Mesalazine Treatment Research Articles

Huang Qin decoction increases SLC6A4 expression and blocks the NFκB-mediated NLRP3/Caspase1/GSDMD pathway to disrupt colitis-associated carcinogenesis

Huang Qin decoction (HQD) is a traditional Chinese medicine formula for treating colitis, but the effects and molecular mechanism of action of HQD in colitis-associated carcinogenesis (CAC) are still unclear. Therefore, we aimed to determine the beneficial effects of HQD on CAC in mice and to reveal the underlying mechanism involved. AOM/DSS was used to induce CAC in mice, and the effects of HQD on tumorigenesis in mice were examined (with mesalazine serving as a positive control). Mesalazine or HQD treatment alleviated body weight loss and decreased the disease activity index in mice induced by AOM/DSS. Mesalazine or HQD treatment also suppressed the shortening of colon tissue length, the number of tumors, and the infiltration of inflammatory cells. The genes targeted by HQD were predicted and verified, followed by knockout experiments. Elevated SLC6A4 and inhibited serotonin production and inflammation were observed in HQD-treated mice. HQD inhibited the NFκB and NLRP3/caspase1/GSDMD pathways. The therapeutic effect of HQD was diminished in SLC6A4-deficient AOM/DSS mice. Additionally, the downregulation of SLC6A4 mitigated the inhibitory effect of HQD-containing serum on MODE-K cell pyroptosis. Our findings suggest that SLC6A4 is a pivotal regulator of HQD-alleviated CAC via its modulation of the NLRP3/caspase1/GSDMD pathway.

Intestinal nontuberculous mycobacteria infection: A case report.

Intestinal nontuberculous mycobacteriosis due to nontuberculous mycobacteria infection has clinical manifestations similar to intestinal tuberculosis and inflammatory bowel disease, causing difficulties in clinical diagnosis. A 42-year-old male patient was admitted to the Sino-Japanese Friendship Hospital of Jilin University in June 2021 for diarrhea and intermittent hematochezia since April 2021. He was diagnosed with inflammatory intestinal disease by colonoscopy and midtransverse colon biopsy. However, the symptoms did not relieve after 2 months of mesalazine treatment. In August 2021, the patient was admitted to the outpatient department for suspected "intestinal tuberculosis." A diagnosis of intestinal nontuberculous mycobacteriosis was confirmed based on pathology and nucleotide-based matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS). After 2 weeks of antimycobacterial therapy, the patient's diarrhea was relieved, and hematochezia no longer appeared. In November 2021, recolonoscopy revealed scattered erosions and ulcers in ileocecal valve and ascending colon, while both nucleotide-based MALDI-TOF MS and next-generation sequencing could still detect Mycobacterium intracellulare. This study reported a patient with an intestinal nontuberculous mycobacteriosis diagnosed by colonoscopy biopsy and nucleotide-based MALDI-TOF MS, and symptoms were relieved after antimycobacterial treatment.

P177 Beta-CGRP in inflammatory bowel disease: a protective neuropeptide of the gut

Abstract Background Experimental models indicate that beta calcitonin gene-related peptide (beta CGRP), libertated by enteric neurons, has a potential role on gastrointestinal mucosa homeostasis, but its real role is not well profiled. We measured beta-CGRP circulating levels in a cohort of subjects with a recent diagnosis of inflammatory bowel disease (IBD), to assess the potential role of this neuropeptide in its pathogenesis. Methods Morning serum beta-CGRP levels were measured by ELISA (CUSABIO, China) in 96 consecutive patients recently diagnosed of IBD patients (< 1 year) and compared with those belonging to 50 matched healthy controls (HC) and 50 chronic migraine (CM) patients matched by age and sex. We only allowed treatment with either steroids or mesalazine, and registered cardiovascular comorbidities, autoimmune concomitant diseases or extraintestinal manifestations. Statistical analysis was made using SPSS®. Results Beta CGRP concentrations were lower in IBD patients (3.1±1.9 pg/mL; 2.9 [2.4-3.4] pg/mL) when comparted to HC (4.7±2.6; 4.9 [4.0-5.8] pg/mL; p<0.001) and CM patients (4.6±2.6; 4.7 [3.3-6.2] pg/mL; p<0.001). Respecting IBD subtypes, beta-CGRP levels were lower in ulcerative colitis patients (3.0±1.9pg/mL; 2.5 [2.1-3.4] pg/mL) as well as Crohn’s disease patients (3.3±2.0 pg/mL; 3.2 [2.4-3.9] pg/mL) to those of HC (p<0.01 and p<0.05, respectively) and CM (p<0.01 and p<0.05, respectively). Beta-CGRP levels in CM did not differ to those with HC (p=0.92). There were no significant differences when patients were classified by presence/absence of cardiovascular risk factors (yes: 3.1±1.7 pg/mL; no: 3.2±2.1 pg/mL; p=0.93); autoimmune comorbidities (yes: 3.4±1.4 pg/mL; no: 3.1±2.0 pg/mL; p=0.24); mesalazine treatment (yes: 3.1±1.9 pg/mL; no: 3.2±1.9 pg/mL; p=0.91); or steroid treatment (yes: 3.0±1.9 pg/mL; 3.2±1.9 pg/mL; p=0.52). Main characteristics and main results are exposed in table 1 and figure 1. Conclusion The reduction in serum beta-CGRP concentrations y patients with recent diagnosis of IBD, compared to two control groups, strongly supports a role for this neuropeptide in the pathophysiology of the disease since its early stages. This decrease was found in both IBD subtypes. Our data indicate a protective role of beta-CGRP in the homeostasis of the gastrointestinal tract. This study has been co-funded by Instituto de Salud Carlos III (ISCIII) through the project PI20/01358 and by Fondos Europeos de Desarrollo Regional (FEDER), "Una manera de hacer Europa".

P534 The preference for controlled-release mesalazine formulation of 2 g-granule sachet in patients already experienced 1 g-tablet

Abstract Background The important factor is a good adherence in the treatment of inflammatory bowel disease (IBD) and the major guidelines recommend that the choice of formulation of mesalazine should consider patient preference and likely adherence. This study was to evaluate the preference for controlled-release (CR) mesalazine 2 g-granule sachet in patients who have been already experienced CR mesalazine 1 g-tablet and its related clinical factors. Methods First was treatment with 4 g CR mesalazine a day as two 2 g-granule sachets for 2 weeks in patients with IBD in remission who have already taken 4 g CR mesalazine a day as four 1 g-tablets for more than 3 months in Kosin University Gospel Hospital, Korea. The patients were consecutively enrolled. Second were the patients’ survey with 10 questionnaires about preferences (Table 1) after the 2 week-treatment and medical review of clinical information of patients. Results A total of 80 patients (46 in ulcerative colitis and 34 in Crohn’s disease, and 54 of male) were enrolled. Previous use of CR mesalazine four 1 g-tablets a day more than 1 year was in 88.6% of patients. In preference of formulation by ease to swallow, 70.0% of patients answered 2 g-granule sachet was better but just 20.0% of patients answered 1 g-tablet was better. In preference of formulation by next prescription, that is about overall preference, 63.8% of patients answered granule was better but 30.0% for tablet. In the number of 1 g-tablet or 2 g-granule sachet able to be swallowed at once, 46.9% of patients could swallow one or less tablet (1 g or less) and 96.1% of patients could swallow one or two sachets (2 g or more) (Fig. 1). When the patients who chose ‘granule was much better or better in overall preference' are classified as granule preference group and the remaining as others group. Number of tablet able to be swallowed at once in the medication before the granule trial was significantly less in granule preference group compared to others group (1.6 tablet vs. 2.0 tablet) (Fig. 2). However, the other factors including age, sex, body weight, height, body mass index, type of disease, concomitant oral medications, previous duration of 1 g-tablet use, were not associated with the overall preference. Conclusion In patients already experienced CR mesalazine 1 g-tablet for a long time, two-thirds of the patients more preferred to be prescribed 2 g-granule sachet and the preference was associated with the ability to swallow 1 g-tablets at once. Not only CR mesalazine 1 g-tablet but also 2 g-granule sachet can be an excellent choice for improving adherence of mesalazine treatment in IBD, especially when it comes to patients who can't take two or more 1 g-tablets at once.

P1023 Variability in Mesalazine Management for Ulcerative Proctitis Include Doses, Route of Administration and Use of Fecal Calprotectin: Insights from Clinical Practice Across Spain Beyond Clinical Guidelines

Abstract Background Despite universal use of mesalazine in ulcerative colitis treatment, many aspects of clinical practice remain unclear or are not even addressed in clinical guidelines, leading to significant variations in mesalazine management among clinicians. We aimed to gather different approaches of mesalazine use in ulcerative proctitis (UP). Methods After discussion of a clinical case, a predefined questionnaire was anonymously answered throughout a series of meetings held at 10 different locations in Spain. Results were categorized according to experience levels and inflammatory bowel disease (IBD) focus. Results 259 IBD treating gastroenterologists were engaged; 84% had <10 years of experience and 25% had a specific focus on IBD. Most participants (84%) manage UP based on clinical symptoms (i.e. fecal urgency). In case of a clinically moderate-severe UP, 81% would initiate treatment with high dose of combined mesalazine, while 11% proposed only suppositories. 60% of participants would assess response at 4 weeks. If clinical remission achieved, 85% would use fecal calprotectin (FC) to assess deep remission. Upon initial failure of combined mesalazine treatment at standard dose, 59% attempt optimizing mesalazine doses, while 38% add beclomethasone dipropionate. Younger physicians without specific focus on IBD prefer modifying mesalazine doses (70.5% vs 37.1%), (P=0,006), whereas more experienced physicians with monographic dedication prefer adding beclomethasone dipropionate (60% vs 29.4%), (P=0,006). For maintenance therapy (oral or topical mesalazine) the most important drivers in therapeutic decision-making were severity of the initial flare (40%) and patient preferences (36%). After a moderate-severe flare of UP, 80% would recommend maintenance therapy with high dose oral mesalazine and 3 suppositories/week. For monitoring, less experienced physicians and those not working in IBD units more frequently relied only on clinical parameters (26.6% vs. 8.7%, p=0.01), using FC to a lesser extent (73% vs. 88%, p=0.1) compared to more experienced and IBD focused physicians. In the case of elevated FC in asymptomatic patients, 49% would prefer to scope, while 47% increase mesalazine dose directly. The preferred high dose of mesalazine was 4g (55%) or 4-5g (44%). 73% would not reduce the dose upon achieving remission. Only 75% actively investigate therapeutic adherence. Conclusion Management of mesalazine in UP patients is highly heterogeneous, and clinical guidelines do not address all issues arising in clinical practice. Nevertheless, clinicians in our setting often use high oral and rectal mesalazine doses for both induction and maintenance and they commonly monitor patients using FC.

Management of Concurrent Immune Thrombocytopenia and Ulcerative Colitis: A Case Report and Literature Review.

We herein report a case of concurrent immune thrombocytopenia (ITP) and ulcerative colitis (UC) that achieved remission following mesalazine treatment. A 16-year-old girl presented with severe thrombocytopenia, abdominal pain, and bloody stool. She was initially diagnosed with ITP and then was treated with prednisolone, resulting in an immediate improvement of symptoms. Upon tapering the steroids, the symptoms recurred, thus leading to a subsequent diagnosis of UC via colonoscopy. Treatment with mesalazine promptly induced the remission of both ITP and UC, which was sustained. We reviewed 24 previously documented cases in which the simultaneous flares of UC and ITP were successfully managed.

Faecalibacterium prausnitzii, Bacteroides faecis and Roseburia intestinalis attenuate clinical symptoms of experimental colitis by regulating Treg/Th17 cell balance and intestinal barrier integrity

Ulcerative colitis (UC) is a severe inflammatory bowel disease (IBD) characterized by multifactorial complex disorders triggered by environmental factors, genetic susceptibility, and also gut microbial dysbiosis. Faecalibacterium prausnitzii, Bacteroides faecis, and Roseburia intestinalis are underrepresented species in UC patients, leading to the hypothesis that therapeutic application of those bacteria could ameliorate clinical symptoms and disease severity. Acute colitis was induced in mice by 3.5% DSS, and the commensal bacterial species were administered by oral gavage simultaneously with DSS treatment for up to 7 days. The signs of colonic inflammation, the intestinal barrier integrity, the proportion of regulatory T cells (Tregs), and the expression of pro-inflammatory and anti-inflammatory cytokines were quantified. The concentrations of SCFAs in feces were measured using Gas–liquid chromatography. The gut microbiome was analyzed in all treatment groups at the endpoint of the experiment. Results were benchmarked against a contemporary mesalazine treatment regime. We show that commensal species alone and in combination reduced disease activity index scores, inhibited colon shortening, strengthened the colonic epithelial barrier, and positively modulated tight junction protein expression. The expression level of pro-inflammatory cytokines was significantly reduced. Immune modulation occurred via inhibition of the loss of CD4 +CD25 +Treg cells in the spleen. Our study proofed that therapeutic application of F. prausnitzii, B. faecis, and R. intestinalis significantly ameliorated DSS-induced colitis at the level of clinical symptoms, histological inflammation, and immune status. Our data suggest that these positive effects are mediated by immune-modulatory pathways and influence on Treg/Th17 balance.

Investigation of mesalazine as an antifibrotic drug following myocardial infarction in male mice.

Myocardial infarction (MI) initiates a complex reparative response during which damaged cardiac muscle is replaced by connective tissue. While the initial repair is essential for survival, excessive fibrosis post-MI is a primary contributor to progressive cardiac dysfunction, and ultimately heart failure. Currently, there are no approved drugs for the prevention or the reversal of cardiac fibrosis. Therefore, we tested the therapeutic potential of repurposed mesalazine as a post-MI therapy, as distinct antifibrotic effects have recently been demonstrated. At 8 weeks of age, MI was induced in male C57BL/6J mice by LAD ligation. Mesalazine was administered orally at a dose of 100 μg/g body weight in drinking water. Fluid intake, weight development, and cardiac function were monitored for 28 days post intervention. Fibrosis parameters were assessed histologically and via qPCR. Compared to controls, mesalazine treatment offered no survival benefit. However, no adverse effects on heart and kidney function and weight development were observed, either. While total cardiac fibrosis remained largely unaffected by mesalazine treatment, we found a distinct reduction of perivascular fibrosis alongside reduced cardiac collagen expression. Our findings warrant further studies on mesalazine as a potential add-on therapy post-MI, as perivascular fibrosis development was successfully prevented.

Treatment with gut-specific nonsteroidal anti-inflammatory drug attenuates metabolic inflammation but not body mass in fattening ground squirrels.

The active season of hibernators corresponds to rapid adiposity in preparation for the next hibernation season. We have previously shown that this dramatic increase in adipose mass is associated with metabolic inflammation similar to what is seen in obesity and metabolic disease. We next sought to determine whether curbing this inflammation at its source (i.e., the gut) would attenuate weight gain in fattening 13-lined ground squirrels (Ictidomys tridecemlineatus). We fed active yearling ground squirrels a diet containing the gut-specific nonsteroidal anti-inflammatory drug mesalazine (5-aminosalicylic acid) for 10 wk. Mesalazine treatment had slight effects on microbial community diversity in the cecum and colon. Not surprisingly, mesalazine treatment decreased inflammatory cytokine levels in the ileum and colon. Mesalazine also decreased proinflammatory and increased anti-inflammatory cytokines in omental white adipose tissue (oWAT). Despite this, body mass was unaffected, and caloric intake increased in mesalazine-treated squirrels, mainly in males. Mass of the primary WAT depot, intra-abdominal WAT (iaWAT), or the highly metabolic oWAT were unaltered by treatment, as was adiposity index. Together, these results suggest that mesalazine treatment has some effects on adiposity in fattening ground squirrels, but this treatment needs to be modified to overcome the strong drive to fatten in this species.NEW & NOTEWORTHY Adiposity and obesity are caused, at least in part, by inflammation of metabolic tissues. Hibernators, like ground squirrels, undergo this same metabolic inflammation during their summer fattening period. We attempted to curb this inflammation, and thus fattening, using mesalazine. We found that mesalazine did curb the inflammation but did not affect fattening, likely due to the strong drive to fatten in hibernators.

Saccharina japonica Ethanol Extract Ameliorates Dextran Sulfate Sodium-Induced Colitis via Reshaping Intestinal Microenvironment and Alleviating Inflammatory Response.

Saccharina japonica belongs to brown macro-alga with various potential health benefits; its antioxidant and anti-inflammatory activities indicate the potential to improve inflammatory bowel diseases. Here, the potential anti-colitis effect of Saccharina japonica extract (SJE) was evaluated on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in C57B/L6 mice. The mice were treated with mesalazine (MES) and various doses of SJE by gavage for 14 days. Results showed that both MES and SJE treatment decreased the disease activity index scores, relieving the short colon. SJE increased the occludin and zonula occludens-1 levels, and the beneficial effects were better than MES. MES and SJE exerted similar effects in decreasing inflammatory cytokines and oxidative stress. Moreover, SJE reshaped the intestinal microbiota by increasing α-diversity and reducing plenty of harmful bacteria. Dietary SJE was significant to relieving the reduction in short-chain fatty acids. The results revealed the protective effect of SJE on colitis and potential mechanisms, which is important for the rational use of SJE in UC prevention.

The Prevalence of Inflammatory Bowel Disease in Greenland.

Inflammatory bowel disease (IBD) is sparsely investigated in Arctic populations. The aim of this study was to estimate the prevalence of ulcerative colitis (UC) and Crohn's disease (CD) in Greenland. Cross-sectional nationwide data on demography, anthropometry, biochemistry, and pharmacotherapy were extracted from the electronic medical records in Greenland. Diagnoses of UC and CD were based on International Classification of Diseases-Tenth Revision and International Classification of Primary Care-Second Edition coding and treatment with mesalazine. Data from Statistics Greenland were used for prevalence calculations. In total, 254 patients in Greenland experienced IBD, with 214 cases of UC and 40 cases of CD. The overall IBD prevalence was 0.45%, distributed as 0.38% with UC and 0.07% with CD. The IBD prevalence was similar across the 5 regions of Greenland. However, a higher prevalence was observed in the region main towns with the largest populations (0.53%) compared with the small towns along the coastline (0.29%). UC patients were prescribed mesalazine treatment with a frequency of 78%. Furthermore, 10% of all IBD patients received treatment with nonspecific immunomodulators and 7% received biologics. This study estimates the prevalence and uncovers characteristics of IBD in Greenland. Although CD may be underdiagnosed or less prevalent, the overall prevalence of IBD in Greenland parallels Scandinavian countries and North America. These results boost the knowledge on autoimmune diseases in arctic populations and may guide clinicians in their management of IBD in Greenland. Furthermore, the results may encourage research in IBD across the Arctic regions.

Meta Analysis of Mesalazine Combined with Chinese Herbal Compound Enema in the Treatment of Ulcerative Colitis

To evaluate the clinical efficacy of mesalazine combined with Chinese herbal compound enema in the treatment of ulcerative colitis, we searched CNKI, Wangfang, VIP, CBM, The Cochrane Libarary, Pubmed, Web of Science and EMBase databases. Randomized controlled trials (RCTS) about mesalazine combined with TCM compound enema for ulcerative colitis were randomized controlled trials (RCTS), all randomized controlled trials were conducted from database establishment to August 2022, in which control group received mesalazine treatment, and treatment group received TCM reenema on the basis of control group. The "risk bias assessment" tool provided by the Cochrane Reviewer's Handbook was used for literature quality assessment, and RevMan5.3 software was used for statistical analysis. Eleven literatures were finally included, all of which were randomized controlled trials with a total of 1029 patients. The results of meta-analysis showed that the clinical effective rate of the treatment group [RR=4.26, 95%CI (2.79,6.50), P<0.00001] was higher than that of the control group. It can effectively reduce Baron score [MD=-0.98, 95%CI (-1.25, -0.71), P<0.00001], DAI score [MD=-1.61, 95%CI (-1.81, -1.42), P<0.00001], CRP value [MD=-6.61, 95%CI (-7.29. 56,-5.93), P<0.00001], the treatment group was more effective than the control group in relieving clinical symptoms, including abdominal pain [MD=-1.03, 95%CI (-1.99, -0.07), P = 0.03), diarrhea (MD = 0.86, 95% CI (1.46, 0.25), P = 0.006), and purulent blood [MD = 0.86, 95% CI (1.62, 0.09), P = 0.03). Funnel plot of clinical response rate showed obvious asymmetry between left and right, suggesting possible publication bias. Mesalazine combined with Chinese herbal compound enema has significant clinical efficacy in the treatment of ulcerative colitis, but the literature included is too few and the quality evaluation is not high, so it needs to be further confirmed by multiple books and high-quality RCT tests in the future.

The effect of tuina on ulcerative colitis model mice analyzed by gut microbiota and proteomics.

Tuina can effectively alleviate ulcerative colitis-related symptoms, but the mechanism of action is unknown. The purpose of this research is to explore potential pathways for the treatment of tuina through gut microbiota and proteomics techniques. Thirty-two male BALB/c mice were divided into four groups, the control, model, mesalazine, and tuina groups. The ulcerative colitis model was established by freely drinking a 3% dextran sulphate sodium solution for 7 days. The mesalazine group and the tuina group, respectively, received 7 days of mesalazine and tuina treatment. Subsequently, their body weights, feces properties, colon length, histomorphological changes, gut microbiota, and colon proteomics were determined. Body weights, disease activity index score, colon histological scores, and microbiota diversity were restored in the tuina group. At the phylum level, Firmicutes was increased and Bacteroidota decreased. At the family level, Lachnospiraceae increased and Prevotellaceae decreased. At the genus level, the Lachnospiraceae_NK4A136_group was increased. Proteomics detected 370 differentially expressed proteins regulated by tuina, enriched to a total of 304 pathways, including biotin metabolism, Notch signaling pathway, linoleic acid metabolism, and autophagy. Tuina can effectively improve the symptoms of weight loss, fecal properties, and colon inflammation in ulcerative colitis mice and restore the gut microbiota diversity, adjusting the relative abundance of microbiota. The therapeutic effects of tuina may be achieved by modulating the signaling pathways of biotin metabolism, Notch signaling pathway, linoleic acid metabolism, and autophagy.

Real-world evidence of quality of life improvement in patients with distal ulcerative colitis treated by mesalazine: the Quartz study.

Distal ulcerative colitis (UC) is responsible for distressing symptoms and reduces quality of life (QoL). Oral and topical formulations of 5-amino-salicylic acid are the first line therapy for mild to moderate distal UC. Our aim was to evaluate the impact of mesalazine treatment for mild to moderate ulcerative proctitis and proctosigmoiditis on patient QoL. Ninety-three patients with mild to moderate ulcerative proctitis and proctosigmoiditis, initiating a treatment with Pentasa, were prospectively included. The primary endpoint was the change from baseline to W8 in patient health-related QoL (HRQoL) as measured by the Short Inflammatory Bowel Disease Questionnaire (SIBDQ) total score. More than 80% of patients were prescribed with a rectal formulation, either alone (47.9%) or with an oral formulation (35.1%), and 17.0% of patients were prescribed oral formulation alone. Mean SIBDQ score was improved at W8 in patients affected with mild and moderate disease ( P &lt; 0.001 versus baseline in both groups, as well as in patients who achieved clinical remission ( P &lt; 0.001). Patients who achieved clinical remission at W8 reached a mean change of +6.7 (±7.1), whereas those who did not achieve clinical remission had a mean change of +1.1 (±8.9). Seventy-five per cent of patients had an improvement of their disability index at W8. Fecal incontinence was also improved at W8. HRQoL measuring with the SIBDQ is proportionally related to disease activity in patients with distal UC treated with mesalazine.

Randomised clinical trial and meta-analysis: mesalazine treatment in irritable bowel syndrome-effects on gastrointestinal symptoms and rectal biomarkers of immune activity.

SummaryBackgroundLow‐grade immune activation in the gut is a potential treatment target in irritable bowel syndrome (IBS).AimsTo determine improvement in IBS symptoms after mesalazine treatment, and the utility of measures of immune activity in the rectal mucosaMethodsThis was a randomised, double‐blind, placebo‐controlled, parallel‐arm, multicentre trial in subjects with IBS (Rome III criteria), with an eight‐week treatment period of mesalazine 2400 mg or plcebo once‐daily. The primary endpoint was the global assessment of satisfactory relief of IBS symptoms in ≥50% of weeks during intervention. IBS symptoms were also measured with the IBS severity scoring system; immune activity was measured by mucosal patch technology. A post hoc meta‐analysis of randomised placebo‐controlled trials of mesalazine in IBS was added.ResultsOf 181 included patients, 91 received mesalazine and 90 received placebo. The primary endpoint was met by 32 (36%) patients after mesalazine and 27 (30%) after placebo (p = 0.40). There were no differences in response rates related to IBS subtype or post‐infection symptom onset. More reduction of abdominal bloating was noted in the mesalazine group (p = 0.02). The meta‐analysis showed no effect of mesalazine on IBS symptoms. No mucosal patch technology measure could predict response to mesalazine, and found no differences in the effects of intervention on levels of immune markers.ConclusionsMesalazine is ineffective in reducing IBS symptoms. Rectal measures of immune activity by the mucosal patch technology cannot predict a higher chance of response to mesalazine.

A preliminary study on the improved efficacy of mesalazine combined with vitamin D3 in ulcerative colitis

Objective: To analyze the influence of vitamin D3 supplementation on the clinical efficacy of mesalazine in patients with ulcerative colitis (UC). Methods: From January 2015 to December 2020, patients with mild-to-moderate active UC were retrospectively and continuously enrolled, who accepted mesalazine treatment for at least 12 months at the Second Affiliated Hospital of Wenzhou Medical University. According to simultaneous supplement of vitamin D3 (125 IU/d), the patients were divided into study group and control group. Demographic and disease characteristics, serum 25-hydroxyvitamin D[25(OH)D] levels and other information were collected through retrieving hospital database. Student's t-test, Mann-Whitney U test and Chi-square test were applied for comparison of disease characteristics. The changes of modified Mayo scores[ΔMayo] and 25(OH)D[Δ25(OH)D] were compared before and after treatment by paired t-test, Wilcoxon signed rank test and Chi-square test. Multiple linear regression model was used to analyze the independent factors affecting ΔMayo and Δ25(OH)D, and variables with P-values less than 0.20 in the univariate analysis were allowed for further multivariate analysis. Results: A total of 74 UC patients (44 males, 30 females), with median age (range) 39.5 (20-76) years old, were analyzed and respectively assigned into study group (n=36) and control group (n=38). In study group, the average level of serum 25(OH)D was significantly increased at month 12 compared with that at baseline [(22.87±7.30) μg/L vs. (18.15±7.48) μg/L,P<0.001]. However, no significant elevation of serum 25(OH)D was found in control group [(19.17±8.49) μg/L vs. (19.82±9.47) μg/L,P=0.466]. Furthermore, there was a significant decrease of modified Mayo score [-3(-4.75, -1.25) vs.-2(-3.25, 0), P=0.034] and a higher clinical remission rate (55.6% vs. 28.9%, P=0.020) at month 12 in study group than those in control group. In addition, according to the baseline level of serum 25(OH)D before mesalazine treatment, 74 UC patients were divided into vitamin D deficiency group (n=38, serum 25(OH)D<20 μg/L) and non-deficiency group (n=36, serum 25(OH)D≥20 μg/L). At month 12 in vitamin D deficiency group, patients with vitamin D3 supplementation had a greater decline in modified Mayo score [-4(-5.75, -2) vs.-2(-4, 0), P=0.048] and a higher clinical remission rate (60.0% vs. 22.2%, P=0.019) compared with those without. Conclusions: In patients with mild-to-moderate active UC receiving mesalazine treatment, vitamin D3 supplementation may improve the clinical efficacy, especially in patients with vitamin D deficiency.

Lower Risk of Recurrence with a Higher Induction Dose of Mesalazine and Longer Duration of Treatment in Ulcerative Colitis: Results from the Dutch, Non-Interventional, IMPACT Study.

The dose and duration of mesalazine treatment for ulcerative colitis (UC) is a potentially important determinant of effectiveness, with evidence suggesting that continuing the induction dose for 6-12 months may improve outcomes; however, real-world data are lacking. We assessed mesalazine use in Dutch clinical practice, including how differences in dose and duration affected UC outcomes. Adults with mild-to-moderate UC who received oral prolonged-release mesalazine de novo or had a dose escalation for an active episode were followed for 12 months in this non-interventional study (ClinicalTrials.gov identifier: NCT02261636). The primary endpoint was time from start of treatment to dose reduction (TDR). Secondary endpoints included recurrence rate, adherence, and work productivity. In total, 151 patients were enrolled, of whom 108 (71.5%) were newly diagnosed with UC. The majority (120; 79.5%) received a dose of ≥4 g/day. Nearly one-third (48; 31.8%) underwent dose reduction, with mean TDR being 8.3 months. Disease extent and endoscopic appearance did not influence duration of induction therapy, while TDR increased with higher baseline UCDAI scores. TDR was longer in patients without (mean 8.8 months) than with (4.1 months) recurrence, although not significantly (p=0.09). Patients on ≥4 g/day had a significantly lower chance of recurrence versus those on 2-<4 g/day (26.6% vs 62.5%, respectively; p=0.04). Longer treatment duration was associated with significantly reduced recurrence risk [hazard ratio >6 months vs 3-6 months: 0.19 (95%CI: 0.08-0.46); p<0.05], particularly for those on ≥4 g/day [0.15 (0.06-0.40) vs 0.26 (0.01-11.9) for 2-<4 g/day). Patients reported significantly increased work productivity, which was maintained throughout follow-up. Mesalazine was effective induction therapy, with treatment duration not meaningfully influenced by disease extent and endoscopic appearance at initiation. A higher induction dose of oral mesalazine (≥4 g/day) and longer duration of treatment (>6 months) was associated with a lower recurrence risk.

CELLULAR AND MOLECULAR IMPACT OF THE MELANOCORTIN RECEPTOR AGONIST PL8177 IN DEXTRAN SODIUM SULFATE (DSS)-INDUCED COLITIS IN RATS

Abstract INTRODUCTION The melanocortin 1 receptor (MC1r)–specific agonist PL8177 and its main metabolite PL8435 have demonstrated MC1r binding affinity and functional activity that mirrors that of α-melanocyte stimulating hormone (a-MSH). a-MSH has been demonstrated to be effective in reducing inflammation in numerous experimental models. This study investigates the effects of PL8177 on inflammation, cell population composition, and gene and protein expression in colons from a DSS–induced rat model of colitis. The objective is to determine the effectiveness of PL8177 in this model and to characterize its underlying mechanism of action. METHODS Male Wistar rats received 5% DSS in drinking water for 3 days to induce colitis. Rats in the sham group received drinking water only (each group n=6). The other groups received vehicle control (placebo)–filled capsules; PL8177-filled capsules at 20, 50, and 100 μg/animal (by oral gavage); or oral mesalazine (positive control). At termination on day 8, 24 hours after the last dosing, colon tissues were harvested, dissected and snap frozen with liquid nitrogen. Colon samples were analyzed for cytokine levels, single nuclei RNA-seq, and data-independent acquisition tandem mass spectrometry (LC/MS DIA). Colitis was assessed by a disease activity index (diarrhea and rectal bleeding), colon length shortening, colon weight gain, and histopathological assessment. The total colitis index, was used to assess inflammatory damage. RESULTS Colitis was induced in rats treated with DSS. Oral PL8177 50 μg/animal treatment showed a significant improvement in colon weight (53% reduction), stool consistency, and fecal occult blood score compared to vehicle. There was a significant (P&amp;lt;0.05) improvement in the total colitis index for the PL8177 100-μg group vs vehicle control group. All PL8177-cohorts showed greater improvement in the total colitis index compared to the mesalazine-treated cohort. PL8177 50 μg/animal showed a significant improvement in colon weight (53% reduction), while mesalazine treatment was associated with significant reduction in colon length, but only moderate improvement (35%) in colon weight. Changes in the cellular population compositions, gene expression changes and protein level data will be presented and discussed at the conference. CONCLUSION Oral PL8177 treatment of inflamed colon showed significant improvement in markers of colitis in the rat model compared to the placebo and mesalazine control groups supporting the aim of treating inflammatory bowel disease in humans. Genomic and proteomic data will be interpreted in the context of disease change to identify alterations in immune and cellular states of the experimental colons.

SARS-CoV-2 vaccine acceptance among gastroenterologists and inflammatory bowel disease patients: VACUNEII project

IntroductionSeveral vaccines against SARS-CoV-2 are currently in use and are recommended in inflammatory bowel disease (IBD) patients. Data are scarce about the gastroenterologists and IBD patient's acceptance of SARS-CoV-2 vaccines. The aim of the study was to evaluate the intention to get vaccination with SARS-CoV-2 vaccine among IBD patients from gastroenterologists and patient's perspective. MethodsAn online anonymous survey was sent to 8000 patients from ACCU-Spain and 1000 members of the GETECCU. Three invitations were sent between October-December 2020. Descriptive analyses were performed, comparing physicians and patients responses by standard statistical analyses. Results144 gastroenterologists [63% female, mean age 43 years (SD 9.5)], and 1302 patients [72% female, mean age 43 years (SD 12)] responded to the survey. 95% of the physicians recommended SARS-CoV-2 vaccine for IBD patients and 87% consider that their vaccination strategies has not changed after the pandemic compared to 12% who considered that they currently refer more patients to vaccination. Regarding to IBD patients, only 43% of patients were willing to receive the vaccine and 43% were not sure. Male sex (p<0.001) and mesalazine treatment (p=0.021) were positively associated with SARS-CoV-2 vaccine acceptance. After multivariate analysis, only male sex was significantly associated with vaccination intent (OR=1.6; 95% confidence interval=1.2–2.0; p=0.001). ConclusionsGastroenterologists and patient's perspective about SARS-CoV-2 are different. Future efforts to increase COVID-19 vaccine and decrease unfounded beliefs among IBD patients are needed.

Systemic mesalazine treatment prevents spontaneous skin fibrosis in PLK2-deficient mice

Skin fibrosis is a complex biological remodeling process occurring in disease like systemic sclerosis, morphea, or eosinophilic fasciitis. Since the knowledge about the underlying pathomechanisms is still incomplete, there is currently no therapy, which prevents or reverses skin fibrosis sufficiently. The present study investigates the role of polo-like kinase 2 (PLK2) and the pro-fibrotic cytokine osteopontin (OPN) in the pathogenesis of cutaneous fibrosis and demonstrates the antifibrotic effects of systemic mesalazine treatment in vivo. Isolated primary dermal fibroblasts of PLK2 wild-type (WT) and knockout (KO) mice were characterized invitro. Skin thickness and histoarchitecture were studied in paraffin-embedded skin sections. The effects of mesalazine treatment were examined in isolated fibroblasts and PLK2 KO mice, which were fed 100 µg/g mesalazine for 6 months via the drinking water. Compared to WT, PLK2 KO fibroblasts displayed higher spontaneous myofibroblast differentiation, reduced proliferation rates, and overexpression of the fibrotic cytokine OPN. Invitro, 72 h of treatment with 10 mmol/L mesalazine induced phenotype conversion in PLK2 KO fibroblasts and attenuated OPN expression by inhibiting ERK1/2. In vivo, dermal myofibroblast differentiation, collagen accumulation, and skin thickening were prevented by mesalazine in PLK2 KO. Plasma creatinine levels indicated good tolerability of systemic long-term mesalazine treatment. The current study reveals a spontaneous fibrotic skin phenotype and ERK1/2-dependent OPN overexpression in PLK2 KO mice. We provide experimental evidence for the antifibrotic effectiveness of systemic mesalazine treatment to prevent fibrosis of the skin, suggesting further investigation in experimental and clinical settings.