Introduction

Fecal microbiota transplantation (FMT) is the most effective therapy in the treatment of recurrent Clostridioides difficile infection (rCDI), and can be offered in fresh, frozen or lyophilized formulation with similar efficacy. Microbial engraftment is thought to be one of the mechanisms mediating its efficacy. However, the importance of microbes has been questioned by two small preliminary clinical studies that showed sterile fecal filtrate could prevent C. difficile recurrence.

Aims & Methods

Aims: 1) determine if lyophilized sterile fecal filtrate (LSFF) is non-inferior to lyophilized FMT (LFMT) in efficacy; 2) evaluate changes in patient reported health related quality of life (HRQOL); 3) understand patient preferences for different attributes of FMT.
Methods: This double-blind, non-inferiority (margin= 10%) study in 4 academic centers in Canada randomized rCDI patients with > 3 CDI episodes to either LSFF or LFMT (1:1) between 2019 and 2023. Each treatment consisted of 15 oral capsules. Primary outcome was proportion of participants without CDI recurrence at 8 week. Secondary outcomes included 1) proportion of participants without CDI recurrence at week 24 weeks, 2) serious adverse events (mortality, hospitalization and infections related to treatments), and 3) minor adverse events (nausea, vomiting, abdominal pain and fever). Exploratory outcomes included changes in HRQOL and relative importance of different attributes of FMT.

Results

137 participants were randomized (mean [SD] age, 61.2 [18.6] years; 89 women [65.4%]; mean CDI episodes 3.8) to LFMT group (66 participants) and LSFF (71 participants) group. In per-protocol analysis, prevention of rCDI 8 weeks after assigned treatment was achieved in 63.8% of participants in LSFF group and 86.9% in LFMT group (difference, -23.1%), resulting in trial termination. Serious adverse events were infrequent: 4 hospitalizations deemed not related and 1 hospitalization possibly related, and 1 death from COVID deemed not related to assigned treatment. Minor adverse events were self-limited and infrequent: nausea (6), vomiting (2), abdominal discomfort (15) and fever (2). Following treatment, participants had significant increases in EQ-5D-5L (n=99) VAS (median change: 10; p <0.001) and index value (median change: 0.04; p<0.001), and Cdiff32 (n=94) physical domain (median change: 16.07; p <0.001), mental domain (median change: 29.46; p<0.001), and social relationships domain (median change: 7.37; p<0.001). Work impairment decreased (n=21; median change: -10%; p<0.001) and activity impairment decreased (n=101; median change: -20%; p<0.001). Participants (n=103) indicated the 3 most important attributes of FMT were: treatment effectiveness, unknown risks of treatment and known risks of treatment.
Table 1. Participant baseline characteristics

Conclusion

Among adults with rCDI, LSFF was inferior to LFMT by oral capsules in preventing recurrent infection over 8 weeks. The result emphasizes the importance of microbes in mediating FMT efficacy. Preserving microbial viability in future development of microbial therapeutics is paramount.

Disclosure

none

Introduction

The Epi-IBD cohort is a prospective European population-based cohort of 1,390 patients diagnosed in 2010 and 2011 with inflammatory bowel disease (IBD) according to Copenhagen criteria in centres from Eastern and Western European countries.

Aims & Methods

The study aims at describing differences in incidence, treatment strategies, disease course and prognosis of Crohn’s disease (CD) across Eastern and Western Europe. CD patients were followed prospectively from the time of diagnosis until December 31^st, 2020, death, emigration or loss of follow-up. Clinical data on surgery, hospitalizations, and medical treatment, were captured throughout the follow-up period and entered into a validated web-database, www.epi-ibd.org. Associations between surgery and covariates were analysed by multivariate Cox regression analyses.

Results

In total, 482 CD patients aged ≥15 years from 21 centres in 5 Eastern and 11 Western European countries were included. At 10-years follow-up, 101 (21%) patients underwent first intestinal resection and 11 out of these 101 patients (11%) underwent additional resections. Furthermore, 176 (37%) patients had at least one CD related hospitalization. Cancer was diagnosed in 21 (4%) patients, including 4 gastrointestinal cancers. The use of IBD medication was comparable between Eastern and Western European centres apart from 5-aminosalicylic acid agents (Table 1).
During follow-up, 60 out of 360 patients (17%) progressed from non-stricturing-non-penetrating disease (B1) at diagnosis to stricturing or penetrating disease (B2 or B3) while 13 out of 83 patients (16%) with stricturing disease (B2) progressed to penetrating disease (B3). The median time to progression was 28 (IQR: 9-64) months from diagnosis. No patients from Eastern Europe were exposed to biological therapy prior to change in behaviour, compared to 23 out of 66 patients (35%) from Western Europe.
Multivariate Cox regression analysis showed no difference in risk of surgery according to European region (Eastern vs. Western Europe, HR: 0.54, 95%CI: 0.24-1.21). Early intervention with biological therapy (within 6 months) did not influence the risk of surgery (HR:0.75, 95%CI: 0.31-1.83), however early introduction of immunomodulators reduced the risk significantly (HR:0.54, 95%CI: 0.30-0.98). Progression in behaviour from B1 was associated with higher risk of surgery (HR:7.62, 95%CI: 3.91-14.87).

Conclusion

After 10 years of follow-up, 21% underwent intestinal resection and 10% required additional resections. Despite the widespread use of immunomodulators and biological therapy, 16% of the patients had disease behavioural progression, which was associated with higher risk of surgery. Early introduction of immunomodulators was found to be beneficial.

Introduction

Exclusive enteral nutrition (EEN) is effective for inducing remission in Crohn's disease (CD) but adherence is challenging. CD-Exclusion Diet (CDED) may be a suitable alternative, but it is structured with mandatory ingredient and requires partial enteral nutrition (PEN). The Tasty&Healthy (T&H) diet excludes processed food, gluten, red meat, and dairy (except for plain yogurt); otherwise, it has no mandatory ingredients and does not require PEN.

Aims & Methods

In this clinician-blinded randomized controlled trial we aimed to assess the tolerability and effectiveness of the T&H diet vs. EEN in children and young adults with CD.
Patients aged 6-25 years with mild-moderate CD were randomized into T&H or EEN for 8-weeks; both groups received weekly dietary support. Explicit nutritional and clinical data, as well as calprotectin were collected at baseline and every 2-weeks thereafter. Tolerability was defined as the discontinuation of the intervention for lack of adherence, or low adherence judged by weekly interviews and 24-hour intake diary. Effectiveness outcomes included clinical remission (i.e. wPCDAI/CDAI), the MINI index that reflects mucosal inflammation (mucosal healing is defined by MINI<8 points), CRP, ESR and calprotectin. Those not tolerating either intervention during the first 24 hours were excluded; otherwise, both ITT and per-protocol (PP) analyses are presented.

Results

Of the 97 randomized patients, 14 were excluded during the first 24 hours and 83 were analyzed, 41 in the T&H arm and 42 in the EEN arm (mean age 14.5±3.7 years). The primary endpoint was met with 36 (88%) patients tolerating T&H vs. 22 (52%) tolerating EEN (OR 6.3 (95%CI 2.2-22; p<0.001).
Week-8 clinical remission rates were similarly high in both groups whether analyzed by ITT (56% in the T&H vs. 38% in the EEN; p=0.1) or PP (67% vs. 76%; p=0.47). The mean MINI index improved significantly from baseline in both the EEN (14.9±5.6 to 7.1±6.1; p<0.001) and T&H (14.5±4.6 to 8.7±6.4; p<0.001) arms, without a difference across groups (p=0.47). In the ITT analysis, MINI<8 at week 8 was higher in the T&H arm (54%) than the EEN arm (41%; OR 2.6 (95%CI 1.1-6.3); p=0.026). Calprotectin decreased significantly from baseline in both arms, without a difference across groups at week-8 (calprotectin <250 was noted in 38% with T&H vs 41% with EEN; p=0.84). There were also no differences between EEN and T&H in ESR and CRP, both improving significantly from baseline (both p<0.01).
There were 3 adverse events reported in this trial with at least possible association with the intervention, all mild, 2 in the EEN arm (nausea and dizziness) and 1 in the T&H arm (constipation).

Conclusion

T&H is a flexible exclusion diet, with similar effectiveness to EEN in mild-moderate CD and higher tolerance. The diet does not include mandatory foods and does not require PEN.

Disclosure

This study was funded by a grant from The Helmsley Charitable Trust