Acalypha australis L. (AAL), a traditional medicinal herb from the Euphorbiaceae family, has been widely used in Chinese medicine for its heat-clearing, detoxifying, and diuretic properties, as well as for treating gastrointestinal disorders such as diarrhea and dysentery. Its reported anti-inflammatory and hemostatic effects are closely linked to inflammatory pathways. While previous studies have demonstrated AAL's efficacy in acute colitis, its therapeutic potential in chronic colitis and the underlying mechanisms remain largely unexplored.

This study aims to investigate the therapeutic efficacy of AAL in dextran sulfate sodium (DSS)-induced chronic colitis and elucidate its anti-inflammatory and barrier-protective mechanisms, with a specific focus on the FABP4/PPARγ/NF-κB signaling pathway.

The chemical composition of AAL was characterized using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). Chronic colitis was induced in mice through three cycles of DSS administration, and the therapeutic effects of AAL were evaluated by assessing body weight, Disease Activity Index (DAI), colon length, and pathological alterations. Enzyme-linked immunosorbent assay (ELISA) was used to quantify inflammatory cytokine levels. Immunohistochemistry and Western blotting were performed to assess mucosal barrier proteins, including Mucin 2 (MUC2), zonula occludens-1 (ZO-1), and Occludin, as well as key signaling proteins such as fatty acid-binding protein 4 (FABP4), peroxisome proliferator-activated receptor gamma (PPARγ), and phosphorylated P65 (p-P65). Proteomic analysis combined with Gene Set Enrichment Analysis (GSEA) was conducted to identify differentially expressed proteins and enriched pathways. The role of the FABP4/PPARγ/NF-κB axis was further validated using the PPARγ antagonist GW9662. Additionally, molecular docking and molecular dynamics simulations were employed to identify bioactive components in AAL and their interactions with FABP4 and PPARγ.

UPLC-QTOF-MS analysis identified 47 compounds in AAL, including flavonoids, terpenoids, and polyphenols. Bergaptol and corilagin were identified as major constituents with potential anti-inflammatory properties. AAL treatment significantly alleviated chronic colitis symptoms, as evidenced by reduced DAI scores, restoration of body weight, and improved colon length. Pathological and immunohistochemical analyses demonstrated that AAL preserved intestinal mucosal integrity by upregulating MUC2, ZO-1, and Occludin expression. Proteomic and GSEA analyses identified the FABP4/PPARγ/NF-κB pathway as a key target of AAL. Western blotting confirmed that AAL suppressed FABP4 expression, enhanced PPARγ levels, and reduced p-P65 expression, indicating inhibition of NF-κB activation. Notably, the therapeutic effects of AAL were abolished by GW9662, further validating the involvement of PPARγ signaling. Molecular docking and molecular dynamics simulations demonstrated strong binding affinities of bergaptol and corilagin to FABP4 and PPARγ, suggesting their role as active compounds responsible for AAL's therapeutic effects.

AAL effectively mitigates chronic colitis by preserving intestinal barrier integrity, suppressing inflammatory responses, and modulating the FABP4/PPARγ/NF-κB pathway. The bioactive compounds bergaptol and corilagin may contribute to these therapeutic effects, highlighting AAL as a promising natural therapeutic agent for ulcerative colitis.

Medical management of ulcerative colitis (UC) and crohn's sisease (CD) is complex. While there is significant overlap in medical therapies used for UC and CD, there remain few distinct differences in their management. The overall goals of therapy are to achieve disease remission, prevent complications, decrease the need for surgical interventions, and restore patients' quality of life. In the current article, we discuss currently available therapies and their mechanisms, limitations and side effects, followed by a comprehensive discussion of key consideration points in regards to the medical management.

Ulcerative colitis (UC) is a chronic, relapsing and remitting, inflammatory bowel disease. Monoclonal antibodies targeting interleukin (IL)-23p19 have been developed to treat chronic inflammatory diseases mediated by aberrant IL23/Th17 responses, including psoriasis, psoriatic arthritis, and Crohn's disease. More recently, these agents have been evaluated for the treatment of moderately-to-severely active UC.

In this review, we summarize and discuss phase 2 and pivotal phase 3 clinical trials informing the efficacy and safety of mirikizumab (AMAC, LUCENT, and SHINE), risankizumab (INSPIRE, COMMAND), and guselkumab (QUASAR, VEGA). The literature search included original research publications, secondary publications, and preliminary data from conference abstracts presented at international gastroenterology meetings from the past 5 years.

The approval of IL23p19 antagonists expands the armamentarium of effective and safe therapies for patients living with moderately-to-severely active UC. These agents demonstrate potent efficacy for both inducing and maintaining symptomatic and objective disease endpoints, including endoscopic, histologic, and biomarker remission. These well-tolerated agents are effective in both advanced treatment-naïve and experienced patients. Accordingly, IL23p19 antagonists have the potential to be used in a diverse population of patients with UC, and as potential platform therapies for future combinations with other targeted immunomodulatory agents.

Targeted immunomodulators (eg, advanced therapies) effectively achieve symptomatic remission in patients with inflammatory bowel disease (IBD). However, ~25%-50% of patients with IBD achieving symptomatic remission with an advanced therapy may have continued endoscopically/radiologically active bowel inflammation, and it is uncertain whether changing alternative advanced therapies in asymptomatic patients with IBD will reduce bowel inflammation and achieve durable deep remission.

The QUality Outcomes Treating IBD to Target (QUOTIENT) study is an open-label, multicentre, pragmatic, randomised, controlled trial that aims to compare the efficacy and safety of switching to an alternative advanced therapy targeting endoscopic/radiological remission (treat-to-target) versus continuing the initial, or index, advanced therapy, in asymptomatic patients with IBD with moderate-to-severe endoscopic/radiological bowel inflammation. Enrolment is planned for ~250 participants in Canada/USA, randomised 1:1 to switching to alternative advanced therapy or continuing index advanced therapy, and then followed 104 weeks within routine clinical practice. Patient-reported outcomes measure efficacy and quality of life/treatment burden/safety. Primary endpoint is the time from randomisation to treatment failure.

The study is conducted in compliance with the protocol, ICH Good Clinical Practice, applicable regulatory requirements and appropriate review boards/independent ethics committees (approval numbers: Pro00077486; Pro00061437; STUDY00002062; 22-004171; i22-01269; IRB22-0890; IRB_00154397; 2000032384; SHIRB#2022.095-2; STUDY00007146; MMC#2024-18; REB#125290; 17784; Pro00142214; 20240660-01H), with documented written informed consent. Findings will be disseminated through peer-reviewed journals, scientific presentations, and publicly available Patient-Centered Outcomes Research Institute (PCORI) websites, including lay summaries. The Crohn's & Colitis Foundation Education, Support, and Advocacy Department, and our patient advocacy stakeholder, will develop educational and marketing resources to communicate findings to a broad audience (>250 000 patients/caregivers/healthcare professionals).

NCT05230173.

Acute severe ulcerative colitis (ASUC) is a life-threatening medical emergency affecting over 20% of patients with ulcerative colitis (UC). Up to 40% of patients are refractory to intravenous corticosteroids (IVCS) and require rescue medical therapy or immediate colectomy. The potent Janus kinase (JAK) inhibitors, upadacitinib and tofacitinib, have proven efficacy in a randomised control trial setting for moderate-to-severe UC, but not ASUC. We describe a case series of sequential rescue therapy with JAK inhibitors following the failure of dose-intensified infliximab in corticosteroid-refractory ASUC. Six adult (>16 years old) patients received sequential rescue therapy with a JAK inhibitor (upadacitinib n = 5, tofacitinib n = 1) following failure of IVCS and dose-intensified infliximab at the Royal Brisbane and Women's Hospital (QLD, Australia) between October 2023 and April 2024. All patients met the Truelove and Witts criteria for ASUC on admission. Data were captured during admission and at 90-days post-discharge. Co-primary outcomes were 90-day colectomy-free survival and inpatient clinical response (<4 non-bloody stools per day) 72 h after JAK-inhibitor initiation. Secondary outcomes included 90-day clinical (PRO-2 score < 1) and biochemical (faecal calprotectin (FCP) < 150 µg/g and C-reactive protein (CRP) < 5 mg/L) corticosteroid-free remission and adverse events. Median CRP on admission was 100 mg/L (interquartile range (IQR) 58-105), median FCP 3400 µg/g (IQR 910-4950) and median Mayo Endoscopic Score 3. Four out of six patients had a clinical response within 72 h of sequential JAK-inhibitor rescue therapy. Two patients underwent emergent inpatient colectomy for refractory disease - one of whom developed post-operative sepsis. Among the four JAK-responders at 90 days, all achieved corticosteroid-free clinical remission and three achieved biochemical remission. No other adverse events were recorded. There is a promising role for JAK inhibitors as sequential rescue therapy following the failure of dose-intensified infliximab in select patients with corticosteroid-refractory ASUC.

Tumor necrosis factor α (TNF-α) inhibitors are widely used to treat inflammatory bowel disease (IBD), but systematic risk assessment of infectious toxicity is still lacking.

We used disproportional analysis to calculate infection-related risk signals for four TNF-α inhibitors and compared them with infection-related signals for seven other therapies.

There were 55,379 reports of infection-related adverse events (AEs) with TNF-α inhibitors as a 'primary suspect (PS)' therapy. The median time to onset of infection-related AEs was 113 days (interquartile range [IQR] 14-612). TNF-α inhibitors present the strongest infectious toxic signal than interleukin 12/23 (IL-12/23) inhibitors, integrin blockers, Jak inhibitors, and S1P receptor modulator. Compared with infliximab, certolizumab pegol, and adalimumab, golimumab showed the strongest signal. The strongest signal corresponding to appendicitis, pulmonary tuberculosis, pneumonia, sepsis, urinary tract infection, otitis media and herpes zoster is golimumab, infliximab, golimumab, natalizumab, certolizumab pegol, infliximab, and infliximab.

Compared with other control therapies, TNF-α inhibitors have the strongest infectious toxicity signal. Compared with other TNF-α inhibitors, golimumab has the strongest infectious toxicity signal. When using TNF-α inhibitors to treat IBD, infection-related AEs should be vigilant.

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) characterized by chronic inflammation of the colonic mucosal lining.

This study aimed to examine unmet needs among patients with UC in Spain.

Data were analyzed from the Adelphi Real World IBD Disease Specific Programme™, a cross-sectional survey of physicians and patients with IBD in Spain between October 2020 and March 2021.

Physicians reported patient clinical characteristics, disease severity, treatment patterns and satisfaction, symptoms, and flare and remission status. Patients were then invited to voluntarily self-complete a form reporting health-related quality of life (HRQoL) and work productivity/activity impairment. Analyses were descriptive.

Overall, 57 physicians reported data for 410 patients with UC presenting a high disease severity profile. The mean (standard deviation) patient age was 45 (15) years, with 88% presenting with moderate-to-severe UC at diagnosis. In the survey, 75% and 63% of patients were treated with conventional therapy and biologics, respectively. After treatment initiation, patients had lower disease severity, but 29% of patients had moderate-to-severe disease despite receiving biologics or Janus kinase inhibitors. Overall, 81% of patients and 86% of physicians were satisfied with treatment. Among patients classified as having moderate-to-severe UC, commonly reported symptoms included abdominal pain (41%), bowel urgency (37%), and bloody diarrhea (37%). The mean number of flares experienced in the past year was 1.7, lasting on average >30 days. Consequently, the HRQoL of these patients was impaired.

While disease severity appeared to be lower after the initiation of current treatment, and despite the high prevalence of treatment satisfaction, almost a third of patients remained classified as moderate-to-severe, experiencing symptoms, flares, and impaired HRQoL. Therefore, there is a need for new therapeutic alternatives to target patient unmet needs.

Inflammatory bowel disease (IBD), particularly ulcerative colitis (UC), is a chronic inflammatory disorder characterized by an unclear etiology, often linked to gut microbiota dysbiosis and immune dysregulation. Existing UC therapies are constrained by suboptimal efficacy and adverse effects, underscoring the necessity for novel therapeutic strategies. Diosmin (DIO), a naturally occurring flavonoid, has demonstrated anti-inflammatory and antioxidant potential, yet its precise mechanisms and therapeutic role in colitis remain poorly understood.

This study aimed to investigate the therapeutic efficacy and mechanistic underpinnings of DIO in dextran sulfate sodium (DSS)-induced colitis, with a focus on its effects on intestinal epithelial cell PANoptosis, gut microbiota composition, fecal metabolites, and an in vitro inflammatory model using human colonic epithelial cells.

A controlled experimental design was employed, utilizing a DSS-induced murine colitis model and an LPS-induced inflammatory model in human colonic epithelial cells (NCM460). Mice were allocated into four groups: normal control, DSS-induced colitis, low-dose DIO (DIO-L, 100 mg/kg), and high-dose DIO (DIO-H, 200 mg/kg). In vitro experiments involved treating NCM460 cells with varying DIO concentrations post-LPS stimulation to assess its impact on inflammation and epithelial barrier integrity.

Mice were administered DIO orally at 100 mg/kg or 200 mg/kg daily. Therapeutic outcomes were evaluated through body weight monitoring, Disease Activity Index (DAI) scoring, and histopathological examination. Gut microbiota composition was analyzed via 16S rRNA sequencing, while untargeted metabolomics was employed to profile fecal metabolites. Data integration was performed using O2PLS and WGCNA to identify microbiota-metabolite correlations. In vitro, immunofluorescence staining and Western blotting were utilized to evaluate the expression of tight junction proteins (ZO-1, E-cadherin, and Occludin).

DIO administration significantly ameliorated colitis symptoms in mice, as evidenced by attenuated weight loss, reduced DAI scores, and preserved colon length. Histopathological analysis confirmed diminished inflammation and tissue damage in DIO-treated groups. Mechanistically, DIO suppressed the expression of PANoptosis-associated genes and proteins, including ZBP1 and Caspase-1, while maintaining epithelial barrier integrity in vitro. Furthermore, DIO modulated gut microbiota composition, promoting beneficial taxa such as Ruminococcus and reducing pathogenic Proteobacteria. Metabolomic profiling revealed alterations in key metabolic pathways, including flavonoid and steroid hormone biosynthesis, which correlated with microbiota changes.

DIO effectively mitigates DSS-induced colitis by inhibiting intestinal epithelial cell PANoptosis, preserving barrier function, and modulating gut microbiota and metabolite profiles. These findings highlight DIO's potential as a therapeutic agent for IBD and warrant further exploration of its clinical applications.

Inflammation significantly influences thrombosis development, with venous thromboembolism (VTE) risk linked to various systemic inflammatory diseases, but not fully established in inflammatory bowel disease (IBD). Using a population-based cohort study conducted in Taiwan, we investigated the impact of IBD on the risk of VTE, deep vein thrombosis (DVT), and pulmonary embolism (PE), as well as the impact of anti-IBD treatments.

A study was conducted on a cohort of patients with IBD diagnosed between 2010 and 2019 using the National Health Insurance database. The risks of VTE, DVT, and PE, as well as anti-IBD treatment use, were examined using Cox proportional hazard regression analysis.

The overall number of person-years recorded for 12,126 patients with IBD (mean age: 49.18 years; 55.31% male) and 12,126 controls (mean age: 49.19 years; 55.31% male) was 64,057 and 72,056, with a follow-up duration for the two cohorts was 5.28 and 5.94 years, respectively. After adjusting for age, gender, and comorbidities, the adjusted hazard ratios (aHRs) of VTE, DVT, and PE in patients with IBD were 5.58 [95% confidence interval (CI) = 3.97-7.87], 5.48 (95% CI = 3.83-7.86), and 4.96 (95% CI = 2.00-12.35) times higher, respectively, than those in the control cohort. Male patients with IBD and those under the age of 50 were more likely to develop VTE (aHR = 8.54, 95% CI = 2.00-12.35; aHR = 15.75, 95% CI = 5.73-43.26, respectively). Compared to the cohort of patients with IBD receiving no treatment, patients receiving anti-IBD treatments did not show a significant change in the risk of developing VTE. Additionally, compared to the IV steroid cohort, patients with IBD who only used oral steroids had a substantially lower incidence of VTE, particularly with average doses of ≤ 80 mg (aHR = 0.24, 95% CI = 0.10-0.59).

Patients with IBD are at an increased risk of developing VTE, particularly DVT and PE. While our study found that anti-IBD treatments did not significantly alter this risk, proactive management of associated factors and close monitoring remains essential for preventing VTE in this population. Identifying and addressing specific associated factors should be prioritized in clinical practice to mitigate the heightened risk of VTE in IBD patients.

While corticosteroids are not recommended for maintenance of remission in inflammatory bowel disease (IBD), they are quite effective for the induction of remission for both Crohn's disease (CD) and ulcerative colitis (UC). We aimed to evaluate if a delay in starting corticosteroids after presentation to the hospital for an acute IBD exacerbation increased the likelihood of poor outcomes.

Retrospective cohort study of IBD-related hospitalizations from 7 area hospitals in Austin, Texas between 2015 and 2020. Patients were included if admitted for an IBD flare and received corticosteroids. CD with intra-abdominal abscesses were excluded. Primary outcomes were length of stay (LOS), ICU stay, IBD-related surgery, and mortality.

Of 478 inpatients, 311 (65%) received corticosteroids within 12 h of arrival. ICU stays (4.2% vs. 5.4%, p = 0.88, early vs. late corticosteroids) and inpatient mortality (1.0% vs. 1.8%, p = 0.75) were not significantly different between groups. However, after adjustment for confounders, LOS (4.7 vs. 5.8 days, p = 0.027) was significantly shorter and IBD-related surgery (3.5% vs. 7.2%, p = 0.048) was reduced for those receiving corticosteroids early. On subgroup analysis, these findings remained significant only for patients with CD and not UC.

For patients admitted with IBD flares without associated abscess, there was an increased LOS and increased risk for IBD-related surgery if corticosteroid therapy was delayed > 12 h after arrival. Guidelines recommend treating acute flares without delay, but guidance on specifics of timing is absent. Our data suggests that treatment should be started within 12 h of presentation, particularly for those with CD.

Patients' and gastroenterologists' views on the relative importance of treatment outcomes and medication attributes for ulcerative colitis (UC) may differ. We aimed to explore which treatment outcomes and medication attributes are considered important by both for therapeutic decisions.

Eight gastroenterologists and 23 patients with UC in Greece participated in semi-structured interviews and focus groups, respectively. The focus groups and interviews were audio-recorded, transcribed and coded, utilizing thematic analysis until data saturation was achieved.

Themes that were discussed included the impact of UC on daily life, UC-related outcomes, drug-related attributes and the patient-doctor relationship. Within these themes, disparities between the perspectives of gastroenterologists and patients were evident on 2 main issues. Gastroenterologists prioritized clinical remission and emphasized long-term objectives, such as mucosal healing, while patients focused on shorter-term outcomes, such as the early and sustained relief of symptoms. Regarding medication attributes, important factors for patients were primarily those that impacted their daily life, such as route of administration, dosage and the need for hospital visits. In contrast, gastroenterologists were more concerned about potential adverse events and non-responsiveness to treatment. There was a consensus regarding the importance of shared decision-making for UC management, emphasized by both patients and clinicians.

Gastroenterologists mostly prioritize objective measures of remission, while patients mainly focus on factors related to their quality of life and overall well-being. Enhancing communication regarding different goals and expectations may strengthen the physician-patient relationship, ultimately resulting in better shared therapeutic decision-making.

Inflammatory bowel disease (IBD) is rising at an alarming rate in south Asia and there is a paucity of data on IBD in this region. For this scoping review, we conducted a systematic search to identify all observational and interventional studies on IBD in south Asia. Of 14 924 potentially eligible studies, 524 were included in this scoping review and summarised under the domains of epidemiology, natural history, phenotype and comorbid conditions, therapeutics, and psychosocial health. According to the literature, IBD incidence and prevalence are rising in south Asia and among south Asian immigrants, and the diagnostic rate is higher in men than in women. Genetic predisposition is an important risk factor in south Asia, whereas environmental risk factors are less clear. Delay in diagnosis, although possibly decreasing over time, is common in south Asia and is associated with worse outcomes. There are no clear differences in IBD phenotype and severity in south Asia relative to Europe and North America. Corticosteroids and immunomodulators are the mainstay of treatment in south Asia whereas the use of biologics is less common. Mental health disorders, malnutrition, and reduced quality of life are prevalent in patients with IBD in south Asia, and the use of complementary and alternative medicines among patients is an important consideration. Key knowledge gaps include the paucity of data from countries other than India, prospective, long-term, follow-up studies, and clinical drug trials in south Asia. IBD is a growing challenge in this region and warrants urgent clinical interventions, research, resource allocation, and health policy implementation.

Tofacitinib is an oral Janus kinase inhibitor for the treatment of ulcerative colitis (UC).

To investigate potential predictors of efficacy in RIVETING.

This post hoc analysis included patients with UC in stable remission (⩾6 months) on tofacitinib 10 mg twice daily (BID) maintenance therapy (⩾2 years of treatment), who received tofacitinib 5/10 mg BID in RIVETING.

Achievement of modified Mayo (mMayo) remission, remission (based on total Mayo score), partial Mayo score (PMS) remission, and modified PMS (mPMS) remission at month (M)6 was analyzed by baseline characteristics, duration of PMS remission at RIVETING entry, biomarkers, and patient-reported outcomes (PROs) to identify factors associated with achieving/maintaining efficacy outcomes, including following dose reduction.

Seventy patients received tofacitinib 5 mg BID. At M6, PMS remission was maintained in 66.7%, 60.0%, 82.4%, 75.0%, and 90.0% of patients with baseline PMS remission durations of 6 to ⩽12, >12 to ⩽24, >24 to ⩽36, >36 to ⩽48, and >48 months, respectively. Patients in mMayo remission at M6 had smaller increases in PMS at M1 compared with those not in mMayo remission at M6, while numerically higher proportions of patients with a stool frequency subscore/rectal bleeding subscore/mPMS of 0 at M1/M3 achieved most efficacy endpoints at M6 compared with patients with respective subscores >0. Maintenance of mMayo remission was independent of the number of tumor necrosis factor inhibitors failed and/or prior corticosteroid use. In multivariable models (which included tofacitinib 10 mg BID data), endoscopic subscores (1 vs 0) at RIVETING baseline were significantly associated with lower odds of mMayo remission at M6 (odds ratio, 0.33; 95% confidence interval, 0.11-0.94; p = 0.0379).

Prior duration of remission/baseline endoscopic subscore may help guide tofacitinib dose reduction, while PROs may be useful early indicators of efficacy. Close monitoring of patients following dose reduction could identify those unlikely to achieve/maintain efficacy. Trial registration: ClinicalTrials.gov: NCT03281304.

Maintenance of remission is essential in inflammatory bowel disease (IBD) in terms of disease course and long-term prognosis. The thiopurines azathioprine and 6-mercaptopurine have longstanding merit in ulcerative colitis, but more therapeutic options have been developed. This review is an update and extension of a review last published in 2016.

To assess the effectiveness and safety of azathioprine and 6-mercaptopurine in monotherapy or combined therapy regimens compared to placebo or active controls for the maintenance of remission in ulcerative colitis.

We searched Cochrane Central Register of Controlled Trials (until May 2023), ClinicalTrials.gov (until May 2023), Embase (until August 2022), MEDLINE (until May 2023), and WHO ICTRP (until May 2023). We checked reference lists of the included studies and, if needed, contacted the authors to request more data or information.

Randomized controlled trials (RCTs) of at least 24 weeks' duration comparing azathioprine or 6-mercaptopurine with placebo or any other medication, or comparing different treatment modalities of azathioprine or 6-mercaptopurine, in persons of any age with quiescent ulcerative colitis were eligible. We only considered studies with mixed IBD populations or with a preceding induction period if separate results on participants with ulcerative colitis in remission were available or could be calculated. The primary outcome was failure to maintain clinical or endoscopic remission (relapse). Secondary outcomes included change in disease activity, quality of life, hospitalization, need for surgery, days off work, adverse events, and withdrawal due to adverse events.

Two authors independently extracted data using standard forms, resolved any disagreements by consensus, and assessed study quality using the Cochrane risk of bias tool (RoB 2). We conducted separate analyses by type of control, calculated pooled risk ratios (RRs) or risk differences (RDs) using the fixed-effect model unless heterogeneity was likely, and assessed the certainty of evidence using the GRADE approach.

We included 10 studies in the review, including 468 adult participants with ulcerative colitis. The risk of bias across these was low for most outcomes, but we considered some outcomes to have some concerns or high risk of bias due to insufficient information on concealment of allocation and outcome measurement. Based on five placebo-controlled studies, azathioprine or 6-mercaptopurine may reduce the risk of failing to maintain remission. In the thiopurine group, 45% (64/143) of participants failed to maintain remission compared to 67% (96/143) of participants receiving placebo (RR 0.66, 95% confidence interval (CI) 0.54 to 0.82; 5 studies, 286 participants; low-certainty evidence). Three studies reported withdrawals due to adverse events. Among participants on azathioprine, 4% (3/80) withdrew due to adverse events compared to 0% (0/82) of placebo participants (RD 0.04, 95% CI -0.02 to 0.09; 3 studies, 162 participants; low-certainty evidence). The evidence is of low certainty when comparing 6-mercaptopurine to 5-aminosalicylate. Based on one three-armed trial, 27% (3/11) of 6-mercaptopurine participants failed to maintain remission compared to 100% (2/2) of 5-aminosalicylate participants (RR 0.35, 95% CI 0.13 to 0.97; 1 study, 13 participants; low-certainty evidence). This trial also involved an induction phase; we only included the results for participants in remission. The single trial comparing 6-mercaptopurine to 5-aminosalicylate did not report separate data on adverse events and withdrawals due to adverse events for the subgroup with successful induction of remission, so we could not analyze these outcomes for this comparison.

Low-certainty evidence suggests that azathioprine or 6-mercaptopurine therapy may be more effective than placebo for the maintenance of remission in ulcerative colitis. More research is needed to evaluate the value of therapeutic drug monitoring and the effects of various treatment modalities on long-term safety.

Data indicate that earlier initiation of anti-tumor necrosis factor alpha (anti-TNF-α) biologic medicines may prevent progression to irreversible bowel damage and improve outcomes for patients with inflammatory bowel disease (IBD), particularly Crohn's disease. However, the high cost of such therapies may restrict access and prevent timely treatment of IBD. Biosimilar anti-TNF-α medicines may represent a valuable opportunity for cost savings and optimized patient outcomes by improving access to advanced therapies and allowing earlier anti-TNF-α treatment initiation. Biosimilar anti-TNF-α medicines have been shown to offer consistent therapeutic outcomes to their reference medicines, yet despite entering the IBD treatment armamentarium over 10 years ago, their implementation in clinical practice remains suboptimal. Factors limiting the 'real' use of biosimilar anti-TNF-α medicines may include an ongoing lack of understanding and acceptance of biosimilars by both healthcare professionals (HCPs) and patients, as well as systemic factors such as formulary decisions outside of the control of the prescriber. In this review, an expert panel of gastroenterologists discusses HCP-level considerations to improve biosimilar anti-TNF-α utilization in IBD in order to support early anti-TNF-α initiation and maximize patient outcomes.

Objectives: This bibliometric analysis investigates recent research trends in biologics and small molecules for treating inflammatory bowel disease (IBD) based on literature from the past decade. Methods: This cross-sectional study involved analyzing data retrieved from the Web of Science Core Collection (WoSCC) database to examine the evolution and thematic trends of biological agents and small-molecular drugs for IBD conducted between 1 January 2014, and 20 September 2024. VOSviewer software was utilized to assess co-authorship, co-occurrence, co-citation, and network visualization, followed by a further discussion on significant sub-themes. Results: From 2014 to 20 September 2024, the annual number of global publications increased by 23%, reflecting an acceleration in research activity. The journal "Inflammatory Bowel Diseases" published the highest number of manuscripts (579 publications) and garnered the most citations (13,632 citations), followed by the "Journal of Crohn's & Colitis" (480 publications) and "Alimentary Pharmacology & Therapeutics" (250 publications). The United States led in productivity with 1943 publications and 66,320 citations, with UC San Diego (291) and authors Sandborn and Vermeire (180) topping the list. The co-occurrence cluster analysis of the top 100 keywords resulted in the formation of six distinct clusters: Disease Mechanisms, Drug Development, Surgical Interventions, Therapeutic Drug Monitoring (TDM), Immunological Targets, and Emerging Therapies. Burst terms (TNF-α inhibitors, JAK inhibitors, and trough-level optimization) highlight trends toward personalized biologics and small-molecule regimens. Conclusions: The bibliometric analysis indicates that IBD therapeutic research and clinical applications focus on biologics and small molecules, with research trends leaning toward precise therapy conversion or the combination in non-responders. Future work will assess monotherapy, the combination, and conversion therapies and investigate new drugs targeting inflammatory pathways.

Ulcerative colitis (UC) is an inflammatory bowel disease in which one-quarter of patients are at risk of developing a severe form of the disease known as acute severe UC (ASUC). This condition exposes patients to serious complications, including toxic megacolon, surgical intervention, and even death. The current therapeutic strategy relies on time-dependent, multi-step algorithms that integrate systemic corticosteroids, calcineurin inhibitors, and biologic agents (specifically infliximab) as medical therapy aimed at avoiding colectomy. Despite this approach, a significant proportion of patients fail to respond to either corticosteroids or infliximab and may require alternative therapeutic options if there is no urgent surgical necessity. These alternatives include other biologics or emerging small molecules, although the evidence supporting these treatments remains extremely low, even considering their well-documented and promising efficacy and safety in moderate-to-severe UC. Conversely, it is necessary to investigate whether infliximab can be effectively replaced or surpassed by other approved biological agents and small molecules as first-line therapy after steroid resistance. This review aims to summarise the available evidence on small molecules, specifically Janus kinase inhibitors and sphingosine-1-phosphate receptor modulators.

Background/Objectives: Therapeutic management of inflammatory bowel diseases (IBD) is rapidly evolving in the era of novel biological therapies. However, real-world data relating to the usage trends and treatment persistence remain inconsistent. This study aimed to investigate trends in biological use, dose intensification, and treatment persistence in IBD patients, who received treatment in a large tertiary center in Greece. Methods: Patients with IBD who underwent at least one biological treatment between 2018 and 2022 were included in this retrospective study. Data on patients' demographics, type of disease, use of biologicals, dose intensification, and treatment persistence were analyzed for time trends. Results: Data from 409 patients with IBD (mean age 39 (range 17-87), female 51%, 56.9% CD, mean duration of disease: 9.3 years) were included in the study. The number of patients on biologics was raised from 133 in 2018 to 368 in 2022 (a 28.1% yearly increase), while the percentage of patients who were treated with anti-TNF biosimilars increased to >60% of the total anti-TNF population in 2022. We observed a gradual increase in non-anti-TNF therapies in bio-naïve patients, in particular vedolizumab (46% of all biologicals in UC; 16% in CD) and ustekinumab (16.3% of all biologicals in UC, 31% in CD). The 3-year persistence rate of IFX was 64% in CD and 56% in UC, whereas it was 61% for ADA in CD. Dose intensification of anti-TNF was efficient in >50% of CD patients and >30% of UC patients; however, the majority of patients who required dose escalation within the first year eventually became unresponsive. The 3-year persistence of vedolizumab as a first-line treatment was 82% for CD and 69% for UC, respectively. The 3-year persistence of ustekinumab as first-line treatment for CD was 65%. No significant differences regarding the efficacy of anti-TNF, ustekinumab, or vedolizumab were detected when they were used as first-line treatments for Crohn's disease; similarly, no significant differences were detected between infliximab and vedolizumab as first-line treatments for UC. Conclusions: There was a gradual increase in the use of biologicals, including biosimilars, between the years 2018-2022, reflecting adherence to current guidance with adoption of an early escalation strategy. Newer, post-anti-TNF biologics such as vedolizumab and ustekinumab have been rapidly incorporated into therapeutic approaches for both CD and UC.

Valeriana jatamansi Jones (V. jatamansi), a traditional Chinese medicine, is widely used in the treatment of gastrointestinal disorders, such as ulcerative colitis (UC). However, the active components of V. jatamansi with protective effect on the intestinal barrier remains elusive.

This investigation was conducted to confirm the efficacy of V. jatamansi ethanol extract for the treatment of UC and to identify the active compounds in ethanol extract of V. jatamansi that have a protective effect against intestinal barrier damage.

The role of V. jatamansi extract was assessed on dextrose sodium sulfate (DSS) induced colitis in vivo. The wound healing, apoptosis and epithelial barrier permeability of intestinal epithelial cells (NCM460 cells) were evaluated in vitro. UHPLC-MS method was used to determine the pharmacokinetic characteristics of V. jatamansi extract after oral administration. The effect of absorbed compounds on the intestinal barrier was assessed on NCM460 cells. Fuzzy matter-element analysis was used to explore the main compounds, and the results were verified by FITC-dextran assay. Network pharmacology was used to predict the potential mechanisms and western blotting was used to validate the results.

The ethanol extract ofV. jatamansi relieves symptoms, inflammatory response and intestinal barrier damage in DSS-induced UC. It effectively alleviated DSS-induced epithelial barrier damage in NCM460 cells. Pharmacokinetic analyses indicated that the five components (chlorogenic acid, hesperidin, valerosidate, isochlorogenic acid B and cryptochlorogenic acid) were quickly absorbed into the blood after oral administration of ethanol extract. The fuzzy matter-element analysis and FITC-dextran assay demonstrated that valerosidate and chlorogenic acid played an important role in the protection of the intestinal barrier damage. Network pharmacological analyses and western blotting analyses showed that the ethanol extract of and absorbed components significantly inhibited the Bcl-2/Bax/Caspase-3 signaling pathway, and suppressed DSS-induced apoptosis in NCM460 cells.

The ethanol extract of V. jatamansi ameliorates intestinal barrier injury in UC mice through multi-components. Valerosidate and chlorogenic acid were identified as anti-colitis compounds. These provided new insights into finding the active components for the treatment of UC and contribute to the clinical application of V. jatamansi.

This article comments on the letter by Lowell et al, which addresses the next generation of combination therapy for inflammatory bowel disease (IBD). As the understanding of the pathogenesis of IBD continues to improve, treatment strategies are evolving rapidly. The letter examines the current status and future directions of combination therapy for IBD, focusing on approaches that combine biologics with immunomodulators and the emerging dual-biologic therapy (DBT). The traditional combination of biologics and immunomodulators has demonstrated preliminary efficacy by enhancing the effects of biologics through immunomodulation. However, concerns regarding long-term safety warrant careful evaluation. Recent trials, including DUET-Crohn's disease and DUET-ulcerative colitis, have shown promising potential for the broader adoption of DBT. Nevertheless, comprehensive data on efficacy and safety, as well as the effective integration of supportive treatments, remain essential to establish new paradigms for the next generation of IBD care.

Widespread use of ocrelizumab, an anti-CD20 monoclonal antibody, for treating patients with multiple sclerosis (MS), has led to an increase in reported adverse events following real-world observation. Among these, drug-induced colitis is a rare, but severe side effect, prompting a recent FDA statement regarding this safety concern. Objectives: We analyzed a cohort of ocrelizumab treated patients in our MS center to evaluate the incidence of drug-induced colitis.

We present a critical review of the available literature on diagnosis and management of anti-CD20 induced colitis and display a case series of 3 suspected patients in our cohort.

Two patients met the full criteria for ocrelizumab-induced colitis, while a third partially met the criteria. Following symptomatic treatment and discontinuation of ocrelizumab, the patients showed favorable outcomes.

Ocrelizumab-induced colitis is a rare, but severe adverse event. Its incidence may be higher than expected, reaching 1,95% in our cohort of MS patients. Further reporting of such cases is essential to broaden our understanding of this side effect.

Several therapeutic advances have been achieved over the past two decades for inflammatory bowel disease (IBD). The expanding therapeutic armamentarium and the increasingly ambitious treatment targets have led to an increased use of advanced therapies and better outcomes. Nevertheless, many patients remain suboptimally treated and are at risk of disease progression, hospital admission, and surgery, even when advanced therapies are cycled, escalated, or combined. Conversely, IBD can also be characterised by an indolent disease course. Top-down and treat-to-target strategies, although beneficial in a substantial proportion of patients, might not be advantageous in patients with mild disease and might risk overtreatment. Identifying patients with mild activity and a benign disease trajectory in the long-term is important; unnecessary exposure to advanced therapies increases the risk of adverse events and increases financial costs and health-care resource utilisation. This Review details the importance of adopting clinical strategies to avoid the pitfalls of undertreating and overtreating IBD.

Although studies have compared on-treatment effectiveness of infliximab and vedolizumab in patients with ulcerative colitis (UC), there has been limited comparison of treatment sequencing and long-term patient-centred outcomes.

To compare infliximab-first and vedolizumab-first strategy in biologic-naïve patients with UC.

We conducted a retrospective cohort study in biologic-naïve patients with UC who were treated first with either infliximab or vedolizumab between 2015 and 2021 and followed over 30 months following initiation. Primary outcomes were the number of hospitalisations, corticosteroid courses and serious infections with either strategy (regardless of switch to alternative therapies) within 30 months. We matched the groups 1:1 through cardinality matching, and fit logistic and zero-inflated negative binomial models to compare outcomes.

We included 181 patients (94 vedolizumab-first and 87 infliximab-first treatment strategy). Of these, 144 were matched 1:1. There was no significant difference in the incidence of IBD-related hospitalisations (incidence rate ratio [IRR], 1.98 [95% CI, 0.64-6.10]), corticosteroid courses (0.66 [0.38-1.15]) and serious infections (5.26 [0.62-45.45]), with comparable incidence of medication switches to alternative advanced therapies (1.08 [0.42-2.81]). At 30 months, there was no difference in proportion of patients in clinical remission (69.4% vs. 76.4%; p = 0.45) and endoscopic remission (55.6% vs. 65.3%; p = 0.36).

In patients with UC, long-term effectiveness and safety outcomes are comparable with infliximab-first and vedolizumab-first treatment strategies at 30 months. This can help to guide selection of treatment strategies in patients with UC.

Inflammaging, a state of chronic, progressive low-grade inflammation during aging, is associated with several adverse clinical outcomes, including frailty, disability, and death. Chronic inflammation is a hallmark of aging and is linked to the pathogenesis of many aging-related diseases. Anti-inflammatory therapies are also increasingly being studied as potential anti-aging treatments, and clinical trials have shown benefits in selected aging-related diseases. Despite promising advances, significant gaps remain in defining, measuring, treating, and integrating inflammaging into clinical geroscience research. The Clin-STAR Inflammation Research Interest Group was formed by a group of transdisciplinary clinician-scientists with the goal of advancing inflammaging-related clinical research and improving patient-centered care for older adults. Here, we integrate insights from nine medical subspecialties to illustrate the widespread impact of inflammaging on diseases linked to aging, highlighting the extensive opportunities for targeted interventions. We then propose a transdisciplinary approach to enhance understanding and treatment of inflammaging that aims to improve comprehensive care for our aging patients.

To describe potential drug-drug interactions (DDIs) with oral advanced therapies among patients with ulcerative colitis (UC) and characterize clinical assessments before ozanimod initiation.

Adults with UC were selected from the Merative MarketScan Commercial Database (01 January 2018-31 January 2023); the index date was the most recent UC diagnosis. Patients had no other immune conditions in the 12-month baseline period before the index date. Those with moderate-to-severe UC were analyzed separately. Potential baseline DDIs were identified as claims for medications that may cause a moderate/severe DDI with Janus kinase (JAK) inhibitors (tofacitinib/upadacitinib) or ozanimod according to the Merative Micromedex Complete Drug Interactions Tool. Clinical assessments before ozanimod initiation were characterized.

Of 58,870 patients with UC, 24,654 (41.9%) had moderate-to-severe UC. All potential DDIs with ozanimod were severe, while JAK inhibitors had moderate and severe potential DDIs. Among patients with UC, mean (standard deviation) number of severe DDIs was 2.0 (2.4) for ozanimod and 0.2 (0.5) for JAK inhibitors; in moderate-to-severe UC, it was 2.3 (2.6) for ozanimod and 0.4 (0.6) for JAK inhibitors. The most common potential DDIs for ozanimod in UC and moderate-to-severe UC were ondansetron (18.6% and 22.7%), azithromycin (11.9% and 12.8%), as well as hydrocodone, fentanyl, albuterol, ciprofloxacin, and metronidazole (9.0%-11.0% each). For JAK inhibitors, these were COVID-19 vaccines (30.7% and 31.4%), infliximab (8.5% and 20.2%), fluconazole (6.1% and 6.8%), and azathioprine (5.5% and 13.0%). Among patients initiating ozanimod, the first claim for a required clinical assessment was on average, 8 months before initiation.

Comorbidities and polypharmacy among patients with UC pose a high risk of DDIs for oral advanced therapies and required pre-treatment clinical assessments can be complicated. This justifies a thorough review of patient profiles for prescribers considering novel treatment options.

Large-scale multicentre studies are needed to understand complex relationships between the gut microbiota, health and disease. Interrogating the mucosal microbiota may identify important biology not captured by stool analysis. Gold standard tissue cryopreservation ('flash freezing') limits large-scale study feasibility. We aimed to compare gut microbiota in gold standard and pragmatic mucosal biopsy storage conditions.

We collected endoscopic recto-sigmoid biopsies from 20 adults with inflammatory bowel disease. Biopsies were preserved using three methods: (i) flash freezing (most proximal and distal biopsy sites); (ii) nucleic acid preservative reagents (QIAGEN Allprotect®, Invitrogen RNAlater™, and Zymo DNA/RNA Shield™); and (iii) formalin fixation with paraffin embedding (FFPE), which is used to preserve tissue for clinical histopathology within healthcare settings. Microbiota were sequenced on the MiSeq platform (V4 region, 16S rRNA gene).

Tissue microbiota were consistent between most proximal and distal tissue suggesting any within-patient variation observed reflected storage condition, not biopsy location. There was no significant difference in alpha-diversity or microbial community profiles of reagent-preserved versus gold standard tissue. FFPE community structure was significantly dissimilar to other tissue samples, driven by differential relative abundance of obligate gut anaerobes; Faecalibacterium, Anaerostipes and Lachnospiraceae. Despite these differences, tissue microbiota grouped by participant regardless of preservation and storage conditions.

Preservative reagents offer a convenient alternative to flash freezing tissue in prospective large-scale mucosal microbiota studies. Whilst less comparable, FFPE provides potential for retrospective microbiota studies using historical samples.

Medical Research Council (MR/T032162/1) and The Leona M. and Harry B. Helmsley Charitable Trust (G-2002-04255).

Inflammatory bowel disease (IBD), encompassing ulcerative colitis and Crohn's disease, is a group of chronic, immune-mediated disorders of the gastrointestinal tract that present substantial clinical challenges owing to their complex pathophysiology and tendency to relapse. A treat-to-target approach is recommended, involving iterative treatment adjustments to achieve clinical response, reduce inflammatory markers and achieve long-term goals such as mucosal healing. Lifelong medication is often necessary to manage the disease, maintain remission and prevent complications. The therapeutic landscape for IBD has evolved substantially; however, a ceiling on therapeutic efficacy remains and surgery is sometimes required (owing to uncontrolled disease activity or complications). Effective IBD management involves comprehensive care, including medication adherence and a collaborative clinician-patient relationship. This Review discusses current therapeutic options for IBD, detailing mechanisms of action, efficacy, safety profiles and guidelines for use of each drug class. We also explore emerging therapies and the role of surgery. Additionally, the importance of a multidisciplinary team and personalized care in managing IBD is emphasized, advocating for patient empowerment and involvement in treatment decisions. By synthesizing current knowledge and emerging trends, this Review aims to equip healthcare professionals with a thorough understanding of therapeutic options for IBD, enhancing informed, evidence-based decisions in clinical practice.

Several conditions exist that do not have their own unique diagnosis code in widely-used clinical terminologies, making them difficult to track and study. Acute severe ulcerative colitis (ASUC) is one such condition. There is no automated method to identify patients admitted for ASUC from observational data, nor any specific billing or diagnosis code for ASUC. Accurate, automated, large-scale identification of hospital admissions for non-coded conditions like ASUC may enable further research into them.

We performed a retrospective cohort study of patients with a history of ulcerative colitis (UC) admitted to a single academic institution from 2014-2019. Clinicians at our institution performed a chart review of these admissions to determine if each was due to a true episode of ASUC or not. Logistic regression, random forest (RF), and support vector machine (SVM) models were trained upon administrative claims data for all admissions.

268 ASUC admissions and 3,725 non-ASUC admissions among UC patients were included. Our RF model exhibited the best performance, correctly classifying 95.5% of admissions as either ASUC or non-ASUC, with a validation AUROC of 0.96 (95% CI 0.94-0.98; AUPRC 0.73). The model had a sensitivity of 81.5% and specificity of 96.5%. The five most important features in the model were endoscopy of sigmoid colon, length of stay, age, endoscopy of rectum, and abdominal x-ray.

There is currently no modality by which ASUC, which does not have its own unique diagnosis code, can be identified from claims databases in a scalable fashion for research or clinical purposes. We have developed a machine learning-based model that identifies clinically significant ASUC and reliably distinguishes them from admissions for non-ASUC reasons among UC patients. The ability to automatically curate large, accurate datasets of non-coded conditions like ASUC episodes can serve as the basis of large-scale analyses to maximize our ability to learn from real-world data, enable future research, and better understand these diseases.

Mesalazine is a widely used medication for treating mild to moderate inflammatory bowel disease (IBD). First identified as a potential cause of acute pancreatitis (AP) in 1989, the link between mesalazine and AP has primarily been established through case reports and a limited number of retrospective studies. This study aims to explore the characteristics of mesalazine-induced AP.

The databases of CNKI, Wanfang Data, VIP, PubMed and Web of Science were searched (up to March, 2024), and the case reports of mesalazine-related AP in IBD patients were collected and descriptively analyzed.

Thirty-four reports were included, describing 42 patients (22 males, 16 females, 4 unspecified) with mesalazine-related AP. The onset of pancreatitis occurred a median of 14 days (range 1-730 days) after starting mesalazine. Common symptoms included abdominal pain (100%), vomiting (38.1%), fever (21.4%), and nausea (21.4%). Most patients had elevated serum amylase and lipase levels, with some showing raised C-reactive protein and erythrocyte sedimentation rate. Imaging tests, such as computed tomography and B-scan ultrasonography, revealed edematous infiltration and inflammation. Discontinuation of mesalazine led to symptom resolution in all patients, with 93.3% improving within a week. Alternative treatments or switching to other forms of 5-aminosalicylic acid may be considered for ongoing management. Rechallenge with mesalazine led to recurrence of AP in 21 cases, with a shorter median time to symptom onset.

Mesalazine-induced AP is a rare but significant adverse reaction, not related to drug dosage, and can occur at any point during treatment, typically within two weeks. The reaction can recur upon rechallenge. Discontinuation of mesalazine and symptomatic treatment typically resolves the condition.

Ulcerative colitis is a chronic inflammatory condition of the colon driven by aberrant immune activation. Although advanced medical therapies form the cornerstone of ulcerative colitis management, unmet needs include failure to induce and sustain remission in a substantial proportion of patients and in managing acute severe ulcerative colitis. We review new treatment strategies that might improve patient outcomes in the management of moderate-to-severe ulcerative colitis.

A literature search was conducted using the PubMed database, including studies published from inception to October 2024, selected for their relevance. Recognizing current limitations, this article reviews strategies to improve treatment outcomes in ulcerative colitis using advanced therapies. These approaches include early treatment initiation, dose optimization, positioning newer agents as first-line therapies, combination therapy, targeting novel therapeutic endpoints, and the management of acute severe ulcerative colitis.

The strategies discussed may contribute to establishing new standards of care aimed at achieving long-term remission and enhancing patient outcomes. Personalized therapy, which tailors treatment based on individual disease characteristics and risk factors, is anticipated to become a critical aspect of delivering more effective care in the future.

Tofacitinib has been approved for the treatment of patients with moderate-to-severe ulcerative colitis independently of prior therapies. We aimed to assess the efficacy and safety of tofacitinib in biologic-naive patients.

This was a retrospective analysis of prospectively collected data extracted from the notes of patients with moderate-to-severe ulcerative colitis naive to advanced therapies, who were treated with tofacitinib [10 mg twice daily (b.i.d.) for 8 or 16 weeks followed by a 5 mg b.i.d. maintenance dose] in six Greek Hospitals, who had a follow-up of at least 26 weeks after treatment initiation.

Overall, 48 patients were included. Clinical response was seen in 30 (62.5%) and 32 (66.6%) patients at week 8 and 16, respectively. Clinical remission, corticosteroid-free clinical remission, biochemical response, and endoscopic remission at week 26 was observed in 26 (54.2%), 26 (54.2%), 28 (60.8%), and 29 (60.4%) patients, respectively. No major adverse events or infections were recorded.

In this retrospective ongoing cohort study, tofacitinib demonstrated clinical response at weeks 8 and 16 in more than 60% and steroid-free clinical remission at week 26 in more than 50% of biologic-naive patients with moderate-to-severe ulcerative colitis with a good safety profile, indicating that tofacitinib is an effective first-line treatment for this group of patients.

Periplanta americana extract (PAE), a traditional Chinese medicine (TCM) from Shen Nong Ben Cao Jing, has been used to treat ulcerative colitis (UC), various types of wounds and ulcers, infantile malnutrition, palpitation, asthma, and so on. However, the exact mechanisms of PAE in UC have still not been fully revealed. The study aims to explore the therapeutic effects and mechanisms of PAE in UC.

The efficacy of PAE was evaluated using a DSS-induced UC mice model and the colon inflammation and mucosal barrier were comprehensively assessed. Furthermore, Network pharmacological analysis was utilized to identify potential targets and signaling pathways of PAE in the UC treatment. The proportion and the markers of Th17 and Treg cells in the spleen and colon were examined. The signal transduction was detected in vivo. In vitro, an activated Notch1-mediated Th17/Treg was modeled, and the effect of PAE on the epithelial cell barrier was examined.

PAE mitigated colon inflammation and intestinal barrier damage in UC mice. Network pharmacological analysis showed that the targets of UC intervention by PAE may be closely related to Th17 cell differentiation, the IL-17 signaling pathway, and cytokine-cytokine receptor interaction. Mechanistically, PAE regulated the balance of Th17/Treg and inhibited the Notch1/Math1 pathway in the colon of UC mice. In vitro, PAE intervention alleviated the activated Notch1-mediated Th17/Treg imbalance in Jurkat T cells. After notch1-activated Jurkat T cells were co-cultured with HCoEpic cells, the expressions of Occludin, ZO1 were higher in the HCoEpic cells.

PAE could alleviate colon inflammation and mucosal barrier damage in UC, which are related to the inhibition of Notch1 and the regulation of the Th17/Treg balance. PAE might be a potential candidate agent for UC treatment.

It is unknown which maintenance therapy is the most effective option for patients admitted for an acute severe ulcerative colitis (ASUC) episode responding to intravenous steroids.

We conducted a multicentre, parallel-group, open-label randomised controlled trial among 23 French centres in thiopurine and biologics-naïve adults admitted for ASUC responding to intravenous steroids. Eligible patients were randomly assigned to receive infliximab (IFX) and azathioprine (AZA) with a 7-day steroid tapering scheme (IFX+AZA arm) or AZA and conventional standardised steroid tapering regimen (AZA arm). The primary composite endpoint was treatment failure at week 52, defined as the absence of steroid-free clinical remission, the absence of endoscopic response, the use of a prohibited treatment for relapse, severe adverse event leading to treatment interruption, colectomy or death. Multiple imputation for missing data was performed.

Among the 64 patients randomised (Lichtiger score 13.5±2.0; median age of 34.5 (P25-P75 26.3-50.3) years, median C reactive protein of 29.0 (12.8-96.8) mg/L at baseline): 32 were assigned to the IFX+AZA arm and 32 to the AZA arm. In the ITT population, treatment failure at week 52 was observed in 22/27 (81.5%) in the AZA arm and 16/30 (53.3%) in the IFX+AZA arm (risk ratio 3.85, 95% CI (1.15 to 12.88), p=0.03). 29 adverse events were severe, including 13 disease exacerbations, 6 severe infections without any difference between both arms.

Combination therapy with IFX+AZA was more effective at 1 year than AZA alone to avoid treatment failure in patients with ASUC responding to intravenous steroids.

NCT02425852.