Therapeutic Advances in Gastroenterology最新文献

Significant progress in the management and modification of inflammatory bowel disease (IBD) has been made; however, significant barriers to the optimization of IBD care in the United States still exist. The majority of these barriers are constructed by insurance carriers and the integration of market pressures into healthcare decision-making. In this review, we highlight the barriers to IBD care optimization within the context of the US insurance system and review current and proposed solutions.

Background: With a 15% incidence, KRAS is one of the most common mutations in biliary tract cancer (BTC) and is a poor prognostic factor. Immune checkpoint inhibitors (ICIs) as salvage therapy have modest activity in BTC.

Objectives: There are limited data on the efficacy of ICIs according to KRAS mutation in BTC. We evaluated the efficacy of ICIs in BTC patients with or without KRAS mutations.

Design: Retrospective observational study.

Methods: We conducted molecular profiling in BTC patients who received ICIs as salvage therapy. The expression of programmed death ligand 1 (PD-L1) on tumor cells was assessed using immunohistochemistry. The TruSight^TM Oncology 500 assay from Illumina was used as a cancer panel. We analyzed overall survival (OS) and progression-free survival (PFS) of ICI in BTC patients according to KRAS mutation and PD-L1 expression.

Results: A total of 62 patients were included in this analysis. The median age was 68.0 years; 47 patients (75.8%) received pembrolizumab and 15 (24.2%) received nivolumab as salvage therapy. All patients received gemcitabine plus cisplatin as the frontline therapy, and 53.2% received fluoropyrimidine plus oxaliplatin (FOLFOX) before ICI. The median number of lines of prior chemotherapy was 2.5. The KRAS mutation was found in 13 patients (19.1%), and 28 patients (45.2%) showed 1% or more of tumor cells out of visible tumor cells positive for PD-L1. There was no statistical correlation between KRAS mutation and PD-L1 expression. The median OS and PFS with ICI were 5.6 [interquartile range (IQR): 3.3-8.0] and 3.8 (IQR: 3.0-4.5) months, respectively. There were no statistically significant differences in PFS with ICIs according to KRAS mutation (mutant type versus wild type) and PD-L1 expression (positive versus negative). In subgroup analysis, patients with both KRAS mutation and PD-L1 positivity had longer PFS compared with patients with KRAS mutation and PD-L1 negativity (10.1 versus 2.6 months, p = 0.047). This finding was not shown in patients with wild-type KRAS.

Conclusion: Our analysis suggested that PD-L1 expression might be a useful biomarker for ICIs in BTC patients with KRAS mutation but not in those with wild-type KRAS.

Background: Japanese guidelines recommend triple therapy with vonoprazan or a proton pump inhibitor (PPI) in combination with antibiotics to treat Helicobacter pylori (H. pylori) infection. While studies have shown improved eradication rates and reduced costs with vonoprazan versus PPIs, there is little data describing healthcare resource use (HCRU) and treatment patterns.

Objectives: To compare patients treated with a vonoprazan-based or PPI-based regimen for H. pylori infection in Japan in terms of their characteristics, HCRU, healthcare costs, clinical outcomes, and treatment patterns.

Design: Retrospective matched cohort.

Methods: We used data from the Japan Medical Data Center claims database (July 2014-January 2020) to identify adult patients with H. pylori infection and a first observed use of vonoprazan or a PPI in 2015 or later (index date). Patients prescribed a vonoprazan-based or a PPI-based regimen were matched 1:1 using propensity score matching. HCRU, healthcare costs, diagnostic tests, a proxy for H. pylori eradication (i.e. no triple therapy with amoxicillin in combination with metronidazole or clarithromycin >30 days after the index date), and second-line treatment were described during the 12-month follow-up period.

Results: Among 25,389 matched pairs, vonoprazan-treated patients had fewer all-cause and H. pylori-related inpatient stays and outpatient visits than PPI-treated patients, resulting in lower all-cause healthcare costs [185,378 Japanese yen (JPY) versus 230,876 JPY, p < 0.001]. Over 80% of patients received a post-treatment test for H. pylori. Fewer vonoprazan-treated than PPI-treated patients subsequently received an additional triple regimen for H. pylori infection (7.1% versus 20.0%, p < 0.001) or a prescription for vonoprazan or a PPI as monotherapy (12.4% versus 26.4%, p < 0.001) between 31 days and 12 months after the index date.

Conclusion: Patients with H. pylori infection who were treated with vonoprazan-based therapy had lower rates of subsequent H. pylori treatment, lower overall and H. pylori-related HCRU, and lower healthcare costs than patients treated with PPI-based therapy.

Current recommendations on Helicobacter pylori (H. pylori) eradication in children differ from adults. In H. pylori-infected adults, the eradication is always recommended because of the risk to develop gastrointestinal and non-gastrointestinal associated diseases. Instead, before treating infected children, we should consider all the possible causes and not merely focus on H. pylori infection. Indeed, pediatric international guidelines do not recommend the test and treat strategy in children. Therefore, gastroscopy with antimicrobial susceptibility testing by culture on gastric biopsies should be performed before starting the eradication therapy in children to better evaluate all the possible causes of the symptomatology and to increase the eradication rate. Whether antibiotic susceptibility testing is not available, gastroscopy is anyway recommended to better set any possible cause of symptoms and not simply focus on the presence of H. pylori. In children the lower antibiotics availability compared to adults forces to treat based on antimicrobial susceptibility testing to minimize the unsuccessful rates. The main antibiotics used in children are amoxicillin, clarithromycin, and metronidazole in various combinations. In empirical treatment, triple therapy for 14 days based either on local antimicrobial susceptibility or on personal antibiotic history is generally recommended. Triple therapy with high dose of amoxicillin is a valid alternative choice, either in double resistance or in second-line treatment. Moving from therapeutic regimens used in adults, we could also select quadruple therapy with or without bismuth salts. However, all the treatment regimens often entail unpleasant side effects and lower compliance in children. In this review, the alternative and not yet commonly used therapeutic choices in children were also analyzed.

The aim of this review is to broadly cover how the COVID-19 pandemic has affected individuals with celiac disease, including perceived risk, risk of contraction or severe infection, considerations regarding vaccination, access to gluten-free food during the pandemic, and possible long-term changes to the practice of celiac disease management spurred by the pandemic. While initially there was increased perceived risk about COVID-19 in the celiac disease population, studies have found that individuals with celiac disease are not at an increased risk of contracting or having a severe course compared to the general population. There is not yet evidence that COVID-19 infection will lead to an increase in celiac disease incidence, though more research on this topic with longer-term follow-up is necessary to make this determination. Limited access to in-person visits led to an increase in telemedicine, which was adopted swiftly by this patient population and may offer improved access in the long term. In summary, individuals with celiac disease do not appear to be at an increased risk of contracting COVID-19 or having a more severe disease course.

Latin America (LATAM) is a large region comprising 47 countries and territories. Each one carries a different cultural and historical background, diverse political systems, and a particular approach to healthcare management. There is a lack of high-quality data on the epidemiology of inflammatory bowel diseases (IBD) in this region, including broad and detailed information about the penetration of biological and advanced therapies as treatment strategies. From an IBD perspective, patients experience, in general, fragmentations and inequities in the healthcare systems, with different and usually delayed access to qualified health services. This review explores the barriers to accessing IBD care throughout LATAM. The authors compiled data from multiple sources, such as studies focusing on epidemiology, biological penetration, and surgical rates. In addition, overall access to IBD treatments was assessed through a questionnaire distributed to physicians in LATAM via email and direct messaging to capture local perspectives.

Background: Vonoprazan, a novel acid-suppressive drug, is non-inferior to proton pump inhibitors (PPIs) for the management of gastric acid-related diseases. However, the safety of vonoprazan has not been systematically evaluated yet.

Objectives: To elucidate the incidence and type of adverse events (AEs) in patients taking vonoprazan.

Design: Systematic review and meta-analysis.

Data sources and methods: PubMed, EMBASE, and Cochrane Library databases were searched for all studies reporting the safety of vonoprazan. The incidences of any AEs, drug-related AEs, serious AEs, AEs leading to drug discontinuation, and common AEs were pooled. Odds ratios (ORs) were calculated to compare the incidence of AEs between patients taking vonoprazan and PPIs.

Results: Seventy-seven studies were included. The pooled incidences of any AEs, drug-related AEs, serious AEs, and AEs leading to drug discontinuation were 20, 7, 1, and 1%, respectively. The incidences of any AEs (OR = 0.96, p = 0.66), drug-related AEs (OR = 1.10, p = 0.44), serious AEs (OR = 1.14, p = 0.36), and AEs leading to drug discontinuation (OR = 1.09, p = 0.55) were not significantly different between patients taking vonoprazan and PPIs. In subgroup analyses, patients with peptic ulcer disease (PUD) had higher incidences of any AEs, serious AEs, and AEs leading to drug discontinuation than those with gastroesophageal reflux disease (GERD), Helicobacter pylori (H. pylori) infection, and artificial ulcer after gastric endoscopic submucosal dissection (ESD), but patients with H. pylori infection had a higher incidence of drug-related AEs than those with PUD, GERD, and artificial ulcer after gastric ESD. The incidence of AEs was higher in patients taking long-term use of vonoprazan than those taking short-term use of vonoprazan.

Conclusion: Vonoprazan is well tolerated and shows similar safety compared to PPIs. The safety of vonoprazan may be primarily influenced by its indications and duration.

Registration: PROSPERO CRD42022314982.

Background: Currently, no guidelines specifically recommend scoring systems and biomarkers for early evaluation of the severity and prognosis of acute pancreatitis in pregnancy (APIP).

Objectives: This study aimed to explore the early predictive value of scoring systems and routine laboratory tests on APIP severity and maternofetal prognosis.

Design: This study retrospectively analyzed 62 APIP cases in a 6-year period.

Methods: The predictive value of scoring systems and routine laboratory tests that were collected 24 h and 48 h after admission, for APIP severity and fetal loss, were analyzed.

Results: To detect severe acute pancreatitis (SAP), a 24-h Bedside Index for severity in acute pancreatitis (BISAP) achieved a higher area under the curve (AUC) value of 0.910 than the Acute Physiology and Chronic Health Evaluation II (AUC = 0.898) and Ranson score (AUC = 0.880). The combination of BISAP, glucose, neutrophil-to-lymphocyte ratio (NLR), hematocrit (Hct), and serum creatinine (Scr) provided an AUC value of 0.984, which had greater predictive power than BISAP (p = 0.015). 24-h BISAP and Hct were independent risk factors for predicting SAP of APIP. The cutoff values of Hct and blood urea nitrogen (BUN) to predict SAP were 35.60% and 3.75 mmol/l in the APIP. Furthermore, 24-h BISAP had the highest predictive power (AUC = 0.958) for fetal loss.

Conclusion: BISAP is a convenient and reliable indicator for the early prediction of SAP and fetal loss in APIP. The combination of BISAP, glucose, NLR, Hct and Scr proved to be the optimal early markers for the prediction of SAP in APIP within 24 h after admission. In addition, Hct > 35.60% and BUN > 3.75 mmol/l may be suitable thresholds for predicting SAP in APIP.

The recent availability of susceptibility testing for Helicobacter pylori infections in the United Sates has resulted in paradigm shifts in the diagnosis, therapy, and follow-up of H. pylori infections. Here, we reviewed the English literature concerning changes in H. pylori diagnosis and therapy with an emphasis on the last 3 years. We focus on the new methods that offer rapid and convenient susceptibility testing using either invasive (endoscopic) or noninvasive (stool) methods of obtaining test material. We also discuss the implications of this availability on therapy and follow-up after therapy. The approach to therapy was categorized into four groups: (1) therapies that can be used empirically, (2) therapies that should be restricted to those that are susceptibility-based, (3) potentially effective therapies that have yet to be optimized for local use, and (4), therapies that contain unneeded antibiotics that should not be prescribed. The most convenient and efficient method of susceptibility testing is by using reflexive stool testing in which if the sample is positive, it is automatically also used for determination of susceptibility. Reflexive testing can also be done via reflexive ordering (e.g., for all positive urea breath tests). The post therapy test-of-cure has emerged as a critical component of therapy as it not only provides feedback regarding treatment success but when combined with susceptibility testing also provide evidence regarding the cause of failure (e.g., poor adherence versus emergence of resistance during therapy. Susceptibility testing has made even the most current H. pylori guidelines for diagnosis and therapy generally obsolete. Clarithromycin, metronidazole, and levofloxacin triple therapies should only be administered as susceptibility-based therapy. Regimens containing unneeded antibiotics should not be given. We provide recommendations regarding the details and indications for all current therapies.