Therapeutic Advances in Gastroenterology最新文献

Background: Ramucirumab in combination with paclitaxel has demonstrated substantial antitumor activity in the treatment of advanced human epidermal growth factor receptor-2 (HER2)-negative gastric cancer (GC) or gastro-esophageal junction cancer (GEJC). However, the cost-effectiveness of this regimen in this patient population remains uncertain, particularly within the Chinese healthcare context.

Objective: This study aimed to assess the cost-effectiveness of ramucirumab plus paclitaxel as a switch maintenance regimen compared to continuing first-line chemotherapy for patients with advanced HER2-negative GC or GEJC, from the perspective of the Chinese healthcare system.

Design: A health economic evaluation was conducted to compare two treatment strategies.

Methods: A partitioned survival model was developed to project the disease progression of HER2-negative GC or GEJC. Data for overall survival and progression-free survival were extracted from the ARMANI trial and were extrapolated to project long-term survival outcomes. Direct medical costs and utility values were gathered. The main outcome measures, including the cost, utility, and incremental cost-utility ratio (ICUR), were used to determine the cost-effectiveness of the ramucirumab plus paclitaxel as switch maintenance regimen. Sensitivity analyses, including one-way sensitivity analysis (OWSA) and probabilistic sensitivity analysis (PSA), were performed to evaluate the robustness of the findings.

Results: The base-case analysis revealed that the ICUR for ramucirumab plus paclitaxel as a switch maintenance regimen was ¥1,097,535 per quality-adjusted life-year (QALY) compared to the continuation of first-line chemotherapy. OWSA showed that the ICUR was sensitive to variations in the cost of ramucirumab, patient weight, and the cost of subsequent treatments in the continuation of first-line chemotherapy group. Results from the PSA indicated that the switch maintenance regimen had a very low probability of cost-effectiveness, at just 0.4%. In contrast, the continuation of the first-line regimen demonstrated a high likelihood of being cost-effective, with a 99.6% probability.

Conclusion: The cost-effectiveness analysis suggested that from the Chinese healthcare system perspective, the switch maintenance regimen at current price is unlikely to be an advantageous regimen in terms of cost-effectiveness for patients with advanced HER2-negative gastric or GEJC at a willingness-to-pay threshold of ¥287,247/QALY.

Background: The value of intestinal ultrasound (IUS) in predicting treatment outcomes in ulcerative colitis (UC) remains underexplored.

Objectives: To compare the predictive accuracy of representative IUS scores for long-term endoscopic outcomes in UC.

Design: A retrospective observational study.

Methods: Consecutive UC patients initiating biologics/small-molecule drugs were enrolled. IUS examinations were performed at baseline, 4-6 months, and at the first colonoscopy reassessment (12-30 months). IUS images were reviewed, and bowel wall thickness (BWT), Milan ultrasound criteria (MUC), and International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) were recorded. Endoscopic response was assessed using the Mayo Endoscopic Score (MES), with remission defined as MES = 0 and improvement as MES ⩽1.

Results: Forty-nine patients were included. All three IUS scores showed significant correlations with concurrent MES, with IBUS-SAS demonstrating the strongest association (BWT, ρ = 0.54; MUC, ρ = 0.55; IBUS-SAS, ρ = 0.69). IBUS-SAS at 4-6 months was the most accurate predictor of long-term endoscopic remission (area under the curve (AUC) 0.767) and endoscopic improvement (AUC 0.770). On multivariable analysis, an IBUS-SAS score <25.5 at 4-6 months was the only independent predictor of endoscopic remission (odds ratio (OR) 7.6, p = 0.005), while an IBUS-SAS score <38.0 was the only independent predictor of endoscopic improvement (OR 5.8, p = 0.006).

Conclusion: The IBUS-SAS score at early follow-up may serve as a valuable predictor of long-term endoscopic outcomes in UC.

Tofacitinib, an oral Janus kinase (JAK) inhibitor, shows promise as a rescue therapy for acute severe ulcerative colitis (ASUC), a life-threatening condition marked by high colectomy rates. This narrative review synthesizes evidence from randomized controlled trials (RCTs), observational studies, and systematic reviews. The efficacy of tofacitinib has been documented, with an 83.01% day-7 response rate in the TACOS trial and 79.9%-86% 90-day colectomy-free survival in steroid-refractory ASUC. However, seven unmet needs impede the adoption of tofacitinib treatment for managing ASUC: (1) a lack of head-to-head RCTs comparing tofacitinib not only to standard rescue therapies like infliximab and ciclosporin but also to other JAK inhibitors like upadacitinib, (2) uncertainty in optimal dosing and duration, (3) ambiguity in positioning tofacitinib in the treatment algorithm, (4) undefined patient selection criteria, notably for those with prior biologic exposure, (5) limited long-term efficacy and cost-utilization data, (6) unresolved safety risks (e.g., infections, thrombosis), and (7) underexplored potential for combination therapy. These gaps undermine the widespread use of tofacitinib in reducing surgical burden and improving outcomes. Collaborative research-especially multi-center RCTs comparing tofacitinib to infliximab, ciclosporin, and next-generation JAK inhibitors-is vital for establishing evidence-based protocols. Addressing these needs could optimize tofacitinib-based ASUC management, offering a rapid, oral alternative to enhance patient care.

Background: The optimal hemodynamic threshold for portal pressure gradient (PPG) following transjugular intrahepatic portosystemic shunt (TIPS) for ascites remains uncertain.

Objective: This study aimed to elucidate the relationship between post-TIPS PPG and clinical outcomes in patients undergoing small-diameter (8-mm) TIPS for ascites.

Design: Single-center retrospective study.

Methods: From June 2015 to June 2023, consecutive patients receiving small-diameter (8-mm) TIPS for refractory or recurrent ascites were considered for inclusion retrospectively. The impact of PPG on clinical outcomes-including ascites response, overt hepatic encephalopathy (OHE), further decompensation, and mortality-was evaluated using Fine and Gray competing risk regression models, both unadjusted and adjusted for potential confounders.

Results: A total of 143 patients were included in the analysis, of whom 65.7% had refractory ascites, with a median Child-Pugh score of 9. Receiver operating characteristic (ROC) curve analysis identified post-TIPS PPG as a reliable predictor of ascites response (cutoff: 10.5 mmHg, area under curves (AUC): 0.733, p < 0.001) and OHE (cutoff: 7.5 mmHg, AUC: 0.716, p < 0.001). Univariate and multivariate Fine and Gray competing risk regression analyses further revealed that patients with PPG between 8 and 10 mmHg had favorable outcomes, including a lower incidence of ascites (>10 vs 8-10 mmHg: hazard ratio (HR) = 5.74, 95% confidence interval (CI) 2.11-15.58, p < 0.001), a reduced risk of OHE (<8 vs 8-10 mmHg: HR = 2.87, 95% CI 1.29-6.35, p = 0.010), and a decreased risk of further decompensation (>10 vs 8-10 mmHg: HR = 2.78, 95% CI 1.43-5.41, p = 0.003; <8 vs 8-10 mmHg: HR = 2.42, 95% CI 1.20-4.90, p = 0.014) after TIPS placement.

Conclusion: This study revealed that post-TIPS PPG was associated with clinical outcomes in patients with refractory or recurrent ascites undergoing small-diameter TIPS. A post-TIPS PPG of 8-10 mmHg seems to be the optimal range, effectively controlling ascites without significantly increasing the risk of shunt-related hepatic encephalopathy, while also reducing the risk of further decompensation.

Background: The influence of social support upon several diseases has been studied and has been found to be beneficial, either by facilitating adjustment to the disease and improving its management, or by influencing the biological responses that lead to disorders.

Objective: The aim of this study was to investigate the role of received social support and its different types (informational, material and emotional) in people with varying stages of Crohn's disease (CD), compared to a sample of healthy individuals.

Design: An observational, double case-control study was conducted using validated scales to assess the impact of received social support and its different types upon CD.

Methods: The sample was divided into three groups: healthy individuals, CD patients experiencing a flare-up and CD patients in remission. Study variables were measured in the three groups, and a multivariate analysis of variance was performed to examine statistical significance. In addition, post hoc analyses were performed using either Tukey's test or the Games-Howell test (depending on the homogeneity of variances) to determine which groups differed.

Results: The principal results revealed statistically significant differences between the groups studied regarding received social support (p = 0.001), satisfaction with this support (p = 0.018), material support type (p = 0.002) and informational support type (p = 0.016). In the majority of cases, the most significant differences were observed between the group of healthy individuals and CD patients in remission, and between the latter group and CD patients experiencing a flare-up.

Conclusion: We propose directly engaging with CD patients in remission to thereby increase their perceived level of received social support, to consequently increase their satisfaction with such support. We also suggest specific interactions to increase the perception of material and informational support. This approach is also directly linked to the type of support provided by healthcare professionals.

Background: Inflammatory bowel disease (IBD) develops from a dysregulated immune response influenced by environmental exposures. Radon, a radioactive gas, has known biological effects, but its role in IBD remains unexplored.

Objectives: To examine the association between residential radon exposure and the risk and clinical course of IBD.

Design: A case-control study with 1-year prospective follow-up of cases.

Methods: We included 178 newly diagnosed IBD patients and 178 age- and sex-matched controls in Santiago de Compostela, Spain, from June 2020 to September 2023. Residential radon levels were measured using passive detectors for 3 months. Outcomes included IBD diagnosis, disease extent, hospitalizations, and flares. Logistic regression was used to estimate odds ratios adjusted for age and sex.

Results: Median residential radon was 144.5 Bq/m³ in IBD cases and 189.5 Bq/m³ in controls. Higher radon levels were associated with reduced odds of IBD (OR 0.5 for 100-299 and >299 Bq/m³ vs 0-99 Bq/m³). No significant association was found between radon levels and hospitalizations or flares. Among ulcerative colitis patients, higher radon was linked to more extensive disease.

Conclusion: Higher residential radon exposure might be inversely associated with IBD risk. However, it does not appear to influence disease progression. Further studies are needed to confirm these findings, since this is the first study on this topic, and chance or selection bias might be present.

Background: The advent of immunotherapy has significantly revolutionized therapies for advanced esophageal cancer (EC). However, clinical data on combining immune checkpoint inhibitors (ICIs) and radiotherapy (RT) in advanced EC remain insufficient.

Objectives: This study aimed to evaluate the effectiveness and safety of combining immunotherapy and radiation as a second or subsequent line of treatment for advanced EC.

Design and methods: We retrospectively analyzed patients with advanced EC who received late-line ICIs and categorized them into two subgroups based on whether they received RT. The differences in survival and adverse events (AEs) were evaluated. Inverse probability of treatment weighting (IPTW) and 1:1 propensity-score matching (PSM) analysis were used to minimize confounding.

Results: The analysis included data from 131 patients. The median progression-free survival (mPFS) was 9.1 months in the RT group, compared to 4.3 months in the non-radiotherapy (NRT) group (p = 0.0087). The median overall survival (mOS) was 13.5 months in the RT group, which is longer than the 7.3 months in the NRT group (p = 0.014). IPTW and 1:1 PSM analysis also showed that the RT group has longer mOS and mPFS. Among them, a higher biologically effective dose (BED) was associated with better survival than the lower dose group (16.1 months vs 10.2 months, p = 0.048). RT was an independent factor of better overall survival and progression-free survival in multivariable analysis, regardless of whether IPTW was used. For any grade of AE, any grade neutropenia (60.7% vs 41.4%, p = 0.028) and esophagitis (21.3% vs 1.4%, p < 0.001) were more common in the RT group. However, the incidence of grade 3-4 AEs did not differ significantly.

Conclusion: Adding RT to second-line or later immunotherapy regimens for EC correlates with enhanced survival outcomes and manageable toxicity.

Background: Managing patients with primary biliary cholangitis (PBC) who demonstrate an inadequate response to ursodeoxycholic acid or experience intolerable side effects remains a significant clinical challenge.

Objectives: This study aims to investigate the efficacy and safety of peroxisome proliferator-activated receptor (PPAR) agonists in the treatment of PBC.

Design: Meta-analysis and systematic review.

Methods: A systematic search of publications in PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials was performed. Randomized controlled trials published in English that involved the treatment of PPAR agonists and reported on the levels of alkaline phosphatase (ALP), biochemical response rates, pruritus score, or severe and serious adverse events (AEs) were selected. The primary outcomes assessed were the effects of PPAR agonists on ALP levels and biochemical response rates. Secondary outcomes included the rates of severe or serious AEs and relief of pruritus.

Results: Fourteen studies with 1137 patients were included. Compared to the control group, PPAR agonists significantly reduced ALP levels by a mean difference of -155.87 U/L (95% confidence interval (CI): -208.30 to -103.44; random-effects). Patients who received PPAR agonists showed a significantly higher biochemical response rate (risk ratio (RR), 4.42; 95% CI: 2.37-8.26; random-effects). Furthermore, there was no significant difference in the rate of severe (RR, 1.05; 95% CI, 0.49-2.28) or serious AEs (RR, 1.02; 95% CI, 0.65-1.60) between the PPAR agonists and placebo groups.

Conclusion: PPAR agonists are effective and safe to treat patients with PBC.

Prospero trial registration: CRD42024545743.