotics or a physiologic defect at a critical age for gut microbiome development.

 

El Matary W, Nugent Z, Yu BN, Lix LM, Targwonik LE, Bernstein CN, Singh H. Trends and predictors of Clostridium difficile infection among children: A Canadian population-based study. Journal of Pediatrics 2019 Mar; 206:20-25.

 

In this paper we report on the incidence rates over time of children with IBD presenting with Clostridium difficile infection. We explored our provincial database on all persons with Clostridium difficile infection between 2005-2014 so that we could identify the rates of this infection in children and what diseases increased the risk for Clostridium difficile infection. In children. The overall Clostridium difficile infection rate over the study period was 7.77 per 100,000. There was no significant increase in Clostridium difficile infection rates over the observation period. Co-morbid conditions that were more prevalent among children with Clostridium difficile infection than matched controls included Hirschsprung’s disease (p<0.001) and IBD (p<0.0001). Recurrent Clostridium difficile infections were responsible for 10.4% of CDI episodes (range 2-6 infections). Children with cancer were 3 times as likely to have recurrent Clostridium difficile infection (Hazard ratio (HR) = 3.0, 95% confidence interval (CI) 1.1, 8.8), children with diabetes were nearly 5 times as likely to have recurrent Clostridium difficile infection (HR=4.8, 95% CI 1.1, 21.4) and children with neurodegenerative diseases were over 8 times as likely to have recurrent Clostridium difficile infection (HR=8.4, 95% CI 1.9, 37.5). We concluded that the incidence of Clostridium difficile infection was not increasing among children in Manitoba. Children with malignancy, diabetes and neurodegenerative disorders are more likely to have recurrent Clostridium difficile infection.

El-Matary W, Leung S, TennakoonA, Benchimol EI, Bernstein CN, Targownik LE. Trends of utilization of tumor necrosis factor antagonists in children with inflammatory bowel disease: A Canadian population-based study. Inflammatory Bowel Diseases 2019; in press.

We aimed to describe the trend of utilization of anti-TNF drugs (infliximab and adalimumab) in children with IBD over time. We assessed all persons diagnosed with IBD prior to age 18y identified in the University of Manitoba IBD Epidemiology Database to determine the time from diagnosis to first anti-TNF in different eras (2005-2008, 2008-2012, 2012-2016). There were 291 persons diagnosed with IBD (157 CD, 134 UC) prior to age 18y. The likelihood of being initiated on anti-TNFs by 1, 2 and 5 years post-diagnosis was 18.4%, 30.5% and 42.6% respectively. The proportion of persons <18 using anti-TNFs increased over time; in 2010, 13.0% of Crohn’s disease (CD) and 4.9% of ulcerative colitis (UC); by 2016 60.0% of CD and 25.5% of UC were actively using an anti-TNF agent. For those diagnosed after 2012, 42.5% of CD and 28.4% of UC had been started on an anti-TNF agent within 1 year of IBD diagnosis. The median cumulative dose of corticosteroids in the year prior to anti-TNF initiation significantly decreased over time (prior to 2008: 4360mg; 2008-2012: 2010mg, 2012-present 1395mg prednisone equivalents) meaning the use of anti-TNF drugs has likely translated into a reduced use of corticosteroids.

 

ten Hove JR, Shah SC, Shaffer SR, Bernstein CN, Castaneda D, Palmela C, Mooiweer E, Elman J, Kumar A, Glass J, Ullman TA, Colombel JF, Torres J, van Bodegraven AA, Hoentjen F, Jansen JM, de Jong M, Mahmmod N, van der Meulen-de Jong AE, Ponsioen CY, van der Woude CJ, Itzkowitz SH, Oldenburg B. Consecutive negative findings on colonoscopy during surveillance predict a low risk of advanced neoplasia in patients with longstanding colitis: results of a 15-year multicenter, multinational cohort study. Gut 2019; 68: 615-622.

 

Surveillance colonoscopy is thought to prevent colorectal cancer in patients with long-standing colonic IBD, but data regarding the frequency of surveillance and the findings thereof are lacking. Our aim was to determine whether consecutive negative surveillance colonoscopies adequately predict low neoplastic risk. A multicentre (Manitoba, NY, Holland) database of patients with long-standing IBD colitis without high-risk features and undergoing regular colorectal cancer surveillance was constructed. A 'negative' surveillance colonoscopy was predefined as a technically adequate procedure having no postinflammatory polyps, no strictures, no endoscopic disease activity and no evidence of neoplasia; a 'positive' colonoscopy was a technically adequate procedure that included at least one of these criteria. The primary endpoint was advanced colorectal neoplasia defined as high-grade dysplasia or colorectal cancer. Of 775 patients with long-standing IBD colitis, 44% (n=340) had at least 1 negative colonoscopy. Patients with consecutive negative surveillance colonoscopies were compared with those who had at least one positive colonoscopy. Both groups had similar demographics, disease-related characteristics, number of surveillance colonoscopies and time intervals between colonoscopies. No advanced colorectal neoplasia occurred in those with consecutive negative surveillance, compared with an incidence rate of 0.29 to 0.76/100 patient-years (P=0.02) in those having at least 1 positive colonoscopy on follow-up of 6.1 years after the index procedure. Within this large surveillance cohort of patients with colonic IBD and no additional high-risk features, having two consecutive negative colonoscopies predicted a very low risk of advanced colorectal neoplasia occurrence on follow-up. Our findings suggest that longer surveillance intervals in this selected population may be safe.

 

The following series of articles was written to update the burden of IBD for Crohn’s and Colitis Canada as of the summer of 2018:

 

Benchimol E, Bernstein CN, Bitton A, Murthy SK, Nguyen GC, Lee K, Cooke-Lauder J, Siddq S, Windsor JW, Carroll M, Coward S, El-Matary W, Griffiths AM, Jones J, Kuenzig E, Lee L, Mack DR, Mawani M, Otley A, Singh H, Targownik LE, Weizman AV, Kaplan GG. The Impact of Inflammatory Bowel Disease in Canada 2018: A Scientific Report from the Canadian Gastro-Intestinal Epidemiology Consortium to Crohn's and Colitis Canada. Journal of the Canadian Association of Gastroenterology 2019; 2 Supplement 1: S1-S5.

 

Kaplan GG, Bernstein CN, Coward S, Bitton A, Murthy SK, Nguyen GC, Lee K, Cooke-Lauder J, Benchimol E. The Impact of Inflammatory Bowel Disease in Canada 2018: Epidemiology. Journal of the Canadian Association of Gastroenterology 2019; 2 Supplement 1: S6-S16.

 

Carroll M, Kuenzig E, Mack DR, Otley A, Griffiths AM, Kaplan GG, Bernstein CN, Bitton A, Murthy SK, Nguyen GC, Lee K, Cooke-Lauder J, Benchimol E. The Impact of Inflammatory Bowel Disease in Canada 2018: Children and Adolescents with IBD. Journal of the Canadian Association of Gastroenterology 2019; 2 Supplement 1: S49-S67.

 

Nguyen GC, Targownik LE, Singh H, Benchimol E, Bitton A, Murthy SK, Bernstein CN, Lee K, Cooke-Lauder J, Kaplan GG. The Impact of Inflammatory Bowel Disease in Canada 2018: IBD in Seniors. Journal of the Canadian Association of Gastroenterology 2019; 2 Supplement 1: S68-S72.

 

Bernstein CN, Benchimol E, Bitton A, Murthy SK, Nguyen GC, Lee K, Cooke-Lauder J, Kaplan GG. The Impact of Inflammatory Bowel Disease in Canada 2018: Extra-intestinal Diseases in IBD. Journal of the Canadian Association of Gastroenterology 2019; 2 Supplement 1: S73-S80.

 

Rose K, Sherman PM, Cooke-Lauder J, Mawani M, Benchimol E, Kaplan GG, Bernstein CN, Bitton A, Murthy SK, Nguyen GC, Lee K. The Impact of Inflammatory Bowel Disease in Canada 2018: IBD Research Landscape in Canada. Journal of the Canadian Association of Gastroenterology 2019; 2 Supplement 1: S81-S91.

Jones J, Nguyen GC, Benchimol E, Bernstein CN, Bitton A, Kaplan GG, Murthy SK, Lee K, Cooke-Lauder J, Otley A. The Impact of Inflammatory Bowel Disease in Canada 2018: Quality of Life. Journal of the Canadian Association of Gastroenterology. 2019; 2 Supplement 1: S42-S48.

Keunzig ME, Lee L, El-Matary W, Weizman AV, Benchimol EI, Targownik LE, Singh H, Kaplan GG, Bernstein CN, Bitton A, Nguyen GC, Lee K, Cooke-Lauder J, Murthy S. The Impact of Inflammatory Bowel Disease in Canada 2018: Direct Costs and Health Services Utilization. Journal of the Canadian Association of Gastroenterology. 2019; 2 Supplement 1: S17-S33.

 

Keunzig ME, Benchimol E, Lee L, Targownik LE, Singh H, Kaplan GG, Nguyen GC, Bernstein CN, Bitton A, Lee K, Cooke-Lauder J, Murthy S. The Impact of Inflammatory Bowel Disease in Canada 2018: Indirect costs of IBD care. Journal of the Canadian Association of Gastroenterology. 2019; 2 Supplement 1: S34-S41.

 

 

Publications // from the Manitoba IBD Epidemiology Database