Objectives and Study

To compare the clinical course of UC before and after the introduction of biologics, and to compare with the IBSEN study.

Methods

Patients under 18 years of age, who were diagnosed with UC and followed from January 2003 to October 2020, were included in the study. Group A (n = 48) was followed between January 2003 and October 2012, and Group B (n = 62) was followed between November 2012 and October 2020. We compared endoscopic remission, drug composition, relapse rate, steroidfree period, and the quality of life of each group. We plotted the clinical course of the included patients using the pediatric UC activity index score, and compared our patients with those in the IBSEN study.

Results

After 2 years of treatment, colonoscopy evaluation revealed different outcomes in the two treatment groups. Remission was confirmed in 14 patients (29.2%) of Group A, and in 31 patients (50.0%) of Group B (P < 0.012). The median cumulative corticosteroid-free period was 3.0 years in Group A and 4.4 years in Group B. Steroid-free period of Group B was significantly longer than that of Group A (P < 0.001). There was a statistically significant difference between the two groups in evaluation of the relapse rate during the observation period (P < 0.001). The plotted clinical course graphs of Group A showed similar proportions to the graphs in the IBSEN study. However, in Group B, the proportion of patients corresponding to curve 1 (remission or mild severity after initial high activity) was high at 76% (47/62).

Conclusions

The incidence of relapse has decreased and the steroid-free period has increased after the introduction of the biological agent. The clinical course also showed a different pattern from that of IBSEN study. The active use of biological agents may change the long-term disease course in moderate to severe pediatric UC.

Objectives and Study

Early–life antibiotic exposure has been associated with a decreased richness of the microbiome, which is associated with the development of inflammatory bowel disease (IBD). The aim of this study was to assess the risk of developing paediatric-onset IBD (pIBD) after being exposed to systemic antibiotics during the first five years of life.

Methods

We identified all patients < 18 years old diagnosed with pIBD in Denmark between 1995-2018 in the National Patient Registry. Data on antibiotic prescriptions during first five years of life were retrieved from the National Prescription Register. PIBD patients were matched with up to ten healthy controls. Risk estimates were presented by Hazard ratios (HR).

Results

We identified 1,808 patients with pIBD (989 Crohn’s disease [CD]/819 ulcerative colitis [UC]) and 17,234 matched controls. As seen in Figure 1, prescription of antibiotics during the first five years of life was associated with a higher risk of developing pIBD (HR = 1.32 [95%CI: 1.2-1.5], p= <0.0001). The risk was further increased if the patient had ≥ 4 antibiotic prescriptions compared to no antibiotic prescription (HR = 1.43 [95%CI: 1.2-1.6], p= <0.0001). Prescription of broad-spectrum antibiotics increased the risk of pIBD compared to prescription of only narrow-spectrum antibiotics (HR: 1.19, [95%CI 1.0-1.4], p=0.04). When stratified by IBD subtypes, only CD was significantly associated with exposure to antibiotics (HR = 1.43 [95%CI: 1.2-1.7], p=0.0003).

Conclusions

In this nationwide registry-based study, we found that antibiotic exposure during first five years of life, was associated with an increased risk of pIBD. Repeated antibiotic exposures increased risk estimates.

Objectives and Study

ECCO-ESPGHAN updated the guideline on the management of paediatric Crohn’s disease (CD) in 2021. This promoted a move to a ‘top-down’ (anti-TNF within 4 weeks of diagnosis) approach for patients who were deemed high-risk. High-risk was defined by extensive panenteric or severe disease, perianal, stricturing and/or penetrating behaviour. We sought to compare the use of anti-TNF therapy against the new guidance by conducting a Scottish nationwide retrospective multi-centre study.

Methods

We retrospectively collected and analysed data from medical records on the use of anti-TNF therapy (infliximab or adalimumab) within 18 months of diagnosis of all new paediatric CD patients diagnosed in Scotland between 01/01/16 and 31/12/20 . Paris location and behaviour at diagnosis were determined, allowing us to split the patient group into high-risk or low/medium-risk.

Results

419 patients were included (259/419 male; median age at diagnosis 13.2 yrs). 225/419 (54%) were classified as high-risk and 194/419 (46%) as low/medium-risk. 171/225 (76%) high-risk and 78/194 (40%) low/medium-risk patients received anti-TNF within 18 months of diagnosis. Figure 1 demonstrates cumulative anti-TNF new starts by month. 49/171 (40%) high-risk and 12/78 (15.3%) low-risk received anti-TNF within 4 weeks of diagnosis. High-risk patients were more likely to receive anti-TNF (76.0% vs 40.2%, p<0.0001). 37 (8.8%) patients underwent surgical intervention; 31/225 (13.7%) high-risk and 6/194 (3.1%) low/medium-risk (13.7% vs 3.1%, p= 0.0002).

Conclusions

The ECCO-ESPGHAN guidance seeks to shift practice towards “top-down” anti-TNF therapy in high-risk patients. Our real-world data supports this view by showing that high-risk patients are more likely to require biologics within 18 months and more likely to require surgery than low/medium-risk patients. The ECCO-ESPGHAN approach would however have led to unnecessary anti-TNF in 24% of our high-risk cohort within 18 months of diagnosis. The financial cost and risk:benefit profile of this group should be considered carefully both in clinical practice and future guidance.

Objectives and Study

Rates of paediatric inflammatory bowel disease (pIBD) have increased globally over the last 25 years. In South Wales, incidence was last reported for 1998-2003 (5.4/100,000) (Ahmed et al., 2006), and subsequent defined national and global cohorts have described increases, particularly in Crohn’s disease. This work aimed to characterise and update the contemporary incidence of pIBD in South Wales, highlighting implications for resource planning in paediatric and adult gastroenterology services.

Methods

Data from the Noah’s Ark Children’s Hospital for Wales in Cardiff prospective pIBD database were retrieved for 2011-2021. Data were classified by age at diagnosis, gender and type of IBD (IBDU, CD, UC). At risk population (<18 years) was determined using 2011 and 2021 UK census data (Office for National Statistics). Population numbers were extrapolated between censuses. Potential differences in age at diagnosis were analysed though ANOVA. Pearson’s correlation coefficients were calculated for analysis of total IBD, UC and Crohn’s incidence by year.

Results

365 patients were included (mean age at diagnosis 12.7, 37.3% female). There were no differences in age at diagnosis over the ten-year period as assessed by ANOVA (F=1.629, p=0.097). Total incidence rose from 2011 (4.28/100,000) to 2018 (6.93/100,000) and again to 2021 (11.24/100,000), β=0.9, p=0.000157. Male pIBD increased from 5.57/100,000 in 2011 to 14.01/100,000 in 2021 and female pIBD increased from 2.29/100,000 to 8.32/100,000.

The largest increase was seen in Crohn’s disease from 2011 (2.85/100,000) to 2021 (8.29/100,000), β=0.8, p=0.03. Ulcerative Colitis incidence did not significantly increase, at 1.43/100,000 in 2011 and 2.76/100,000 in 2021, β=0.46, p=0.154.

Conclusions

The incidence of pIBD continues to rise across South Wales, with increases in affected males and those with Crohn’s disease. This is in keeping with contemporary trends. Increases are likely driven by multifactorial environmental triggers and highlight continued need to map incidence. These ongoing increases represent significant implications for services.

Objectives and Study

Infliximab is considered superior to adalimumab in patients with ulcerative colitis, especially in severe cases. Whether such approach is also true for patients with colonic involvement in Crohn’s disease (CD) is unclear. The aim of the study was to compare the clinical effectiveness of infliximab vs. adalimumab in pediatric CD patients with ileocolonic (L3) phenotype.

Methods

This single-center, retrospective study included patients aged <18 years diagnosed with L3 CD between 2014-2021 that were treated with infliximab or adalimumab. Primary outcome was steroid-free clinical remission by week 52, defined as PCDAI≤10. Secondary outcome was clinical remission by end of induction (EOI).

Results

We identified 115 patients: 74 treated with adalimumab and 41 treated with infliximab, with comparable demographic features. Concomitant immunomodulator therapy at biologic initiation was significantly lower in the adalimumab group (28% vs. 85%, P<0.001). The median drug levels were 6.9 mcg/mL and 10.2 mcg/mL at EOI, and 10 mcg/mL and 10.4 mcg/mL at 52 weeks, in the infliximab and adalimumab groups, respectively (P=non-significant). Rates of drug intensification were statistically higher in the infliximab group, both at EOI and by 52 weeks (55% vs. 32% and 88% vs 46%, P<0.001). Given significant differences between initial median PCDAI scores (20.0 [IQR 15.0-27.5] vs. 11.0 [IQR 7.5-20.0] for infliximab and adalimumab groups, respectively, P<0.001), propensity score matching for initial PCDAI was performed. After matching, inflammatory markers and fecal calprotectin were comparable between groups at initiation of anti-TNFa, EOI and at 52 weeks. However, PCDAI was lower among patients treated with adalimumab vs. infliximab both at EOI (12.5, IQR 5-19.4 vs 5, IQR 0-5, P=0.003) and at 52 weeks (0, IQR 0-0 vs. 1.25, IQR 0-6.9, P=0.03). Rates of drug discontinuation, IBD-associated admission and surgery were similar (Figure 1).

Conclusions

Treatment with adalimumab is non-inferior to infliximab in pediatric patients with ileo-colonic CD.

Objectives and Study

Previous studies have shown conflicting findings on the association between exposure to antibiotics and future risk of developing Inflammatory Bowel Disease (IBD). The purpose of this study is to utilize a nationwide cohort of IBD patients and matched controls to explore the relationship between pre-diagnostic early life antibiotic exposure and future development of IBD.

Methods

Data of children (0-18 years) diagnosed with IBD in the epi-IIRN cohort from 2005-2021 were retrieved covering 98% of the national population. Each case was matched to 3 non-IBD control by sex, year of birth, district of residence. The date of diagnosis was considered as the index date of controls (in the same age). We counted the number of antibiotic courses within each 3-month period prior to the index date. Pairwise comparisons were made between the Crohn’s disease (CD)/Ulcerative colitis (UC) patients and their controls using the estimated marginal means.

Results

2,692 children with IBD and matched controls were included (1,803 (67%) CD) and 889 (33%) UC). While the utilization of antibiotics in non-IBD controls declined with age, the corresponding use in CD and UC patients increased towards the diagnosis (Figure). At 5 years before diagnosis, the number of antibiotic courses was significantly higher in both CD and UC vs their controls (248±4 CD vs 195±4 controls, p<0.001 and 121±2 UC vs 99±2 controls, p<0.001, respectively).

Conclusions

Antibiotic use prior to IBD diagnosis is associated with future diagnosis of both CD and UC compared to controls. Further studies are needed to understand whether the antibiotic treatment is associated with pre-diagnosis inflammation-related yet undiagnosed IBD or with events that increase the risk of developing IBD (e.g. microbiome change or infections).