Introduction

Both exclusive enteral nutrition (EEN) and steroids are effective therapies to induce remission in children with Crohn’s disease (CD), but comparative data accounting for disease location are scarce.

Aims & Methods

We aimed to compare the effectiveness of EEN and steroids induction treatment in isolated ileal pediatric CD using data from two large real-world data cohorts. Children (age 2-18 years) with newly-diagnosed CD with an isolated ileal disease phenotype prospectively enrolled in the multicenter Canadian CIDsCaNN or predominantly European PIBD-SETQuality inception cohorts, who received either EEN or systemic steroids induction treatment, were eligible for this study. Demographics and extensive clinical data were collected prior to treatment and longitudinally until the last follow-up. Outcomes, including [sustained] steroid free remission ([S]SFR), normal CRP remission (NCR; defined as remission with CRP <0.5 mg/dl), and (delta) height and BMI z-scores were compared at 3 months and 1 year. Time-to-first-biologic and time-to-luminal-resection were determined by Kaplan Meier curves and compared between groups using the log-rank test.

Results

A total of 221 children (n=134 [61%] CIDsCaNN, n=87 [39%] PIBD-SETQuality) with Crohn’s disease with an isolated ileal phenotype receiving EEN (n=158 [72%]) or steroids (n=63 [28%]) as induction treatment were eligible for analysis (median follow-up 868 days [IQR 539 – 1443]). Disease phenotype, clinical and biochemical disease activity indices as well as demographics and anthropometrics, were similar between treatment groups (Table 1) and between cohorts. At 1 year, rates of SSFR (33% vs. 38%; p=0.56) and NCR (53% vs. 44%; p=0.27) were comparable between EEN and steroids-treated patients. Linear growth was borderline reduced in the steroids treated group (median height Z-score –0.42 [IQR –1.21 - 0.12]) compared to the EEN treated group (0.02 [IQR –0.94 - 0.59; p=0.050). Type of induction treatment did not affect time-to-first-biologic (p=0.84) or time-to-luminal-resection (p=0.11). At 3 months, combined rates of SFR + NCR were higher in patients who received EEN (38/111 [34%]) compared to those who received steroids (9/47 [19%]; p=0.058), largely because of differences in steroid exposure (14/121 [12%] with EEN, 19/39 [48%] with steroids; p<0.001), and normal CRP (68/108 [57%] and 18/43 [42%] respectively, p=0.084). Only in 20/220 (9%) of patients (15/157 [10%] with EEN, 5/63 [8%] with steroids; p=0.71), an additional induction therapy agent (EEN, steroids, biological, surgery) was started within 30 days after the start of induction treatment.

Conclusion

EEN and steroids induction therapy show comparable short- and long-term clinical effectiveness in children with isolated ileal CD, but EEN trended towards better linear growth outcomes at one year.

Table 1 Patient and disease characteristics at diagnosis of children with Crohn’s disease with isolated ileal disease (L1), stratified by induction therapy

Introduction

Faecal microbiota transplantation (FMT) has shown promise as treatment in inducing remission in patients with ulcerative colitis (UC), however effectiveness varies (1). Optimizing FMT protocols involving anaerobic stool processing to improve bacterial viability, dual-route administration and donor selection may improve efficacy.

Aims & Methods

Our aim was to evaluate the effectiveness of an optimized FMT protocol using anaerobically prepared stool from pre-selected donors in a randomized controlled multi-centre trial using dual-route administration in patients with mild-to-moderately active UC. A total of 85 patients were randomized to either receive donor FMT (n = 44) or autologous FMT (n = 41) via four weekly FMTs comprising two dual-route administrations, nasoduodenal administration combined with enema, and two single enemas. The study was performed at the Amsterdam University Medical Centre and University Medical Centre Groningen from June 2020 till January 2025. Follow-up time is 12 months and ongoing. Donors were selected based on their microbiota profile, informed by our previous TURN trial (2, 3). The primary outcome was steroid-free clinical remission at week 8 defined as a total adapted Mayo score of ≤2, with a stool frequency subscore of ≤1, a rectal bleeding subscore of 0, and an endoscopic subscore of ≤1. Open-label extension was offered to patients in the autologous FMT group who did not reach clinical remission.

Results

Eighty-five patients were randomized (mean age 43.6 years, 48% female), with 76 (89%) patients completing all four treatments. In the modified intention-to-treat analysis, meaning all patients that received at least one FMT treatment (n = 82), primary endpoint was reached in 10 of 44 (23%) patients receiving donor FMT and in 2 of 38 (5%) patients receiving autologous FMT, (two-sided χ², p = 0.026). A further total of 26 patients received donor FMT in open-label extension of which 21 (81%) received all four treatments with 7/26 (27%) reaching the primary endpoint. Serious adverse events occurred in 6/44 (14%) in the donor FMT group vs 4/41 (10%) the autologous group. Two events were deemed related to the FMT treatment (pneumothorax after nasoduodenal placement and overnight hospitalization for abdominal pain one-day post FMT).

Conclusion

In this multi-centre randomized controlled trial, anaerobically processed, donor-selected, dual-route FMT demonstrated a higher likelihood of inducing clinical remission with donor FMT compared to autologous FMT at 8 weeks. The protocol proved feasible and generally safe. Larger trials are warranted to confirm efficacy and to optimize donor and patient selection strategies. ClinicalTrial.gov. Number: NCT05998213

References

1. Imdad A, Pandit NG, Zaman M, Minkoff NZ, Tanner-Smith EE, Gomez-Duarte OG, et al. Fecal transplantation for treatment of inflammatory bowel disease. Cochrane Database Syst Rev. 2023;4(4):Cd012774.
2. Fuentes S, Rossen NG, van der Spek MJ, Hartman JH, Huuskonen L, Korpela K, et al. Microbial shifts and signatures of long-term remission in ulcerative colitis after faecal microbiota transplantation. Isme j. 2017;11(8):1877-89.
3. Rossen NG, Fuentes S, van der Spek MJ, Tijssen JG, Hartman JH, Duflou A, et al. Findings From a Randomized Controlled Trial of Fecal Transplantation for Patients With Ulcerative Colitis. Gastroenterology. 2015;149(1):110-8.e4.

Disclosure

The authors report no COI with regard to this study

Introduction

Microscopic colitis (MC) is a chronic disabling inflammatory disease. Yet, the economic impact of MC is still largely unknown. In this nationwide study, we investigated societal costs, comprised of healthcare costs and productivity losses, in relation to MC diagnosis.

Aims & Methods

We identified 8,659 biopsy-verified patients diagnosed with MC between 2008 and 2017. Patients were followed from 4 years before diagnosis until either 4 years after diagnosis, emigration, death, or 2019 (end of follow-up), whichever came first. Each patient was compared to up to 5 general-population comparators matched on birthyear, sex, county of residence, and calendar year. Using real-world data from Swedish national registers, we determined healthcare costs from prescribed medications, non-primary outpatient visits, and hospitalizations, while costs for productivity losses were derived from lost workdays due to sick leave or disability leave. All costs were adjusted for inflation and converted from Swedish currency, SEK, to USD (1 USD = 10.61 SEK).

Results

Patients with MC had 1.54 times higher societal costs than their general-population comparators already at 4 years before diagnosis, and the excess cost further increased during the years leading up to diagnosis. The excess cost of MC peaked during the year of diagnosis when patients with MC had 2.11 times the cost of comparators, corresponding to a mean annual excess cost of $6,402 (adj. mean difference [95%CI]: $6,460 [$6,099; $6,820]).

Although the mean cost of MC decreased after diagnosis, it did not return to pre-diagnostic levels. Instead, the cost of MC persisted at 1.85 times the costs of their comparators 4 years after diagnosis. The absolute excess cost of MC was also significantly higher 4 years after diagnosis compared with 4 years before diagnosis ($4,654 vs $2,926; P-value <0.05). Stratification by age, sex, and education level showed similar cost trajectories, with cost ratios peaking in the year of diagnosis and persisting at higher levels after diagnosis.

While work loss was the largest contributor to the absolute excess cost of MC both before and after diagnosis, the cost ratio (1.83) was lower than for other cost categories. Compared with the general population, the relative excess cost was highest for outpatient visits with a cost ratio of 3.00 during the year of diagnosis, followed by 2.54 for medications and 2.36 for hospitalizations.

Table 1. Mean societal costs of patients with microscopic colitis (MC) and general-population comparators (control) in relation to year of diagnosis.

Conclusion

Patients with MC have higher societal costs than the general population before diagnosis, and the excess costs increase and persist for several years after diagnosis. While excess costs may be multifactorial, improved disease control could provide opportunities to reduce the post-diagnostic cost of MC.

Disclosure

The authors report no conflicts of interest related to this abstract.

Introduction

Chronic low-grade inflammation, known as inflammageing, has been implicated in the pathogenesis of various digestive diseases. However, large-scale systematic evaluations of the association between inflammageing biomarker profiles and digestive system disorders remain scarce. Understanding these associations may have important implications for early detection and intervention strategies.

Aims & Methods

Leveraging the multidimensional data from the UK Biobank, this study aimed to investigate the longitudinal relationships between circulating inflammatory markers and major digestive diseases. A total of 45,475 participants were included, with inflammageing levels calculated as the average of standardized values of four circulating inflammatory markers: TNF, IL1RN, IL18, and IL6.
Digestive disease outcomes were identified from hospital records (HES) and death registries, covering 25 major diagnoses, including gastroesophageal reflux disease (GERD), inflammatory bowel disease (IBD), and non-alcoholic fatty liver disease (NAFLD). Cox proportional hazards models were used to estimate hazard ratios (HRs), adjusting for age, sex, BMI, smoking, and other potential confounders.
In addition, Mendelian randomization (MR) analysis was conducted using GWAS data derived from inflammageing scores to evaluate potential causal effects on digestive outcomes. Mediation and subgroup analyses were performed to explore possible mediating factors.

Results

In the Cox regression analysis, 22 out of 25 digestive outcomes showed significant associations with baseline inflammageing levels (Bonferroni-corrected P < 0.05), with HRs ranging from 1.2 to 2.4.
Mediation analysis identified neutrophil counts and LDL-C as important mediators in these associations, suggesting potential biological pathways linking inflammageing to digestive disease development.

Conclusion

Elevated baseline inflammageing levels were significantly associated with a wide spectrum of digestive system diseases. The findings highlight a potential mechanistic role of systemic inflammation in digestive disease pathogenesis. The use of inflammageing-related biomarkers may aid in early identification of high-risk individuals, offering opportunities for early prevention and targeted interventions.