Therapeutic Advances in Gastroenterology最新文献

Background: The success of anti-tumor necrosis factor (TNF) drug strategies in the treatment of inflammatory bowel disease (IBD) is altered by the development of anti-drug antibodies that reduce their efficacy. Studies have shown that the HLA-DQA1⋆05 allele increases the risk of immunogenicity to anti-TNF drugs approximately twofold.

Objective: Analyze whether the presence of the HLA-DQA1⋆05 allele is associated with the development of immunogenicity and to evaluate the disease response to anti-TNF drugs (infliximab (IFX) and adalimumab (ADA)), according to the presence of this allele.

Design: This is an observational retrospective cohort study, single center, to determine the impact of HLA-DQA1⋆05 on disease activity in patients with IBD at the Hospital Universitario Virgen Macarena.

Methods: In total, 200 IBD patients were included: 109 treated with IFX and 91 with ADA. Data were collected using the computerized medical records from the DIRAYA program of the Servicio Andaluz de Salud. Response-defined as improvement-and remission-defined as the disappearance of symptoms and analytical/endoscopic signs-were assessed using activity indices (partial Mayo, Harvey-Bradshaw) in all patients. Anti-TNF drug levels were also determined, as well as the presence or absence of anti-IFX and anti-ADA antibodies. The reporting of this study conforms to the Strengthening the Reporting of Observational Studies in Epidemiology statement.

Results: The HLA-DQA1⋆05 haplotype was present in 70 (35%) patients, including 39 (36%) treated with IFX and 31 (34%) with ADA. The risk of withdrawal, intensification, as well as antibody development, was higher in patients carrying the allele and on treatment with IFX or ADA.

Conclusion: In our study, we demonstrated that there is an increased risk of immunogenicity in patients carrying the HLA-DQA1⋆05 genotype, which would support the idea of screening for this genetic variant before starting anti-TNF therapy, as its prevalence is high in the general population and increases the risk of treatment discontinuation due to loss of response.

Background: Endoscopic retrograde cholangiopancreaticography (ERCP) is the standard endoscopic procedure for the diagnosis and treatment of diseases of the pancreas and bile ducts. Cholangioscopy provides direct visualization of the bile ducts. It offers the possibility of more detailed diagnostic and therapeutic indications. Today, cholangioscopy is often performed as a single-operator (SOC) procedure.

Objectives: We were interested in the clinical efficacy of our SOC procedure in comparison with published studies, and performed this retrospective data analysis of all our consecutive patients from 2016 to 2022 to analyze the feasibility, safety, and efficacy of SOC.

Design and methods: A retrospective single-center analysis of patients undergoing SOC at a tertiary center from 2016 to 2022 (N = 196) was performed. Demographic data, indication for SOC, exam-specific data, efficacy, and complications were included. Sensitivity and specificity for diagnosing indeterminate biliary strictures were calculated.

Results: The most common indications for SOC were indeterminate biliary strictures (n = 117; 60%), treatment of biliary stones (n = 45; 23%), and other indications (n = 34; 17%), for example, foreign body removal or intraoperative SOC. In 97% of the SOC (n = 191), the procedure was technically successful. The diagnostic or therapeutic goal was achieved in 91% of SOC (n = 173). In the subgroup where the SOC result was confirmed by subsequent surgery (n = 93), sensitivity was 86%, specificity 99%, and SOC treatment of stones was successful in 89%. Complications occurred in (20%; n = 37). The majority of these patients (n = 18; 10%) had minor bleeding requiring no intervention.

Conclusion: SOC is an effective and safe procedure that should be the standard of care when primary diagnostic and/or therapeutic ERCP has failed. The sensitivity and specificity for determining the dignity of biliary strictures and the efficacy for the treatment of difficult-to-treat stones are reproducibly very high.

Background: The usability of subcutaneous vedolizumab (s.c. VDZ) treatment in inflammatory bowel diseases (IBD; ulcerative colitis (UC), Crohn's disease (CD)) has been proven via clinical trials while real-world data collection is ongoing.

Objectives: Our study evaluates the effectiveness, safety, patients' preferences, and psychological factors associated with s.c. VDZ treatment, after switching from intravenous (i.v.) formulation.

Design: Prospective, multicenter cohort study including IBD patients switching from i.v. VDZ to s.c. treatment and were evaluated over 52 weeks.

Methods: Serum VDZ levels and C-reactive protein (CRP) were measured at the baseline and w52. At w12, a questionnaire on the patient's satisfaction and psychological characteristics was administered. The primary outcome was the drug persistence rate (cessation was due to loss of response (LOR), adverse events, patient request, and other causes) at w52, while the secondary outcomes were the changes in the clinical corticosteroid-free remission (CSFR) and biochemical remission (BR; CRP ⩽ 5 mg/L) rates, safety issues, serum drug levels, patients' preferences, and psychological features.

Results: In total, 70 IBD patients were evaluated (32 CD patients, 38 UC patients; male/female ratio: 41.4%; median age: 43.2 years). In the CD group, 81.3% were in CSFR and 65.6% were in BR, while in the UC group, 71.7% were in CSFR and 69.4% were in BR. Overall, 17.1% of the patients ceased s.c. VDZ treatment after a median of 26.2 (interquartile range 20-47) weeks. LOR was registered in 3/12 ceased patients. In addition, CSFR and BR rates were stable, while serum VDZ levels increased by w52 (p < 0.001).

Conclusion: The transition from i.v. to s.c. VDZ treatment was effective, the overall persistence rate was associated with high serum drug levels, and no novel safety issues were reported. Although s.c. administration after induction can save resources, some patients still insisted on i.v. VDZ treatment, due to its proven formulation.

The prevalence of anxiety, depression, and other psychological comorbidities among patients with inflammatory bowel disease (IBD) significantly exceeds that of the general population. Moreover, a bidirectional relationship exists between psychological comorbidities and IBD. This intricate interplay has substantial clinical implications, impacting treatment adherence, therapeutic efficacy, and disease recurrence rates. In this review, we explore the multifaceted mechanisms through which psychological factors influence IBD progression, treatment response, and prognosis. Specifically, we delve into the involvement of the hypothalamic-pituitary-adrenal axis, autonomic nervous system, enteric nervous system, microbiota-gut-brain axis, systemic inflammatory cytokines, and immune cell function. Additionally, we discuss the potential benefits of antidepressant therapy in mitigating IBD risk and the role of psychotropic drugs in reducing peripheral inflammation. Recognizing and addressing psychological comorbidity is pivotal in comprehensive IBD management. We advocate for the integration of biopsychosocial approaches into IBD treatment strategies, emphasizing the need for innovative psychological interventions as adjuncts to conventional therapies. Rigorous research investigating the impact of antidepressants and behavioral interventions on IBD-specific outcomes may herald a paradigm shift in IBD management.

Background: An orodispersible form of budesonide has recently been approved for the targeted treatment of eosinophilic oesophagitis in the United Kingdom, Europe, Australia, Canada and the United States, following favourable results from a randomised controlled trial. This is the first dedicated real-world study exploring the safety and efficacy of budesonide orodispersible tablets for induction therapy in the treatment of eosinophilic oesophagitis while providing insights into its management.

Objectives: The primary objective was histologic remission, defined as less than 5 eosinophils per high-powered field. The secondary objectives included histologic response (>50% reduction in peak eosinophil count), clinical remission (complete resolution of symptoms documented on clinic letters), clinical response (improvements in symptoms as reported on clinical letters), endoscopic remission (Endoscopic Reference Score (EREFS) score = 0), and endoscopic response (improvement in EREFS score). The EREFS scores were calculated based on the severity and presence of rings, longitudinal furrows, strictures, oedema and exudates on endoscopic images. Adverse events and safety profiles were also recorded.

Design: A multicentre cohort study examining the effectiveness of 1 mg, twice daily, budesonide orodispersible tablet induction therapy for the treatment of eosinophilic oesophagitis.

Methods: Ethics approval was obtained through the Western Australia Health: Governance, Evidence, Knowledge, Outcomes system for assessment of Audit and Quality Activities. The study adhered to the Strengthening the Reporting of Observational Studies in Epidemiology guidelines.

Results: A total of 43 patients (29 males, 14 females; median age 39) were recruited. Forty-one patients were included in the analysis. After induction therapy, 30 patients (73%) achieved histologic remission, and 35 patients (85%) demonstrated histologic response. Thirty-nine patients (95%) achieved clinical response, and 28 patients (68%) achieved clinical remission. An endoscopic response was seen in 37 patients (90%), and 16 patients (39%) achieved endoscopic remission. No significant adverse events were identified.

Conclusion: Budesonide orodispersible tablet is an effective induction therapy for eosinophilic oesophagitis, as evidenced by its high histologic remission rate and favourable safety profile.

Background: Treatments and strategies for inflammatory bowel disease (IBD) have gradually evolved in the 2000s.

Objectives: We investigated whether the prescription of corticosteroids (prednisolone and budesonide) in patients with IBD in the first 5 years after diagnosis changed in patients diagnosed between 2006 and 2018.

Design: Retrospective observational study.

Methods: The cumulative prescribed dosage of corticosteroids for the first 5 years after diagnosis was registered in all patients with IBD (n = 386) at our clinic for those diagnosed between 2006 and 2018.

Results: The proportion of patients with IBD who were prescribed at least one prescription of corticosteroids in year 1-5 after diagnosis was 55.3%, 27.9%, 22.7%, 14.1%, and 14.6%, respectively. The proportion of patients who had a cumulative dose of prednisolone >1 g in the first 5 years after diagnosis was 40.1% for ulcerative colitis and 34.9% for Crohn's disease (CD). The cumulative prescribed dosage (within 3 years after diagnosis) of prednisolone had declined (rs = -0.164, p = 001), but had increased for budesonide (rs = 0.202, p < 0.001) between 2006 and 2020. The prescription of any immunomodulator for IBD in the first 5 years from diagnosis was stable between 2006 and 2018 (rs = 0.056, p = 0.257), but there was a minor increase in the prescription of Tumor Necrosis Factor (TNF)-inhibitors (rs = 0.119, p = 0.020). The use of five-acetyl salicylic acid (5-ASA) decreased in patients with CD (rs = -201, p = 0.012).

Conclusion: There was a decrease in the prescription of prednisolone and an increase in the prescription of budesonide treatment from 2006 to 2023; however, the cumulative exposure to corticosteroids in patients with IBD remains at a relatively high level.

Background: Faecal microbiota transplantation (FMT) is a highly effective treatment for Clostridioides difficile infection. Its use is backed by solid evidence, but application methods differ. Encapsulated FMT is a non-invasive, patient-friendly and scalable application method that may be preferred over colonoscopy or nasoduodenal tube application.

Objectives: We describe a detailed protocol, the Glyprotect protocol, for producing glycerol-based capsules to increase FMT accessibility.

Design: Using iterative quality improvement methods, we developed and validated the Glyprotect protocol as a reproducible protocol for cryopreserving minimally processed donor faeces in a standard hospital laboratory setting.

Methods: We describe detailed standard operating procedures for producing glycerol-based capsules, including all necessary materials and troubleshooting guidelines. Capsule integrity was tested at various temperatures and pH levels. Flow cytometry was used to measure microbiota counts and dose accuracy.

Results: The Glyprotect protocol has been used for more than 2500 capsule-based FMT treatments and complies with European tissue and cell standards. The protocol is optimised to preserve microbes and minimise modulation of the donated microbiota by removing debris and water, which also reduces the number of capsules needed per FMT treatment. The intestinal microbiota is preserved in glycerol for cryoprotection and to prevent capsule leakage. Each capsule contains 650 µL microbe-glycerol mass, estimated to contain an average of 2.5 × 10⁸ non-specified bacteria.

Conclusion: The Glyprotect protocol enables hospitals and tissue establishments to set up capsule production in a standard laboratory, improving patients' access to FMT. The protocol facilitates the scalability of FMT services because capsule FMT is less time-consuming and less expensive than liquid-suspension FMT applied by colonoscopy or nasojejunal tube.

Trial registration: Not applicable.

Background: No head-to-head trial directly compares the effectiveness of vedolizumab (VDZ) and infliximab (IFX) in patients with ulcerative colitis (UC) who were naïve to biologic therapy.

Objectives: We aimed to compare the clinical and endoscopic effectiveness of VDZ and IFX in biologic-naïve patients with UC in real-world settings.

Design: It was a multicenter, observational, real-world cohort study conducted at five centers.

Methods: Patients diagnosed with UC and treated with either IFX or VDZ as their first-line biologic therapy were retrospectively enrolled. Steroid-free remission, clinical response, clinical remission, and endoscopic healing at week 14 and week 52 were compared between the two groups after propensity score weighting.

Results: A total of 199 patients (117 VDZ and 82 IFX) were included in the study. There were no significant differences in steroid-free remission (64.6% vs 56.1%, p = 0.224), clinical response (83.4% vs 73.4%, p = 0.086), or clinical remission (69.4% vs 60.1%, p = 0.174) at week 14. However, VDZ showed better results in steroid-free remission (67.5% vs 44.4%, p = 0.004), clinical response (69.7% vs 47.1%, p = 0.005), and clinical remission (67.5% vs 44.4%, p = 0.004) at week 52. In terms of endoscopic healing, VDZ was similar to IFX at week 14 (25.7% vs 17.4%, p = 0.185), but VDZ had a significantly higher rate at week 52 (29.5% vs 11.8%, p = 0.027). VDZ was found to be superior to IFX in therapeutic continuation (hazard ratio = 0.339, 95% CI: 0.187-0.614, p < 0.001). The rate of adverse events was similar between the two groups (6.8% vs 8.5%, p = 0.655).

Conclusion: VDZ demonstrated similar clinical and endoscopic effectiveness to IFX at week 14 in biologic-naïve patients with UC, but appeared to be superior at week 52. The safety outcomes were comparable between the groups.

Background: Combining antegrade stenting (AGS) and hepaticogastrostomy (HGS) is an increasingly used endoscopic ultrasound-guided intervention when stenting by endoscopic retrograde cholangiopancreatography is impossible.

Objectives: We comprehensively assessed the benefits and downsides of combined AGS and HGS (HGS procedure with AGS, HGAS).

Data sources and methods: From 788 HGS and 295 HGAS cases, a random-effects meta-analysis was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol. Five electronic databases were searched for studies on HGS with or without AGS from inception until May 2024. The odds ratio (OR) and pooled rates were used for single and two-arm comparisons with 95% confidence intervals (CI).

Results: From 26 eligible studies. The pooled technical and clinical success was 94% (CI: 92%-96%) and 88% (CI: 84%-91%) for HGS and 89% (CI: 83%-93%) and 94% (CI: 89%-97%) for HGAS, respectively. Pooled OR of HGAS and HGS showed an OR = 0.38 (CI: 0.07-2.00) for technical success and an OR = 1.02 (CI: 0.50-2.06) for clinical success. The pooled adverse event rates were 20% (CI: 16%-25%) for HGS and 14% (CI: 9%-20%) for HGAS, whereas pooled OR showed an OR = 1.09 (CI: 0.30-3.94). For re-intervention, an OR = 0.37 (CI: 0.27-0.52) was found. Time to stent dysfunction increased, HGAS 333 (CI: 280-Not reached) and HGS 209 (CI: 120-325) with no change in overall survival HGS 117 (CI: 94-147) and 140 (CI: 105-170).

Conclusion: The use of HGAS appears to increase clinical success and reduce the need for re-intervention. Overall adverse event rates were similar but bile leakage prevalence was decreased. Time to stent dysfunction seems to increase with no change in overall survival.

Trial registration: Our protocol was prospectively registered with PROSPERO (CRD42024509412).

Background: Fruquintinib is a third-line and subsequent targeted therapy for patients with metastatic colorectal cancer (mCRC). Identifying survival predictors after fruquintinib is crucial for optimizing the clinical use of this medication.

Objectives: We aimed to identify factors influencing the prognosis of patients with mCRC treated with fruquintinib and to leverage these insights to develop a nomogram model for estimating survival rates in this patient population.

Design: Multicenter retrospective observational study.

Methods: We collected patient data from January 2019 to October 2023, with one healthcare institution's data serving as the training cohort and the other three hospitals' data serving as the multicenter validation cohort. The nomogram for overall survival was calculated from Cox regression models, and variable selection was screened using the univariate Cox regression analysis with additional variables based on clinical experience. Model performance was measured by the concordance index (C-index), calibration curves, decision curve analyses (DCA), and utility (patient stratification into low-risk vs high-risk groups).

Results: Data were ultimately collected on 240 patients, with 144 patients included in the training cohort and 96 included in the multicenter validation cohort. Predictors included in the nomogram were CA199, body mass index, T stage, the primary site of the tumor, and other metastatic and pathological differentiation. The C-index of the nomogram in the training set and multicenter validation was 0.714 and 0.729, respectively. The models were fully calibrated and their predictions aligned closely with the observed data. DCA curves indicated the promising clinical benefits of the predictive model. Finally, the reliability of the model was also verified through the risk classification using the nomogram.

Conclusions: We constructed a nomogram for mCRC treated with fruquintinib based on six variables that may be used to assist in personalizing the use of the drug.