Mesalazine Treatment Research Articles

Effectiveness of treatment moderate ulcerative colitis with prolonged-release ethylcellulose-coated mesalazine in real clinical practice in Moscow

Background and purpose. The aim of this work is to evaluate the efficacy of treatment patients with moderate left-sided and total ulcerative colitis (UC) with prolonged-release ethylcellulose-coated mesalazine. Materials and methods. The clinical analyses of results of treatment UC patients with prolonged-release ethylcellulose-coated mesalazine was performed. Eighty-seven patients with UC, treated with ethylcellulose coated microgranules of mesalazine, were examined: 38 (43,7%) men and 49 (56,3%) women. The age of patients was from 26 to 49 years, median age 38,3±12,6 year. Results. After 2 weeks prolonged-release ethylcellulose coated mesalazine treatment the response to therapy was demonstrated in majority of UC patients -71 (81,6%). After 12 weeks treatment prolonged remission persisted in 71 (81,6%) UC patients. Mayo score decreased from 7,6±0,99 to 2,6±0,25 points. Significant decrease of inflammation markers (CRP, ESR, leukocytosis, fecal calprotectin etc) was determined. After 26 weeks of treatment Mayo score was 2,2-2,3 points. Thirty-two (36,8%) UC patients showed healing of colon mucosa. After 1 year of prolonged-release ethylcellulose-coated mesalazine treatment clinical remission was determined in 69 (79,3%) UC patients with response to therapy, clinical-endoscopic remission — in 32 (36,8%) patients. During 1 year follow-up no cases of surgical procedure and readmission because of UC reccurence were noted. Conclusion. Treatment of moderate active UC should be started with oral mesalazine > 3 gr per day and rectal mesalazine. The most appropriate effective and high compliance forms of mesalazine are prolonged-release forms of meselazine.

P561 Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and Mayo Endoscopic Score (MES) in predicting the therapeutic effect of mesalazine in UC patients

Abstract Background The Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and the Mayo Endoscopic Score (MES) were developed as an objective method of the endoscopic severity in ulcerative colitis (UC); however, it was still unclear whether UCEIS and MES could guide the mesalazine treatment in UC. Methods Consecutive UC patients who had undergone colonoscopy within 1 month before starting mesalazine between October 2011 and July 2016 were retrospectively evaluated. Demographic data, previous therapy, clinical observations, laboratory parameters, medical therapy and endoscopic assessments were documented. The primary outcome was the need for ‘step up’ treatment (containing the use of corticosteroids, immunomodulatory or surgery.) during admission and follow-up. Results Sixty-five patients were enrolled, 12(18.5%) needed ‘step up’ treatment’ due to primary or secondary nonresponse to mesalazine. UCEIS score is a predictor of primary or secondary nonresponse to mesalazine in multivariate analysis (OR, 25.65; 95% CI, 3.048–45.985; P =0.003). Receiver-operator characteristic (ROC) area of UCEIS is 0.95, with a sensitivity of 100% and specificity of 84.6%, using cut-off value of 6, which outperforms MES with the ROC area of 0.70; When UCEIS score ≥6, 60% of patients eventually need ‘step up’ treatment. Conclusion UCEIS score is a useful instrument for evaluating endoscopic improvement in UC patients treated with mesalazine. The high probability of mesalazine treatment failure and benefits of other therapy should be discussed in patients with baseline UCEIS ≥ 6.

Anti-IL-4Ralpha monoclonal antibody dupilumab mimics ulcerative colitis: a case report

BackgroundVarious molecular-targeted therapeutic agents that inhibit cytokines and immune checkpoints are used in clinical practice. Some of these biologics that control immunity, such as anti-interleukin-17, anti-programmed cell death protein-1, and anti-cytotoxic T-lymphocyte-associated protein antibodies, affect intestinal immune homeostasis and cause intestinal inflammation. Development of enteritis due to dupilumab (an anti-IL-4Ralpha monoclonal antibody) therapy is not yet reported in the literature.Case presentationA 17-year-old man was administered an injection of dupilumab and continued to receive it for refractory atopic dermatitis. After 3 months of initiating dupilumab therapy, he developed intermittent abdominal pain, tenesmus, and had diarrhea. Colonoscopy examination showed decreased vascularity, mild friability, and erythema in the cecum, part of the ascending colon, sigmoid colon, and rectum without any pathogenic bacteria. Histological examination revealed moderate mixed inflammatory cell infiltration, cryptitis, destruction of the crypt, decreased goblet cells, mucosal erosions, and edema. He was diagnosed with UC and was prescribed oral mesalazine (4800 mg/day) treatment. Within a month of the treatment, his diarrhea improved and the frequency of defecation decreased.ConclusionsThis is a first report that dupilumab mimicked ulcerative colitis. Careful monitoring for adverse effects with the onset of an intestinal inflammation will be recommended after dupilumab administration.

Use of the ulcerative colitis endoscopic index of severity and Mayo endoscopic score for predicting the therapeutic effect of mesalazine in patients with ulcerative colitis

ObjectiveThe ulcerative colitis endoscopic index of severity (UCEIS) and the Mayo endoscopic score (MES) are developed as objective methods of evaluating endoscopic severity in patients with ulcerative colitis (UC). The aim of this study is to investigate the diagnostic accuracy of the UCEIS and MES in predicting the patient's response to mesalazine. MethodsConsecutive patients with UC who had undergone colonoscopy within 1 month before starting mesalazine between October 2011 and July 2016 were retrospectively collected at the Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine. The median follow-up was 81 months, and all the data were analyzed in January 2021. The primary outcome was the need for step-up treatment, which included the use of corticosteroids, immunomodulatory, or surgery during admission and follow-up. Data were analyzed using the χ2 or Fisher exact test, Spearman test, t-test, and Mann–Whitney U test. ResultsTotally, 65 patients were enrolled, of whom 12 (18.5%) needed step-up treatment due to nonresponse to mesalazine. The UCEIS score, MES, and the ulcerative colitis disease activity index (UCDAI) score were significantly higher in patients who had nonresponse to mesalazine (UCEIS score: 6.92 ± 0.69 vs. 4.45 ± 1.17, p < 0.001; MES: 2.67 ± 0.49 vs. 2.15 ± 0.69, p = 0.024; UCDAI score: 9.33 ± 1.87 vs. 6.70 ± 2.38, p = 0.002). In the multivariate analysis, the UCEIS score (OR = 25.65, 95% CI: 3.048–45.985, p = 0.003), UCDAI score (OR = 1.605, 95% CI: 1.144–2.254, p = 0.006), and C-reactive protein level (OR = 1.056, 95% CI: 1.006–1.108, p = 0.026) were independent risk factors of nonresponse. The area under the ROC curve of UCEIS was 0.95, with a sensitivity of 100% and specificity of 84.6%, a cut-off value of 6, which outperformed the MES with an area under the ROC curve of 0.70. When the UCEIS score ≥6, 60% of patients eventually needed step-up treatment. ConclusionsThe UCEIS is a useful instrument for predicting the therapeutic effect in patients with UC treated with mesalazine. The high probability of mesalazine treatment failure and benefits of other therapies should be discussed in patients with baseline UCEIS score ≥6.

CircRNA expression profiling of colon tissue from mesalazine-treated mouse of inflammatory bowel disease reveals an important circRNA-miRNA-mRNA pathway.

Mesalazine (5-aminosalicylic acid, 5-ASA) has been widely used to treat inflammatory bowel disease (IBD). However, it remains unclear about the underlying biological mechanisms of IBD pathogenesis and mesalazine treatment, which could be partially clarified by exploring the profiling of circular RNAs (circRNAs) using RNA-seq. A total of 15 mice (C57BL/6) were randomly assigned to three equally sized groups: control, dextran sulfate sodium (DSS, using DSS to induce IBD), and DSS+5-ASA (using mesalazine to treat IBD). We randomly selected three mice of each group to collect colon tissues for RNA-seq and then performed bioinformatic analysis for two comparisons: DSS vs. control and DSS+5-ASA vs. DSS. Comparisons of a series of indicators (e.g., body weight) verified the establishment of DSS-induced IBD mouse model and the effectiveness of mesalazine in treating IBD. We identified 182 differentially expressed circRNAs, including 55 up-regulated and 47 down-regulated circRNAs when comparing the DSS+5-ASA with the DSS group. These 102 circRNA-associated genes were significantly involved in the N-Glycan biosynthesis and lysine degradation. The network analysis of circRNA-miRNA-mRNAs identified an important pathway, i.e., chr10:115386962-115390436+/mmu-miR-6914-5p/Atg7, which is related to autophagy. The findings provide new insights into the biological mechanisms of IBD pathogenesis and mesalazine treatment, particularly highlighting the circRNA-miRNA-mRNA pathway.

Anti-inflammatory effect, plasma effective components and therapeutic targets of Huanglian Jiedu Decoction on ulcerative colitis mice

This paper was to investigate the effect of Huanglian Jiedu Decoction(HLJD) on ulcerative colitis(UC) in mice, and determine the effective components in plasma, and virtually screen its therapeutic target, and predict its mechanism. Sixty Balb/c mice were randomly divided into blank group, model group, mesalazine treatment group(0.3 g·kg~(-1)), and HLJD treatment groups(24.66, 12.33, 6.17 g·kg~(-1)). Excepted for the blank group, all the mice in HLJD and mesalazine treatment groups were gavage administration. All mice freely drank 2.5% DSS solution for seven days to induce UC. The disease activity index(DAI) was detected each day. At the end of the experiment, HE staining was used to observe the pathological changes in colon. The content of IL-1β, IL-6 and TNF-α in colon were determined by ELISA. The effective components in plasma were determined by UPLC-Q-TOF-MS. The reverse docking in PharmMapper was used to screen the component targets. The disease targets of UC were collected by searching TTD, OMIM and GeneCards databases. The intersection of the component targets and disease targets was selected as the therapeutic targets. Then the therapeutic targets were imported into the STRING for GO and KEGG enrichment analysis. Discovery Studio was used to simulate the docking between the components and the targets. RESULTS:: showed that the DAI in the model group increased significantly(P&lt;0.05), and the number of inflammatory cells and infiltration degree increased significantly compared with the blank group. The DAI in HLJD treatment group was significantly reduced(P&lt;0.05), and the number and infiltration degree of inflammatory cells were reduced compared with the model group. The ELISA results showed that the levels of IL-1β, IL-6 and TNF-α were increased significantly in the model group(P&lt;0.01) compared with the blank group, and significantly down regulated in the HLJD treatment group(P&lt;0.05) compared with the model group. After UPLC-Q-TOF-MS analyse, ten components were identified. The network pharmacology analysis showed that the action targets were significantly enriched in 129 of biological processes, such as response to organic substance, chemical and oxygen-containing compound, etc., as well as 16 of signal pathways, such as IL-17, TNF and hepatitis B signal pathways, were enriched too. The results of molecular docking showed that limonin, palmatine and berberine could bind to CASP3 and MMP9 by hydrogen bond. In conclusion, HLJD could alleviate the colonic mucosal inflammatory infiltration and mucosal damage in UC mice. The mechanism may be related to the anti-inflammatory effect on UC mice by reducing the levels of IL-1β, IL-6 and TNF-α in colon through limonin, palmatine and berberine regulating IL-17 signal pathway and TNF signal pathway via CASP3 and MMP9 meditated.

Repurposing mesalazine against cardiac fibrosis in vitro

Cardiovascular diseases are exacerbated and driven by cardiac fibrosis. TGFβ induces fibroblast activation and differentiation into myofibroblasts that secrete excessive extracellular matrix proteins leading to stiffening of the heart, concomitant cardiac dysfunction, and arrhythmias. However, effective pharmacotherapy for preventing or reversing cardiac fibrosis is presently unavailable. Therefore, drug repurposing could be a cost- and time-saving approach to discover antifibrotic interventions. The aim of this study was to investigate the antifibrotic potential of mesalazine in a cardiac fibroblast stress model. TGFβ was used to induce a profibrotic phenotype in a human cardiac fibroblast cell line. After induction, cells were treated with mesalazine or solvent control. Fibroblast proliferation, key fibrosis protein expression, extracellular collagen deposition, and mechanical properties were subsequently determined. In response to TGFβ treatment, fibroblasts underwent a profound phenoconversion towards myofibroblasts, determined by the expression of fibrillary αSMA. Mesalazine reduced differentiation nearly by half and diminished fibroblast proliferation by a third. Additionally, TGFβ led to increased cell stiffness and adhesion, which were reversed by mesalazine treatment. Collagen 1 expression and deposition—key drivers of fibrosis—were significantly increased upon TGFβ stimulation and reduced to control levels by mesalazine. SMAD2/3 and ERK1/2 phosphorylation, along with reduced nuclear NFκB translocation, were identified as potential modes of action. The current study provides experimental pre-clinical evidence for antifibrotic effects of mesalazine in an in vitro model of cardiac fibrosis. Furthermore, it sheds light on possible mechanisms of action and suggests further investigation in experimental and clinical settings.

Is mesalazine treatment effective in the prevention of diverticulitis? A review.

Diverticulitis is the most severe form of Diverticular disease (DD). An effective treatment strategy for its prevention has not yet been defined. This review aimed to provide a viewpoint on the role of mesalazine, also note as 5-aminosalicylic acid (5-ASA), in the prevention of diverticulitis. A systematic electronic search of relevant articles was performed using PubMed, Embase, Scopus, and Cochrane. Randomized controlled trials (RCTs), open trials, and retrospective studies, published between January 1999 and January 2020, were identified. Twelve eligible studies that analyzed primary or secondary outcomes of diverticulitis were included. The population included patients with symptomatic uncomplicated diverticular disease (SUDD), or patients with a history of diverticulitis. All studies compared 5-ASA to placebo, rifaximin, or other treatments. Two studies, including 359 patients, assessed the efficacy of 5-ASA in preventing the first appearance of diverticulitis in patients with SUDD. Of these, one showed that 5-ASA was effective, and one did not. Ten studies, including 2.995 patients, assessed the efficacy of 5-ASA treatment in preventing the recurrence of diverticulitis in patients with a history of diverticulitis. Four studies showed that 5-ASA had a certain degree of efficacy. All four RCTs demonstrated that 5-ASA did not significantly reduce the rate of diverticulitis recurrence. In a retrospective trial, 5-ASA was less effective than rifaximin in preventing diverticulitis recurrence. In an open trial, there was no difference between 5-ASA and probiotic treatment. Overall, there is currently conflicting evidence regarding the efficacy of 5-ASA treatment in the prevention of diverticulitis and further RCTs are needed.

Time to Symptom Resolution in Ulcerative Colitis With Multimatrix Mesalazine Treatment: A Pooled Analysis

Patients with ulcerative colitis [UC] require rapid and complete relief of symptoms, particularly stool frequency and rectal bleeding. The aim of this study was to determine time to symptom resolution in patients with UC during induction treatment with multimatrix mesalazine, and the proportion of patients remaining symptom-free and in endoscopic remission after 12 months of maintenance. A pooled analysis of 5 pivotal clinical trials, including >1300 patients, evaluating multimatrix mesalazine for treatment of mild-to-moderate active UC was conducted. Time to symptom resolution was defined as the period between first drug dosage date and first 3 consecutive days of induction therapy when the patient achieved a score of 0 [normal] on a modified UC Disease Activity Index for stool frequency and/or rectal bleeding. Median [95% confidence interval] time to resolution of stool frequency was 52 (45-not estimable [NE]) days for placebo versus 38 [34-41] days for multimatrix mesalazine [combined dose groups, 2.4 or 4.8 g/day]; time to resolution of rectal bleeding was 35 [20-NE] days for placebo versus 15 [14-17] days for multimatrix mesalazine [combined dose groups]. Among those who achieved resolution of both stool frequency and rectal bleeding during induction, 67.4% maintained symptom scores of 0 at Month 12. No relationship was observed between rapidity of symptom resolution during induction treatment and achievement of endoscopic remission at Month 12. Induction with multimatrix mesalazine provided rapid and prolonged symptom resolution in addition to endoscopic remission at Month 12.

PGI20 MULTIMATRIX VERSUS TIME-DEPENDENT DELIVERY OF MESALAZINE FOR ULCERATIVE COLITIS THERAPY IN KAZAKHSTAN: A HEALTH ECONOMIC EVALUATION

Heavy costs associated with the treatment of unspecified ulcerative colitis necessitate the choice of drugs that provide the optimal treatment outcomes within the existing budget constraints. In this study, we compared the multimatrix (MMX) delivery type versus time-dependent delivery of mesalazine for treatment of unspecified ulcerative colitis in terms of their clinical and economic effectiveness. A review of clinical effectiveness was conducted using a sensitive search strategy. 5 high-quality trials identified and used to inform clinical effectiveness parameters in the model. The economic assessment involved the construction of a Markov model comparing the two delivery types over both a short-term (5 years) and a long-term horizon (30 years) using local treatment guidelines and costs, an additional budget impact analysis and a sensitivity analysis of model parameters. The exchange rate used is dated by June 2019 according to the current market rate in Kazakhstan. According to the model, MMX delivery of mesalazine as first-line therapy for unspecified ulcerative colitis was found to be the dominant therapy compared to time-dependent delivery, producing better outcomes at lower costs (additional 0.015 QALY) and averted costs of 193662 KZT (504.32 USD) per patient in the 5-year model, additional 0.038 QALY and averted costs of 1066659 KZT (2777.7 USD) per patient in the 30-year model). MMX mesalazine was associated with a longer remission stage and fewer relapses. The model was found to be sensitive to MMX mesalazine treatment response period, probability of progression to remission on MMX mesalazine and treatment-related costs. Using the MMX delivery of mesalazine in favor of time-dependent delivery for the treatment of unspecified ulcerative colitis appears to be a cost-effective option in the context of healthcare system of Kazakhstan, with potentially improved outcomes and considerable healthcare budget savings.

Protective effect of Saccharomyces boulardii on intestinal mucosal barrier of dextran sodium sulfate-induced colitis in mice.

Background:The effect and mechanism of Saccharomyces boulardii (Sb) in inflammatory bowel disease are unclear. The objective of the study was to evaluate the impact of Sb on intestinal mucosal barrier and intestinal flora in a colitis mouse model.Methods:Forty C57BL/6J male mice were randomly assigned to five groups: normal control group (A), pathologic control group (B), Sb treatment group (C), mesalazine treatment group (D), and Sb combined with mesalazine treatment group (E). Colitis was induced by the addition of 2.5% (wt/vol) dextran sodium sulfate (DSS) in the drinking water ad libitum for 7 days. The general condition, weight change, stool property, and bloody stool level of mice were observed to evaluate the disease activity index. The expression of zona occludens-1 (ZO-1) and occludin in intestinal tissue were measured by immunohistochemistry. The level of tumor necrosis factor-α (TNF-α) and interleukin (IL)-8 in plasma was measured by enzyme linked immunosorbent assay. Inter-cellular tight junctions were observed by transmission electron microscopy. The feces and intestinal contents were collected sterilely, and intestinal flora was analyzed by 16S rRNA sequencing.Results:Compared with group B, Sb reduced the disease activity index and histological score of group C (disease activity index: group B 2.708 ± 0.628, group C 1.542 ± 0.616, PBC = 0.005; histological score: group B 9.875 ± 3.271, group C 4.750 ± 1.832, PBC = 0.005) in DSS-induced colitis in mice. Sb exerted a protect effect on the expression of ZO-1 (group B 2.075 ± 1.176, group C 4.225 ± 1.316, PBC = 0.019) and occludin (group B 2.200 ± 0.968, group C 3.525 ± 1.047, PBC = 0.023). Compared with group B, Sb decreased the level of TNF-α and IL-8 of group C (TNF-α: group B 716.323 ± 44.691 ng/L, group C 521.740 ± 90.121 ng/L, PBC = 0.001; IL-8: group B 128.992 ± 11.475 pg/mL, group C 106.283 ± 15.906 pg/mL, PBC = 0.012). Treatment with Sb preserved the tight junctions and ameliorated microvilli and inter-cellular space. Treatment with Sb also showed its own characteristics: a higher percentage of Bacteroidetes and a lower percentage of Firmicutes, with significant differences or a significant trend. The proportion of the S24-7 family was increased significantly in the Sb treatment group.Conclusions:Sb shows an anti-inflammatory effect and has a protective effect on the intestinal mucosal mechanical barrier. Sb may up-regulate the abundance of family S24-7 specifically, and maybe a mechanism underlying its function.

Utility of Mesalazine in Familial Adenomatous Polyposis: Clinical Report of Reduction of Polyp Size in Patients with Ulcerative Colitis, and Safety Examination in Familial Adenomatous Polyposis Patients

Mesalazine is the gold standard drug for treatment of ulcerative colitis (UC). Here, we describe 4 cases of familial adenomatous polyposis (FAP) patients with UC that showed reduction of intestinal polyp diameter by mesalazine treatment. Of note, the effects of mesalazine on the development of intestinal polyps in FAP patients have not been reported, and we further investigated whether the short-term use of high-dose mesalazine (4 g/day) has harmful effects on FAP patients or not. The authors found that the treatment showed slightly adverse events in FAP patients. However, mesalazine tended to reduce the number of colon polyps in male subjects with FAP. This report provides basic information for planning a double-blind, randomized, clinical trial that aims to show mesalazine’s potential to suppress intestinal polyp development in FAP.

Przestrzeganie zaleceń w chorobach przewlekłych na przykładzie leczenia mesalazyną w nieswoistych zapalnych chorobach jelit

Przestrzeganie zaleceń w chorobach przewlekłych na przykładzie leczenia mesalazyną w nieswoistych zapalnych chorobach jelit

Consensus recommendations for patient-centered therapy in mild-to-moderate ulcerative colitis: the i Support Therapy-Access to Rapid Treatment (iSTART) approach.

Symptomatic ulcerative colitis (UC) can be a chronic, disabling condition. Flares in disease activity are associated with many of the negative impacts of mild-to-moderate UC. Rapid resolution of flares can provide benefits to patients and healthcare systems. i Support Therapy–Access to Rapid Treatment (iSTART) introduces patient-centered care for mild-to-moderate UC. iSTART provides patients with the ability to self-assess symptomology and self-start a short course of second-line treatment when necessary. An international panel of experts produced consensus statements and recommendations. These were informed by evidence from systematic reviews on the epidemiology, mesalazine (5-ASA) treatment, and patient use criteria for second-line therapy in UC. Optimized 5-ASA is the first-line treatment in all clinical guidelines, but may not be sufficient to induce remission in all patients. Corticosteroids should be prescribed as second-line therapy when needed, with budesonide MMX® being a preferred steroid option. Active involvement of suitable patients in management of UC flares has the potential to improve therapy, with patients able to show good accuracy for flare self-assessment using validated tools. There is a place in the UC treatment pathway for an approach such as iSTART, which has the potential to provide patient, clinical and economic benefits.

Endoscopic balloon dilatation after rectal mesalazine treatment within an uncertainty of colonic anastomosis

Anastomoz darlıkları kolorektal cerrahinin bilinen bir komplikasyonu olmasına rağmen benign hastalıklarda komplet kolonik anastomoz obstrüksiyonu nadirdir. Benign darlıklar low-anterior rezeksiyon sonrası yapılan kolorektal anastomozda nispeten sık görülen bir komplikasyondur ve kolorektal anastomozların %5-22’sinde gelişebilir. Günümüzde benign anastomoz darlıklarının tedavisinde ilk seçenek endoskopik girişimlerdir. Çeşitli endoskopik teknikler tarif edilmesine rağmen optimal yaklaşım için kontrollü prospektif çalışma verileri eksiktir. Bu çalışmada ileri derecede anastomoz darlığı gelişmiş ve endoskopik balon dilatasyon uygulanan bir hastanın sunulması amaçlandı. Hastaya bir haftalık rektal mesalazin tedavisinden sonra bir kez ayaktan balon dilatasyonu uygulandı ve darlık giderildi. Rektal mesalazin uygulamasının darlık bölgesindeki inflamutuvar sürece olumlu etkisi oldu ve balon dilatasyon sayısını azalttı. Kolorektal darlıkların tedavisinde endoskopik balon dilatasyon 1985’ten beri kullanılmaktadır. Minimal invaziv bir yöntemdir, başarı oranı yüksektir, güvenle direkt görüş altında yapılabilir, tekrarlanabilir ve hastanede yatış gerektirmez.

Evaluation of the drug-induced lymphocyte stimulation test for diagnosing mesalazine allergy.

Background/AimsMesalazine is an effective drug for treating ulcerative colitis (UC), but causes allergic symptoms in a few cases. Therefore, the objective of this study was to evaluate the usefulness of the drug-induced lymphocyte stimulation test (DLST) for the diagnosis of mesalazine allergy.MethodsPatients with UC treated with mesalazine with or without a history of associated adverse events (AEs) were enrolled at Kyorin University Hospital from July 2016 to April 2017.ResultsThe DLST was performed in 104 patients with UC, of which 24 had a history of AEs due to mesalazine treatment. The control value of DLST was 337.4±296.3 counts per minute (cpm) in the AE+ group and 408.0±371.9 cpm in the AE− group. The measured value of DLST was 578.8±424.7 cpm in the AE+ group and 476.5±471.8 cpm in the AE− group. The stimulation index (SI) was 243.9%±291.1% in the AE+ group and 119.8%±53.0% in the AE− group. The SI value and DLST positivity were significantly higher in the AE+ group than in the AE− group (P=0.030 and P=0.029, respectively). The test sensitivity and specificity were 0.240 and 0.805, respectively, and the false-positive and false-negative rate was 0.195 and 0.760, respectively.ConclusionsThe DLST for mesalazine showed low sensitivity and high specificity, suggesting that it may be useful for the definitive diagnosis of allergy to mesalazine.

Clozapine induced diarrhea

IntroductionClozapine (CZP) is the only antipsychotic approved for resistant schizophrenia 1. Due to its side effects, CZP is not the first therapeutic option in a psychotic episode. Its anticholinergic effects often cause constipation, however, diarrhea have also been described in literature.ObjectivesWe describe a patient with two episodes of severe diarrhea after clozapine initiation, which lead to CZP discontinuation.AimsDiscuss about the differential diagnosis of diarrhea in CZP patients and the needing of a further studies for clarify the more appropriate management in CZP induced diarrhea.MethodsWe present a case report of a 46 years man diagnosed with schizoaffective disorder who presented two episodes of severe diarrhea with fever, which forced his transfer to internal medicine and UCI after CZP initiation.ResultsAt the first episode analytical, radiological and histological findings led to Crohn's disease diagnosis, which required budesonide and mesalazine treatment. In the second episode, the digestive team concluded that the episode was due to clozapine toxicity despite the controversial findings (clostridium toxin and Crohn's compatible biopsies)ConclusionsDiarrhea caused by CZP has been controversial in the literature. However due to the severity of digestive episodes and the paucity of alternative treatments further studies for a better understanding of its physiopathology are warranted.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Efficacy and safety of a novel high-dose mesalazine tablet in mild to moderate active ulcerative colitis: a double-blind, multicentre, randomised trial.

Adherence to mesalazine treatment is essential for the successful treatment of ulcerative colitis. The objective of this study was to compare the efficacy, safety and preference of a novel high-dose 1000 mg mesalazine tablet versus conventional treatment for ulcerative colitis remission. This pivotal phase III trial compared one 1000 mg mesalazine tablet (M1000 group) versus two registered 500 mg mesalazine tablets (M2x500 group), both taken three times daily, in patients with mild to moderately active ulcerative colitis. The primary efficacy variable was clinical remission at week 8. A total of 306 patients were considered for intent-to-treat analysis. Clinical remission was achieved in 45.0% of the patients in the M1000 group versus 41.9% in the M2x500 group (P < 0.001 for non-inferiority). Mucosal healing was achieved by 68.9% of the patients in the M1000 group and 68.4% in the M2x500 group. The majority of patients preferred the intake of one high-dose tablet (47.7%) over two low-dose tablets (10.5%). Oral treatment with high-dose 1000 mg mesalazine tablets was well tolerated without new safety signals. The novel high-dose 1000 mg mesalazine tablet is effective, non-inferior to the registered 500 mg mesalazine tablet, and safe for ulcerative colitis treatment. It was preferred by a majority of patients and may improve ulcerative colitis treatment adherence.

Experiencia clínica en el tratamiento con mesalazina MMX en monoterapia en los pacientes con colitis ulcerosa

5-ASA are the first-line treatment of mild to moderate UC, the rectal being the most used for distal colitis and combination with oral formulations in the most extensive. Oral formulation is often patient preference and it affects crucially on patient adherence to the prescribed treatment. The MMX system allows the sustained release of the active ingredient throughout the colon allowing its use in monotherapy. A retrospective analysis was conducted to assess the degree of response to MMX mesalazine depending on the disease extension. At MMX mesalazine treatment beginning, 71% of patients had active UC and 29% were in remission. Regarding the extension, 31% of the cases were proctitis, 23% proctosigmoiditis and 46% left side colitis. The initial dose was 4.8g/day in most active UC cases (54.4%) and 2.4g/day (79.2%) in remission. After treatment initiation 55% resolved symptoms; no relation with the extension of the disease was observed.

Post-infectious irritable bowel syndrome (PI-IBS) after infection with Shiga-like toxin-producing Escherichia coli (STEC) O104:H4: A cohort study with prospective follow-up.

In May/June 2011, the new Shiga-like toxin-producing Escherichia coli (STEC) strain O104:H4 caused the severest outbreak ever recorded of hemorrhagic enterocolitis in 3842 patients in Germany. As bacterial enterocolitis is an established risk factor of subsequent irritable bowel syndrome (IBS), we aimed to estimate prevalence and incidence of post-infectious (PI)-IBS after six and 12 months in a cohort of STEC O104:H4 patients and to prospectively identify associated somatic and psychometric risk factors. A total of 389 patients were studied prospectively at baseline and at six and 12 months after STEC infection using STEC disease-related questionnaires and validated instruments for IBS (Rome III) and psychological factors. Frequencies and logistic regression models using multiple imputations were applied to assess predictor variables. Prevalence of IBS increased from 9.8% prior to STEC infection to 23.6% at six and 25.3% at 12 months after STEC infection. In patients without IBS symptoms prior to STEC infection, incidence of new IBS was 16.9%. Logistic regression models indicated higher somatization and anxiety scores as risk factors for, and mesalazine treatment during, STEC infection as the only significant protective factor against IBS. No other factor analyzed, including disease severity, showed an association. PI-IBS rates following this unusually severe STEC outbreak were similar to what has been observed after other infectious gastroenteritis outbreaks. Our findings suggest that mesalazine may have reduced the risk of subsequent PI-IBS. As altered mucosal immune activity is a pivotal pathogenic factor in PI-IBS, our observation of a potential protective effect of mesalazine might be explained by its known modulatory action on mucosal immunity, and may warrant further investigation.