Therapy For Ulcerative Colitis Research Articles

Differential efficacy of medical therapies for ulcerative colitis according to disease extent: patient-level analysis from multiple randomized controlled trials

Disease extent in Ulcerative Colitis (UC) has prognostic implications for disease course. It is unclear whether the efficacy of medical therapies for moderate to severely active UC vary according to disease extent at enrollment. We analyzed patient level data from 11 Phase 2 and 3 clinical trials of advanced therapies in patients with moderate-to-severe UC to assess modifications of advanced therapy effects by disease extent. Primary outcome was clinical response and secondary outcomes were clinical remission, endoscopic response/remission and endoscopic improvement, and Mayo clinic subscore for both induction and maintenance studies. Binary and continuous outcomes were analyzed using the modified Poisson regression model and the mixed-effects model, respectively, adjusting for age, sex, disease duration, concomitant steroid use and prior anti-TNF use. Effect modifications with binary outcomes were quantified by ratios of risk ratio for left-sided to that for extensive colitis while effect modifications with the Mayo subscores were quantified by differences of the differences between mean scores of the left-sided and extensive colitis. Results were presented with point estimates and 95% confidence intervals as well as p-values. Eleven clinical trials enrolling 5450 UC patients (infliximab=2, adalimumab=2, golimumab=2, vedolizumab=2, tofacitinib=3) were included. In induction trials, there was evidence to suggest effect modification by disease extent for clinical response with tofacitinib (the ratio of RRs 0.67, 95% CI [0.45, 0.99], p=0.049) and clinical remission with infliximab (ratio of RRs 0.33, 95% CI [0.13, 0.85], p=0.020) favoring patients with extensive colitis. There was no evidence to suggest effect modification for endoscopic improvement and clinical outcomes. There was evidence to suggest effect modification by disease extent for clinical remission with tofacitinib (ratio of RRs 0.44, 95% CI [0.22, 0.89], p=0.020) favoring patients with extensive colitis. For symptom subscores from the Mayo Clinic score, tofacitinib was associated with a greater reduction in both stool frequency (difference of differences 0.37, 95% CI [0.08, 0.65], p=0.012) and rectal bleeding scores (difference of differences 0.25, 95% CI [0.03, 0.47], p=0.026) in patients with extensive colitis compared to left sided. These findings underscore the possibility of differential efficacy of medical therapies according to disease distribution. These results warrant further exploration in forthcoming trials to better inform treatment strategies and consideration of disease distribution as a baseline stratification factor in clinical trials. This study did not receive any financial support.

Inpatient Infliximab Biosimilar Cost-Savings - Cost analysis of inpatient treatment with originator Infliximab (Remicade™) vs biosimilar Infliximab (Renflexis™) for acute severe ulcerative colitis. .

Infliximab (IFX) is a standard, salvage therapy for 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 inpatient treatment of ASUC. Methods: Retrospective clinical and financial data was obtained from 34 patients with refractory ASUC who received Renflexis (n=17) or Remicade (n=17) between 2019-2021. Clinical data included admission and discharge lab values. Financial data included a decision support drug cost (DSDC), constituting the total cost associated with inpatient infliximab administration, and total inpatient cost of care. No differences were found in baseline or discharge clinical parameters. Median unadjusted ratio of DSDC to total inpatient cost of care was 0.387 vs. 0.241 in the Remicade vs. Renflexis groups (p=0.0025), respectively, representing an absolute difference of ~14%. Median adjusted rDSDC was 0.04 vs. 0.024 in the Remicade vs. Renflexis groups, respectively, representing a relative cost reduction of ~40% (p = 0.0001) Discussion: The unadjusted absolute cost reduction and adjusted relative cost reduction were respectively 14% and 40% in the Renflexis group as compared to Remicade. Our calculation included median decision support drug cost as a percentage of the total inpatient cost of care, controlling for infliximab dose and length of stay. This reduced cost structure promotes use of Renflexis for ASUC inpatients and may reduce costs for patients and hospitals.

Effectiveness and Safety of Ustekinumab in Pediatric Ulcerative Colitis: A Multi-center Retrospective Study from the Pediatric IBD Porto Group of ESPGHAN.

Current data on ustekinumab therapy in children with ulcerative colitis (UC) or unclassified inflammatory bowel disease (IBDU) are limited. We aimed to evaluate the effectiveness and safety of ustekinumab in pediatric UC and IBDU. This multicenter retrospective study included 16 centers affiliated with the IBD Interest and Porto groups of ESPGHAN. Children with UC or IBDU treated with ustekinumab were enrolled. Demographic, clinical, laboratory, endoscopic, and imaging data as well as adverse events were recorded. Analyses were all based on the intention-to-treat principle. Fifty-eight children (39 UC and 19 IBDU, median age 14.5 [IQR 11.5-16.5] years) were included. All had failed biologic therapies, and 38 (66%) had failed two or more biologics. Corticosteroid-free clinical remission (CFR) was observed in 27 (47%), 33 (57%), and 37 (64%) children at 16, 26, and 52 weeks, respectively. Normalization of C-reactive protein and calprotectin <150μg/g were achieved in 60% and 52%, respectively, by 52 weeks. Endoscopic and radiologic remissions were reached in 8% and 23%, respectively. The main predictors of CFR were diagnosis of UC compared with IBDU (hazard ratio [HR] 2.2, 95% CI 1.03-4.85; p=0.041) and no prior vedolizumab therapy (HR 2.1, 95% CI 1.11-4.27; p=0.023). Ustekinumab serum levels were not associated with disease activity. Adverse events were recorded in six (10%) children, leading to discontinuation of the drug in three. Based on these findings, ustekinumab appears as an effective therapy for pediatric refractory UC and IBDU. The potential efficacy should be weighed against the risks of serious adverse events.

Aegeline attenuates TNBS-induced colitis by suppressing the NFƙB-mediated NLRP3 inflammasome pathway in mice.

A chronic inflammatory condition of the intestine, ulcerative colitis (UC), is challenging to successfully manage once diagnosed. Currently, available medical therapies for UC exhibit minimal efficacy with unacceptable side effects, while inventive biological agents are expensive and yetnotwell accepted by patients. Discovering more effective and safer treatments to treat UC is therefore essential. One of the primary alkaloids found in Aegle marmelos, aegeline, has anti-inflammatory and antioxidant properties as well as being able to suppress severalpro-inflammatory cytokines responsible for inflammation. The study aimed to investigate the effectiveness of aegeline in alleviating 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis through the NFƙB-mediated NLRP3 inflammasome pathway. Mice were randomly allocated into six groups, Normal control (NC), Model control (MC-TNBS, 2,4,6-trinitrobenzene sulfonic acid), STD (TNBS + sulfasalazine 100mg/kg), AG1, AG2, and AG3 (TNBS + aegeline 5, 10, 20mg/kg) respectively. Physical parameters such as a change in body weight, stool consistency, rectal bleeding, colon length, myeloperoxidase (MPO) levels and nitric oxide (NO) levels, and disease activity index (DAI) were assessed and supporting gene expression studies of various pro-inflammatory cytokines and enzymes were evaluated and histopathological changes observed. Administration of aegeline (10, 20mg/kg) was found to be effective in colon protection by lowering the disease activity score and myeloperoxidase level and improving other physical parameters. Aegeline in high dose significantly downregulated the gene expression of NFƙB, iNOS, COX-2, NLRP3, IL-1β, and IL-18, conferring great anti-inflammatory potential. Suggestive of the findings, aegeline reduced the damage to the colon by downregulating transcriptional genes and enzymes leading to inflammation and mitigated TNBS-induced colitis probably through the NFƙB-mediated NLRP3 inflammasome pathway.

Infliximab (Remsima SC)

We recommend that Remsima SC be reimbursed by public drug plans as maintenance treatment for adults with moderately to severely active ulcerative colitis (UC) whose disease has had an inadequate response, or who were intolerant, to conventional therapy if certain conditions are met. Remsima SC maintenance treatment should only be covered to treat adults with moderately to severely active UC whose disease has had an inadequate response, or who are intolerant, to conventional therapy. Patients are required to achieve a clinical response to induction therapy with infliximab IV at week 10 of treatment to continue with Remsima SC as maintenance therapy. Remsima SC should only be reimbursed if prescribed by a physician experienced in diagnosing and managing UC and should not be reimbursed if used in combination with other advanced therapies for UC. The cost of Remsima SC should not exceed the drug program cost of treatment with the least costly biologic therapy reimbursed for the treatment of UC.

Simultaneous Treatment of 5-Aminosalicylic Acid and Treadmill Exercise More Effectively Improves Ulcerative Colitis in Mice.

Ulcerative colitis (UC) is characterized by continuous mucosal ulceration of the colon, starting in the rectum. 5-Aminosalicylic acid (5-ASA) is the main therapy for ulcerative colitis; however, it has side effects. Physical exercise effectively increases the number of anti-inflammatory and anti-immune cells in the body. In the current study, the effects of simultaneous treatment of treadmill exercise and 5-ASA were compared with monotherapy with physical exercise or 5-ASA in UC mice. To induce the UC animal model, the mice consumed 2% dextran sulfate sodium dissolved in drinking water for 7 days. The mice in the exercise groups exercised on a treadmill for 1 h once a day for 14 days after UC induction. The 5-ASA-treated groups received 5-ASA by enema injection using a 200 μL polyethylene catheter once a day for 14 days. Simultaneous treatment improved histological damage and increased body weight, colon weight, and colon length, whereas the disease activity index score and collagen deposition were decreased. Simultaneous treatment with treadmill exercise and 5-ASA suppressed pro-inflammatory cytokines and apoptosis following UC. The benefits of this simultaneous treatment may be due to inhibition on nuclear factor-κB/mitogen-activated protein kinase signaling activation. Based on this study, simultaneous treatment of treadmill exercise and 5-ASA can be considered as a new therapy of UC.

Fecal calprotectin and platelet count predict histologic disease activity in pediatric ulcerative colitis: results from a projection-predictive feature selection.

Especially for pediatric patients, proxies of mucosal inflammation are needed. The Pediatric Ulcerative Colitis Activity Index (PUCAI) has been established to predict clinical and endoscopic disease activity. However, histologic inflammation might persist. We applied a special variable selection technique to predict histologic healing in pediatric ulcerative colitis (UC) as parsimoniously (but still as precisely) as possible. The retrospective analysis included data from two study cohorts, comprising 91 visits from 59 pediatric patients with UC. A Bayesian ordinal regression model was used in combination with a projection-predictive feature selection (PPFS) to identify a minimal subset of clinical and laboratory parameters sufficient for the prediction of histologic disease activity. Following the PPFS, CEDATA-GPGE patient registry data were analyzed to investigate the relevance of the selected predictors in relation to PUCAI and Physician Global Assessment (PGA) in up to 6697 patient visits. Fecal calprotectin (FC) and platelet count were identified as the minimal subset of predictors sufficient for prediction of histologic disease activity in pediatric UC. FC and platelet count also appeared to be associated with increasing disease activity as measured by PUCAI and PGA in the CEDATA-GPGE registry. Based on the selected model, predictions can be performed with a Shiny web app. Conclusion: Our statistical approach constitutes a reproducible and objective tool to select a minimal subset of the most informative parameters to predict histologic inflammation in pediatric UC. A Shiny app shows how physicians may predict the histologic activity in a user-friendly way using FC and platelet count. To generalize the findings, further prospective studies will be needed. What is Known: • Histologic healing is a major endpoint in the therapy of ulcerative colitis (UC). • The PUCAI score has been established to predict disease activity in pediatric UC but is not suitable for the prediction of histologic healing. What is New: • Our Bayesian ordinal regression model in combination with a projection-predictive feature selection is a reproducible and objective tool to select the minimal subset of clinical and laboratory parameters to predict histologic inflammation in pediatric UC. • Histologic inflammation in pediatric UC can be non-invasively predicted based on the combination of fecal calprotectin levels and platelet count.

Effects of Thiopurine Withdrawal on Vedolizumab-Treated Patients With Ulcerative Colitis: a Randomized Controlled Trial

Background and aimsThe impact of thiopurine de-escalation whilst on vedolizumab versus continuing thiopurine therapy in ulcerative colitis (UC) is unclear. We aimed to determine the effect of thiopurine withdrawal for patients with UC in remission on vedolizumab. MethodsThis multi-centre randomized controlled trial recruited UC patients on vedolizumab 300mg IV every 8 weeks and a thiopurine. Patients in steroid-free clinical remission for ≥6 months and endoscopic remission/improvement (Mayo endoscopic subscore[MES]≤1) were randomized 2:1 to withdraw or continue thiopurine. Primary outcome was comparing week 48 vedolizumab trough concentrations. Secondary outcomes were clinical relapse (partial Mayo score≥3 and fecal calprotectin>150μg/g or increase in MES≥1 from baseline), fecal calprotectin remission (<150μg/g), C-reactive protein remission (<5mg/L), centrally-read endoscopic remission (MES=0), histologic remission (Nancy index=0), histo-endoscopic remission and adverse events. ResultsIn total, 62 patients were randomized to continue (n=20) or withdraw (n=42) thiopurine. At week 48, vedolizumab trough concentrations were not significantly different between continue and withdrawal groups (14.7μg/mL [IQR:12.3-18.5μg/mL] versus 15.9μg/mL [IQR:10.1-22.7μg/mL] respectively, P=0.36). The continue group had significantly higher fecal calprotectin remission (95.0% [19/20] versus 71.4% [30/42], P=0.03), histologic remission (80.0% [16/20] versus 48.6% [18/37], P=0.02) and histo-endoscopic remission (75.0% [15/20] versus 32.4% [12/37], P=0.002) than the withdrawal group. Histological activity (HR:15.5 [95%CI:1.6-146.5],P=0.02) and prior anti-TNF exposure (HR:6.5 [95%CI:1.3-33.8],P=0.03) predicted clinical relapse after thiopurine withdrawal. ConclusionThiopurine withdrawal did not affect vedolizumab trough concentrations. However, it may increase fecal calprotectin, histologic and histo-endoscopic activity. Histological activity and prior anti-TNF exposure may predict disease relapse upon thiopurine withdrawal for patients using vedolizumab for UC; Australian and New Zealand Trial Registry, number ACTRN12618000812291.

Construction of hyaluronic acid-functionalized magnolol nanoparticles for ulcerative colitis treatment

Oral targeted anti-inflammatory drugs have garnered significant interest in treating ulcerative colitis (UC) due to their potential in reducing medical costs and enhancing treatment efficacy. Magnolol (Mag), a natural anti-inflammatory compound, has demonstrated protective effects against UC. However, its application as an alternative therapeutic agent for UC is limited by poor gastrointestinal stability and inadequate accumulation at inflamed colonic lesions. This study introduces a novel nanoparticle (NPs) formulation based on Mag, functionalized with hyaluronic acid (HA) for targeted UC therapy. Bovine serum albumin (BSA) was modified with 2-thiamine hydrochloride to synthesize BSA·SH. Thiol-ene click reaction with Mag led to the formation of BSA·SH-Mag NPs, which were further modified with HA through dehydration condensation, regular spherical inflammation-targeting HA-BSA·SH-Mag nanoparticles with a charge of −23.6 mV and a particle size of 403 ± 4 nm were formed. In vitro studies revealed significant macrophage targeting and enhanced uptake by colon epithelial cells. Oral administration of HA-BSA·SH-Mag facilitated colon mucosal barrier repair by modulating pro-inflammatory cytokines (TNF-α, IL-6, IL-1β), anti-inflammatory cytokines (IL-10), and tight junction proteins (ZO-1, Claudin, Occludin). Crucially, HA-BSA·SH-Mag was found to inhibit the JAK2/STAT3/NF-κB signaling pathway, reducing DSS-induced colon tissue inflammation. This research provides valuable insights into the oral use of natural compounds in UC therapy, highlighting the therapeutic potential of HA-BSA·SH-Mag NPs.

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.

Development of an emulsion composition with fennel and caraway essential oils for use in the combined therapy of ulcerative colitis

The aim of the study is to develop the composition of an emulsion containing essential oils of Fennel and Caraway seeds for use in the symptomatic complex therapy of ulcerative colitis with the aim of eliminating functional intestinal disorders. Materials and methods. The objects of the study were samples of emulsions containing active pharmaceutical ingredients (essential oils of Fennel and Caraway), purified water, oils (refined sunflower oil, refined olive oil, refined sesame oil), emulsifiers (polyethylene glycol 40 hydrogenated castor oil, polysorbate 80, polyethylene glycol 100 stearate, acacia gum, guar gum, xanthan gum, soya lecithin), viscosity regulator - apple pectin and flavouring agents (food additives with cherry and tarragon flavour). Organoleptic properties, stability, rheological parameters, pH, particle size determination by microscopy, and a taste test were carried out with model emulsion samples. Research to establish the optimal technological parameters was carried out in parallel. Results. The main parameters of the technological process have been established, which allow to obtain an emulsion with evenly distributed particles: 15 minutes at maximum speed. The concentration of emulsifiers at which the emulsions are stable was selected. It was found that the samples containing polyethylene glycol 100 stearate, gums, and soy lecithin have satisfactory organoleptic properties. The sample with soy lecithin emulsifier differs from the others in its ability to form microemulsions, but it has low viscosity. To improve the rheological properties, apple pectin was added to the emulsion. The taste test showed that among vegetable oils, refined sesame oil has a more neutral taste, and the flavouring additive "Tarkhun" balances the taste better. The release of active pharmaceutical ingredients (APIs) from the emulsion base was confirmed by thin-layer chromatography. Conclusions. A microemulsion with essential oils based on refined sesame oil, soy lecithin, with the addition of viscosity and flavour correctors was developed. The obtained emulsion has satisfactory organoleptic properties and conforms to the requirements for emulsion quality indicators

Probiotics for Inflammatory Bowel Disease; A Deep Dive into Their Impact on Disease Course and Associated Health Risks.

To date, the underlying pathology of inflammatory bowel disease (IBD) is undetermined. Disturbance of intestinal gut microbiota was implicated in many health diseases, including IBD. Increasing evidence suggests that probiotics play a beneficial role in restoring the balance of the gut ecosystem. This review searched multiple databases for relevant works that examined probiotics' possible benefits in adults with IBD. Probiotic mode of action in ulcerative colitis patients and Crohn's disease were examined with respect to probiotic strain, their benefits, and their advantages in adult cases. Eligible studies for inclusion were assessed and analyzed. They were effective in reducing IBD disease course, inducing and maintaining remission, particularly for ulcerative colitis patients, with good efficacy and safety profile. However, the evidence for Crohn's disease was lacking. Probiotics positively affect IBD-related risks, reducing the risk of gastrointestinal malignancy and optimizing treating them. Additionally, they improved reduced fertility odds for both genders. The osteoporosis risk among IBD patients was also reduced, although the duration of use and dose were still not established. There was an encouraging role for them in reducing IBD -cardiovascular risks among cases with acute myocardial infarction and those with chronic heart failure. Finally, they had novel use in reducing IBD-related depression and improved overall mental health. In conclusion, we recommend probiotics as an adjuvant therapeutic option for IBD therapy for ulcerative colitis; however, their role in Crohn's disease needs further research.

Cytokine Profile in Predicting the Effectiveness of Advanced Therapy for Ulcerative Colitis: A Narrative Review.

Cytokine-targeted therapies have shown efficacy in treating patients with ulcerative colitis (UC), but responses to these advanced therapies can vary. This variability may be due to differences in cytokine profiles among patients with UC. While the etiology of UC is not fully understood, abnormalities of the cytokine profiles are deeply involved in its pathophysiology. Therefore, an approach focused on the cytokine profile of individual patients with UC is ideal. Recent studies have demonstrated that molecular analysis of cytokine profiles in UC can predict response to each advanced therapy. This narrative review summarizes the molecules involved in the efficacy of various advanced therapies for UC. Understanding these associations may be helpful in selecting optimal therapeutic agents.

Meta-analysis: Persistence of advanced therapies in the treatment of inflammatory bowel disease.

The expanding options in advanced therapies for ulcerative colitis (UC) and Crohn's disease (CD) present challenges in treatment selection. Persistence analysis assesses drug durability in real-world settings, acting as a surrogate marker for medication efficacy and tolerance. Unlike traditional comparative studies, persistence analysis provides insights extending beyond the initial year of treatment. To provide real-world evidence on treatment effectiveness, tolerability and preferences of physicians and patients regarding various advanced therapies for IBD. We conducted a systematic review of observational studies up to March 2023 assessing advanced therapies' persistence in UC and CD. Advanced therapies under examination included infliximab, adalimumab, vedolizumab, ustekinumab, golimumab, certolizumab and tofacitinib. We pooled the persistence of each agent and conducted a meta-analysis to compare the persistence of newer agents with traditional TNF inhibitors (TNFi)-specifically infliximab and adalimumab. Among 63 observational studies, vedolizumab had the highest 1-year persistence in UC (73.8%, 95% CI: 70.0%-77.6%) and ustekinumab in CD (77.5%, 95% CI: 72.9%-82.1%). Compared to TNFi, vedolizumab demonstrated increased persistence with a relative risk (RR) of 1.30 (95% CI: 1.19-1.41) for UC and 1.14 (95% CI: 1.09-1.20) for CD at 1 year, while ustekinumab demonstrated a RR of 1.15 (95% CI: 1.07-1.23) for CD at 1 year. Vedolizumab exhibited sustained increased persistence in UC over 2 years compared to TNFi (RR: 1.33, 95% CI 1.14-1.54). This meta-analysis highlights the superior persistence of ustekinumab and vedolizumab over TNFi, and offers valuable insights for clinicians navigating the challenging landscape of UC and CD therapeutic choices.

Potential mitigating impact of a dipeptidyl peptidase-IV inhibitor, vildagliptin, on oxazolone-induced ulcerative colitis: Targeting the role of PI3K/AKT/mTOR and AMPK/Nrf2 signaling pathways

Growing evidence suggests that phosphoinositide 3-kinase (PI3K) and adenosine monophosphate-activated protein kinase (AMPK) signaling cascades are critical in ulcerative colitis (UC) pathophysiology by influencing gut mucosal inflammation. Recently, the coloprotective properties of dipeptidyl peptidase-IV (DPP-IV) inhibitors have emerged. Thus, this study assessed for the first time the potential mitigating impact of a DPP-IV inhibitor, vildagliptin (Vilda), on oxazolone (OXZ)-induced colitis in rats, targeting the role of PI3K/AKT/mTOR and AMPK/Nrf2 pathways. Thirty-two adult Albino rats were divided into four groups: control, Vilda (10 mg/kg/day orally), OXZ (300 µL of 5 % OXZ in 50 % aqueous ethanol solution introduced once into the colon via catheter), and Vilda+OXZ. Inflammatory cytokines (interleukin 13, tumor necrosis factor-α, interleukin 10), oxidative/endoplasmic reticulum stress markers (myeloperoxidase, reduced glutathione, catalase, CHOP), mitochondrial reactive oxygen species, adenosine triphosphate levels, and mitochondrial transmembrane potential were estimated. p-AMPK, p-AKT, beclin-1, and SQSTM1 levels were immunoassayed. Nrf2, PI3K, and mTOR expression levels were quantified using the real-time polymerase chain reaction. Furthermore, p-NF-ĸBp65 and LC3II immunoreactivity were evaluated. Vilda administration effectively ameliorated OXZ-induced colitis, as evidenced by the reduced Disease Activity Index, macroscopic colon damage score, colon weight/length ratio, ulcer index, and histopathological and electron microscopic changes in the colon tissues. Vilda treatment also counteracted OXZ-triggered inflammation, oxidative/endoplasmic reticulum stress, mitochondrial dysfunction, and enhanced autophagy in the colon. Vilda substantially suppressed PI3K/AKT/mTOR and activated the AMPK/Nrf2 pathway. Vilda has potent coloprotective and anti-ulcerogenic properties, primarily attributed to its antiinflammatory, antioxidant, and modulatory impact on mitochondrial dysfunction and autophagy activity. These effects were mostly mediated by suppressing PI3K/AKT/mTOR and activating AMPK/Nrf2 signaling cascades, suggesting a potential role of Vilda in UC therapy.

Gut-associated lymphoid tissue attrition associates with response to anti-α4β7 therapy in ulcerative colitis.

Vedolizumab (VDZ) is a first-line treatment in ulcerative colitis (UC) that targets the α4β7- mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1) axis. To determine the mechanisms of action of VDZ, we examined five distinct cohorts of patients with UC. A decrease in naïve B and T cells in the intestines and gut-homing (β7+) plasmablasts in circulation of VDZ-treated patients suggested that VDZ targets gut-associated lymphoid tissue (GALT). Anti-α4β7 blockade in wild-type and photoconvertible (KikGR) mice confirmed a loss of GALT size and cellularity because of impaired cellular entry. In VDZ-treated patients with UC, treatment responders demonstrated reduced intestinal lymphoid aggregate size and follicle organization and a reduction of β7+IgG+ plasmablasts in circulation, as well as IgG+ plasma cells and FcγR-dependent signaling in the intestine. GALT targeting represents a previously unappreciated mechanism of action of α4β7-targeted therapies, with major implications for this therapeutic paradigm in UC.

Effectiveness and Persistency of Ustekinumab Treatment for Ulcerative Colitis: A Phoenix retrospective Cohort Study.

Real-world data regarding ustekinumab (UST) for ulcerative colitis (UC) particularly in biologics-naïve patients is currently limited. This study aimed to elucidate the real-world effectiveness and safety of UST for UC. Overall, 150 patients with UC treated with UST from March 2020 to January 2023 were enrolled across 7 referral hospitals. To assess the clinical efficacy and persistence of UST, retrospective analyses were conducted from weeks 8 to 56. Predictive factors concerning the response and persistence of UST were examined through univariate and multivariate analyses. Of the 150 patients, 125 received UST for remission induction, including 36% biologics-naïve. The response and remission rates were 72.8% and 56.0% at week 8 and 73.2% and 63.4% at week 56, respectively. Biologics-naïve patients represented higher response and remission rates at week 8 (84.4% and 73.3%) than those with biologics exposure (66.2% and 46.2%). Patients with prior antitumor necrosis factor (anti-TNF) and vedolizumab (VDZ) exposure had relatively lower response and remission rates (34.5% and 24.1%, respectively). The 1-year cumulative persistence rate was 84.0%. Multivariate analysis revealed that the chronic continuous type and prior anti-TNF and VDZ exposure were negative predictive factors for week 8 responsiveness. Clinical response at week 8 was a predictor of 1-year persistence. Adverse event incidence remained notably low at 6.4%. This study highlights the safety and effectiveness of UST as an induction and maintenance therapy for UC. Chronic continuous type and previous anti-TNF and VDZ exposure negatively contributed to short-term effectiveness, whereas short-term effectiveness provided good persistency.

A practical guide to selecting and using new ulcerative colitis therapies.

Several new biologics (mirizikizumab) and small molecules (upadacitinib, ozanimod, etrasimod) are approved for the treatment of moderate-to-severe ulcerative colitis. To date, there are no head-to-head trials to guide positioning and use of these newer agents. From phase III clinical trials, in the biologic experienced patient, induction with ozanimod, etrasimod, and mirizikizumab had lower clinical remission rates, whereas upadacitinib's clinical remission rates remained similar. Indirect evidence using network meta-analysis suggests upadacitinib may be more efficacious than other advanced therapies for the treatment of ulcerative colitis in both the bio-naive and experienced patient. Upadacitinib was found to have the highest risk for adverse events. These newer agents add novel mechanisms of action to the expanding therapeutic armamentarium of advanced therapies to treat ulcerative colitis. Based on expert opinion and available data to date, we propose a practical guide on positioning of these new agents for the treatment of ulcerative colitis. In mild-to-moderate disease, one should consider using ozanimod or etrasimod as first-line agents. In moderate-to-severe disease, we favor using mirizikizumab as first-line agent. In patients who have failed an anti-tumor necrosis factor agent, upadacitinib or mirizikizumab should be considered using patient factors and safety to guide one's decision between these two agents.

Selecting first-line advanced therapy for ulcerative colitis: A clinical application of personalized medicine.

Ulcerative colitis (UC) is a chronic autoimmune inflammatory disease that affects the colon, leading to symptoms of bloody diarrhea, abdominal cramps, and urgency. The treatment of UC has evolved over the past few decades from locally active anti-inflammatory compounds to more selective therapies that target specific arrays of the immune system. The challenge of selecting the first advanced therapy became apparent in this rapidly expanding landscape of medications. No current investigational tools, such as genetic, immunologic, or biological markers, can guide the identification of the safest and most effective therapeutic option for each patient. Hence, physicians must carefully assess patient/disease characteristics and match them with the most suitable drug through a clinically driven assessment. In this paper, we outline patient and drug characteristics that play a role in selecting first-line advanced therapies for UC and propose an algorithm for selection.

Mid-infrared spectroscopic identification of the right-baked rhubarb for ulcerative colitis therapy

Clinical and experimental evidences have confirmed the significant therapeutic effects of rhubarb on ulcerative colitis (UC), but the strong purgative function of rhubarb also aggravates UC symptoms such as bloody diarrhea. Stir-baking to scorch is a traditional Chinese medicinal processing method that can eliminate the adverse purgative function while keep or even enhance the UC therapeutic function of rhubarb. However, the under-baked rhubarb still have the undesirable purgative function, but the over-baked rhubarb may lose the required medicinal functions. Therefore, the determination of the right endpoint is the primary quality concern about the baking process of rhubarb. In this research, typical anthraquinone compounds and mid-infrared (MIR) spectra were recruited to determine the best baking degree of rhubarb for UC therapy. Raw rhubarb slices were baked at 180 °C with rotation to prepare the rhubarbs with different baking degrees. The right-baked rhubarb was defined according to the UC therapeutic responses as well as the traditional color criterion. Referring to the typical anthraquinone compounds in rhubarb slices and extracts, the baking degree of rhubarb may be assessed by the conversion ratio of anthraquinone glycosides to anthraquinone aglycones. MIR spectra showed the gradual decompositions of organic compounds including anthraquinone glycosides and tannins during the baking process. Rhubarbs with different baking degrees can be distinguished clearly by MIR-based principal component analysis. In conclusion, the ratio of anthraquinone glycosides to anthraquinone aglycones may be a reasonable chemical indicator of the right-baked rhubarb. Meanwhile, MIR spectroscopy can identify the right-baked rhubarb simply and rapidly.