Johanna C. Escher

Heterogeneity in disease severity and treatment response in inflammatory bowel disease (IBD) likely evolves from individual differences in host-microbiota-immune interactions. Histological evaluation of intestinal biopsies is central to diagnosis, but histological parameters that define underlying immune mechanisms are limited. We investigated histological features that distinguish individual patient immune profiles in therapy-naive pediatric IBD patients (age 6–18 years) using biopsy immunohistochemistry and transcriptomics and plasma proteomics across two cohorts. High colonic epithelial expression of secretory leukocyte protease inhibitor (SLPI), a microbiota-induced regulator of epithelial function, occurred in IBD patients with high clinical disease activity and more severe endoscopic and microscopic disease activity. SLPI expression was related to increased neutrophil infiltration, transcriptomic signatures of activation, and genes known to associate with therapeutic resistance. High SLPI colocalized with high densities of IL-17–secreting cells and was associated with high plasma concentrations of Th17-related immune proteins. Additionally, patients with high intestinal SLPI had an intrinsically different immunotype, in which circulating neutrophils exhibited altered transcription of genes involved in neutrophil granule formation, phagocytosis, oxidative phosphorylation, and interferon signaling. Thus, high colonic SLPI expression at diagnosis associates with severe IBD, increased IL-17A–neutrophil pathway responses, and altered transcriptomic wiring of circulating neutrophils.

Background and Aims: The effectiveness of transition programs from pediatric to adult healthcare in adolescents with inflammatory bowel disease (IBD) is not clear, as prospective studies using validated outcome measures for transition are lacking. This study aimed to develop and validate a quantitative Transition Success Score (TSS), and to apply it in a multicenter setting to assess the effectiveness of transitional care. Methods: The Top 10 outcome items related to a successful transition, identified through an international Delphi study with IBD stakeholders, were integrated into a generic questionnaire, the TSS. In a prospective, multicenter study, the TSS was scored by adult healthcare providers, young adult patients, and caregivers, 9-15 months after transfer of care. Results: In 7 Dutch hospitals, 160 patients completed the TSS. The mean score was 25 (range 17-27), 25.6% of patients achieving maximum score. Hypothesis testing for construct validity revealed significant associations with characteristics related to transitional care, such as knowledge, independence, and quality of life (p < 0.005). Structural validation indicated the score was most effective at discerning lower levels of transition success. Internal consistency was acceptable (0.64). High disease burden, exacerbation during or after transfer, and certain personality profiles were associated with lower scores. Conclusions: The TSS serves as a quantitative tool to evaluate the effectiveness of transitional care interventions and to identify IBD patients at risk of encountering challenges during the transition to adult healthcare.

Summary: Background: Data on cost‐effectiveness of first‐line infliximab in paediatric patients with Crohn's disease are limited. Since biologics are increasingly prescribed and accompanied by high costs, this knowledge gap needs to be addressed.Aim: To investigate the cost‐effectiveness of first‐line infliximab compared to conventional treatment in children with moderate‐to‐severe Crohn's disease.Methods: We included patients from the Top‐down Infliximab Study in Kids with Crohn's disease randomised controlled trial. Children with newly diagnosed moderate‐to‐severe Crohn's disease were treated with azathioprine maintenance and either five induction infliximab (biosimilar) infusions or conventional induction treatment (exclusive enteral nutrition or corticosteroids). Direct healthcare consumption and costs were obtained per patient until week 104. This included data on outpatient hospital visits, hospital admissions, drug costs, endoscopies and surgeries. The primary health outcome was the odds ratio of being in clinical remission (weighted paediatric Crohn's disease activity indexp = 0.981). The odds ratio of first‐line infliximab versus conventional treatment to be in clinical remission over 104 weeks was 1.56 (95%CI 1.03–2.35, p = 0.036).Conclusions: First‐line infliximab treatment resulted in higher odds of being in clinical remission without being more expensive, making it the dominant strategy over conventional treatment in the first 2 years after diagnosis in children with moderate‐to‐severe Crohn's disease.Trial registration number: NCT02517684.

Objectives: Transition readiness can predict a successful transition from pediatric to adult care. This study aimed to validate and develop age‐dependent reference scores for the (Dutch version of) Transition Readiness Assessment Questionnaire (TRAQ), in adolescents and young adults (AYAs) with inflammatory bowel disease (IBD).Methods: TRAQ has 20 items (score 1–5) distributed over 5 domains (total sum score 100) and is completed by AYAs. Following the COnsensus‐based Standards for the selection of health Measurement INstruments methodology, we conducted the translation, back‐to back translation, pretesting, and validation of the final Dutch version of TRAQ (TRAQ‐NL) questionnaire. We used a Rasch model for structural validation, hypothesis testing for construct validity, and Cronbach alpha to demonstrate reliability. Reference scores were calculated using percentiles.Results: Two hundred fifty TRAQ questionnaires were evaluated in 136 AYAs with IBD [56% Crohn disease, 58% male, median age 17.5 years (range 15.7–20.4)]. The overall mean item score was 3.87 (range 1.45–5). With good reliability (Cronbach alpha 0.87), TRAQ‐NL discriminated well between knowledge levels, especially in the lower levels. Transition readiness was defined as low, moderate, adequate, or excellent in patients with TRAQ percentile scores (PC) 4.7). Younger patients, concomitant illness, fewer visits to the transition clinic, and parental dependence were associated with significantly lower TRAQ scores.Conclusion: TRAQ(‐NL) is reliable and valid, with age‐dependent PC to identify (in)adequate transfer readiness. TRAQ can now be more easily used as a patient‐reported outcome measure to monitor transition readiness longitudinally in routine care for AYAs IBD patients.