Citations

INTRODUCTION: Recurrent Clostridioides difficile infection (rCDI) is associated with substantial morbidity, healthcare utilization, and costs. US FDA-approved microbiota-based therapies, fecal microbiota spores, live-brpk (VOS) and fecal microbiota, live-jslm (RBL), reduce recurrence risk, but cost-effective placement within the rCDI treatment pathway remains uncertain. METHODS: We performed a US payer-perspective cost-effectiveness analysis using decision-tree modeling according to CHEERS 2022 guidelines. Adults with rCDI entered the model after the first or second recurrence and were followed for <1 year. Effectiveness inputs were derived from ECOSPOR III/IV (VOS), PUNCH CD3/CD3-OLS (RBL) trials, and published literature for standard-of-care (SoC) comparators. Outcomes included costs (2025 USD), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). Probabilistic and deterministic sensitivity analyses were performed using a willingness-to-pay threshold (WTP) of $150,000/QALY. ICERs were interpreted across $50,000, $100,000, $120,000, and $150,000/QALY. RESULTS: After the first recurrence, RBL was cost-effective vs SoC alone ($25,415/QALY). Early initiation remained favorable compared with delayed use for VOS ($27,239/QALY) and RBL ($26,704/QALY). After the second recurrence, VOS remained cost-effective vs SoC (ICER $53,983/QALY), whereas RBL exceeded the WTP threshold (ICER $171,496/QALY). Exploratory cross-trial VOS vs RBL comparisons yielded ICERs of $124,636/QALY after first recurrence and $137,350/QALY after second recurrence, indicating threshold-sensitive product-to-product comparisons. DISCUSSION: Earlier initiation of microbiota-based therapies after the first rCDI provides greater health benefits at acceptable cost-effectiveness thresholds compared with delayed use, supporting earlier integration into rCDI treatment strategies. VOS vs RBL comparisons should be interpreted as exploratory indirect comparisons pending comparative real-world or head-to-head data.

Abstract Recurrent Clostridioides difficile infection (CDI) is a clinical syndrome, a trial end point, and a surveillance construct. Epidemiologic and administrative datasets count repeat positive tests or coded episodes, but conflate colonization or test of cure with recurrence. Trials operationalize recurrent CDI with symptoms and testing, but have variable follow-up. Clinically, recurrent CDI requires response, and recurrent illness requires excluding postinfection bowel dysfunction and mimics. Relapse and reinfection remain difficult to distinguish without strain typing, which is more relevant for research. We propose a pragmatic lens: explicitly name the definition used, match it to the decision, and adjudicate clinical recurrence before escalating therapy.

INTRODUCTION: Clostridioides difficile infection (CDI) presents a significant challenge in patients with inflammatory bowel disease (IBD), with high recurrence rates and complications. Predicting recurrent CDI (rCDI) in patients with IBD is crucial for implementing targeted interventions to improve patient outcomes. This study aimed to develop and validate a predictive model (RecurCDI-IBD) using supervised machine learning to identify patients with IBD at high risk of developing rCDI. METHODS: Data were collected from adult patients with IBD diagnosed with CDI between 2013 and 2021. Inclusion criteria included adult patients with a confirmed diagnosis of CDI and a history of IBD. The Gradient Boosting Machine learning model (XGBoost) was used to train a binary classification model. Feature engineering included demographic data (age and sex), clinical data (IBD subtype, medication use, and comorbidities), and laboratory data. The primary outcome was the occurrence of rCDI within 60 days of the initial CDI episode. RESULTS: The RecurCDI-IBD model achieved an accuracy of 80.05% and an Area Under the Curve of 0.88 for predicting rCDI. Key predictive features included IBD subtype, sex, specific medications (such as steroids and anti-TNF agents), and comorbidities (such as chronic pulmonary and renal disease). DISCUSSION: The RecurCDI-IBD model demonstrates good discriminatory ability with balanced precision and recall in identifying patients with IBD at higher risk for rCDI. These findings highlight the potential of data-driven approaches to support clinical risk assessment. Further studies incorporating larger and more diverse cohorts and prospective external validation are needed to confirm generalizability and optimize clinical applicability.

Lay Summary This multicenter study evaluated clinical outcomes in pregnancy for women with ulcerative colitis and an ileal pouch-anal anastomosis. Close monitoring is needed with a multidisciplinary team for management of inflammatory complications of the pouch such as pouchitis in pregnancy and postpartum.

Lay Summary In this study we evaluated the effectiveness of vedolizumab (anti-integrin) vs ustekinumab/risankizumab (anti-interleukin) therapy for isolated small-bowel Crohn’s disease using a real-world, multicenter national database. We found that anti-interleukin therapy was more effective for inducing steroid-free remission and reducing hospitalizations.

ABSTRACT Introduction Chronic pouchitis is a major therapeutic challenge in patients with ulcerative colitis following ileal pouch‐anal anastomosis. Methods We conducted a real‐world, propensity‐matched cohort study of 856 patients from a healthcare database to compare ustekinumab and vedolizumab. Results Ustekinumab was associated with significantly lower relapse rates (aHR = 0.69; p < 0.001), longer time to relapse, reduced hospitalisation and decreased need for steroids or antibiotics. No differences were observed in surgery rates or therapy switching. Conclusion Our findings suggest that ustekinumab may offer advantages over vedolizumab in the management of chronic pouchitis.

Abstract Background The term “incomplete microscopic colitis” (MCi) has been suggested to define patients with chronic watery diarrhea not fulfilling the complete histologic criteria for MC. There are inconsistent data on the epidemiology of MCi and the optimal management of these patients. Methods A systematic search of randomized control trials (RCTs) and observational studies of adults with biopsy-proven MCi (incomplete lymphocytic colitis and collagenous colitis) was conducted using Cochrane, Medline, Scopus, and Embase from inception to May 6, 2025. Data were extracted on (1) incidence and prevalence of MCi, (2) patient features and risk factors, (3) clinical response with treatment, and (4) relapse after treatment cessation. Data were pooled using the random-effects model to calculate weighted pooled estimates and 95% confidence intervals (CIs). Results Of 136 potentially relevant publications identified, 49 passed abstract screening, and 17 studies (1 RCT and 16 observational) were included, with a total of 1370 patients with MCi (median age of 62 years and 69.6% women). The incidence rate of MCi ranged from 0.96 to 5.0 cases per 100 000 person-years. The pooled proportion of concurrent autoimmune disease with MCi was 18% (95% confidence interval [CI], 0.07-0.28; I2 = 95%), and 46% (95% CI, 0.28-0.64; I2 = 95%) were on medications associated with microscopic colitis (MC). The pooled clinical remission rate with any induction therapy was 78% (95% CI, 0.68-0.89; I2 = 81%) and 85% (95% CI, 0.72-0.98; I2 = 88%) with budesonide. Conclusions Patients with MCi share similar characteristics with full MC including demographics, risk factors, and response to therapy, indicating that the histologic criteria for MC should potentially be broadened.

Abstract Background Clostridioides difficile infection (CDI) treatment guidelines suggest varied approaches for patients with first (frCDI) or multiply recurrent CDI (mrCDI). Low microbial diversity, elevated primary bile acids (BA), and low secondary BA concentrations favor germination of C. difficile spores into toxin-producing bacteria and are believed to increase rCDI risk. Greater understanding of the gastrointestinal (GI) microbiome in rCDI may inform management of the disease. We describe a post hoc comparison of GI microbiome and bile acid profiles between patients with frCDI and mrCDI in a Phase 3 open-label trial, ECOSPOR IV, of fecal microbiota spores, live-brpk (VOWST®; VOS, formerly SER-109), an orally-administered live microbiome therapeutic. Methods Patients received VOS following symptom resolution after standard-of-care antibiotics. Pretreatment baseline (within 3 days following antibiotic completion) and Week 1 post-dosing stool samples were collected for whole metagenomic sequencing and metabolomics. Diversity was calculated from MetaPhlAn2 species profiles. Concentrations of primary and secondary BAs were measured via targeted LC-MS/MS. Results rCDI rates through Week 8 were similarly low in both frCDI and mrCDI patients (6.5% versus 9.7%, respectively). Baseline microbial diversity was similarly low between frCDI and mrCDI subgroups (P &gt; .05). Diversity and secondary BA concentrations increased in both subgroups, whereas primary BA concentrations declined following VOS dosing, leading to few differences between subgroups at Week 1. Conclusions These data suggest commonalities in microbiome disruption in patients with frCDI and mrCDI that contribute to recurrence and suggest that antibiotics followed by a live microbiome therapy may be an optimal treatment strategy for rCDI, regardless of number of prior CDI recurrences.