BACKGROUND: Lumen-apposing metal stents (LAMS) are widely used to drain walled-off necrosis (WON). LAMS occlusion is a significant clinical problem and identification of risk factors for LAMS occlusion could contribute to novel preventive strategies. A previous study suggested contradictory effects of proton pump inhibitors (PPIs) on occlusion and necrosectomy rates. METHODS: We conducted a Europe-wide multicenter retrospective cohort study assessing WONs drained by LAMS. The primary aims were to assess the strength of association between PPI intake and LAMS occlusion and necrosectomy rates, respectively. The secondary aim was to assess the strength of association between PPI intake and other LAMS-associated complications. Multiple mixed-effects models were used to control for possible confounding covariates. RESULTS: 893 patients with 967 LAMS from 17 centers were included. After excluding incomplete datasets and patients who took PPIs intermittently, 768 LAMS remained. The overall occlusion rate was 28.0 %. Most occlusions occurred within 10 days. Most patients received PPIs continuously (n = 577 vs. no intake n = 191). In patients who did not use PPIs continuously, lower rates of LAMS occlusion (odds ratio [OR] 0.61, P = 0.04) and necrosectomies (incidence rate ratio 0.8, P = 0.006) were observed. A post hoc analysis exhibited a dose- and compound-dependent effect of PPI intake on necrosectomy rate. No increase in other complications in the non-PPI group, such as bleeding events (OR 1.14) were observed. CONCLUSION: PPI intake was associated with higher rates of LAMS occlusion and necrosectomy.

• MeSH
• Pancreatitis, Acute Necrotizing * surgery   MeSH
• Drainage * instrumentation   methods   MeSH
• Proton Pump Inhibitors * therapeutic use   adverse effects   administration & dosage   MeSH
• Middle Aged MeSH
• Humans MeSH
• Necrosis surgery   MeSH
• Retrospective Studies MeSH
• Risk Factors MeSH
• Aged MeSH
• Stents * adverse effects   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Geographicals
• Europe MeSH
• Names of Substances
• Proton Pump Inhibitors * MeSH

PURPOSE: To evaluate the role of an anti-reflux diet in the treatment of patients with chronic cough caused by laryngopharyngeal reflux (LPR). METHODS: This prospective observational study included patients with chronic cough (lasting over 3 months) and laryngopharyngeal reflux (LPR) confirmed by hypopharyngeal-esophageal 24-h multichannel intraluminal impedance-pH monitoring (HEMII-pH), according to Dubai criteria. Participants were categorized based on cough severity using a visual analog scale (VAS) from 1 to 10. A VAS < 5 was considered to indicate mild cough, whereas a VAS ≥ 5 were considered to indicate severe cough. Patients with mild cough were treated by anti-reflux diet only, while those with severe cough received additional treatment with proton pump inhibitors (PPIs) and alginates. After 3 months, treatment effectiveness was evaluated by assessing the reduction in cough severity. RESULTS: In patients with mild cough, anti-reflux diet alone proved to be effective, yielding improvement in 83.3% of cases. Among patients with severe cough, a combination of anti-reflux diet, proton pump inhibitors (PPIs), and alginates proved was effective in 81.8% of cases. CONCLUSION: Diet alone is an effective and sufficient treatment for mild chronic cough in patients with LPR. For patients with severe chronic cough with LPT, combined anti-reflux measures are effective.

• Keywords
• Bronchial asthma, Chronic cough, Diet, Laryngopharyngeal reflux, Proton pump inhibitors, Proximal acid exposure time,
• MeSH
• Alginates therapeutic use   MeSH
• Chronic Disease MeSH
• Chronic Cough MeSH
• Adult MeSH
• Proton Pump Inhibitors * therapeutic use   MeSH
• Cough * etiology   diet therapy   MeSH
• Laryngopharyngeal Reflux * complications   diet therapy   MeSH
• Middle Aged MeSH
• Humans MeSH
• Esophageal pH Monitoring MeSH
• Prospective Studies MeSH
• Aged MeSH
• Severity of Illness Index MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Observational Study MeSH
• Names of Substances
• Alginates MeSH
• Proton Pump Inhibitors * MeSH

OBJECTIVES: To assess the efficacy and safety of pharmacological interventions for preventing upper gastrointestinal (GI) bleeding in people admitted to intensive care units (ICUs). DESIGN AND SETTING: Systematic review and frequentist network meta-analysis using standard methodological procedures as recommended by Cochrane for screening of records, data extraction and analysis. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the certainty of evidence. PARTICIPANTS: Randomised controlled trials involving patients admitted to ICUs for longer than 24 hours were included. SEARCH METHODS: The Cochrane Gut Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and Latin American and Caribbean Health Science Information database (LILACS) databases were searched from August 2017 to March 2022. The search in MEDLINE was updated in April 2023. We also searched ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP). MAIN OUTCOME MEASURES: The primary outcome was the prevention of clinically important upper GI bleeding. RESULTS: We included 123 studies with 46 996 participants. Cimetidine (relative risk (RR) 0.56, 95% CI 0.40 to 0.77, moderate certainty), ranitidine (RR 0.54, 95% CI 0.38 to 0.76, moderate certainty), antacids (RR 0.48, 95% CI 0.33 to 0.68, moderate certainty), sucralfate (RR 0.54, 95% CI 0.39 to 0.75, moderate certainty) and a combination of ranitidine and antacids (RR 0.13, 95% CI 0.03 to 0.62, moderate certainty) are likely effective in preventing upper GI bleeding.The effect of any intervention on the prevention of nosocomial pneumonia, all-cause mortality in the ICU or the hospital, duration of the stay in the ICU, duration of intubation and (serious) adverse events remains unclear. CONCLUSIONS: Several interventions seem effective in preventing clinically important upper GI bleeding while there is limited evidence for other outcomes. Patient-relevant benefits and harms need to be assessed under consideration of the patients' underlying conditions.

• Keywords
• Drug-Related Side Effects and Adverse Reactions, Gastrointestinal Diseases, Hematology, Systematic Reviews as Topic,
• MeSH
• Cimetidine therapeutic use   MeSH
• Gastrointestinal Hemorrhage * prevention & control   MeSH
• Proton Pump Inhibitors therapeutic use   MeSH
• Intensive Care Units * MeSH
• Humans MeSH
• Anti-Ulcer Agents therapeutic use   MeSH
• Randomized Controlled Trials as Topic MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Network Meta-Analysis MeSH
• Systematic Review MeSH
• Names of Substances
• Cimetidine MeSH
• Proton Pump Inhibitors MeSH
• Anti-Ulcer Agents MeSH

BACKGROUND: Bismuth quadruple therapies (BQTs) including bismuth, a proton pump inhibitor (PPI) and two antibiotics have been shown to be highly effective for treating Helicobacter pylori infection even in areas of high bacterial antibiotic resistance. OBJECTIVE: To describe the time trends of use, effectiveness and safety of BQT in Europe using the European Registry on Helicobacter pylori Management (Hp-EuReg). DESIGN: Patients registered in the Hp-EuReg from 2013 to 2021 who had received BQT were included. The regimens prescribed, the number of eradication attempts, effectiveness, adherence and safety were analysed. The effectiveness was assessed by modified intention to treat (mITT). Time-trend and multivariate analyses were performed to determine variables that predicted treatment success. RESULTS: Of the 49 690 patients included in the Hp-EuReg, 15 582 (31%) had received BQT. BQT use increased from 8.6% of all treatments in 2013 to 39% in 2021. Single-capsule BQT-containing bismuth, metronidazole and tetracycline-plus a PPI (single-capsule BQT, ScBQT) was the most frequent treatment mode (43%). Schemes that obtained an effectiveness above 90% were the 10-day ScBQT and 14-day BQT using tetracycline plus metronidazole, or amoxicillin plus either clarithromycin or metronidazole. Only ScBQT achieved above 90% cure rates in all the geographical areas studied. Using the ScBQT scheme, adherence, the use of standard or high-dose PPIs, 14-day prescriptions and the use of BQT as first-line treatment were significantly associated with higher mITT effectiveness. CONCLUSION: The use of BQT increased notably in Europe over the study period. A 10-day ScBQT was the scheme that most consistently achieved optimal effectiveness. TRIAL REGISTRATION NUMBER: NCT02328131.

• Keywords
• ANTIBIOTIC THERAPY, HELICOBACTER PYLORI - TREATMENT, HELICOBACTER THERAPY,
• MeSH
• Amoxicillin therapeutic use   administration & dosage   MeSH
• Anti-Bacterial Agents * therapeutic use   adverse effects   administration & dosage   MeSH
• Bismuth * therapeutic use   administration & dosage   MeSH
• Adult MeSH
• Helicobacter pylori * drug effects   MeSH
• Helicobacter Infections * drug therapy   MeSH
• Proton Pump Inhibitors * therapeutic use   administration & dosage   adverse effects   MeSH
• Clarithromycin therapeutic use   administration & dosage   MeSH
• Drug Therapy, Combination * MeSH
• Middle Aged MeSH
• Humans MeSH
• Metronidazole therapeutic use   administration & dosage   MeSH
• Registries * MeSH
• Aged MeSH
• Tetracycline therapeutic use   administration & dosage   MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Observational Study MeSH
• Geographicals
• Europe MeSH
• Names of Substances
• Amoxicillin MeSH
• Anti-Bacterial Agents * MeSH
• Bismuth * MeSH
• Proton Pump Inhibitors * MeSH
• Clarithromycin MeSH
• Metronidazole MeSH
• Tetracycline MeSH

Although immune checkpoint inhibitors (ICI) and/or tyrosine kinase inhibitors (TKI) are the standard treatment of advanced unresectable or metastatic renal cell carcinoma (RCC), the impact of concomitant medications remains unclear. We aimed to evaluate the impact of concomitant medications on survival outcomes in patients treated with systemic therapy for advanced unresectable or metastatic RCC. In August 2024, PubMed, Scopus, and Web of Science were queried for studies evaluating concomitant medications in patients with advanced unresectable or metastatic RCC (PROSPERO: CRD42024573252). The primary outcome was overall survival (OS). A fixed- or random-effects model was used for meta-analysis according to heterogeneity. We identified 22 eligible studies (5 prospective and 17 retrospective) comprising 16,072 patients. Concomitant medications included proton pump inhibitors (PPI) (n = 3959), antibiotics (n = 571), statins (n = 5466), renin-angiotensin system inhibitors (RASi) (n = 6615), and beta-blockers (n = 1964). Both concomitant PPI and antibiotics were significantly associated with worse OS in patients treated with ICI (PPI: HR: 1.22, P = .01, and antibiotics: HR: 2.09, P < .001). Concomitant statins, RASi, or beta-blocker were significantly associated with improved OS in patients treated with TKI (statins: HR: 0.81, P = .03, RASi: HR: 0.63, P < .001, beta-blocker: HR: 0.69, P < .001, respectively). In patients treated with ICI, RASi was significantly associated with improved OS (HR: 0.64, P = .02). Concomitant use of antibiotics or PPI with ICI can reduce its oncologic efficacy. Conversely, concomitant statins, RASi, or beta-blockers can enhance the oncologic efficacy of TKI. When initiating systemic therapy for metastatic RCC, it may be important for clinicians to assess baseline co-medications and recognize their possible positive or negative effects.

• Keywords
• Chemotherapy, Concomitant medications metastatic renal cell carcinoma, Immune checkpoint inhibitors,
• MeSH
• Survival Analysis MeSH
• Adrenergic beta-Antagonists therapeutic use   MeSH
• Immune Checkpoint Inhibitors therapeutic use   MeSH
• Protein Kinase Inhibitors therapeutic use   MeSH
• Proton Pump Inhibitors therapeutic use   administration & dosage   MeSH
• Carcinoma, Renal Cell * drug therapy   mortality   secondary   MeSH
• Drug Interactions MeSH
• Humans MeSH
• Kidney Neoplasms * drug therapy   mortality   pathology   MeSH
• Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Meta-Analysis MeSH
• Systematic Review MeSH
• Names of Substances
• Adrenergic beta-Antagonists MeSH
• Immune Checkpoint Inhibitors MeSH
• Protein Kinase Inhibitors MeSH
• Proton Pump Inhibitors MeSH
• Hydroxymethylglutaryl-CoA Reductase Inhibitors MeSH

Helicobacter pylori colonizes the human gastric mucosa of more than half of the human population and has a unique lipopolysaccharide (LPS) structure. LPS is the most dominant and suitable pathogen-associated molecular pattern that is detected via pattern recognition receptors. Although the priming effect of H. pylori LPS on reactive oxygen species (ROS) production of PMNs is lower than that of Escherichia coli O111:B4 LPS, LPS released from H. pylori associated with antibiotics eradication therapy may activate PMNs and increase ROS production. In addition, we describe the effects of H. pylori and E. coli O111:B4 LPSs on gene expression and the anti-inflammatory effect of lansoprazole (LPZ) in human polymorphonuclear leukocytes. LPS isolated from H. pylori and E. coli O111:B4 alters toll-like receptor 2 (TLR) and TLR4 expressions similarly. However, LPS from E. coli O111:B4 and H. pylori caused a 1.8-fold and 1.5-fold increase, respectively, in CD14 expression. All LPS subtypes upregulated TNFα and IL6 expression in a concentration-dependent manner. Although E. coli O111:B4 LPS upregulated IL8R mRNA levels, H. pylori LPS did not (≦ 100 ng/mL). Gene expression levels of ITGAM demonstrated no significant change on using both LPSs. These different effects on the gene expression in PMNs may depend on variations in LPS structural modifications related to the acquired immunomodulatory properties of H. pylori LPS. Proton pump inhibitors, i.e., LPZ, are used in combination with antibiotics for the eradication therapy of H. pylori. LPZ and its acid-activated sulphenamide form AG-2000 suppress ROS production of PMNs in a dose-dependent manner. These results suggest that LPZ combination with antibiotics for H. pylori eradication reduces gastric inflammation by suppressing ROS release from PMNs.

• Keywords
• H. pylori, LPS, Lansoprazole, Polymorphonuclear leukocyte, RT-PCR,
• MeSH
• Cytokines metabolism   genetics   MeSH
• Escherichia coli drug effects   genetics   MeSH
• Helicobacter pylori * drug effects   genetics   MeSH
• Proton Pump Inhibitors * pharmacology   chemistry   MeSH
• Lansoprazole * pharmacology   chemistry   MeSH
• Humans MeSH
• Lipopolysaccharides * metabolism   pharmacology   MeSH
• Neutrophils * drug effects   immunology   MeSH
• Reactive Oxygen Species metabolism   MeSH
• Toll-Like Receptor 4 metabolism   genetics   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Cytokines MeSH
• Proton Pump Inhibitors * MeSH
• Lansoprazole * MeSH
• lipopolysaccharide, Helicobacter pylori MeSH Browser
• Lipopolysaccharides * MeSH
• Reactive Oxygen Species MeSH
• Toll-Like Receptor 4 MeSH

BACKGROUND: This study aims to review the existing knowledge on the cost-effectiveness and item costs related to the diagnosis and treatment of gastroesophageal reflux disease (GERD) patients at different stages. METHODS: The study adhered to the PRISMA guidelines. The systematic search involved several steps: finding and identifying relevant articles, filtering them according to the set criteria, and examining the final number of selected articles to obtain the primary information. The number of articles published between 2013 and September 2024 in the Web of Science and PubMed databases was considered. The CHEERS checklist was used for the risk of bias assessment. Ultimately, 36 studies were included. RESULTS: Regarding the cost-effectiveness of GERD treatment, Proton pump inhibitors (PPIs) appeared to be the dominant solution for non-refractory patients. However, this might change with the adoption of the novel drug vonoprazan, which is more effective and cheaper. With advancements in emerging technologies, new diagnostic and screening approaches such as Endosheath, Cytosponge, and combined multichannel intraluminal impedance and pH monitoring catheters should be considered, with potential implications for optimal GERD management strategies. DISCUSSION: The new diagnostic methods are reliable, safe, and more comfortable than standard procedures. PPIs are commonly used as the first line of treatment for GERD. Surgery, such as magnetic sphincter augmentation or laparoscopic fundoplication, is only recommended for patients with treatment-resistant GERD or severe symptoms. OTHER: Advances in emerging technologies for diagnostics and screening may lead to a shift in the entire GERD treatment model, offering less invasive options and potentially improving patients' quality of life.

• Keywords
• Cost-effectiveness, Diagnostic methods, Gastroesophageal reflux disease, Gastrointestinal diseases,
• MeSH
• Cost-Benefit Analysis * MeSH
• Gastroesophageal Reflux * diagnosis   therapy   economics   drug therapy   MeSH
• Proton Pump Inhibitors * therapeutic use   economics   MeSH
• Humans MeSH
• Cost of Illness MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Systematic Review MeSH
• Names of Substances
• Proton Pump Inhibitors * MeSH

BACKGROUND: Adherence to Helicobacter pylori (H. pylori) eradication treatment is a cornerstone for achieving adequate treatment efficacy. OBJECTIVE: To determine which factors influence compliance with treatment. METHODS: A systematic prospective non-interventional registry (Hp-EuReg) of the clinical practice of European gastroenterologists. Compliance was considered adequate if ≥90% drug intake. Data were collected until September 2021 using the AEG-REDCap e-CRF and were subjected to quality control. Modified intention-to-treat analyses were performed. Multivariate analysis carried out the factors associated with the effectiveness of treatment and compliance. RESULTS: Compliance was inadequate in 646 (1.7%) of 38,698 patients. The non-compliance rate was higher in patients prescribed longer regimens (10-, 14-days) and rescue treatments, patients with uninvestigated dyspepsia/functional dyspepsia, and patients reporting adverse effects. Prevalence of non-adherence was lower for first-line treatment than for rescue treatment (1.5% vs. 2.2%; p < 0.001). Differences in non-adherence in the three most frequent first-line treatments were shown: 1.1% with proton pump inhibitor + clarithromycin + amoxicillin; 2.3% with proton pump inhibitor clarithromycin amoxicillin metronidazole; and 1.8% with bismuth quadruple therapy. These treatments were significantly more effective in compliant than in non-compliant patients: 86% versus 44%, 90% versus 71%, and 93% versus 64%, respectively (p < 0.001). In the multivariate analysis, the variable most significantly associated with higher effectiveness was adequate compliance (odds ratio, 6.3 [95%CI, 5.2-7.7]; p < 0.001). CONCLUSIONS: Compliance with Helicobacter pylori eradication treatment is very good. Factors associated with poor compliance include uninvestigated/functional dyspepsia, rescue-treatment, prolonged treatment regimens, the presence of adverse events, and the use of non-bismuth sequential and concomitant treatment. Adequate treatment compliance was the variable most closely associated with successful eradication.

• Keywords
• adherence, adverse effects, bismuth, dyspepsia, effectiveness, efficacy, first line, rate, regimens, rescue,
• MeSH
• Amoxicillin * therapeutic use   administration & dosage   MeSH
• Anti-Bacterial Agents * therapeutic use   adverse effects   MeSH
• Bismuth therapeutic use   administration & dosage   adverse effects   MeSH
• Adult MeSH
• Dyspepsia drug therapy   microbiology   MeSH
• Helicobacter pylori * drug effects   MeSH
• Assessment of Medication Adherence * MeSH
• Helicobacter Infections * drug therapy   MeSH
• Proton Pump Inhibitors * therapeutic use   administration & dosage   MeSH
• Clarithromycin therapeutic use   MeSH
• Drug Therapy, Combination * MeSH
• Middle Aged MeSH
• Humans MeSH
• Metronidazole therapeutic use   administration & dosage   MeSH
• Prospective Studies MeSH
• Registries * MeSH
• Aged MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Europe MeSH
• Names of Substances
• Amoxicillin * MeSH
• Anti-Bacterial Agents * MeSH
• Bismuth MeSH
• Proton Pump Inhibitors * MeSH
• Clarithromycin MeSH
• Metronidazole MeSH

BACKGROUND: Dupilumab is a human monoclonal antibody that blocks interleukin-4 and interleukin-13 pathways and has shown efficacy in five different atopic diseases marked by type 2 inflammation, including eosinophilic esophagitis in adults and adolescents. METHODS: In this phase 3 trial, we randomly assigned, in a 2:2:1:1 ratio, patients 1 to 11 years of age with active eosinophilic esophagitis who had had no response to proton-pump inhibitors to 16 weeks of a higher-exposure or lower-exposure subcutaneous dupilumab regimen or to placebo (two groups) (Part A). At the end of Part A, eligible patients in each dupilumab group continued the same regimen and those in the placebo groups were assigned to higher-exposure or lower-exposure dupilumab for 36 weeks (Part B). At each level of exposure, dupilumab was administered in one of four doses tiered according to baseline body weight. The primary end point was histologic remission (peak esophageal intraepithelial eosinophil count, ≤6 per high-power field) at week 16. Key secondary end points were tested hierarchically. RESULTS: In Part A, histologic remission occurred in 25 of the 37 patients (68%) in the higher-exposure group, in 18 of the 31 patients (58%) in the lower-exposure group, and in 1 of the 34 patients (3%) in the placebo group (difference between the higher-exposure regimen and placebo, 65 percentage points [95% confidence interval {CI}, 48 to 81; P<0.001]; difference between the lower-exposure regimen and placebo, 55 percentage points [95% CI, 37 to 73; P<0.001]). The higher-exposure dupilumab regimen led to significant improvements in histologic, endoscopic, and transcriptomic measures as compared with placebo. The improvements in histologic, endoscopic, and transcriptomic measures between baseline and week 52 in all the patients were generally similar to the improvements between baseline and week 16 in the patients who received dupilumab in Part A. In Part A, the incidence of coronavirus disease 2019, nausea, injection-site pain, and headache was at least 10 percentage points higher among the patients who received dupilumab (at either dose) than among those who received placebo. Serious adverse events were reported in 3 patients who received dupilumab during Part A and in 6 patients overall during Part B. CONCLUSIONS: Dupilumab resulted in histologic remission in a significantly higher percentage of children with eosinophilic esophagitis than placebo. The higher-exposure dupilumab regimen also led to improvements in measures of key secondary end points as compared with placebo. (Funded by Sanofi and Regeneron Pharmaceuticals; EoE KIDS ClinicalTrials.gov number, NCT04394351.).

• MeSH
• Child MeSH
• Double-Blind Method MeSH
• Eosinophilic Esophagitis * drug therapy   immunology   pathology   MeSH
• Eosinophils immunology   pathology   MeSH
• Esophagus drug effects   immunology   pathology   MeSH
• Antibodies, Monoclonal, Humanized * therapeutic use   adverse effects   MeSH
• Remission Induction MeSH
• Proton Pump Inhibitors therapeutic use   MeSH
• Injections, Subcutaneous MeSH
• Interleukin-13 antagonists & inhibitors   MeSH
• Interleukin-4 antagonists & inhibitors   MeSH
• Infant MeSH
• Humans MeSH
• Child, Preschool MeSH
• Treatment Outcome MeSH
• Dose-Response Relationship, Drug MeSH
• Check Tag
• Child MeSH
• Infant MeSH
• Humans MeSH
• Male MeSH
• Child, Preschool MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial, Phase III MeSH
• Multicenter Study MeSH
• Randomized Controlled Trial MeSH
• Names of Substances
• dupilumab MeSH Browser
• Antibodies, Monoclonal, Humanized * MeSH
• Proton Pump Inhibitors MeSH
• Interleukin-13 MeSH
• Interleukin-4 MeSH

BACKGROUND: Concomitant medications may potentially affect the outcome of cancer patients. In this sub-analysis of the ARON-2 real-world study (NCT05290038), we aimed to assess the impact of concomitant use of proton pump inhibitors (PPI), statins, or metformin on outcome of patients with metastatic urothelial cancer (mUC) receiving second-line pembrolizumab. METHODS: We collected data from the hospital medical records of patients with mUC treated with pembrolizumab as second-line therapy at 87 institutions from 22 countries. Patients were assessed for overall survival (OS), progression-free survival (PFS), and overall response rate. We carried out a survival analysis by a Cox regression model. RESULTS: A total of 802 patients were eligible for this retrospective study; the median follow-up time was 15.3 months. PPI users compared to non-users showed inferior PFS (4.5 vs. 7.2 months, p = 0.002) and OS (8.7 vs. 14.1 months, p < 0.001). Concomitant PPI use remained a significant predictor of PFS and OS after multivariate Cox analysis. The use of statins or metformin was not associated with response or survival. CONCLUSIONS: Our study results suggest a significant prognostic impact of concomitant PPI use in mUC patients receiving pembrolizumab in the real-world context. The mechanism of this interaction warrants further elucidation.

• Keywords
• ARON-2 study, Immunotherapy, Metformin, Proton pump inhibitors, Statins, Urothelial cancer,
• MeSH
• Proton Pump Inhibitors MeSH
• Carcinoma, Transitional Cell * MeSH
• Humans MeSH
• Metformin * therapeutic use   MeSH
• Urinary Bladder Neoplasms * MeSH
• Retrospective Studies MeSH
• Hydroxymethylglutaryl-CoA Reductase Inhibitors * therapeutic use   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Proton Pump Inhibitors MeSH
• Metformin * MeSH
• pembrolizumab MeSH Browser
• Hydroxymethylglutaryl-CoA Reductase Inhibitors * MeSH