Therapeutic Advances in Gastroenterology最新文献

Background: Infliximab (IFX) and vedolizumab (VDZ), frequently used biologics in inflammatory bowel disease (IBD), are available as intravenous (IV) and subcutaneous (SC) formulations; however, comparative data are limited.

Objectives: To compare the rates of discontinuation due to lack of efficacy during maintenance treatment with infliximab (subcutaneous) and vedolizumab (intravenous and subcutaneous) in patients with moderate-to-severe IBD.

Design: Systematic literature review and meta-analysis.

Data sources and methods: Three medical databases, PubMed, Embase, and the Cochrane Library, were systematically searched from January 2010 to May 2024 to identify phases I-III randomized controlled trials. The primary outcome was discontinuation of study drug due to lack of efficacy (per definitions used in the included studies) during maintenance treatment (PROSPERO number CRD42023438330). Rates of discontinuation due to adverse events during maintenance treatment were examined in additional exploratory analyses.

Results: We identified three eligible clinical trials in IBD for subcutaneous infliximab (591 patients) and five for vedolizumab (intravenous and subcutaneous formulations; 2117 patients). Rates of discontinuation due to lack of efficacy (per individual study definition) were significantly lower in patients treated with subcutaneous infliximab (0.05 (95% confidence interval (CI): 0.03, 0.06)) than in patients treated with vedolizumab (0.29 (95% CI: 0.20, 0.38)); rates remained significantly lower with subcutaneous infliximab versus vedolizumab, respectively, in the subgroups of patients with Crohn's disease (0.05 (95% CI: 0.02, 0.07) vs 0.37 (95% CI: 0.27, 0.47)) or ulcerative colitis (0.05 (95% CI: 0.02, 0.07) vs 0.24 (95% CI: 0.11, 0.36)). Rates of discontinuation due to adverse events were lower in subcutaneous infliximab-treated patients (0.04 (95% CI: 0.02, 0.05) than in vedolizumab-treated patients (0.08 (95% CI: 0.05, 0.11)).

Conclusion: In this meta-analysis, rates of discontinuation due to lack of efficacy during maintenance treatment were lower with subcutaneous infliximab than with vedolizumab (intravenous and subcutaneous formulations) in patients with moderate-to-severe IBD.

Trial registration: PROSPERO number CRD42023438330.

Following the expiration of the adalimumab originator patent, there has been a rapid increase in the availability and uptake of adalimumab biosimilars. While chemically and clinically similar in effects, there are substantial non-pharmacological differences in these products. This global review compares the originator versus currently available adalimumab biosimilars, focusing on variations in formulations and patient support systems across different countries. The goal is to provide prescribers with guidance on selecting the most appropriate products. Data on adalimumab biosimilars were collected from global medication registries and Product Information documents, supplemented by direct inquiries to pharmaceutical companies, with data collection completed in September 2024. Experts from nine countries assessed the local patient support system and collaborated to illustrate the diversity of adalimumab. Including the originator, there are 29 adalimumab products available globally. We highlighted products with favorable characteristics, including delivery device, concentration, citrate content, the range of dosages, latex content, and shelf life. Patient support services helped to differentiate these products further, to capture market share. Among the reviewed countries, Australia, the United States, and Canada offered the most comprehensive patient support systems, including injection training, reminders, as well as nursing and other patient support services. This review highlights the global diversity of adalimumab products, emphasizing key usability factors, such as formulation, dosing flexibility, shelf life, and patient support. A comparative table is provided to aid clinicians in selecting the most appropriate option based on individual patient needs.

Background: Evidence suggests a relationship between ustekinumab (UST) concentrations and therapeutic outcomes in inflammatory bowel disease.

Objectives: This study aimed to evaluate the association between UST concentrations during the induction phase and treatment outcomes at week 24 in patients with Crohn's disease (CD) and ulcerative colitis (UC). The primary outcome was endoscopic remission at week 24, defined as a simple endoscopic score (SES-CD) ⩽2 for CD and a Mayo endoscopic score = 0 for UC. Secondary outcomes included endoscopic response, clinical remission, and treatment persistence.

Design: This was a prospective observational study assessing clinical and endoscopic outcomes in CD and UC patients starting UST therapy.

Methods: Consecutive patients with CD and UC were included at the initiation of UST treatment. Trough UST concentrations were measured at weeks 8, 16, and 24 after the first intravenous dose, and the main outcomes were assessed at week 24. Endoscopic and clinical parameters were used to evaluate treatment efficacy and persistence.

Results: Seventy patients (45 with CD) were enrolled. Those achieving endoscopic remission and response at week 24 had higher UST levels at week 8 (4.5 vs 2.6 μg/mL, p = 0.0028; 4.1 vs 2.4 μg/mL, p = 0.0024, respectively). Patients with UST concentrations in the fourth quartile (Q4) at week 8 (>4.5 μg/mL) had higher rates of endoscopic remission (66.7% (Q4) vs 20% (Q1); 33.3% (Q2); 28.6% (Q3); p = 0.012). A UST concentration threshold of 4.5 μg/mL at week 8 was the best predictor of endoscopic remission (AUC = 0.7, sensitivity 54.5%, specificity 83.8%), while 3.5 μg/mL predicted endoscopic response (AUC = 0.732, sensitivity 53.8%, specificity 87%). Longer disease duration correlated with a higher risk of UST discontinuation (odds ratio, 1.034, 95% confidence interval, 1.002-1.068, p = 0.035). Higher UST concentrations in Q4 did not result in greater drug persistence (p = 0.319).

Conclusion: UST concentrations at week 8 were positively associated with endoscopic outcomes at week 24, with a threshold of 4.5 μg/mL reliably predicting endoscopic remission. Further randomized clinical trials are warranted to explore whether optimizing UST treatment based on post-induction concentrations can enhance therapeutic outcomes.

Background: Immune checkpoint inhibitors (ICIs), including Pembrolizumab, Nivolumab, Sintilimab, Tislelizumab, and Sugemalimab, have been approved in China as first-line treatments for advanced HER2-negative gastric cancer (GC) and gastroesophageal junction cancer (GEJC). However, the latest COMPASSION 15 study showed that Cadonilimab in combination with chemotherapy provided significant survival benefits.

Objective: This study aims to evaluate the cost-effectiveness of Cadonilimab plus chemotherapy versus chemotherapy alone and the ICIs approved in China for first-line treatment of advanced HER2-negative gastric cancer or gastroesophageal junction carcinoma (GC/GEJC) from the perspective of Chinese payers.

Design: The cost-effectiveness analysis.

Methods: Based on the research data from COMPASSION-15, KEYNOTE-859, CheckMate-649, ORIENT-16, RATIONALE-305, and GEMSTONE-303, we constructed a 15-year Markov model to evaluate the cost and health outcomes of Cadonilimab combined with chemotherapy versus chemotherapy alone and other ICIs in advanced HER2-negative GC and GEJC. This evaluation includes total cost, life years (LYs), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER).

Results: Cadonilimab produced 0.73 QALYs (1.10 LYs) at a cost of $26,591. It required an additional investment of $17,826 to gain 0.25 QALYs (0.37 LYs), resulting in an ICER of $72,492.29 per QALY compared to chemotherapy alone. In comparison, other ICIs approved in China-Pembrolizumab, Nivolumab, Sintilimab, Tislelizumab, and Sugemalimab-incurred total costs of $11,735, $13,970, $16,346, $10,765, and $14,857, respectively, generating 0.68 QALYs (1.04 LYs), 0.69 QALYs (1.04 LYs), 0.73 QALYs (1.12 LYs), 0.82 QALYs (1.26 LYs), and 0.81 QALYs (1.25 LYs). Sensitivity analysis revealed that the cost of Cadonilimab, the utility value of progressive disease, and the risk of platelet decline in the Cadonilimab group were the most influential factors affecting the model's stability. At a willingness-to-pay threshold of $37,386, Cadonilimab is not a cost-effective option for the first-line treatment of advanced GE/GEJC.

Conclusion: Cadonilimab is not a cost-effective option for the first-line treatment of advanced HER2-negative GC/GEJC. In comparison to other ICIs approved in China, Tislelizumab appears to be a more favorable option.

There exists a significant care gap in the diagnosis, treatment, and management of inflammatory bowel diseases (IBD) in Latin America compared to the United States and Europe. This review aims to assess the clinical effectiveness of advanced therapies for patients with moderate to severe ulcerative colitis (UC) and Crohn's disease (CD) in Latin America. We conducted a targeted literature review of studies reporting clinical outcomes of advanced IBD therapies in Latin American countries. After applying pre-defined inclusion and exclusion criteria, 14 articles were included. Data were extracted regarding patient populations, therapeutic agents, clinical outcomes, and geographic distribution. The majority of studies focused on biologic therapies, including adalimumab, infliximab, ustekinumab, and vedolizumab. These therapies demonstrated favorable clinical remission and response rates in Brazil, Argentina, Mexico, and Colombia for both UC and CD. Reported outcomes were largely consistent with observational data from North America and Europe, supporting the generalizability of therapeutic efficacy across regions. Advanced therapies for IBD appear to be effective in Latin American populations, with clinical outcomes comparable to those reported globally. Increasing access to these treatments may improve patient outcomes, reduce disease burden, and potentially decrease long-term healthcare costs in the region.

Background: Despite the established efficacy of ustekinumab (UST) in Crohn's disease (CD), real-world studies reveal suboptimal treatment persistence and limited endoscopic healing. Current optimization paradigms remain constrained by suboptimal durability and escalating therapeutic demands.

Objectives: To evaluate the clinical utility and safety of intravenous (IV) ustekinumab maintenance therapy in CD.

Design: This was a single-center retrospective cohort study.

Methods: This study included CD patients receiving ⩾2 IV-UST maintenance infusions between June 2020 and October 2023 (N = 234). The protocol featured weight-based induction-equivalent dosing (260-520 mg) at response-guided intervals. The primary endpoint was the corticosteroid-free clinical remission rate at Week 24.

Results: At 24 weeks, 88.1% (185/210) achieved steroid-free remission with C-reactive protein (CRP) normalization in 90.0% (44/88). Median Harvey-Bradshaw Index decreased from 4 (interquartile range (IQR) 2-5) to 2 (IQR 1-3; p < 0.001). 52-week endoscopic remission (simplified endoscopic score for Crohn's disease ⩽3) reached 48.7% (56/115), with fecal calprotectin normalization in 33.6% (35/104). Multivariate analysis identified baseline CRP >5 mg/L (adjusted odds ratio (aOR) 3.62, 1.16-11.25), intensive dosing (⩾6 cycles/year; aOR 12.06, 1.99-73.05), and disease duration ⩾1 year (aOR 3.53, 1.08-11.54) as predictors of endoscopic non-remission. Safety analysis demonstrated 44.4% adverse event incidence (104/234) and 3.0% serious adverse events (7/234).

Conclusion: IV-UST maintenance demonstrates high rates of corticosteroid-free clinical remission and endoscopic healing with manageable safety in CD.

Background: Endoscopic ultrasonography is crucial for diagnosing solid pancreatic lesions. Tissue acquisition using rapid on-site evaluation (ROSE) significantly improves diagnostic efficiency.

Objectives: This study evaluates the efficacy of tissue acquisition from pancreatic tumors with and without ROSE.

Design: Systematic review and meta-analysis.

Data sources and methods: A search was conducted in PubMed and other databases covering the period up to February 2024. Eligible randomized control trials (RCTs) reporting data on comparing the efficacy of ROSE and no ROSE were included in this study. We compare the two groups using odd ratios (OR) and mean difference approach.

Results: This meta-analysis included seven RCTs, including 1723 patients (909 in the ROSE and 814 in the no-ROSE group) with pancreatic masses. The fundamental characteristics of the studies were almost identical in both groups. There was no significant difference (p > 0.05) in the mean procedure time (1.49 min, 95% CI: -2.76, 5.75), needle passes (-0.34 passes, 95% CI: -1.00, 0.32), The OR of sample adequacy 1.34 (95% CI: 0.29, 6.25), diagnostic sensitivity 1.95 (95% CI: -0.79, 4.82), accuracy 1.28 (95% CI 0.54, 3.00), negative predictive value 1.05 (95% CI 0.54, 2.06), and adverse events 0.87 (95% CI 0.16, 4.87) with significant higher heterogeneity. Subgroup analysis also showed no difference between the FNA + ROSE versus FNA and FNB.

Conclusion: The ROSE and non-ROSE approaches showed similar outcomes regarding mean needle passes, sample adequacy, diagnostic accuracy, and adverse event rates.

Trial registration: This systematic review and meta-analysis was registered at PROSPERO (https://www.crd.york.ac.uk/PROSPERO/) with PROSPERO Number CRD42024520977.

Background: Music has been shown to reduce pain and anxiety in patients undergoing colonoscopy. Distraction, a newer technique with less available evidence, has shown similar effective outcomes.

Objectives: This systematic review and meta-analysis evaluate the current evidence available on music and task distraction and its potential to reduce pain in colonoscopy.

Design: The study was performed within PRISMA guidelines and registered with PROSPERO. Inclusion criteria comprised peer-reviewed randomised controlled trial publications in English. Exclusion criteria comprised duplicate studies, non-peer-reviewed and non-English studies.

Methods: A literature search was conducted with Medline, Embase, Cochrane and Google. Two independent clinicians reviewed the studies to avoid inclusion bias. Visual analogue score mean pain and Spielberger State-Trait Anxiety Inventory (STAI) mean anxiety were collected. Inverse variance DerSimonian-led meta-analytical approach was conducted using a random effects model and statistical software STATA.

Results: Music intervention reported a significant (p < 0.05) weighted mean reduction of 1.50 for pain scores (95% CI 0.69-2.31) and a significant weighted mean reduction of 3.56 for anxiety scores (95% CI 0.86-6.27).Distraction intervention reported a significant weighted mean reduction of 1.59 for pain scores (95% CI 0.79-2.39) and a significant weighted mean reduction of 7.49 for anxiety scores (95% CI 3.64-11.35). There was high heterogeneity recorded for both pain and anxiety studies (I² >90%).

Conclusion: Music and distraction intervention has the ability to be introduced at minimal cost. Furthermore, no changes to endoscopy infrastructure are required. This allows a clinical real-world option that is immediately implementable for patients. This meta-analysis has demonstrated that there is a potential role for music and task distraction to reduce pain and anxiety for patients undergoing a colonoscopy. It supports a low cost and safe option for patients who may not be eligible for sedation. Whilst the body of evidence is growing, it is plausible to claim these interventions can be implemented and established into daily clinical practice.

Background: As no direct comparison is available between drugs to prevent endoscopic postoperative recurrence (POR) in Crohn's disease (CD), hierarchizing these therapeutic options remains challenging.

Objectives: We aimed to compare the effectiveness of treatments to prevent CD endoscopic POR.

Design: Systematic review and network meta-analysis using a random-effects model.

Data sources and methods: We include studies comparing treatments to prevent CD POR according to PRISMA guidelines. The primary endpoint was endoscopic POR (Rutgeerts score ⩾i2). Surface under the cumulative ranking (SUCRA) was used to hierarchize the treatments.

Results: Twenty studies were included (2414 patients). Overall heterogeneity was moderate (τ = 0.34). Ustekinumab (odds ratio (OR) = 0.23 (0.07-0.70); OR = 0.29 (0.08-0.99)), vedolizumab (OR = 0.17 (0.05-0.59); OR = 0.22 (0.06-0.85)), infliximab (OR = 0.18 (0.36-0.88); OR = 0.23 (0.09-0.54)), and adalimumab (OR = 0.17 (0.07-0.42); OR = 0.22 (0.08-0.59)) were more effective to prevent endoscopic POR than placebo or 5-ASA, respectively, contrary to thiopurines (OR = 0.52 (0.22-1.24); OR = 0.66 (0.25-1.76)). Adalimumab (OR = 0.33 (0.15-0.74)) and infliximab (OR = 0.34 (0.13-0.87)) were more effective than thiopurines. While no difference was observed between the four biologics, adalimumab (SUCRA = 0.81), infliximab (SUCRA = 0.80), vedolizumab (SUCRA = 0.79), and ustekinumab (SUCRA = 0.72) had the highest likelihood of being the most effective drug, contrary to thiopurines (SUCRA = 0.41), 5-ASA (SUCRA = 0.24), or placebo (SUCRA = 0.16).

Conclusion: This network meta-analysis confirms the efficacy of anti-TNF agents, vedolizumab, and ustekinumab in preventing endoscopic CD POR without any difference between them. When a prophylactic therapy is needed, biologics should be preferred to 5-ASA or thiopurines.

Trial registration: PROSPERO registration number CRD42024555528.