Objectives and Study

Pediatric Inflammatory bowel diseases (PIBD) are on the rise. The aim of this study is to explore the needs and reflect on the current care situation of children and adolescents with PIBD in Germany as well as to improve understanding of what patients with PIBD and their parents know and still want to learn (patient empowerment) about the disease.

Methods

A nationwide paper and online survey was conducted from October 2021 to April 2022. The survey was distributed throughout Germany by the largest IBD patient organization DCCV (Deutsche Morbus Crohn / Colitis ulcerosa Vereinigung) and specialized centers of CEDATA GPGE (IBD patient registry).

Results

1,158 participants responded, including 450 adolescents aged 12-17 years and 708 parents of children aged 0-17 years with PIBD.

39% of adolescents surveyed would like to know more about the causes of PIBD (parents 10%), 37% need more information about transition (parents 10%), and 32 % require more information about the comorbidities of PIBD (parents 8%). Similarly, 32% would like to know more about socio legal issues (parents 10%), and 31% are interested in complications of progressive disease (parents 8%). 30% do not yet have enough information about dealing with PIBD in school and education (parents 9 %).

Topics of interest in the future are PIBD in general (adolescent 26%, parents 7%), nutrition (adolescents 25%, parents 9 %) and pharmaceutical treatment options (adolescents 28%, parents 10%). Other topics include vaccinations (adolescent 21%, parents 5%) and side effects of medications (adolescent 24%, parents 8%).

Conclusions

The answers in the CEDNA Study point towards topics that must be addressed in future patient empowerment initiatives to meet current and future patient and family needs, e.g. nutritional counseling, school and education or new pharmaceutical treatment options.

The CED-KQN project is funded by the „Gemeinsamen Bundesausschuss“ (Federal Joint Committee Germany), CEDKQN, VSF17054.

Objectives and Study

Torque Teno Virus (TTV), an ubiquitous virus, is described as a biomarker of level of immunosuppression in HIV-infected, bone-marrow and solid-transplanted patients. Its evaluation in IBD patients has never been assessed, even though, a lot of IBD patients are under immunosuppression treatments. Our aim was to evaluate plasma TTV viral loads in a cohort of pediatric patients followed over 1 year and treated by anti-TNFα.

Methods

Our cohort consists of 19 children with Crohn's disease or ulcerative colitis. Their clinical, biological data including plasma TTV viral load were recorded at inclusion, 6 months and 12 months.

Results

We included 19 patients, 14 had Crohn's disease (75%) and 5 had ulcerative colitis (25%). Median PCDAI was 29 (0-87) and median PUCAI was 45 (9-85). Median fecal calprotectin at inclusion was 1984 µg/g (71-5107), median albumin 35 g/L (14-50), and median CRP 26 mg/L (1-80). TTV viral load was positive at inclusion for 13 patients (68%) with a median of 2.73 log (1.57-4.12). 5 TTV PCRs turned positive at 6 months with a median of 3 log (2.2-3.79; n = 17). At 1-year follow-up, 7 TTV PCRs were negative, 1 TTV PCR turned positive and median TTV plasma viral load was 3.85 log (1.04-4.33; n = 12). At last follow-up, among patients who relapsed (n=5), 4 TTV PCRs (80%) were positive with a median of 3.69 log (1.66-4.33), and 1 TTV PCR from an ulcerative colitis was negative. Among patients in remission (n =14), 8 TTV PCR were positive (57%) with a median of 3 log (1.04-4.25), and 6 TTV PCRs were negative.

Conclusions

Overall, our study highlighted for the first time the dynamic of plasmatic TTV viral load in a cohort of pediatric IBD patients. Further studies are required to evaluate the potential use of TTV as a biomarker of relapse.

Objectives and Study

Treatment by anti-TNFα antibodies (aTNFα) is known to change the dysbiotic faecal bacteriome in Crohn’s disease (CD). However, it has not been explored whether these changes are solely due to decreasing mucosal inflammatory activity or whether similar bacteriome reactions may also be observed in gut-healthy subjects. Therefore, we aimed to characterize faecal bacteriome and metabolite changes upon aTNFα administration in children with CD and contrast those to the effects in aTNFα treated children with juvenile idiopathic arthritis (JIA).

Methods

Faecal samples collected before and during anti-TNFα therapy were analysed for bacteriome by massively parallel sequencing of the V4 region of the 16S rRNA and for faecal metabolome by ¹H nuclear magnetic resonance. Faecal calprotectin levels with MINI index assessed the mucosal inflammation in CD.

Results

We analysed 530 stool samples from 121 children (CD 54, JIA 18, healthy 49). Bacterial community composition reacted on aTNFα in CD but not in JIA. An increase in abundance was noted in three members of class Clostridia (genera Intestinibacter, Ruminococcus and Flavonifractor), whereas the genus Alistipes (class Bacteroidia) decreased (Figure 1). Among faecal metabolites, glucose and glycerol increased, whereas isoleucine and uracil decreased. Some of these changes differed by the intensity of response to the aTNFα therapy. No significant changes upon aTNFα therapy were noted in JIA: neither in the bacteriome nor in the metabolome.

Conclusions

Our findings imply that gut mucosal healing is responsible for the bacteriome and metabolome changes observed in CD, rather than any general effect of aTNFα blockade: this is supported by the contrast to the resilient bacteriome communities in gut-healthy JIA children.

Objectives and Study

This study aimed to define disease activity’s cluster and prognostic factors of the disease course in a well-characterized cohort of children with Crohn’s disease (CD).

Methods

Patients with CD from the SIGENP IBD registry with a follow-up of at least 5 years were included. Active disease was defined for each yearly semester as follows: clinical activity (wPCDAI≥12,5 or MINI index ≥8), need for treatment escalation, hospitalization, or surgery, active disease on endoscopy (SES-CD >3), or imaging. Formula-based clusters were generated based on previously published activity patterns in adults.

Results

Data from 332 patients were analyzed. Ninety-six (29%) had a quiescent course; 52 (16%) and 34 (10%) had a moderate-to-severe chronically active and chronic intermittent disease; 107 (32%) and 43 (13%) had an active disease at two years after diagnosis and remission thereafter and the opposite course, respectively. Overall, 129 (39%) presented active disease at 5 years of follow-up; no patient off-therapy. Surgery at diagnosis was significantly associated with a quiescent course [OR 10.05 (CI 3,05-25,22), p 0.0005], while growth impairment at the diagnosis and need for corticosteroids at six months were inversely related to the quiescent group [OR 0.48 (CI 0,27-0,81) p 0.007 and OR 0.35 (CI 0,16-0,71) p 0.005, respectively]. Perianal involvement at diagnosis and moderate-severe activity at 6 months positively correlated with disease progression at follow-up [OR 2.55 (CI 1,05-6,07) p<0.04 and OR 3.85 (CI 1,20-12,85) p 0.02].

Conclusions

Approximately one-third of our cohort of CD patients had a quiescent course during the first five years after diagnosis. In contrast, more than one-third had a chronically or intermittently active disease during follow-up, or an initial remission followed by persistent activity. Surgery at diagnosis, mild disease onset without growth impairment, and lower disease activity without corticosteroid use at six months after diagnosis predicted a quiescent course over time.

Objectives and Study

This study aimed to set up a Dutch Priority Setting Partnership (PSP), to determine a ‘top 10 research priorities’ for inflammatory bowel disease (IBD) in children and adolescents, from the point of view of patients, parents and healthcare professionals.

Methods

This PSP was conducted in collaboration with the James Lind Alliance (JLA), the patient organization Crohn & Colitis Netherlands and the Kids with Crohn’s, Colitis (KiCC) Working Group for Collaborative Pediatric IBD Research. A steering group including children and adolescents with IBD, parents and healthcare professionals was established. Research uncertainties were gathered using an online survey. These were refined into indicative questions, followed by an evidence check to verify whether the questions were already answered in the literature. In an interim prioritization survey, patients, parents and healthcare professionals were requested to identify their top 10 questions from the list of ‘verified uncertainties’. The resulting top 25 of most ranked items will be carried forward to a stakeholder workshop for reaching consensus on the ‘top 10 research priorities’.

Results

Via the first survey, 763 uncertainties were submitted by 222 respondents (74 patients, 89 parents and 59 healthcare professionals). These uncertainties were categorized into 13 themes, and refined into 64 indicative questions. Five of these questions were considered answered in the literature. The interim prioritization survey including the remaining 59 uncertainties is currently being distributed in the Netherlands. This survey is completed by 157 respondents so far, and will be closed in January 2023. In March 2023, the final ‘top 10 priorities’ will be agreed upon in the workshop.

Conclusions

This JLA PSP enables young people and parents with lived experience to engage in developing shared research priorities. The final ‘top 10 research priorities’ in pediatric IBD will be presented to the parties involved in pediatric IBD research, hereby indicating future directions of research.

Objectives and Study

Current data on dual biologic therapy in children are limited. This multicenter study aimed to evaluate the effectiveness and safety of dual therapy in pediatric patients with inflammatory bowel disease (IBD).

Methods

A retrospective study from 14 centers affiliated with the IBD Interest and Porto Groups of ESPGHAN. Included were children with IBD who underwent combinations of biologic agents or biologic and small molecule therapy for at least 3 months. Demographic, clinical, laboratory, endoscopic, and imaging data were collected. Adverse events were recorded.

Results

Sixty-two children [35 Crohn's disease, 27 ulcerative colitis (UC)] with a median age of 15.5 (13.1-16.8) years were included. All had failed previous biologic therapies and 47 (76%) failed at least 2 biologic agents. The dual therapy included an anti-TNF agent and vedolizumab in 30 children (48%), anti-TNF and ustekinumab in 21 children (34%), vedolizumab and ustekinumab in 8 children (13%), and tofacitinib and other biologics in 3 children (5%). Clinical remission was observed in 21 (35%), 30 (50%), and 38 (63%) children at 3, 6, and 12 months, respectively. Normalization of C-reactive protein and decrease in fecal calprotectin to <250 mcg/g were achieved in 75% and 64%, respectively, at 12 months of follow-up. Male sex and diagnosis of UC were associated with higher likelihood of clinical remission (p=0.017 and p=0.020, respectively). Adverse events were reported in 29 (47%) children. While most adverse events were mild, 8 were regarded as serious and 6 led to discontinuation of dual therapy. The serious adverse events included infusion reaction to infliximab, fatigue and headache following vedolizumab infusion, severe skin eruptions, cellulitis and skin abscess, elevated liver enzymes and deep vein thrombosis.

Conclusions

Dual biologic therapy may be effective in children with refractory IBD. The potential efficacy should be weighed against the risk of serious adverse events.