Therapeutic Advances in Gastroenterology最新文献

Over the last 40 years, the role of endoscopic ultrasound (EUS) has evolved from being diagnostic to therapeutic. EUS-guided gallbladder drainage (EUS-GBD) and EUS-guided gastroenterostomy (EUS-GE) are emerging techniques in recent years; however, there are limited studies and inconsistent results regarding these techniques. In addition, EUS has become a more common alternative to traditional interventions due to its super minimally invasive nature, but the mobility of both the gallbladder and intestine makes it challenging to introduce stents. An increasing number of researchers are dedicating themselves to solving this problem, leading to the development of various assisted technologies. Consequently, this review focused on the comparison of EUS-GBD and EUS-GE with other alternative approaches and explored the various assisted techniques employed for EUS-GBD and EUS-GE.

Background: Data regarding multiple switches including reverse switching between infliximab and its biosimilars are scarce in the field of inflammatory bowel diseases (IBD).

Objectives: We investigated the clinical effectiveness as primary outcome measure after repeated switches. Secondary endpoints included C-reactive protein (CRP) levels, immunogenicity (trough levels (TL); anti-drug antibodies (ADA), safety and drug persistence.

Design: This study is a prospective, single-centre, observational cohort study. IBD patients receiving originator infliximab were switched to biosimilar SB2 and then reverse switched after 96 weeks and followed up for another 48 weeks.

Methods: Clinical disease activity (Harvey-Bradshaw-index (HBI) in Crohn's disease (CD), partial Mayo score (pMS) in ulcerative colitis (UC)), CRP, TL, ADA, therapy-discontinuations and (serious) adverse events ((S)AE)) were monitored throughout the study.

Results: Ninety-five patients (60 CD, 38 female) were enrolled. The median HBI was 2 (interquartile range (IQR) 1-4) at baseline and 2 (1-4) at week 48, resulting in a mean intra-individual change of 0.0 (standard deviation (SD) 1.5). The median pMS was 1 (IQR 0-1) at baseline and 0.5 (0-1) at week 48 resulting in a mean intra-individual change of 0.0 (SD 0.8). Clinical remission was achieved in 80% at baseline and 82% at week 48. Median CRP 2.0 mg/l (IQR 1.0-4.1) at baseline and 2.4 mg/l (1.1-5.2) at week 48 resulted in a mean change of 1.7 (SD 5.8) and no significant differences in CD (p = 0.3) and UC (p = 0.9). Median TL were 7.2 µg/ml (IQR 3.8-19.3) at baseline and 5.5 µg/ml (3.5-13.1) at week 48, resulting in a mean change of -1.0 (SD 7.4) with no statistical significance (CD p = 0.26, UC p = 0.41). De-novo-ADA were developed by 3.4%. The discontinuation rate was 14.7%. Safety signals were consistent with previous studies.

Conclusion: Reverse switching had no impact on efficacy of infliximab therapy in our cohort of IBD patients. The switch didn't influence immunogenicity or safety of therapy.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by growing incidence and prevalence around the world in the last few decades. The range of available existing treatment and strategies for its management is being implemented. Given the introduction of newly developed molecules and the lack of specific guidelines, drug positioning may represent a tough clinical challenge. UC management is mostly medical, and it has been shifting toward a more personalized approach with the aim to create a tailored strategy depending on the patient's profile. A treat-to target strategy seems to be the best approach to reach disease control as it allows to carry out therapeutic choices based on objective and specific parameters: histological, ultrasonographic, and molecular targets may add to the already used clinical, endoscopic, and biochemical targets. In addition, dual-targeted therapy has emerged as an attractive therapeutic strategy for patients not achieving remission. This review aims to provide an overview of the available strategies to raise the bar in UC.

The intestine, as a crucial organ of the human body, has remained enigmatic despite the remarkable advancements in modern medical technology. Over the past decades, the invention of endoscopic technology has made the noninvasive intervention of the intestine a reality, expanding diagnostic and therapeutic options for diseases. However, due to the single-treatment feature of endoscopic procedures, continuous or repeated medication administration, sampling, and decompression drainage within the intestine have yet to be fulfilled. These limitations persisted until the invention of colonic transendoscopic enteral tubing (TET) in 2014, which realized repeated fecal microbiota transplantation, medication administration, and decompression drainage for the treatment of colon perforation and intestinal obstruction, as well as in situ dynamic sampling. These breakthroughs have not gone unnoticed, gaining global attention and recommendations from guidelines and consensuses. TET has emerged as a novel microbial research tool that offers new paradigms for human microbiome research. This review aims to update the research progress based on TET.

Background: The acute and chronic pancreatitis (CP) can lead to severe complications like walled-off necrosis, large symptomatic pseudocyst or multiorgan failure. The treatment of these complications is multivariate and can differ from conservative, symptomatic treatment or minimal-invasive, endoscopic transgastral stenting to transgastral necrosectomy.

Objectives: This study aims to analyse the clinical course for patients that develop local complications of severe pancreatitis.

Design: This is a retrospective observational single-centre study on 46 patients with severe pancreatitis.

Methods: In this retrospective single-centre study, 46 out of 474 inpatients from January 2014 to December 2020, who were treated because of an acute or CP, developed acute pancreatitis complications and could be included. We analysed and compared the clinical course of different treatments (lumen apposing metal stents, transgastral double pigtail stent, endoscopic retrograde cholangiopancreatography, operation, conservative treatment) and different complications (walled-off necrosis (WON), pancreatic pseudocyst (PPC)).

Results: Forty-six patients developed an acute complication due to severe pancreatitis. Twenty-seven patients developed a WON, while 19 patients suffered from PPC. 48% of the whole cohort had an alcoholic aetiology of pancreatitis. 78% were treated with antibiotics, 48% suffered from infected pancreatitis and 22% needed intensive care treatment. WON patients more often had a longer hospitalization of more than 21 days. PPC patients were correlated with an alcoholic aetiology, whereas WON patients were inversely correlated with an alcoholic aetiology. Increased lactate dehydrogenase, lipase, and C-reactive protein levels as well as leucocyte count could be associated with a higher probability to exhibit a WON instead of another local complication. The mortality rate was low with 7% in our study.

Conclusion: WON and PPC differ in certain patients and laboratory characteristics such as aetiology, elevated laboratory values, antibiotic treatment or the duration of hospitalization. Invasive treatment is not required in all severe pancreatitis cases.

Background: Patients with HER2-negative locally advanced or unresectable metastatic gastric cancer and gastroesophageal junction (G/GEJ) adenocarcinoma have limited first-line treatment options and a poor prognosis. The GLOW clinical trial showed that zolbetuximab plus capecitabine plus oxaliplatin (CAPOX) significantly prolonged these patients' overall survival (OS) and progression-free survival (PFS).

Objectives: This study evaluated the cost-effectiveness of zolbetuximab plus CAPOX as a first-line treatment for HER2-negative locally advanced or unresectable metastatic G/GEJ adenocarcinoma in the United States and China.

Design: The cost-effective analysis.

Methods: Based on the GLOW clinical trial data (NCT03653507), we constructed a 10-year Markov model to assess the cost-effectiveness of the zolbetuximab or placebo plus CAPOX treatment regimen. Only direct medical costs were considered. The primary outcomes of the model were quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs). One-way and probabilistic sensitivity analyses were employed to assess the robustness of the model.

Results: In the United States, zolbetuximab plus CAPOX added 0.24 QALYs and resulted in an incremental cost of $196,791.11 compared with placebo plus CAPOX, which had an ICER of $821,515.65 per QALY gained. For China, the zolbetuximab group gained 0.23 QALYs at an incremental cost of $62,822.69, resulting in an ICER of $273,568.01/QALY. One-way sensitivity analysis revealed that the results were most sensitive to the price of zolbetuximab. Zolbetuximab plus CAPOX had 0% cost-effectiveness at the willingness-to-pay thresholds of $150,000/QALY in the United States and $38,188/QALY in China.

Conclusion: Zolbetuximab plus CAPOX may be a cost-effective option for patients with locally advanced, unresectable, or metastatic G/GEJ adenocarcinoma when the price of zolbetuximab reduced by 83.37% ($367.7/100 mg) in the United States and 82.25% ($110.8/100 mg) in China.

Inflammatory bowel diseases (IBD) and psoriasis are chronic inflammatory conditions belonging to the heterogeneous group of immune-mediated inflammatory diseases (IMIDs). A significant bidirectional link between these two entities has been observed, conditioning an increased risk of IBD in patients with psoriasis and vice-versa. Biological therapies used for IBD may lead to the occurrence of psoriasis as a "paradoxical reaction." The objective of this study is to analyze the current evidence on the association between psoriasis and IBD, particularly finding case reports of the appearance or aggravation of psoriasis under therapy with interleukin-12/23 (IL-12/23) and IL-23 inhibitors. We conducted comprehensive research to identify studies examining the association between psoriasis and IBD and to find case presentations that reported the appearance or aggravation of psoriasis under biologic therapy with IL-12/23 and IL-23 inhibitors up to March 2024. Clinical trials for IL-12/23 and IL-23 inhibitors in IBD were analyzed to find cases of paradoxical psoriasis as registered adverse events. The sources of evidence are PubMed and ClinicalTrials.gov. For each included case report, data on patient characteristics concerning their age, sex, and comorbidities were selected. Moreover, information regarding the indication for biologic therapy, time to onset of paradoxical psoriasis after starting treatment, clinical presentation, and management of the paradoxical psoriasis was extracted. We found 10 reported cases of ustekinumab-induced new-onset or worsening psoriasis and one reported case of paradoxical psoriasis induced by risankizumab in the literature. Four cases of paradoxical psoriasis have been also registered in clinical trials involving ustekinumab treatment in IBD. Psoriasis can constitute a rare paradoxical adverse event of ustekinumab treatment, but further studies are needed to better clarify the cytokine imbalance that leads to this phenomenon induced by inhibition of IL-12/23 and IL-23. Still, few real-world data exist to draw any conclusions, but risankizumab may positively treat psoriasis induced by ustekinumab.

Background: The Crohn's Disease (CD) Activity Index (CDAI), Inflammatory Bowel Disease (IBD) Questionnaire (IBDQ), and IBD-Fatigue (IBD-F) scale are useful patient-reported outcome (PRO) tools for assessing the treatment benefits of vedolizumab (VDZ) beyond clinical trial endpoints in patients with CD.

Objectives: To assess clinical response, clinical remission, steroid-free remission, changes from baseline for PROs, and safety in a real-world cohort of patients with moderate-to-severe active CD treated with VDZ.

Design: POLONEZ II was a multicenter, observational, prospective study across 10 Polish centers from April 2020 to October 2023 for 54 weeks in patients with CD eligible for reimbursed VDZ.

Methods: Primary endpoints at week 54 (W54) were clinical response (⩾70-point reduction in CDAI and >25% reduction vs baseline), remission (CDAI score ⩽150), and steroid-free remission. Other outcomes were changes in PROs (CDAI score and health-related quality of life) and safety. Kaplan-Meier survival analyses were performed.

Results: Of 98 patients with CD, the mean age was 35.2 years, 57.1% were male, and 72.4% had an ileocolonic disease. At W54 (n = 98), 63.3% of patients achieved clinical response, 48.0% remission, and 36.0% steroid-free remission. The durability of clinical response, remission, and steroid-free remission (W14-W54) were 68.9%, 62.9%, and 57.1%, respectively. By W54, a significant reduction in the PROs, such as the total CDAI score (p < 0.001), stool frequency (p < 0.001), abdominal pain score (p < 0.001), IBDQ (p < 0.001), IBD-F (p < 0.05), and fatigue impact on daily activities (p < 0.001), was observed. During VDZ treatment, arthralgia (23.7%-8.7%) and anemia (22.6%-15.9%) decreased between baseline and W54. Non-serious adverse events (SAEs; 12.2%), SAEs (7.1%), and VDZ-related rash (1.0%) were reported. Mean CD-related hospitalization duration decreased from baseline (10.2 days) to the end of the study (5.3 days).

Conclusion: POLONEZ II demonstrated long-term real-world benefits of VDZ toward effectiveness, safety, and improved PROs and patients' quality of life.

Trial registration: ENCePP (EUPAS32716).

The rapid emergence of inflammatory bowel disease (IBD) in Asia in the last two decades is anticipated to pose significant challenges to the healthcare systems of developing countries including India. Several epidemiological factors in the Asia Pacific region have been explored as risk factors for the development of IBD. In this narrative review, we discuss the evolution of adult-onset and paediatric IBD in South Asia and India, in relation to the current global epidemiology, over the last decade. The focus lies on the changing epidemiological landscape of IBD in Asia which signals a paradigm shift in the disease trajectory of a chronic, relapsing, complex disease. We enumerate the disease burden of IBD in India and Asia, analyse the risk factors for its recent rise in incidence and briefly discuss the unique entity of very early-onset IBD. We also list the locoregional challenges in diagnosis and management along with suggestions to overcome them. We highlight the lacunae in data which warrants further research. The anticipated infrastructural challenges and disease evolution are likely to be similar in most newly industrialized countries across South Asia. A combined effort led by IBD experts in the region to understand the true disease burden is important. A strong collaborative network on research and formulation of preventive strategies relevant to the region will help reduce the burden in the future.