Epidemiology and natural history of paediatric-onset inflammatory bowel disease in Scotland
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Date
27/06/2020Author
Cameron, Fiona Louise
Metadata
Abstract
Background
Inflammatory bowel disease (IBD) is a chronic lifelong condition which comprises
Crohn’s disease (CD), ulcerative colitis (UC) and inflammatory bowel disease unclassified
(IBDU). Around 8% of IBD cases diagnosed each year present in childhood (under 18
years)(1) and can cause impairment of linear growth and pubertal development, affecting
education and future employment. The incidence of paediatric IBD (PIBD) is increasing both
within Scotland, as evidenced by previous publications, but also worldwide as
demonstrated in a recent systematic review. As the number of cases are increasing, it has
become critical that effective treatments are available to manage symptoms in this patient
cohort. Anti-TNF alpha antagonists have been used to treat PIBD and shown in large single
centre studies to be effective at the induction and maintenance of remission, however,
these studies may not reflect the general PIBD patients’ clinicians treat daily so “real life”
experience are needed to inform clinical practice.
Aims
The aims of my thesis were 1) to determine if the incidence and prevalence of PIBD
continue to increase worldwide and to examine the durability of any incidence rise seen in
Scotland, 2) to investigate in a nationwide population-based study the incidence and
natural history of IBDU, 3) to examine the efficacy, safety and long-term effects of anti-TNF
alpha drugs and lastly 4) to assess the long-term risk of PIBD on cancer and mortality rates
in a nationwide population-based study.
Methods
Data was collected from all 4 PIBD centers across Scotland (Glasgow, Edinburgh,
Aberdeen and Dundee) from 2009-2014 on new cases of IBD as well as those diagnosed
with IBDU from 2003-2013, those treated with anti-TNF drugs from 2000-2012 and cases of
cancer/deaths within the PIBD population from 2003-2013.
Results
Thirty-six studies from 18 countries were included in the incidence systematic
review, most from North America and Western Europe. The highest incidence was 15.2 per
100,000 in Nova Scotia, Canada with the lowest 0.47 per 100,000 in Saudi Arabia, for CD
the highest incidence was 9.2 per 100,000 in Nova Scotia and lowest in Saudi Arabia at 0.27
per 100,000 whilst for UC rates were highest in Finland at 8 per 100,000 and lowest in
Saudi Arabia at 0.2 per 100,000. In the prevalence systematic review, 27 studies were
included from 12 countries with the highest prevalence of 301 per 100,000 in Israel and
lowest in Libya at 3.6 per 100,000. CD was highest in Sweden at 41 per 100,000 and lowest
in Libya at 2.0 per 100,000 which was similar for UC with a high of 30.7 per 100,000 in
Sweden and lowest at 1.36 in Libya. Most studies that reported on temporal trends saw an
increase in PIBD, CD and UC. Significant heterogeneity existed in studies in both incidence
and prevalence due to varying methodological approaches, age cut offs and diagnostic
algorithms so meta-analysis was not performed.
The incidence of PIBD in Scotland demonstrated a significant and sustained rise from
430 cases in 2003-2008 with an incidence rate of 7.6 per 100,000 (95%CI 7.1-8.6) to 582
cases in 2009-2014 and incidence of 10.6 per 100,000 (95%CI 9.8-11.5) (p<0.001); primarily
due to an increase in paediatric Crohn’s disease. When compared with historical data there
was a sustained and durable increase over the last 40 years, again mostly driven by
increasing CD. The incidence of IBDU also increased from 2003-2013, accounting for around 20% of new PIBD cases in Scotland. Most children with this subtype had a relatively mild
disease course, however 43% required immunosuppression and a small number escalated
to anti-TNF therapy. 23% of IBDU patients had their diagnosis changed after endoscopic re
evaluation, most 62%, to CD. A Scottish nationwide registry of all children treated with anti
TNF drugs (infliximab (IFX) and adalimumab (ADA) was created from 2000-2012. 87% had
improvement of their symptoms within 3 months post induction to IFX and 86% achieved
remission with ADA. Growth was improved after one year of treatment with IFX but only in
those children who responded after induction, had been diagnosed for over 2 years with
IBD and were in the early stages of puberty (Tanner stage 1 and 2). Anti-TNF agents were
generally safe and well tolerated with only 13% having an acute adverse reaction to IFX,
ADA was also well tolerated with 16/57 having an adverse event. Death in children with
PIBD was a rare occurrence with only 3 cases over 10 years, 2 cases were PIBD related with
2 cases of malignancy were observed, both had been treated with azathioprine with one
subsequent death.
Conclusions
The incidence and prevalence of PIBD is increasing worldwide with the highest
incidence rates from Nova Scotia, Canada and highest prevalence rates from Israel,
although there is a propensity of data from North America and Western Europe.
In these population-based studies of paediatric-onset inflammatory bowel disease in
Scotland, the number of new cases continue to rise with IBDU, as a subtype of IBD, more
commonly diagnosed compared to other countries. Most children with IBDU had a mild
disease course with 23% changing diagnosis following endoscopic reassessment most, 62%
to CD. In Scotland, anti-TNF drugs are effective at managing symptoms of IBD with
relatively few serious side effects with other benefits including improving linear growth in those treated with infliximab. Finally, cancer and death are a rare outcome in children with
IBD in Scotland. The continued increase in incidence of PIBD with higher rates of IBDU
observed in Scotland may suggest environmental factors, such as urbanization or latitude,
influencing the onset of PIBD. Prospective case control studies can further explore these
environmental risk factors taking advantage of the nationwide collaborative approach to
care and research within Scotland.