Inflammatory Bowel Disease Therapy Research Articles

Use of Upadacitinib as Salvage Therapy for Ulcerative Colitis in Pregnancy: A Case Report.

Use of Upadacitinib as Salvage Therapy for Ulcerative Colitis in Pregnancy: A Case Report.

Factors Associated with Delays in Initiating Biologic Therapy in Patients with Inflammatory Bowel Disease.

Expeditious initiation of biologic therapy is important in patients with inflammatory bowel disease (IBD). However, initiation of biologics in the outpatient setting may be delayed by various clinical, social, and financial variables. To evaluate the delay in initiation of an advanced therapy in IBD and to identify factors that contributed to this delay. This was a multi-center retrospective study. Outpatients who were initiated on a biologic therapy from 3/1/2019 to 9/30/20 were eligible for the study. Univariate and multivariate linear regression analyses were performed to identify variables associated with a delay in biologic treatment initiation. Delay was defined as the days from decision date (prescription placement) to first infusion or delivery of medication. In total 411 patients (Crohn's disease, n = 276; ulcerative colitis, n = 129) were included in the analysis. The median [interquartile range-(IQR)] delay for all drugs was 20 [12-37] days (infliximab, 19 [13-33] days; adalimumab, 10 [5-26] days; vedolizumab, 21 [14-42] days; and ustekinumab, 21 [14-42] days). Multivariate linear regression analysis identified that the most important variables associated with delays in biologic treatment initiation was self-identification as Black, longer distance from treatment site, and lack of initial insurance coverage approval. There may be a significant delay in biologic treatment initiation in patients with IBD. The most important variables associated with this delay included self-identification as Black, longer distance from site, and lack of initial insurance coverage approval.

Precision therapy for ulcerative colitis: insights from mitochondrial dysfunction interacting with the immune microenvironment

Precision therapy for ulcerative colitis: insights from mitochondrial dysfunction interacting with the immune microenvironment

Curcumin-Encapsulated Co-ZIF-8 for Ulcerative Colitis Therapy: ROS Scavenging and Macrophage Modulation Effects

Curcumin-Encapsulated Co-ZIF-8 for Ulcerative Colitis Therapy: ROS Scavenging and Macrophage Modulation Effects

The role of selenium in the pathogenesis and therapy of inflammatory bowel diseases

In recent decades, Russia, as well as around the world, has recorded a steady increase in the incidence of inflammatory bowel diseases, which include ulcerative colitis and Crohn’s disease. The incidence of inflammatory bowel diseases in Russia accounts for 4.1 per 100 thousand of the population for ulcerative colitis and 0.8 per 100 thousand – for Crohn’s disease. The prevalence of inflammatory bowel diseases in Russia is 19.3–29.8 cases per 100 thousand of the population for ulcerative colitis and 3.0–4.5 per 100 thousand – for Crohn’s disease. In recent years, selenium has attracted the attention of researchers due to its anti-inflammatory and antioxidant properties as well as its ability to influence the intestinal flora. There is evidence that inflammatory bowel diseases has deficiency of trace elements, which is more often detected during active period of the disease than during remission. The purpose of the review is to summarize and analyze current literature data on the relationship between selenium and inflammatory bowel diseases, with special emphasis on the mechanism and function of selenium in intestinal inflammation as well as to discuss the possible therapeutic use of selenium in inflammatory bowel diseases. The authors conducted a search for publications in the electronic databases PubMed and eLibrary. After the selection procedure, 87 studies were included in the review. Due to its anti-inflammatory and antioxidant properties, the concentration of selenium can be crucial in the occurrence and development of inflammatory bowel diseases. Dietary recommendations with the inclusion of selenium gradually improve the quality of life of patients with inflammatory bowel diseases. The development and use of selenium drugs have also provided new therapy strategies. In the future, a large number of experimental and clinical studies are still needed to confirm the relationship between selenium and inflammatory bowel diseases, which, in turn, will mark a new turn in the prevention and treatment of these severe chronic diseases.

Proactive Therapeutic Drug Monitoring Is Associated With Increased Drug Persistence in Patients With Inflammatory Bowel Disease Treated With Intravenous Vedolizumab.

There are limited data regarding therapeutic drug monitoring (TDM) of non-anti-tumor necrosis factor therapy in inflammatory bowel disease (IBD). This study aimed to evaluate the efficacy of proactive TDM in IBD patients treated with intravenous (iv) vedolizumab (VDZ). This single-center retrospective cohort study included consecutive IBD patients treated with maintenance iv VDZ therapy undergoing TDM from November 2016 to March 2023. Patients were followed through June 2023 and were divided in to 2 groups: those who had at least 1 proactive TDM vs those who underwent only reactive TDM. A survival analysis was performed to evaluate drug persistence, defined as no need for drug discontinuation due to loss of response, serious adverse event, or an IBD-related surgery. The study population consisted of 94 patients (proactive TDM, n = 72) with IBD (ulcerative colitis, n = 53). Patients undergoing at least 1 proactive TDM compared with patients having only reactive TDM demonstrated a higher cumulative probability of drug persistence (Log-rank P < .001). In multivariable Cox proportional hazard regression analysis, at least 1 proactive TDM was the only factor associated with drug persistence (hazard ratio, 14.3; 95% confidence interval [CI], 3.8-50; P < .001). A ROC analysis identified a VDZ concentration of 12.5 µg/mL as the optimal drug concentration threshold associated with drug persistence (area under the ROC curve: 0.691; 95% CI, 0.517-0.865; P = .049). In this single-center retrospective study reflecting real-life clinical practice, proactive TDM was associated with increased drug persistence in patients with IBD treated with iv VDZ.

Inflammatory Gene Panel Guiding the Study of Genetics in Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a complex disease that develops through a sequence of molecular events that are still poorly defined. This process is driven by a multitude of context-dependent genes that play different roles based on their environment. The complexity and multi-faceted nature of these genes make it difficult to study the genetic basis of IBD. The goal of this article is to review the key genes in the pathophysiology of IBD and highlight new technology that can be used in further research. This paper examines Nanostring RNA probe technology, which uses tissue analyzed without the use of enzymes, transcription, or amplification. Nanostring offers several panels of genes to test, including an inflammation panel of 234 genes. This article analyzes this panel and reviews the literature for each gene's effect in IBD for use as a framework to review the pathophysiology of the disease. The panel was narrowed to 26 genes with significant evidence of mechanistic potential in IBD, which were then categorized into specific areas of pathogenesis. These include gut barrier breakdown, inappropriate recognition of commensal bacteria, immune cell activation, proinflammatory cytokine release, and subsequent impairment of the anti-inflammatory response. The eventual goal of this paper is the creation of a customized panel of IBD genes that can be used to better understand the genetic mechanism of IBD and aid in the development of future therapies in IBD.

Revolution in diet therapy for inflammatory bowel disease.

Until recently, diet as a therapeutic tool to treat inflammatory bowel disease (IBD) has not been proven effective. Nearly a century in the making we are in the grips of a revolution in diet therapies for IBD, driven by emerging data revealing diet as a key environmental factor associated with IBD susceptibility, and observational studies suggesting that dietary intake may play a role in the disease course of established IBD. This review summarizes the current evidence for diets trialed as induction and maintenance therapy for IBD. For Crohn's disease, exclusive enteral nutrition and the Crohn's disease exclusion diet with partial enteral nutrition are supported by emerging high-quality evidence as induction therapy, but are short-term approaches that are not feasible for prolonged use. Data on diet as maintenance therapy for Crohn's disease are conflicting, with some studies supporting fortification, and others suppression, of certain food components. For ulcerative colitis, data are not as robust for diet as induction and maintenance therapy; however, consistent themes are emerging, suggesting benefits for diets that are plant-based, high in fiber and low in animal protein. Further studies for both Crohn's disease and ulcerative colitis are eagerly awaited, which will allow specific recommendations to be made. Until this time, recommendations default to population based healthy eating guidelines.

Current and future microbiome-based therapies in inflammatory bowel disease.

The role of the microbiome and dysbiosis is increasingly recognized in the pathogenesis of inflammatory bowel disease (IBD). Intestinal microbiota transplant (IMT), previously termed fecal microbiota transplant has demonstrated efficacy in restoring a healthy microbiome and promoting gut health in recurrent Clostridioides difficile infection. Several randomized trials (RCTs) highlighted IMT's potential in treating ulcerative colitis, while smaller studies reported on its application in managing Crohn's disease and pouchitis. This review delves into the current understanding of dysbiosis in IBD, highlighting the distinctions in the microbiota of patients with IBD compared to healthy controls. It explores the mechanisms by which IMT can restore a healthy microbiome and provides a focused analysis of recent RCTs using IMT for inducing and maintaining remission in IBD. Lastly, we discuss the current knowledge gaps that limit its widespread use. The body of evidence supporting the use of IMT in IBD is growing. The lack of a standardized protocol impedes its application beyond clinical trials. Further research is needed to identify patient profile and disease phenotypes that benefit from IMT, to delineate key donor characteristics, optimize the delivery route, dosage, and frequency.

Importance of Gut Microbiota in Patients with Inflammatory Bowel Disease

Inflammatory bowel diseases (IBDs), such as Crohn’s disease (CD) and ulcerative colitis (UC), are chronic diseases of the digestive system with a multifactorial and not fully understood etiology. There is research suggesting that they may be initiated by genetic, immunological, and lifestyle factors. In turn, all of these factors play an important role in the modulation of intestinal microflora, and a significant proportion of IBD patients struggle with intestinal dysbiosis, which leads to the conclusion that intestinal microflora disorders may significantly increase the risk of developing IBD. Additionally, in IBD patients, Toll-like receptors (TLRs) produced by intestinal epithelial cells and dendritic cells treat intestinal bacterial antigens as pathogens, which causes a disruption of the immune response, resulting in the development of an inflammatory process. This may result in the occurrence of intestinal dysbiosis, which IBD patients are significantly vulnerable to. In this study, we reviewed scientific studies (in particular, systematic reviews with meta-analyses, being studies with the highest level of evidence) regarding the microflora of patients with IBD vs. the microflora in healthy people, and the use of various strains in IBD therapy.

Oral microsphere formulation of M2 macrophage-mimetic Janus nanomotor for targeted therapy of ulcerative colitis

Oral microsphere formulation of M2 macrophage-mimetic Janus nanomotor for targeted therapy of ulcerative colitis

Development of Enteric-Coated Tablet with a Unique Combination of Therapeutic and Nutraceutical Actives to Treat Colitis

The primary objectives of the current investigation were to design and characterize enteric-coated oil of ginger tablets in coconut water powdered form as a therapy for ulcerative colitis. One source that is both anti-inflammatory and high in electrolytes is a combination of ginger oil and powdered coconut water. By reducing inflammation and improving electrolyte and water balance, this combination will hasten the healing process. Starch 1500, microcrystalline cellulose, and ethyl cellulose were used to create enteric-coated tablets of ginger oil alone and in combination with coconut water powder. The results corroborated the findings that there were no unique interactions between any of the substances, as demonstrated by the examination of both tablets, which included morphology, micrometric features, and fourier transform infrared (FTIR) spectroscopic capabilities. We studied the dissolving characteristics of coated tablets at pH 1.2, 6.8, and 7.4 in a buffer. Quantification of gingerol was accomplished by use of reverse-phase high-performance liquid chromatography (RP-HPLC) technology. The selected formulation’s therapeutic efficacy was lastly confirmed using a colitis model generated by 2,4,6-trinitrobenzene sulfonic acid. Tablets containing either ginger oil or a powdered combination of ginger oil as well as coconut water were compared in the research. Myeloperoxidase, lipid peroxidase, and histological assessment were calculated using the colitis model. The colon/body weight ratio was also measured. Research on animals has shown that a combination of the coated oil of ginger and the oil of coconut tablets, as opposed to ginger oil tablets alone, considerably improved the sick conditions in Wistar rats. The gain in weight and clinical improvements in the macroscopic and microscopic factors of induced colitis served as evidence of this. These results demonstrate the potential of coated tablets formulated with coconut water powder for the targeted delivery of ginger oil to the colon as well as for the improvement of colon health through the balance of micronutrients and water content. It is not practical to increase the dosage to compensate for metabolic loss while using ginger oil because of its strong taste and strength. Therefore, the formulation of choice is enteric coating. As enteric coating tablets target the intestine as the site of action, it is possible to use less potent ginger oil. Due to the inclusion of coconut water powder, the formulation not only helps cure the illness state but also promotes and supports a speedy recovery.

HSD78 Prescribing Patterns of Novel Oral Therapies for Ulcerative Colitis in a Large Integrated Delivery Network

HSD78 Prescribing Patterns of Novel Oral Therapies for Ulcerative Colitis in a Large Integrated Delivery Network

Timing Is Everything: The Lifesaving Potential of Early Medical Therapy in Acute Severe Ulcerative Colitis.

Timing Is Everything: The Lifesaving Potential of Early Medical Therapy in Acute Severe Ulcerative Colitis.

Zinc and Inflammatory Bowel Disease: From Clinical Study to Animal Experiment.

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract (GI) with a high incidence rate globally, and IBD patients are often accompanied by zinc deficiency. This review aims to summarize the potential therapeutic value of zinc supplementation in IBD clinical patients and animal models. Zinc supplementation can relieve the severity of IBD especially in patients with zinc deficiency. The clinical severity of IBD were mainly evaluated through some scoring methods involving clinical performance, endoscopic observation, blood biochemistry, and pathologic biopsy. Through conducting animal experiments, it has been found that zinc plays an important role in alleviating clinical symptoms and improving pathological lesions. In both clinical observation and animal experiment of IBD, the therapeutic mechanisms of zinc interventions have been found to be related to immunomodulation, intestinal epithelial repair, and gut microbiota's balance. Furthermore, the antioxidant activity of zinc was clarified in animal experiment. Appropriate zinc supplementation is beneficial for IBD therapy, and the present evidence highlights that alleviating zinc-deficient status can effectively improve the severity of clinical symptoms in IBD patients and animal models.

Inpatient Infliximab Biosimilar Cost-Savings: Cost Analysis of Inpatient Treatment with Originator Infliximab (Remicade™) versus Biosimilar Infliximab (Renflexis™) for Acute Severe Ulcerative Colitis.

Infliximab (IFX) is a standard, inpatient salvage therapy for the treatment of refractory acute severe ulcerative colitis (ASUC). Remicade™ is the originator IFX. Its biosimilar Renflexis™ offers a reduced cost structure. We performed a cost-minimization analysis to compare costs with Remicade™ and Renflexis™ for the inpatient treatment of ASUC. Retrospective clinical and financial data were obtained from 34 inpatients with refractory ASUC who received Renflexis™ (n = 17) or Remicade™ (n = 17) between 2019 and 2021. Clinical data included admission and discharge laboratory values. Financial data included a decision support drug cost (DSDC), constituting the total cost associated with inpatient IFX administration, and total inpatient cost of care. The following equation generated a ratio (rDSDC) representing the percentage of drug cost (or DSDC) of the total inpatient cost of care, after controlling for IFX dose and length of stay: [DSDC of IFX/Number of Units of IFX] ÷ [Total Inpatient Cost of Care/Length of Stay in Days]. Median and non-parametric Wilcoxon ranked sum test were used for analyzing patient demographics, clinical, and financial data. No differences were found in baseline or discharge clinical parameters. The median unadjusted ratio of DSDC to total inpatient cost of care was 0.387 versus 0.241 in the Remicade™ versus Renflexis™ groups (p = 0.0025), respectively, representing an absolute difference of ∼14%. Median adjusted rDSDC were 0.04 versus 0.024 in the Remicade™ versus Renflexis™ groups, respectively, representing a relative cost reduction of ∼40% (p = 0.0001). The unadjusted absolute cost reduction and adjusted relative cost reduction were, respectively, 14% and 40% in the Renflexis™ group as compared to Remicade™, when treating inpatient ASUC. Our calculation included median DSDC as a percentage of the total inpatient cost of care, controlling for IFX dose and length of stay. This reduced cost structure promotes use of Renflexis™ for ASUC inpatients and may reduce costs systemically.

Exosomes derived from mesenchymal stem cells containing berberine for ulcerative colitis therapy

Berberine (Ber), an isoquinoline alkaloid, is a potential drug therapy for ulcerative colitis (UC) because of its anti-inflammatory activity, high biological safety, and few side effects. Nevertheless, its clinical application is hindered by its limited water solubility and low bioavailability. Currently, compared to synthetic nanocarriers, exosomes as carriers possess advantages such as low toxicity, high stability, and high specificity. Human placental mesenchymal stem cell-derived exosomes (HplMSC-Exos) have emerged as a promising drug delivery system, offering intrinsic anti-inflammatory and antioxidant activities. Therefore, we engineered MSC-Exos loaded with Ber (Exos-Ber) to enhance the solubility and bioavailability of Ber and for colon targeting, revealing a novel approach for treating UC with natural compounds. Structurally and functionally, Exos-Ber closely resembled unmodified Exos. Both in vitro and in vivo investigations confirmed the antioxidant and anti-inflammatory properties of Exos-Ber. Notably, Exos-Ber exhibited reparative effects on injured epithelial cells and reduced cellular apoptosis. Furthermore, Exos-Ber concurrently demonstrated anti-inflammatory and antioxidant activities, contributing to the mitigation of UC, possibly through its modulation of the MAPK signaling pathway. Overall, our findings demonstrate the potential of Exos-Ber as a promising therapeutic option for alleviating UC, highlighting its capacity to enhance the clinical applicability of Ber.

Wogonin preconditioning of MSCs improved their therapeutic efficiency for colitis through promoting glycolysis.

Inflammatory bowel diseases (IBDs) are prevalent and debilitating diseases with limited clinical treatment strategies. Mesenchymal stem cell (MSCs) are pluripotent stem cells with self-renewal capability and multiple immunomodulatory effects, which make them a promising therapeutic approach for IBDs. Thus, optimization of MSCs regimes is crucial for their further clinical application. Wogonin, a flavonoid-like compound with extensive immunomodulatory and adjuvant effects, has been investigated as a potential pretreatment for MSCs in IBD treatment. In this study, we employed the DSS-induced acute colitis mouse model to compare the therapeutic effectiveness of MSCs in pretreated with or without wogonin and furtherexploretheunderlyingmechanism. Compared to untreated MSCs, MSCwogonin (pretreated with wogonin) showed greater effectiveness in the treatment of colitis. Further experiments revealed that wogonin treatment activated the AKT signaling pathway, resulting in higher cellular glycolysis. Inhibition of AKT phosphorylation by perifosine not only decreased glycolysis but impaired the therapeutic efficiency of MSCwogonin. Consistent with these results, qPCR data indicated that wogonin treatment induced the expression of immunomodulatory molecules IL-10, IDO, and AGR1, which were reduced by perifosine. Together, our data demonstrated that wogonin preconditioning strategy further augmented the therapeutic efficacy of MSCs via promoting glycolysis, which should be a promising strategy for optimizing MSCs therapy in IBDs.

Polysaccharides extracted from larvae of Lucilia sericata ameliorated ulcerative colitis by regulating the intestinal barrier and gut microbiota

Pest management technology has been a promising bioconversion method for waste resource utilization. Unlike many pests that consume waste, the larvae of Lucilia sericata, also known as maggots, have many outstanding advantages as following: with their strong adaption to environment and not easily infected and exhibiting a medicinal nutritional value. Herein, the potential efficacies of maggot polysaccharides (MP), as well as their underlying mechanisms, were explored in Dextran sulfate sodium (DSS)-induced colitis mice and TNF-α-elicited Caco-2 cells. We extracted two bioactive polysaccharides from maggots, MP-80 and MP-L, whose molecular weights were 4.25 × 103 and 2.28 × 103 g/mol, respectively. MP-80 and MP-L contained nine sugar residues: 1,4-α-Arap, 1,3-β-Galp, 1,4,6-β-Galp, 1,6-α-Glcp, 1-α-Glcp, 1,4-β-Glcp, 1-β-Xylp, 1,2-α-Manp, and 1-β-Manp. We demonstrated that MP-80 and MP-L significantly ameliorated DSS-induced symptoms and histopathological damage. Immuno-analysis revealed that compared with MP-L, MP-80 could better restore intestinal barrier and reduced inflammation by suppressing NLRP3/NF-κB pathways, which might be attributed to its enriched galactose fraction. Moreover, 16S rRNA sequencing revealed that MP-80 and MP-L both improved the dysbiosis and diversity of gut microbiota and acted on multiple microbial functions. Our study sheds new light on the possibility of using maggot polysaccharides as an alternative therapy for colitis.

A case of dual-targeted therapy for pediatric refractory inflammatory bowel disease

A case of dual-targeted therapy for pediatric refractory inflammatory bowel disease