Therapeutic Advances in Gastroenterology最新文献

Background: Tofacitinib is an oral Janus kinase inhibitor for the treatment of ulcerative colitis (UC).

Objectives: To investigate potential predictors of efficacy in RIVETING.

Design: This post hoc analysis included patients with UC in stable remission (⩾6 months) on tofacitinib 10 mg twice daily (BID) maintenance therapy (⩾2 years of treatment), who received tofacitinib 5/10 mg BID in RIVETING.

Methods: Achievement of modified Mayo (mMayo) remission, remission (based on total Mayo score), partial Mayo score (PMS) remission, and modified PMS (mPMS) remission at month (M)6 was analyzed by baseline characteristics, duration of PMS remission at RIVETING entry, biomarkers, and patient-reported outcomes (PROs) to identify factors associated with achieving/maintaining efficacy outcomes, including following dose reduction.

Results: Seventy patients received tofacitinib 5 mg BID. At M6, PMS remission was maintained in 66.7%, 60.0%, 82.4%, 75.0%, and 90.0% of patients with baseline PMS remission durations of 6 to ⩽12, >12 to ⩽24, >24 to ⩽36, >36 to ⩽48, and >48 months, respectively. Patients in mMayo remission at M6 had smaller increases in PMS at M1 compared with those not in mMayo remission at M6, while numerically higher proportions of patients with a stool frequency subscore/rectal bleeding subscore/mPMS of 0 at M1/M3 achieved most efficacy endpoints at M6 compared with patients with respective subscores >0. Maintenance of mMayo remission was independent of the number of tumor necrosis factor inhibitors failed and/or prior corticosteroid use. In multivariable models (which included tofacitinib 10 mg BID data), endoscopic subscores (1 vs 0) at RIVETING baseline were significantly associated with lower odds of mMayo remission at M6 (odds ratio, 0.33; 95% confidence interval, 0.11-0.94; p = 0.0379).

Conclusion: Prior duration of remission/baseline endoscopic subscore may help guide tofacitinib dose reduction, while PROs may be useful early indicators of efficacy. Close monitoring of patients following dose reduction could identify those unlikely to achieve/maintain efficacy. Trial registration: ClinicalTrials.gov: NCT03281304.

Background: Colonic diverticular bleeding is the most common cause of lower gastrointestinal bleeding in adults and carries a significant risk of recurrence. However, there are many uncertainties regarding the management of the prevention of diverticular rebleeding.

Objectives: To review the current evidence on the potential role of lifestyle, pharmacological and endoscopic treatments and to discuss the unmet needs in the prevention of colonic diverticular rebleeding.

Design: A systematic review.

Data sources and methods: Based on the identified Patients-Interventions-Comparators-Outcomes questions, a detailed and comprehensive literature search was conducted, from inception to 12 January 2024, without language restriction, according to the modified Preferred Reporting Items for Systematic review and Meta-Analyses reporting guidelines.

Results: We did not find any dietary or lifestyle interventions (fibre intake, smoking, physical activity, alcohol consumption, BMI) to prevent colonic diverticular rebleeding. We also did not find any interventional studies of specific pharmacological treatments (such as rifaximin, mesalazine or probiotics) to prevent diverticular rebleeding. Data comparing endoscopic and conservative approaches used during the index episode come from observational studies and show conflicting results. Finally, there is a paucity of data regarding the timing of resumption of antiplatelet and anticoagulant therapy after an episode of colonic diverticular bleeding, and this remains to be determined.

Conclusion: This review highlights the paucity of data on the possible role of lifestyle, pharmacological and endoscopic treatments in the prevention of colonic diverticular rebleeding and advocates future studies aimed at finding effective therapeutic strategies.

Background: Crohn's disease (CD) exclusion diet combined with partial enteral nutrition (CDED + PEN) or exclusive enteral nutrition (EEN) is effective in inducing remission in mild-to-moderate pediatric CD. Although CDED + PEN is better tolerated and has higher compliance compared to EEN, a subset of patients does not achieve remission. Diet-induced remission is shown to be positively associated with specific changes in tryptophan-metabolites.

Objectives: To investigate whether the abundance of baseline fecal tryptophan-metabolites predicts dietary therapy outcomes in pediatric CD.

Design: Diagnostic accuracy study and secondary analysis of previously conducted Randomized Controlled Trial (RCT).

Methods: Twenty-six patients from previously performed RCT of mild-to-moderate pediatric CD were included. The patients were classified as having clinical remission (R) (n = 19 in total; CDED + PEN = 10 and to EEN = 9) or No-Remission (NR) (n = 7 in total; CDED + PEN = 3 and EEN = 4) following 6 weeks of therapy, based on the Pediatric Crohn's Disease Activity Index score (⩽10 = remission). We performed a targeted quantitative analysis of 21 tryptophan-metabolites in baseline (t = 0) fecal samples from both groups, utilizing liquid chromatography coupled with quadrupole mass spectrometry. Receiver operator characteristic curve (ROC) and random forest analysis (RFA) were used to assess the predictive power of fecal tryptophan-metabolites for dietary outcomes at baseline. Ratios of tryptophan-metabolites were compared to investigate different downstream tryptophan pathways.

Results: Baseline fecal kynurenine level was significantly higher in NR compared to R for CDED + PEN (p = 0.02) and EEN (p = 0.04). ROC analysis highlighted the robust predictive power of kynurenine for CDED + PEN (area under the curve (AUC = 0.97)) and EEN (AUC = 0.88)-induced remission. RFA corroborated these observations. The ratio serotonin/kynurenine was the strongest predictor of CDED + PEN-induced remission (AUC = 1). The ratio 5-hydroxytryptophan/kynurenine (AUC = 0.88) predicted EEN-induced remission. By combining data from CDED + PEN and EEN, kynurenine (AUC = 0.91) and ratios of quinolinic acid/kynurenine (AUC = 0.93) and kynurenine/indole-3-acetic acid (AUC = 0.88) demonstrated strong predictive performance for dietary therapy-induced remission.

Conclusion: Baseline tryptophan metabolites have the potential to serve as a biomarker for dietary remission in pediatric CD. Some tryptophan metabolite ratios showed the most promising predictive capabilities. If confirmed in validation studies, baseline fecal tryptophan markers may be able to provide much-needed guidance to personalize dietary intervention within the management of pediatric CD.

Trial registration: NCT01728870.

Background: Fecal microbiota transplantation (FMT) is a successful therapy for Clostridioides difficile infection (CDI). FMT from overweight donors is speculated to influence the recipient's body mass index (BMI) after administration for CDI.

Objectives: We investigated changes in the recipient's BMI after FMT in relation to the donor's BMI.

Design: We conducted a retrospective cohort study involving patients who underwent FMT for recurrent CDI at Mayo Clinic between 2012 and 2019.

Methods: We analyzed demographic and donor data for patients undergoing FMT at Mayo Clinic (2012-2019). Recipient BMI (pre- and post-FMT) and donor BMI were extracted from medical records. Mixed-effects linear regression was used to evaluate the impact of donor BMI, donor BMI category, recipient baseline BMI, time before and after FMT, and interactions between these variables on overall BMI change and BMI change per month. Kaplan-Meier curves were used to assess BMI changes (⩾5 units) based on the last recorded post-FMT BMI.

Results: We analyzed data from 401 patients with recorded BMI measurements before and after FMT. The median age of the recipients at the time of FMT was 59.1 years (interquartile range (IQR): 40.5-70.1 years), with 61.6% being female. The median BMI for recipients prior to FMT was 26.7 kg/m² (IQR: 22.7-31.6 kg/m²), while the median BMI of the donors was 24.5 kg/m² (IQR: 23.9-27.5 kg/m²). Stool from donors with a normal BMI was used for 58.2% of recipients, while 41.8% received stool from pre-obese donors. Donor BMI data were missing for 3.2% of recipients. Donor BMI was not significantly associated with changes in recipient BMI; for each 1-unit increase in donor BMI, a 0.01-unit monthly increase was observed (95% confidence interval: -0.0003, 0.02; p = 0.11). The log-rank test for BMI increases (⩾+5) and decreases (⩽-5) revealed no significant differences among the donor BMI groups (Chi-squared = 4.4, p = 0.1 for increases, Chi-squared = 2, p = 0.4 for decreases).

Conclusion: The lack of impact of donor BMI on BMI changes post-FMT suggests that these changes are more dependent on the recipient's metabolic profile. Prospective, controlled trials are required to analyze these results more comprehensively.

Integrating artificial intelligence (AI) into clinical trials for inflammatory bowel disease (IBD) has potential to be transformative to the field. This article explores how AI-driven technologies, including machine learning (ML), natural language processing, and predictive analytics, have the potential to enhance important aspects of IBD trials-from patient recruitment and trial design to data analysis and personalized treatment strategies. As AI advances, it has potential to improve long-standing challenges in trial efficiency, accuracy, and personalization with the goal of accelerating the discovery of novel therapies and improve outcomes for people living with IBD. AI can streamline multiple trial phases, from target identification and patient recruitment to data analysis and monitoring. By integrating multi-omics data, electronic health records, and imaging repositories, AI can uncover molecular targets and personalize trial strategies, ultimately expediting drug development. However, the adoption of AI in IBD clinical trials encounters significant challenges. These include technical barriers in data integration, ethical concerns regarding patient privacy, and regulatory issues related to AI validation standards. Additionally, AI models risk producing biased outcomes if training datasets lack diversity, potentially impacting underrepresented populations in clinical trials. Addressing these limitations requires standardized data formats, interdisciplinary collaboration, and robust ethical frameworks to ensure inclusivity and accuracy. Continued partnerships among clinicians, researchers, data scientists, and regulators will be essential to establish transparent, patient-centered AI frameworks. By overcoming these obstacles, AI has the potential to enhance the efficiency, equity, and efficacy of IBD clinical trials, ultimately benefiting patient care.

Background: Functional dyspepsia (FD) is common but few efficacious therapies exist. Itopride, a prokinetic, acts via dopamine D2 receptor antagonism and acetylcholinesterase inhibition, and is now approved in Japan, Mexico, and Europe for FD. However, long-term efficacy and safety data have not been published.

Objective: To evaluate the long-term safety and potential effectiveness of itopride.

Design: A long-term open-label drug effectiveness study.

Methods: Males and females, 18-65 years, with FD (Rome II) and the absence (by upper endoscopy) of any relevant structural disease were recruited. After the double-blind treatment phase, patients were treated in an open-label extension phase.

Results: A total of 798 patients were included in these two open-label trials and received at least one dose of study medication; 551 patients (69.0%) completed 6 months of treatment, and 294 patients (36.8%) completed a 12-month period. Response rates based on the global physician assessment were 61.7%, 64.8%, 69.0 %, 69.1%, 70.1%, 73.1%, and 77.9% at weeks 8, 16, 24, 32, 40, 48, and 52, respectively. Compliance was above 95%. The safety and tolerability profiles were as expected, with the majority of adverse events being gastrointestinal. Prolactin elevations occurred in 3% of the cases but were not clinically significant. No ECG changes were identified.

Conclusion: In this population, itopride, given for up to 12 months, was safe, and up to two-thirds appeared to maintain symptom benefit.

Trial registration: NCT00110968 and NCT00112203.

Background: Crohn's disease (CD) is a chronic autoimmune inflammatory bowel disease. It is estimated that approximately 40% of individuals with CD are non-adherent to medical prescriptions. This lack of adherence to treatment plans has been linked to an increased risk of hospitalisation and surgical procedures, which can have a detrimental impact on the patient's quality of life (QoL). Furthermore, the CD can impose significant stress on individuals, affecting their mental health and sense of mastery. The term 'mastery' is used to describe an individual's awareness of their abilities and capacities that are essential for effectively managing life events and situations.

Objectives: This study aimed to investigate the role of mastery in relation to medical adherence, distress, perceived social support, QoL, depressive and anxious symptoms and interoception in persons with a diagnosis of CD.

Design: This is a cross-sectional study, involving 261 adults diagnosed with CD.

Methods: Participants completed an online questionnaire comprising validated clinical and psychological scales, which lasted approximately 20 min. Participants were permitted to provide their most recently available medical report.

Results: Patients with CD reported discrete levels of mastery. Two factorial ANOVA highlighted statistically significative differences in mastery in relation to clinical conditions (F(2, 253) = 11.22, p < 0.001) and a significative interaction effect between gender and symptomatology (F(2, 253) = 7.22, p < 0.001). Multiple linear regression illustrated a statistically significant association between mastery, clinical conditions, QoL, stress and interoception (adjusted R square = 0.558; F(14, 211) = 21.32, p < 0.001). Concerning the possible mediator role of mastery between psychological state and medical adherence, no statistically significant results emerged from the mediation model analysis.

Conclusion: This study highlighted an effective impairment of mastery in CD patients, especially among men experiencing mild disease activity. A positive association between mastery and enteroception was outlined. The higher prevalence of distress, anxiety and depressive symptoms connected to mastery was substantiated. Future research should deepen the relationship between mastery with medical adherence.

Background: Vedolizumab (VDZ), a humanized monoclonal antibody that selectively inhibits the binding of the α4β7 integrin, has been approved for treating inflammatory bowel disease (IBD). Long-term safety studies of VDZ in clinical trials identified Clostridium difficile infection (CDI) as the major opportunistic infection.

Objectives: We aimed to address the incidence and risk factors of C. difficile colonization (CDC) and CDI in a real-world setting among IBD patients treated with VDZ.

Design: Retrospective multicenter study.

Methods: We retrospectively included IBD patients who tested negative for C. difficile before initiating standard VDZ therapy at four tertiary hospitals from November 1, 2021, to November 31, 2023. The primary outcome was the occurrence of CDC after VDZ initiation, and the secondary outcome was the occurrence of CDI and severe CDI.

Results: A total of 454 patients were included in the final analysis. The median follow-up time was 12.9 (8.2-16.3) months, and the study was followed for 2488.6 person-months. The CDC occurred in 28 patients (6.2%), including 23 (11.4%) patients with ulcerative colitis (UC; 18 asymptomatic carriers and 5 with symptomatic CDI) and 5 (2.0%) patients with Crohn's disease (asymptomatic carriers). Multivariate analysis showed that age >40 years old and UC were independent risk factors for the occurrence of the CDC after VDZ initiation. The incidence of CDI was 1.1%, and all patients were able to continue VDZ therapy after receiving antibiotic treatment. No risk factors were found to be significantly associated with CDI. There were no cases of severe CDI or deaths within 30 days.

Conclusion: The incidence of CDC after VDZ treatment was 6.2% and the majority of patients identified as asymptomatic carriers and were able to continue VDZ treatment. Age (>40 years old) and UC were the risk factors for CDC.

Background: The rising incidence of hilar malignant bile duct strictures poses challenges for diagnosis and treatment. While endoscopic treatment is essential for relieving obstruction, it carries a high risk of postoperative cholangitis. Sequential cutting of nasobiliary tubes as an alternative to stent placement after nasobiliary drainage may emerge as an effective strategy to mitigate these complications.

Objectives: This study aimed to evaluate the efficacy and safety of nasobiliary tube cutting after nasobiliary drainage versus conventional stent placement in reducing postoperative cholangitis in patients with hilar malignant biliary strictures.

Design: A retrospective cohort study.

Methods: From 2015 to 2023, 208 patients were divided into two groups: nasobiliary tube cutting group (n = 103) and conventional stent group (n = 105). The primary outcome was postoperative cholangitis, with secondary outcomes including drainage success, bilirubin reduction, re-interventions, complications, and hospital stay.

Results: Cholangitis occurred in 11.7% of the nasobiliary tube cutting group and 26.7% of the conventional stent group (p = 0.006). Successful drainage was achieved in 84 patients (81.6%) in the nasobiliary tube cutting group and 78 patients (74.3%) in the conventional stent group, with no statistically significant difference (p = 0.207). Patients whose total bilirubin reduction >50% within 7 days were significantly higher in the nasobiliary tube cutting group (48.5% vs 27.6%, p = 0.002). There were no significant differences between the groups in the number of endoscopic retrograde cholangiopancreatography procedures or re-interventions required (p > 0.05). Except for postoperative cholangitis, other postoperative complications were comparable between the groups (p > 0.05). The postoperative hospital stay was significantly longer in the nasobiliary tube cutting group, with a median duration of 10.0 (7.0, 14.0) days compared to 7.0 (5.5, 12.5) days in the conventional stent group (p = 0.024). Bismuth-Corlette Type IV was identified as an independent risk factor for cholangitis (OR = 3.207, 95%CI: 1.253-8.210, p = 0.015).

Conclusion: For patients with hilar malignant biliary stricture, sequential cutting of nasobiliary tubes as an alternative to stent placement after nasobiliary drainage may reduce the incidence of postoperative cholangitis and achieve early successful drainage, but it may result in a prolonged postoperative hospital stay. Bismuth-Corlette Type IV is an independent risk factor for the development of postoperative cholangitis.

Background: Clostridioides difficile infection (CDI) is a clinical challenge associated with poor outcomes in patients with inflammatory bowel disease (IBD).

Objectives: To identify clinical risk factors for CDI and its recurrence among patients with IBD.

Design: Case-control cohort study of IBD patients with and without episodes of CDI.

Methods: A case-control study of 279 IBD patients with CDI. Medical history and IBD-related symptoms 3 months preceding a toxin-positive CDI were recorded and compared with age- and sex-matched IBD patients without CDI. Outcomes of CDI in IBD patients were recorded 2-6 months after CDI.

Results: Based on clinical symptoms and fecal calprotectin levels, IBD is active before CDI. Recently diagnosed IBD seemed to increase the risk for CDI. Corticosteroid usage frequently preceded CDI episodes. Advanced therapies were not associated with CDI. Antibiotic intake was not registered before CDI in 30% of the episodes. Recurrent CDI (rCDI) occurred in 30% (84/279) of IBD-CDI patients and 67% (90/135) of those episodes were registered within 90 days from the preceding episode. Most (79%) rCDI patients had ulcerative colitis (UC). CDI could complicate underlying IBD by increasing the need for escalation in IBD-related medical therapy and leading to hospitalization but it did not seem to increase the risk of colectomy.

Conclusion: The major risk factors associated with CDI in IBD patients were IBD activity before infection, UC and colonic Crohn's disease, short duration of IBD, corticosteroid usage, and hospitalization. Patients with active IBD and a shorter disease duration may benefit from more frequent follow-ups in the early stages, as they appear to be at higher risk of developing CDI.