Search

Crohn's disease (CD) is a chronic, complex inflammatory disorder of the gastrointestinal tract that presents significant therapeutic challenges. Despite the availability of a wide range of treatments, many patients experience primary non-response, secondary loss of response, or adverse events, limiting the overall effectiveness of current therapies. Clinical trials often report response rates below 60%, partly due to stringent inclusion criteria. Emerging therapies that target novel pathways offer promise in overcoming these limitations. This review explores the latest investigational drugs in phases I, II, and III clinical trials for treating both luminal and perianal CD. We highlight promising therapies that target known mechanisms, including selective Janus kinase inhibitors, anti-adhesion molecules, tumor necrosis factor inhibitors, and IL-23 selective inhibitors. In addition, we delve into novel therapeutic strategies such as sphingosine-1-phosphate receptor modulators, miR-124 upregulators, anti-fractalkine (CX3CL1), anti-TL1A, peroxisome proliferator-activated receptor gamma agonists, TGFBRI/ALK5 inhibitors, anti-CCR9 agents, and other innovative small molecules, as well as combination therapies. These emerging approaches, by addressing new pathways and mechanisms of action, have the potential to surpass the limitations of existing treatments and significantly improve CD management. However, the path to developing new therapies for inflammatory bowel disease (IBD) is fraught with challenges, including complex trial designs, ethical concerns regarding placebo use, recruitment difficulties, and escalating costs. The landscape of IBD clinical trials is shifting toward greater inclusivity, improved patient diversity, and innovative trial designs, such as adaptive and Bayesian approaches, to address these challenges. By overcoming these obstacles, the drug development pipeline can advance more effective, accessible, and timely treatments for CD. Plain language summary: Crohn's disease: hope on the horizon with new therapies in development Crohn's disease (CD) is a chronic inflammatory bowel disease (IBD) that affects millions of people worldwide. Many people with CD do not respond well to current treatments, and researchers are looking for new options. Clinical trials are research studies that test new drugs and treatments. They are carefully designed to protect the safety of participants. Several new approaches to treating CD are currently undergoing clinical trials. These include drug candidates in various stages of development, from early research to large-scale phase III trials. Cellular therapies are also being tested, involving the injection of cells locally or intravenously to promote healing. Crohn's disease (CD) is a long-term condition that causes inflammation in the digestive tract. It can be difficult to treat, as current medications don't always work for everyone, and some people experience side effects or stop responding to treatment over time. Even in clinical trials, where new treatments are tested, less than 60% of patients show positive responses. Researchers are working on new treatments that target different pathways involved in Crohn's disease. This review looks at drugs being tested in early to late-stage clinical trials. Some of these drugs target well-known pathways, like JAK inhibitors and IL-23 blockers, while others focus on newer areas, such as specific receptors or molecules involved in inflammation. These emerging therapies aim to provide better, longer-lasting relief for patients. However, developing new treatments isn't easy. Clinical trials for Crohn's disease face many challenges, including complicated trial designs, ethical concerns about using placebos, difficulties in recruiting enough patients, and high costs. To overcome these issues, researchers are exploring more flexible and inclusive trial methods, which could help bring new treatments to patients more quickly and efficiently. [ABSTRACT FROM AUTHOR]

Background: Regular physical activity (PA) is desirable, regardless of age, even in patients with chronic conditions such as inflammatory bowel disease (IBD). Aims: This study aims to assess PA levels and related barriers/facilitators in IBD patients, stratifying them into age groups (with a threshold of 50 years). Methods: The International PA Questionnaire (IPAQ) assessed PA levels regarding resting metabolic rate (Met) in minutes per week (min/wk). Patient-reported outcomes 2 (PRO-2) evaluated disease activity. Results: Among the 237 enrolled patients, PA rates were found to differ significantly in terms of patients being sufficiently active (55% vs. 39.8%), inactive (39.6% vs. 59.1%), and engaging in health-enhancing PA (5.4% vs. 1.1%) between patients under and at least 50 years old, respectively (p < 0.001). Overall, PA levels followed this trend, being higher in younger patients [892 (446.5–1439) vs. 545.25 (257–1210.47) Met min/wk, p = 0.007]. Individuals aged at least 50 years tend to have lower PA at regression analysis (OR: 3.302, p = 0.018). Patients aged at least 50 years perceived IBD as more of a barrier to PA (p = 0.04). Bowel urgency is a significant barrier, especially in older patients (p = 0.022). Conclusions: Age is an unmodifiable factor impacting and influencing PA levels. Strategies to recover exercise levels in older IBD patients should be encouraged. [ABSTRACT FROM AUTHOR]

Background/Objectives: Restorative proctocolectomy with ileo-anal pouch anastomosis (IPAA) remains the preferred surgical treatment for ulcerative colitis (UC). However, complications like pouchitis can occur. This study aimed to describe patients who underwent IPAA for inflammatory bowel disease (IBD) at Padua Hospital from 2005 to 2023 and identify risk factors for pouchitis. Secondary objectives included evaluating the effectiveness of biological therapy in chronic antibiotic-refractory pouchitis (CARP), Crohn's disease of the pouch (CDP), and Crohn's-like inflammation of the pouch (CDLPI), and assessing risk factors for pouch failure. Methods: This retrospective, observational study included 109 patients whose data were collected from medical records. Univariate logistic regression was used to analyze associations between preoperative and postoperative factors and outcomes such as acute pouchitis and pouch failure. The effectiveness of biological therapy was assessed by measuring changes in the Pouchitis Disease Activity Index (PDAI) and the Modified Pouchitis Disease Activity Index (mPDAI) over a 12-month treatment period. Results: Univariate logistic regression revealed significant associations between preoperative extraintestinal manifestations (OR 3.569, 95% CI 1.240–10.720), previous diagnosis of Crohn's disease (OR 10.675, 95% CI 1.265–90.089), and transmural inflammation at cross-sectional imaging before surgery (OR 3.453, 95% CI 1.193–9.991) with an acute pouchitis risk. Pouch failure was significantly associated with a previous diagnosis of Crohn's disease (OR 9.500, 95% CI 1.821–49.571) and post-surgical fistulas (OR 41.597, 95% CI 4.022–430.172). Biological therapy led to a significant reduction in the PDAI score in patients with CARP, decreasing from a median of 10 to 4 (p = 0.006). Similarly, in patients with CDP or CDLPI, the mPDAI score was significantly reduced from a median of 9 to 1 (p = 0.034), with remission achieved in 5/6 (83.3%) of these patients. Conclusions: This study provides valuable insights into the management of IPAA patients and highlights the importance of early identification and treatment of risk factors for pouchitis and failure. Biological therapy demonstrated significant effectiveness in reducing disease activity in patients with CARP, CDP, and CDLPI, suggesting its role as a crucial component in managing these complications. [ABSTRACT FROM AUTHOR]

The esophagus, traditionally viewed as a sterile conduit, is now recognized as a dynamic habitat for diverse microbial communities. The emerging evidence suggests that the esophageal microbiota plays an important role in maintaining esophageal health and contributing to disease. The aim of this systematic review was to synthesize the current knowledge on the esophageal microbiota composition, its variation between healthy individuals and those with esophageal diseases, and the potential mechanisms through which these microorganisms influence esophageal pathology. A systematic literature search was conducted using multiple databases, including PubMed, Scopus, and Web of Science, to identify relevant studies published up to July 2024. The inclusion criteria encompassed original research articles that used molecular techniques to characterize the esophageal microbiota in human subjects, comparing healthy individuals with patients affected by esophageal conditions such as gastroesophageal reflux disease (GERD), Barrett's esophagus, eosinophilic esophagitis, and esophageal cancer. The primary outcomes were the composition and diversity of the esophageal microbiota, and the secondary outcomes included the correlations between microbial profiles and disease states. The esophageal microbiota of healthy individuals was dominated by Gram-positive bacteria, particularly Streptococcus. Conversely, the esophageal microbiota is considerably altered in disease states, with decreased microbial diversity and specific microbial signatures associated with these conditions, which may serve as biomarkers for disease progression and as targets for therapeutic intervention. However, the heterogeneous study designs, populations, and analytical methods underscore the need for standardized approaches in future research. Understanding the esophageal microbiota's role in health and disease could guide microbiota-based diagnostics and treatments, offering novel avenues for managing esophageal conditions. [ABSTRACT FROM AUTHOR]

Introduction: Therapeutic drug monitoring (TDM) has proven to be a valuable strategy for optimizing biologic therapies, among which are anti-tumor necrosis factor (anti-TNF) treatments in inflammatory bowel disease (IBD). In particular, reactive TDM has been shown to manage treatment failures more cost-effectively than empirical dose adjustments for anti-TNF drugs. However, several challenges currently impede the widespread adoption of TDM in clinical practice, particularly addressing the delay between sample collection and result availability. To overcome this limitation, the use of point-of-care technology tests (POCTs) is a potential solution. Point-of-care technology tests are medical diagnostic tests performed at the site of patient care to provide immediate results, allowing for quicker decision-making and treatment. The current standard of care (SOC) for drug level measurement relies on the enzyme-linked immunosorbent assay (ELISA), a method that is time-consuming and requires specialized personnel. This study aims to evaluate a novel, user-friendly, and efficient POCT method (ProciseDx Inc.) and compare its performance with the SOC ELISA in assessing infliximab and adalimumab levels in blood samples from IBD patients. Methods: In this prospective, single-center study, we collected blood samples from IBD patients, both CD and UC, receiving infliximab (87 IBD patients; 50% UC and 50% CD) or adalimumab (60 patients; 14% UC and 48% CD) and we analyzed the blood's drugs levels using both the ProciseDx Analyzer POC and the SOC ELISA. We examined the correlation between the two methods using statistical analyses, including the Deming regression test. Additionally, we assessed the ease of use, turnaround time, and overall practicality of the POCT in a clinical setting. Results: The ProciseDx test demonstrated a strong correlation with the SOC ELISA for measuring both infliximab and adalimumab levels. In particular, the overall correlation between the ProciseDx POCT and the ELISA assessments showed an r coefficient of 0.83 with an R squared value of 0.691 (95% CI 0.717–0.902) for IFX measurements, and an r coefficient of 0.85 with an R squared value of 0.739 (95% CI 0.720–0.930). Conclusions: the ProciseDx POC test offers significantly faster turnaround times and is more straightforward to use, making it a viable alternative for routine clinical monitoring. Despite its promising potential, further refinement and validation of the ProciseDx test are necessary to ensure its effectiveness across diverse patient populations and clinical settings. Future research should focus on optimizing the POC tests' performance and evaluating its long-term impact on IBD management. [ABSTRACT FROM AUTHOR]

Background. Data on resilience, the ability to recover from adversity, in coeliac disease (CeD) are lacking. Aim. To assess the degree of resilience in patients with CeD on a gluten-free diet (GFD), and its association with clinical features, sociodemographic factors, psychological morbidity, and quality of life (QOL). Methods. A cross-sectional multicentre Italian study was conducted on adult CeD patients between May 2022 and April 2023. Connor–Davidson Resilience Scale (CD-RISC), the Coeliac Disease-specific Quality of Life Scale (CD-QOL), the State–Trait Anxiety Inventory scale (STAI-Y), and the Beck Depression Inventory scale (BDI) were used to evaluate resilience, QOL, anxiety, and depression, respectively. A multivariate analysis was conducted to identify factors independently associated with the degree of resilience. Results. A total of 305 patients (221 F, mean age at CeD diagnosis 36 ± 16 years) on a long-term GFD (median 8 years, IQR 3–17) were enrolled. A total of 298/305 patients (98%) had a high level of resilience (CD-RISC ≥ 35). At univariate analysis, resilience was statistically associated with male gender (p = 0.03), age at enrolment (p = 0.02), marital status (p = 0.03), QOL (p < 0.001), anxiety (p < 0.001), and depression (p < 0.001). On multivariate regression analysis, trait anxiety (STAI-Y2, p < 0.001) and depression (BDI, p = 0.02) were independent predictors of lower levels of resilience. Conclusions. Higher trait anxiety predicts lower levels of resilience. Targeted interventions in this subgroup of patients may be helpful for their management and follow-up. [ABSTRACT FROM AUTHOR]