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Background: Treatments and strategies for inflammatory bowel disease (IBD) have gradually evolved in the 2000s. Objectives: We investigated whether the prescription of corticosteroids (prednisolone and budesonide) in patients with IBD in the first 5 years after diagnosis changed in patients diagnosed between 2006 and 2018. Design: Retrospective observational study. Methods: The cumulative prescribed dosage of corticosteroids for the first 5 years after diagnosis was registered in all patients with IBD (n = 386) at our clinic for those diagnosed between 2006 and 2018. Results: The proportion of patients with IBD who were prescribed at least one prescription of corticosteroids in year 1–5 after diagnosis was 55.3%, 27.9%, 22.7%, 14.1%, and 14.6%, respectively. The proportion of patients who had a cumulative dose of prednisolone >1 g in the first 5 years after diagnosis was 40.1% for ulcerative colitis and 34.9% for Crohn's disease (CD). The cumulative prescribed dosage (within 3 years after diagnosis) of prednisolone had declined (rs = −0.164, p = 001), but had increased for budesonide (rs = 0.202, p < 0.001) between 2006 and 2020. The prescription of any immunomodulator for IBD in the first 5 years from diagnosis was stable between 2006 and 2018 (rs = 0.056, p = 0.257), but there was a minor increase in the prescription of Tumor Necrosis Factor (TNF)-inhibitors (rs = 0.119, p = 0.020). The use of five-acetyl salicylic acid (5-ASA) decreased in patients with CD (rs = −201, p = 0.012). Conclusion: There was a decrease in the prescription of prednisolone and an increase in the prescription of budesonide treatment from 2006 to 2023; however, the cumulative exposure to corticosteroids in patients with IBD remains at a relatively high level. Plain language summary: The use of steroids in patients with inflammatory bowel disease diagnosed between 2006 and 2020 In the 1950s, corticosteroids and immunomodulators were introduced, and in combination with improved surgery, the mortality rates dramatically decreased in patients with inflammatory bowel disease (IBD) Although corticosteroids are effective in the short term they have no proven efficacy in long-term therapy for IBD, and owing to the risk of side effects, their long-term use should be restricted. Based on the evolution of treatments and treatment strategies for IBD in the 2000s, we aimed to study to the extent to which corticosteroids have been used in the first five years after diagnosis for patients with IBD diagnosed at our clinic between 2006 and 2020. To what extent is prednisolone prescribed in the first five years after diagnosis? Has the pattern of corticosteroid prescription changed after the introduction of advanced therapy and biosimilars to TNF inhibitors? We found that the proportion of patients with IBD who were prescribed at least one prescription of corticosteroids in year one to five after diagnosis was 55.3%, 27.9%, 22.7%, 14.1%, and 14.6%, respectively. The proportion of patients who had a cumulative dose of prednisolone >1g in the first five years after diagnosis was 40.1% for ulcerative colitis (UC) and 34.9% for Crohns disease (CD). The cumulative prescribed dosage (within 3 years after diagnosis) of prednisolone had declined but increased for budesonide between 2006-2020. The prescription of any immunomodulator for IBD in the first five years from diagnosis was stable between the years 2006-2018, but there was a minor increase in the prescription of TNF-inhibitors. The use of 5-ASA decreased in patients with CD. We conclude that there was a decrease in the prescription of prednisolone and an increase in the prescription of budesonide treatment from 2006 to 2023; however, the cumulative exposure to corticosteroids in patients with IBD remains on relatively high level. [ABSTRACT FROM AUTHOR]

Mild-to-moderate ulcerative colitis (UC) management is centred on 5-aminosalicylic acid (5-ASA) derivatives. Whether supplementing 5-ASA with nutraceuticals can provide real advantages in UC-relevant outcomes is unclear. This retrospective multicentre study compared clinical remission, response rates, and faecal calprotectin levels in a two-arm design, including patients treated with 5-ASA alone and those with additional H. erinaceus-based multi-compound supplementation. In the 5-ASA alone group, clinical response rates were 41% at three months (T1) and 60.2% at six months (T2), while corresponding clinical remission rates were 16.9% and 36.1%. In the nutraceutical supplementation group, clinical response rates were 49.6% (T1) and 70.4% (T2), with clinical remission rates of 30.4% (T1) and 50.9% (T2). No significant differences in clinical response rates between the groups at T1 (p = 0.231) and T2 (p = 0.143) emerged. Clinical remission rates differed significantly at both time points (p = 0.029 and p = 0.042, respectively). Faecal calprotectin levels decreased significantly in both groups during the retrospective follow-up (p < 0.05), and this was more pronounced in nutraceutical supplementation patients at both T1 (p = 0.005) and T2 (p = 0.01). No adverse events were reported. This multi-component nutraceutical supplementation offers real-world potential in controlling disease activity in patients with mild-to-moderate UC. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease [IBD] is associated with various immune-mediated disorders including spondylarthritis, pyoderma gangrenosum, primary sclerosing cholangitis, and uveitis. Chronic kidney disease [CKD] is defined by a reduction in kidney function (estimated glomerular filtration rate [eGFR] less than 60 ml/min/1.73m2] and/or damage markers that are present for at least 3 months, regardless of the aetiology. Case reports and cohort studies suggest that IBD is associated with CKD. The extent and magnitude of a potential association is unknown. A comprehensive search was conducted in EMBASE, MEDLINE, Web of Science, the Cochrane database, and SCOPUS. Two separate reviewers were involved in the process of article selection and evaluation. Odds ratios were calculated in those papers with a comparison between an IBD population and a non-IBD control population, the Mantel Haenszel test was employed, using a random effect model. The systematic review was registered in PROSPERO [RD42023381927]. A total of 54 articles was included in the systematic review. Of these, eight articles included data on prevalence of CKD in IBD patients [ n  = 102 230] vs healthy populations [ n  = 762 430]. Of these, diagnosis of CKD was based on International Classification of Diseases [ICD] codes in five studies vs on eGFR in three studies. The overall odds ratio of developing CKD in the IBD population is 1.59, [95% CI 1.31-1.93], without any difference between studies using diagnostic coding (odds ratio [OR] 1.70, 95% CI 1.33-2.19] vs diagnosis based on eGFR [OR 1.36, 95% CI 1.33-1.64]. IBD is associated with a clinically meaningful increased CKD prevalence. We provide recommendations on diagnostic evaluation, as well as suggestions for future research. [ABSTRACT FROM AUTHOR]

Medical therapy is the cornerstone of ulcerative colitis (UC) management and aims to induce and maintain remission. In case of mild-to-moderate UC, mesalamine (5-ASA) is the first-line option. 5-ASA requires local release at the level of the inflamed mucosa to exert its therapeutic action. While rectal preparations are useful in distal colitis, in cases of UC of at least rectosigmoid extent, guidelines suggest the association of oral and rectal 5-ASA. Mesalamine with Multi Matrix System® technology (MMX mesalamine) is an oral, high-strength (1.2 g/tablet), once-daily formulation of 5-ASA, designed to provide delayed and prolonged release throughout the entire colon. Clinical trials demonstrated a strong efficacy in inducing and maintaining clinical and endoscopic remission in active mild-to-moderate UC. The efficacy is related to specific colonic drug-delivery, to its high-dosage and once-daily administration, thus improving patients' adherence and outcomes. The specific colonic-delivery is also associated with very low rates of systemic absorption and adverse events (AEs). With this comprehensive review we aimed to summarize current knowledge on MMX mesalamine in mild-to-moderate UC, in terms of clinical pharmacology, efficacy and safety, also compared to other 5-ASA products. In addition we provided an expert opinion on the topic, examining the implications on clinical practice. [ABSTRACT FROM AUTHOR]

Renal involvement in inflammatory bowel disease is rather uncommon. This study aims to describe the spectrum of renal involvement in pediatric patients with IBD and reduce delay in detection and management. This is a retrospective study of the renal function of all patients, aged <18 years, who have been followed for IBD in our pediatric gastroenterology department from January 2019 till January 2023. From the 75 IBD patients included in this study 16 % had renal manifestations. The urinalysis revealed proteinuria in 7 patients, proteinuria and hematuria in 3 and proteinuria and glycosuria in 2 patients. All 12 patients with abnormal urinalysis underwent further investigation in order to determine the cause of renal damage and the results are as follows: 2 patients had glomerulonephritis and in other 2 patients renal damage was due to medication adverse effect, 1 had pyelonephritis in combination with chronic active tubulointerstitial nephritis and another 1 had thin basement membrane disease. Three patients had IBD-related dependent renal involvement and 1 resulted in chronic renal failure due to amyloidosis. It is important for all clinicians to be aware of the possibility of renal manifestations in IBD patients for the early diagnosis and prevention of these manifestations and complications. [ABSTRACT FROM AUTHOR]

Introduction: Although there are well-defined guidelines for the management of mild-to-moderate ulcerative colitis (UC), there are still unmet needs. For this reason, we conducted an international expert consensus to standardize the management of patients with mild-to-moderate UC and provide practical guidance to clinicians. Areas covered: Based on Delphi methodology, 15 statements were approved after two rounds of voting, addressing several aspects of disease management from sequencing to treatment duration, from monitoring to optimization techniques and safety profile. Expert opinion: Growing knowledge of mild-to-moderate UC has led to the development of new ambitious outcomes such as histological remission and disease clearance. Furthermore, noninvasive tools for patient monitoring such as fecal calprotectin and intestinal ultrasound are now available. Their implementation in clinical practice will allow clinicians to tightly monitor disease activity and promptly adapt treatment, avoiding complications and disease progression and targeting better disease control. [ABSTRACT FROM AUTHOR]

Mesalazine is an established and recommended first-line treatment for mild-tomoderate ulcerative colitis (UC). For patients with moderately active UC, the choice to use mesalazine or to initiate treatment with an oral corticosteroid or anti-tumor necrosis factor (TNF) agent is not clearly informed from current guidelines. The use of mesalazine is supported by robust clinical evidence supporting its efficacy at inducing remission in patients with moderately active disease. A key advantage of mesalazine is its tolerability profile being similar to that of placebo, which contrasts with that of the corticosteroids and advanced therapies, where there is the potential for significant toxicities. Mesalazine also has cost advantages over anti-TNFs and other advanced therapies. Evidence supports the consideration of all patients with moderately active UC for first-line mesalazine therapy at an optimized dose of ≥4g/d (± 1g/d rectal). Patients responding to treatment within 2 weeks should continue at ≥4g/d for at least 6 months before a dose reduction is considered, since this then alters the pattern of disease. [ABSTRACT FROM AUTHOR]

Background/Objectives: The treatment of patients with mild-to-moderate ulcerative colitis (UC) is challenging. Although there are commonly used guidelines, therapy optimization is not standardized. We conducted a survey to investigate the management and treatment of patients with mild-to-moderate UC. Methods: Physicians with experience in treating inflammatory bowel diseases (IBD) were invited to participate in an anonymous, multiple-choice survey between June and July 2023. The survey addressed various issues of patient care such as patient monitoring, treatment optimization, follow-up, treatment decision making, and therapy de-escalation. Results: The survey included 222 physicians (59.9% men; mean age = 50.4 years) from 66 countries worldwide. Gastroenterologists were the most represented specialists (89.6%), followed by surgeons (3.2%), and internal medicine doctors (2.7%). Two-thirds of the participants (66.7%) had >10 years of experience in the field of IBD. The combination of oral (≥4 g/day) and rectal 5-aminosalicylic acid (5-ASA) was the preferred choice when optimizing therapy. Budesonide MMX (41.8%) and systemic steroids (39.9%) were preferred in patients who failed 5-ASA. Treatment decisions were predominantly based on endoscopic (99.0%) or clinical (59.8%) activity. A significant percentage of clinicians did not optimize therapy in the case of increased fecal calprotectin alone (45.1%) or radiological/ultrasound activity (39.8%) alone. Conclusions: The guidelines for the management of mild-to-moderate UC are well accepted in clinical practice. Endoscopic remission remains the main therapeutic target, followed by clinical remission. Fecal calprotectin and intestinal ultrasound still elicit complaints from physicians. [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC) is a chronic gastrointestinal disease that can be managed with 5-aminosalicylic acid (5-ASA), the standard treatment for UC. However, the effectiveness of 5-ASA is not always optimal. Our study revealed that despite 5-ASA treatment, cells continued to experience excessive ferroptosis, which may hinder mucosal healing in UC and limit the success of this treatment approach in achieving disease remission. We found that combining 5-ASA with the ferroptosis inhibitor Fer-1 led to a significant inhibition of ferroptosis in macrophages present in the colon tissue, along with an increase in the proportion of M2 macrophages, suggesting that targeting ferroptosis in M2 macrophages could be a potential therapeutic strategy for alleviating UC. Our study also demonstrated that M2 macrophages are more susceptible to ferroptosis compared to M1 macrophages, and this susceptibility is associated with the activated arachidonic acid (AA) metabolism pathway mediated by ERK-cPLA2-ACSL4. Additionally, we found that the expression of cPLA2 gene pla2g4a was increased in the colon of UC patients compared to healthy controls. Furthermore, targeted metabolomics analysis revealed that the combination treatment group, as opposed to the 5-ASA treatment group, exhibited the ability to modulate AA metabolism. Overall, our findings emphasize the importance of addressing macrophage ferroptosis in order to enhance macrophage anti-inflammation, improve mucosal healing, and achieve better therapeutic outcomes for patients with UC. [Display omitted] • The ferroptosis susceptibility of M2 is greater than that of M1. • The ferroptosis susceptibility of M2 is associated with the ERK-cPLA2-ACSL4 pathway. • The dysregulation of AA contributes to the ineffectiveness of 5-ASA in rescuing ferroptosis in M2. [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC) is a chronic inflammatory bowel disease with a significant health-care burden worldwide. While medical therapy aims to induce and maintain remission, optimal management of mild to moderate UC remains challenging due to heterogeneity in severity classifications and non-standardized approaches. This comprehensive review summarizes current evidence and knowledge gaps to optimize clinical decision-making in patients with mild to moderate UC. After an extensive literature search of PubMed, Medline, and Embase through August 2023, we provide an overview of definitions utilized to characterize mild to moderate UC severity and established therapeutic targets. Current medical treatments including mesalazine formulations, corticosteroids, and their combinations are surveyed. The role of emerging intestinal ultrasound, telemedicine, and home testing is explored. Individualized, patient-centered paradigms aiming to streamline care delivery through proactive identification of relapses are also examined. Addressing inconsistencies in disease activity stratification will better align tailored regimens with each patient's profile. Advancing noninvasive technologies like ultrasound criteria and home testing could improve UC management by enabling personalized models. Realizing individualized plans through informed shared-decision making between health-care providers and fully engaged patients holds promise to maximize quality of life outcomes. Continuous improvement relies on innovation bridging different domains to overcome current limitations and push the field toward more predictive and tailored care. [ABSTRACT FROM AUTHOR]

Mesalazine is an established and recommended first-line treatment for mild-to-moderate ulcerative colitis (UC). For patients with moderately active UC, the choice to use mesalazine or to initiate treatment with an oral corticosteroid or anti-tumor necrosis factor (TNF) agent is not clearly informed from current guidelines. The use of mesalazine is supported by robust clinical evidence supporting its efficacy at inducing remission in patients with moderately active disease. A key advantage of mesalazine is its tolerability profile being similar to that of placebo, which contrasts with that of the corticosteroids and advanced therapies, where there is the potential for significant toxicities. Mesalazine also has cost advantages over anti-TNFs and other advanced therapies. Evidence supports the consideration of all patients with moderately active UC for first-line mesalazine therapy at an optimized dose of ≥4g/d (± 1g/d rectal). Patients responding to treatment within 2 weeks should continue at ≥4g/d for at least 6 months before a dose reduction is considered, since this then alters the pattern of disease.

Abstract Patients with inflammatory bowel disease (IBD) always suffer from severe abdominal pain and appear to be at high risk for colorectal cancer. Recently, the co-delivery of targeted drugs and gut microbiota has developed into an attractive strategy. A new strategy using gut microbiota fermentation to overcome the interspace diffuse resistance from the mucus layer to control drug release in inflammatory bowel sites (IBS sites) has not yet been available. Here, we designed an alginate hydrogel microsphere encapsulating bifidobacterium (Bac) and drug-modified nanoscale dietary fibers (NDFs). The hydrogel microsphere is responsible for protecting drugs from acidic and multi-enzymatic environments and delivering drugs to the colorectum. Subsequently, the fermentation of Bac by digesting NDFs and proteins as carbon and nitrogen sources can promote drug release and play a probiotic role in the gut microbiota. In vitro evidence indicated that small-sized NDF (NDF-1) could significantly promote short-chain fatty acid (SCFA) expression. Notably, NDF-1 hydrogel microspheres showed a boost release of 5-ASA in the IBS sites, resulting in the amelioration of gut inflammation and remodeling of gut microbiota in chronic colitis mice. This study developed a controlled release system based on microbial fermentation for the treatment of IBD.

Mild-to-moderate ulcerative colitis (UC) management is centred on 5-aminosalicylic acid (5-ASA) derivatives. Whether supplementing 5-ASA with nutraceuticals can provide real advantages in UC-relevant outcomes is unclear. This retrospective multicentre study compared clinical remission, response rates, and faecal calprotectin levels in a two-arm design, including patients treated with 5-ASA alone and those with additional H. erinaceus-based multi-compound supplementation. In the 5-ASA alone group, clinical response rates were 41% at three months (T1) and 60.2% at six months (T2), while corresponding clinical remission rates were 16.9% and 36.1%. In the nutraceutical supplementation group, clinical response rates were 49.6% (T1) and 70.4% (T2), with clinical remission rates of 30.4% (T1) and 50.9% (T2). No significant differences in clinical response rates between the groups at T1 (p = 0.231) and T2 (p = 0.143) emerged. Clinical remission rates differed significantly at both time points (p = 0.029 and p = 0.042, respectively). Faecal calprotectin levels decreased significantly in both groups during the retrospective follow-up (p < 0.05), and this was more pronounced in nutraceutical supplementation patients at both T1 (p = 0.005) and T2 (p = 0.01). No adverse events were reported. This multi-component nutraceutical supplementation offers real-world potential in controlling disease activity in patients with mild-to-moderate UC.

The prevalence of ulcerative colitis (UC) in the Middle East is increasing, impacting the economic and healthcare burden. The management of patients with mild to moderate UC is still a challenge as several factors can affect optimal care, including drug choice, induction and maintenance dose, treatment optimization and de-escalation, therapy duration, monitoring, and safety profile. We conducted an expert consensus to standardize the management of patients with mild to moderate UC. Sixteen experts in inflammatory bowel diseases, through a well-established and accepted Delphi methodology, voted and approved eight statements in order to provide practical guidance to clinicians in the Middle East. [ABSTRACT FROM AUTHOR]

Patients with inflammatory bowel disease (IBD) always suffer from severe abdominal pain and appear to be at high risk for colorectal cancer. Recently, the co-delivery of targeted drugs and gut microbiota has developed into an attractive strategy. A new strategy using gut microbiota fermentation to overcome the interspace diffuse resistance from the mucus layer to control drug release in inflammatory bowel sites (IBS sites) has not yet been available. Here, we designed an alginate hydrogel microsphere encapsulating bifidobacterium (Bac) and drug-modified nanoscale dietary fibers (NDFs). The hydrogel microsphere is responsible for protecting drugs from acidic and multi-enzymatic environments and delivering drugs to the colorectum. Subsequently, the fermentation of Bac by digesting NDFs and proteins as carbon and nitrogen sources can promote drug release and play a probiotic role in the gut microbiota. In vitro evidence indicated that small-sized NDF (NDF-1) could significantly promote short-chain fatty acid (SCFA) expression. Notably, NDF-1 hydrogel microspheres showed a boost release of 5-ASA in the IBS sites, resulting in the amelioration of gut inflammation and remodeling of gut microbiota in chronic colitis mice. This study developed a controlled release system based on microbial fermentation for the treatment of IBD. [ABSTRACT FROM AUTHOR]

Inflammatory Bowel Diseases had their first peak in incidence in countries in North America, Europe, and Oceania and are currently experiencing a new acceleration in incidence, especially in Latin America and Asia. Despite technological advances, 90 years after the development of the first molecule for the treatment of IBD, we still do not have drugs that promote disease remission in a generalized way. We carried out a narrative review on therapeutic advances in the treatment of IBD, the mechanisms of action, and the challenges facing the therapeutic goals in the treatment of IBD. Salicylates are still used in the treatment of Ulcerative Colitis. Corticosteroids have an indication restricted to the period of therapeutic induction due to frequent adverse events, while technologies with less systemic action have been developed. Most immunomodulators showed a late onset of action, requiring a differentiated initial strategy to control the disease. New therapeutic perspectives emerged with biological therapy, initially with anti-TNF, followed by anti-integrins and anti-interleukins. Despite the different mechanisms of action, there are similarities between the general rates of effectiveness. These similar results were also evidenced in JAK inhibitors and S1p modulators, the last therapeutic classes approved for the treatment of IBD. [ABSTRACT FROM AUTHOR]

Background Inflammatory bowel diseases (IBD) are characterized by chronic inflammation of the gastrointestinal tract but can have multiorgan involvement. Mesalazine (5-ASA) is a key therapeutic agent in IBD. Mesalazine has rare but potentially life-threatening side effects such as cardiac injury. Case summary We present two cases of myopericarditis, documented also with cardiac magnetic resonance, that we attributed to 5-ASA hypersensitivity: the first is a young woman with ulcerative colitis who developed myopericarditis after the initiation of 5-ASA, with a good clinical response after discontinuation; the second is a 79-year-old man who developed symptoms of heart failure after the diagnosis of IBD and the introduction of 5-ASA. Discussion Mesalazine may cause rare but potentially life-threatening cardiac injury, which can be difficult to distinguish from acute IBD-induced cardiac inflammation. [ABSTRACT FROM AUTHOR]

Background: Mesalamine is one of the most-used drugs in inflammatory bowel disease (IBD), especially ulcerative colitis. Regulatory agencies have listed mesalamine as an unsafe drug in subjects with glucose-6-phosphate dehydrogenase (G6PD) deficiency based on the risk of hemolysis, although scientific evidence is lacking. The occurrence of acute and/or chronic hemolytic anemia in IBD patients with G6PD deficiency exposed to mesalamine was evaluated. Methods: In this multicenter study, IBD patients with G6PD deficiency (cases) receiving mesalamine were retrospectively evaluated for acute, and prospectively for chronic, hemolysis. The presence of hemolytic anemia was based on red blood cell and reticulocyte count, hemoglobin, lactate dehydrogenase, unconjugated bilirubin, and haptoglobin levels. Cases were compared with controls (IBD patients with normal G6PD). Results: A total of 453 IBD patients (mean age 52.1 ± 16.0 years; 58.5% female) were enrolled. Ulcerative colitis was present in 75% of patients. G6PD deficiency was detected in 17% of patients. Oral mesalamine was used in 67.9% of ulcerative colitis and in 32.4% of Crohn's disease cases. None of the 78 IBD patients with G6PD deficiency receiving mesalamine underwent hospitalization or specific treatment for acute hemolytic anemia. Relevant differences in chronic hemolysis markers were not observed in 30 cases compared with 112 controls receiving mesalamine (≤4500 mg/day). Marker modifications were also observed in mesalamine-free cases, consistent with the basal rate of erythrophagocytosis in G6PD deficiency. Ex vivo experiments showed the release of methemoglobin by G6PD deficient RBCs upon mesalamine challenge, only above 2.5 mg/mL, a concentration never reached in the clinical setting. Conclusions: This study provides, for the first time, evidence that mesalamine is safe in G6PD deficiency at a dosage of up to 4500 mg/day. [ABSTRACT FROM AUTHOR]

We encapsulated mesalazine (MSZ) in nanoparticles (NP) of acetylated cashew gum (ACG) in order to improve its absorption in the colon. NPs were synthesized by the dialysis method and different polymer:drug ratios (10:1, 10:2 and 10:5) were investigated. The NP-ACG-MSZ had a size of 273 ± 6.76 nm, PDI 0.10 ± 0.02 and zeta potential -43.2 ± 8.15 mV. SEM demonstrated spherical morphology. XRD analysis showed that the incorporation of the drug in crystalline state into polymeric nanoparticles made it more stable. In vitro release studies showed that switching to pH 6.8 increased release to 62.08 ± 6.03%, which remained at pH 7.4 and sustained release of 95.61 ± 3.25% was observed. In vitro cytotoxicity test demonstrated that NP-ACG (with or without MSZ) showed no basal cytotoxicity in CT26 cells up to a concentration of 131 μg/mL. NP-ACG has shown to be a promising vector for the sustained release of MSZ in the colon when administered orally .

Abstract Background Multi-matrix mesalazine (MMX) is an important treatment for ulcerative colitis (UC); however, it is often excreted intact, which increases the risk of relapse. This study aimed to clarify the risk factors for insoluble MMX excretion. Methods The subjects were 102 UC patients who were newly prescribed MMX alone to induce remission. Their stools were evaluated on the Bristol Stool Form Scale (BSFS), the presence/absence of insoluble MMX excretion was investigated in interviews, and defecation frequency at the start of treatment and disease type were retrospectively investigated by examining their medical records. Results The insoluble excretion rate (IER) was 14.7%. It tended to be higher in the patients with left-sided colitis or extensive colitis, although the differences among the disease types were not significant (p = 0.053). The mean defecation frequency of the patients that reported insoluble MMX excretion was significantly higher than that of the patients that did not report it (6.27 ± 5.28 vs. 3.69 ± 3.17, p

Individual differences in IBD illness severity, behavior, progression, and therapy response are evident. Since a break in the intestinal epithelial barrier causes IBD to begin, mucosal gene expression in IBD is crucial. Due to its high sensitivity and dynamic nature, molecular analysis of biomarkers in intestinal biopsies is feasible and provides a reliable means of evaluating localized inflammation. The goal of this investigation was to discover alterations in gene expression in the inflamed mucosa of IBD patients undergoing treatment with 5-amino salicylic acid (5ASA) (N = 39) or anti-TNF drugs (N = 22). The mucosal expression of numerous IBD-related genes was evaluated using qPCR. We discovered that the levels of the proteins Lipocalin-2 (LCN2), Nitric Oxide Synthase 2 (NOS2), Mucin 2 (MUC2), Mucin 5AC (MUC5AC), and Trefoil factor 1 (TFF1), which are overexpressed in untreated IBD patients compared to non-IBD subjects, are decreased by both therapy regimens. On the other hand, anti-TNF medicine helped the levels of ABCB1 and E-cadherin return to normal in IBD patients who were not receiving treatment. [ABSTRACT FROM AUTHOR]

Background: Endoscopic and histological activity scores in ulcerative colitis (UC) are associated with clinical outcomes and have become important targets of clinical trials. However, these endpoints have been scarcely investigated in patients receiving only conventional treatment. Objective: We aimed to assess the deep and complete remission rates after 3 months of conventional treatment in patients with newly diagnosed UC with moderate to severe endoscopic activity. We also aimed to investigate whether selected clinical and biochemical variables at baseline were associated with complete remission status after 3 months. Design: This was a prospective cohort study. Methods: Newly diagnosed patients with active UC commencing 5-aminosalicylate, corticosteroid, and/or azathioprine treatment were consecutively included. Clinical, biochemical, endoscopic, and histological data were collected at baseline and after 3 months. Rates of clinical remission (Partial Mayo Score ⩽ 2), mucosal healing (Mayo Endoscopic Score ⩽ 1), and histologic healing (Nancy Index ⩽ 1) were determined. Deep remission was assessed as clinical remission plus mucosal healing and complete remission as deep remission plus histologic healing. Predictors of complete remission were identified by logistic regression. Results: A total of 180 patients were included in the study. Deep remission and complete remission occurred in 62.8% and 42.2% of patients, respectively. Thus, of patients in deep remission one-third had persistent histologic activity. Histologic activity in mucosally healed patients was associated with higher symptom scores and faecal calprotectin levels. Of baseline variables, less endoscopic distribution and disease activity showed strongest association with achieving complete remission, and limited distribution in combination with moderate activity gave highest odds for complete remission (odds ratio: 4.1, 95% confidence interval: 7.69–2.18). Conclusion: In patients with mucosal healing, persistent histologic activity was a common finding and was associated with increased disease activity. Pancolitis and severe inflammatory activity at baseline were associated with lower complete remission rates. [ABSTRACT FROM AUTHOR]

We encapsulated MSZ in zein nanoparticles (NP-ZN) using a desolvation method followed by drying in a mini spray dryer. These nanoparticles exhibited a size of 266.6 ± 52 nm, IPD of 0.14 ± 1.1 and zeta potential of −36.4 ± 1.5 mV, suggesting colloidal stability. Quantification using HPLC showed a drug-loaded of 43.8 µg/mg. SEM demonstrated a spherical morphology with a size variation from 220 to 400 nm. A FTIR analysis did not show drug spectra in the NPs in relation to the physical mixture, which suggests drug encapsulation without changing its chemical structure. A TGA analysis showed thermal stability up to 300 °C. In vitro release studies demonstrated gastroresistance and a sustained drug release at pH 7.4 (97.67 ± 0.32%) in 120 h. The kinetic model used for the release of MSZ from the NP-ZN in a pH 1.2 medium was the Fickian diffusion, in a pH 6.8 medium it was the Peppas–Sahlin model with the polymeric relaxation mechanism and in a pH 7.4 medium it was the Korsmeyer–Peppas model with the Fickian release mechanism, or "Case I". An in vitro cytotoxicity study in the CT26.WT cell line showed no basal cytotoxicity up to 500 μg/mL. The NP-ZN showed to be a promising vector for the sustained release of MSZ in the colon by oral route. [ABSTRACT FROM AUTHOR]

Inflammatory Bowel Diseases had their first peak in incidence in countries in North America, Europe, and Oceania and are currently experiencing a new acceleration in incidence, especially in Latin America and Asia. Despite technological advances, 90 years after the development of the first molecule for the treatment of IBD, we still do not have drugs that promote disease remission in a generalized way. We carried out a narrative review on therapeutic advances in the treatment of IBD, the mechanisms of action, and the challenges facing the therapeutic goals in the treatment of IBD. Salicylates are still used in the treatment of Ulcerative Colitis. Corticosteroids have an indication restricted to the period of therapeutic induction due to frequent adverse events, while technologies with less systemic action have been developed. Most immunomodulators showed a late onset of action, requiring a differentiated initial strategy to control the disease. New therapeutic perspectives emerged with biological therapy, initially with anti-TNF, followed by anti-integrins and anti-interleukins. Despite the different mechanisms of action, there are similarities between the general rates of effectiveness. These similar results were also evidenced in JAK inhibitors and S1p modulators, the last therapeutic classes approved for the treatment of IBD.

With increasing urbanization and industrialization, the prevalence of inflammatory bowel diseases (IBDs) has steadily been rising over the past two decades. IBD involves flares of gastrointestinal (GI) inflammation accompanied by microbiota perturbations. However, microbial mechanisms that trigger such flares remain elusive. Here, we analyzed the association of the emerging pathogen atypical enteropathogenic E. coli (aEPEC) with IBD disease activity. The presence of diarrheagenic E. coli was assessed in stool samples from 630 IBD patients and 234 age- and sex-matched controls without GI symptoms. Microbiota was analyzed with 16S ribosomal RNA gene amplicon sequencing, and 57 clinical aEPEC isolates were subjected to whole-genome sequencing and in vitro pathogenicity experiments including biofilm formation, epithelial barrier function and the ability to induce pro-inflammatory signaling. The presence of aEPEC correlated with laboratory, clinical and endoscopic disease activity in ulcerative colitis (UC), as well as microbiota dysbiosis. In vitro, aEPEC strains induce epithelial p21-activated kinases, disrupt the epithelial barrier and display potent biofilm formation. The effector proteins espV and espG2 distinguish aEPEC cultured from UC and Crohn’s disease patients, respectively. EspV-positive aEPEC harbor more virulence factors and have a higher pro-inflammatory potential, which is counteracted by 5-ASA. aEPEC may tip a fragile immune–microbiota homeostasis and thereby contribute to flares in UC. aEPEC isolates from UC patients display properties to disrupt the epithelial barrier and to induce pro-inflammatory signaling in vitro.

Background: Multi-matrix mesalazine (MMX) is an important treatment for ulcerative colitis (UC); however, it is often excreted intact, which increases the risk of relapse. This study aimed to clarify the risk factors for insoluble MMX excretion.Methods: The subjects were 102 UC patients who were newly prescribed MMX alone to induce remission. Their stools were evaluated on the Bristol Stool Form Scale (BSFS), the presence/absence of insoluble MMX excretion was investigated in interviews, and defecation frequency at the start of treatment and disease type were retrospectively investigated by examining their medical records.Results: The insoluble excretion rate (IER) was 14.7%. It tended to be higher in the patients with left-sided colitis or extensive colitis, although the differences among the disease types were not significant (p = 0.053). The mean defecation frequency of the patients that reported insoluble MMX excretion was significantly higher than that of the patients that did not report it (6.27 ± 5.28 vs. 3.69 ± 3.17, p < 0.05). The IER tended to be higher among the patients with soft stools (4.5%, 21.9%, and 23.1% in those with BSFS scores of ≤ 4, 5, and ≥ 6, respectively). In ROC analysis of defecation frequency, ≥ 3.5 defecations was found to exhibit sensitivity and specificity of 66.7% and 65.5%, respectively, for predicting insoluble MMX excretion.Conclusions: The likelihood of insoluble MMX excretion is influenced by defecation frequency and the extent of inflammation. It is important to keep the possibility of insoluble excretion in mind when prescribing MMX. [ABSTRACT FROM AUTHOR]

Five-aminosalicylic acid (5-ASA) is an anti-inflammatory drug indicated in the treatment of inflammatory bowel diseases such as ulcerative colitis and Crohn's disease. Among the analytical methods of quantification of 5-ASA described in the literature, the High Efficiency Liquid Chromatography stands out, a sensitive technique but with a high cost. In recent years, alternative methods have been developed, presenting efficiency and reduced cost, such as UV/visible spectrophotometric, spectrofluorescent, and electrochemical methods, techniques recommended for the application in quality control and quantification of 5-ASA in pharmaceutical forms and biological fluids. This article aims to review the physicochemical characteristics, pharmacokinetics, mechanisms of action, controlled release systems, and the different analytical and bioanalytical methods for the quantification of 5-ASA. [ABSTRACT FROM AUTHOR]

Kartikeya Tripathi,1 Jeffrey Dong,2 Brooke F Mishkin,2 Joseph D Feuerstein2 1Department of Gastroenterology, University of Massachusetts Medical School - Baystate Campus, Springfield, MA, USA; 2Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USACorrespondence: Joseph D FeuersteinDivision of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, 110 Francis St 8e Gastroenterology, Boston, MA, 02215, USATel +1 617 632 8623Fax +1 617 632 9199Email Jfeuerst@bidmc.harvard.eduAbstract: Ulcerative colitis (UC) is a chronic inflammatory disorder that requires sustained treatment for optimal outcomes. The 5-aminosalicylate (5-ASA) class of medications are first-line for the treatment of mild-to-moderate UC but suffer from suboptimal adherence rates in real-world settings. This review summarizes the literature on adherence and patient preference to 5-ASA in patients with UC. We begin by highlighting key studies that measure real-world adherence rates, as well as some of the pitfalls associated with certain techniques. We examine the data on the consequences of non-adherence, which range from decreased quality of life and higher risk of colorectal cancer at the individual level to increased costs to the overall healthcare system. We then turn to the reasons and risk factors for non-adherence and summarize the current understanding of the barriers towards adherence. Afterwards, we describe the research on patient preferences between 5-ASA formulations and dosing regimen. Finally, we summarize the evidence regarding interventions to improve 5-ASA adherence. While adherence remains a challenge in practice, understanding the current state of the field can better inform future efforts towards increasing adherence, and thus clinical outcomes, in UC.Keywords: UC, 5-ASA, ulcerative colitis, adherence, compliance

Background and aims: The evolution of inflammatory bowel diseases was significantly improved during the last decade by the new therapeutic options. Classical medications as corticosteroids and 5-aminosalycilates (5-ASA) are still highly used. In order to evaluate the pattern of corticosteroid usage we used a dedicated online tool-the steroid assessment tool. Our purpose was to evaluate if this tool can permit a change in the therapeutic habits and an improvement of quality of care. We succeeded to outline a therapeutic profile for a series of IBD patients in a tertiary centre from Romania. Methods: Two consecutive assessments were made using an online tool named Steroid Assessment Tool (SAT). Corticosteroid pattern of use and all previous and current treatments were registered and analyzed. Also the epidemiological and clinical data were collected and analyzed. The statistical analysis was performed using SPSS® software. Results: Results showed that most of our IBD patients (90%) had been treated with 5-ASA, with 29.2% of CD patients and 54.3% of UC patients currently using 5-ASA. Also, we had more CD patients (78%) than UC patients (56.5%) treated with anti-TNF inhibitors. The rate of thiopurine use was small (2.3%) and of anti-integrin therapy, interleukin 12/23 inhibitors as well. The rate of corticosteroid use was 34% in 2019 and in 2020 it dropped to 25% while the rate of corticosteroid excess was 20.4% in 2019 with a statistically significant decrease in 2020 (p=0,01) when it was 5.95%. Discussion: We managed to draw a therapeutic profile of IBD patients in a tertiary IBD center from Romania using an online tool named SAT. We noticed that the majority of patients were treated with 5-ASA. Even though 5-ASA are not recommended by recent therapeutic guidelines as treatment for CD, we have 29.2% of CD patients treated with this class of drugs, a rate smaller than other reports but still outside guidelines. In the same time, we have a higher rate of anti-TNF agents use compared to other studies, but a lower rate of thiopurine use. Corticosteroid use was higher the other reports, but we succeeded to lower the rate of corticosteroid use and the rate of corticosteroid excess. Conclusions: The therapeutic profile and habits of prescription in a tertiary IBD center were analyzed twice using an easy-to-use online tool. The results obtained in our first evaluation led to a change in the therapeutic management, improving our adherence to guideline’s recommendations.

Incorporating 5-aminosalicylic acid (5-ASA) into a colon-specific carrier is crucial for treating inflammatory bowel diseases (IBD), as it enhances therapeutic efficacy, targets the affected regions directly, and minimizes side effects. This study evaluated the impact of incorporating cellulose nanofibers (CNF) on the in vitro and in vivo biological performance of retrograded starch/pectin (RS/P) microparticles (MPs) containing 5-ASA. Using Fourier Transform Infrared (FTIR) Spectroscopy, shifts in the spectra of retrograded samples containing CNF were observed with increasing CNF proportions, suggesting the establishment of new supramolecular interactions. Liquid absorption exhibited pH-dependent behaviors, with reduced absorption in simulated gastric fluid (∼269 %) and increased absorption in simulated colonic fluid (∼662 %). Increasing CNF concentrations enhanced mucoadhesion in porcine colonic sections, with a maximum force of 3.4 N at 50 % CNF. Caco-2 cell viability tests showed biocompatibility across all tested concentrations (0.0625–2.0000 mg/mL). Evaluation of intestinal permeability in Caco-2 cell monolayers demonstrated up to a tenfold increase in 5-ASA permeation, ranging from 29 % to 48 %. An in vivo study using Galleria mellonella larvae, with inflammation induced by LPS, showed reduction of inflammation. Given the scalability of spray-drying, these findings suggest the potential of CNF-incorporated RS/P microparticles for targeted 5-ASA delivery in IBD. [Display omitted] [ABSTRACT FROM AUTHOR]

To understand current thinking and clinical decision-making in the treatment and management of patients with mild-to-moderate ulcerative colitis (UC). This multinational, survey-based study was conducted in 2021. Two meetings were held, involving 11 IBD specialists, that used a series of questions and discussion to identify all factors possibly related to the management of UC. The importance of identified factors was assessed using an online questionnaire covering three scenarios – active disease, remission and patient empowerment. Each factor was scored on a scale of 0 (very-unimportant) to 100 (very-important) within each scenario, by a separate group of healthcare professionals working in IBD. A total of 157 individual factors were identified by the 11 IBD specialists and scored in the three scenarios by 56 respondents (52; 93% specialist gastroenterologists) from Europe and North America (25; 45%), South America (19; 34%) and the Middle East, Asia and Australia (12; 21%). For all scenarios, factors related to educating patients regarding UC and its treatment and understanding of patient goals ranked highest, ahead of clinical considerations regarding disease activity and treatment history. Setting realistic short-term treatment targets was a key consideration. 5-ASA optimisation and use of faecal calprotectin monitoring were core strategies across the three scenarios tested. Support for patients during longer-term management of their disease, starting from initial flare, was an important recurring theme. The current management approach for mild-to-moderate UC was found to be guided primarily by the patient's perspectives and goals, alongside assessment of their medical and disease history. [ABSTRACT FROM AUTHOR]

Background & Aims: 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. Methods: 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. Results: 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

The article highlights modern concepts of inflammatory diseases in adults and children in terms of genetic possibilities for diagnosing Crohn's disease and ulcerative colitis. It names the main candidate genes, which, in the presence of their specific polymorphisms, indicate the occurrence of a high risk of inflammatory bowel disease. The principles of modern therapy, the possibilities of pharma-cogenetic testing in predicting the effectiveness or risks of reducing the safety of drug therapy are described. The article focuses on modern trends and perspectives in ulcerative colitis and Crohn's disease treatment.

Individual differences in IBD illness severity, behavior, progression, and therapy response are evident. Since a break in the intestinal epithelial barrier causes IBD to begin, mucosal gene expression in IBD is crucial. Due to its high sensitivity and dynamic nature, molecular analysis of biomarkers in intestinal biopsies is feasible and provides a reliable means of evaluating localized inflammation. The goal of this investigation was to discover alterations in gene expression in the inflamed mucosa of IBD patients undergoing treatment with 5-amino salicylic acid (5ASA) (N = 39) or anti-TNF drugs (N = 22). The mucosal expression of numerous IBD-related genes was evaluated using qPCR. We discovered that the levels of the proteins Lipocalin-2 (LCN2), Nitric Oxide Synthase 2 (NOS2), Mucin 2 (MUC2), Mucin 5AC (MUC5AC), and Trefoil factor 1 (TFF1), which are overexpressed in untreated IBD patients compared to non-IBD subjects, are decreased by both therapy regimens. On the other hand, anti-TNF medicine helped the levels of ABCB1 and E-cadherin return to normal in IBD patients who were not receiving treatment.

We encapsulated MSZ in zein nanoparticles (NP-ZN) using a desolvation method followed by drying in a mini spray dryer. These nanoparticles exhibited a size of 266.6 ± 52 nm, IPD of 0.14 ± 1.1 and zeta potential of −36.4 ± 1.5 mV, suggesting colloidal stability. Quantification using HPLC showed a drug-loaded of 43.8 µg/mg. SEM demonstrated a spherical morphology with a size variation from 220 to 400 nm. A FTIR analysis did not show drug spectra in the NPs in relation to the physical mixture, which suggests drug encapsulation without changing its chemical structure. A TGA analysis showed thermal stability up to 300 °C. In vitro release studies demonstrated gastroresistance and a sustained drug release at pH 7.4 (97.67 ± 0.32%) in 120 h. The kinetic model used for the release of MSZ from the NP-ZN in a pH 1.2 medium was the Fickian diffusion, in a pH 6.8 medium it was the Peppas–Sahlin model with the polymeric relaxation mechanism and in a pH 7.4 medium it was the Korsmeyer–Peppas model with the Fickian release mechanism, or “Case I”. An in vitro cytotoxicity study in the CT26.WT cell line showed no basal cytotoxicity up to 500 μg/mL. The NP-ZN showed to be a promising vector for the sustained release of MSZ in the colon by oral route.

Mesalazine, also known as 5-aminosalicylic acid (5-ASA), is a synthetic drug from the family of nonsteroidal anti-inflammatory drugs (NSAIDs) used for inflammatory diseases of the gastrointestinal tract. However, 5-ASA has also been used for various other diseases due to its pharmacological effects, but they are usually scattered across various publications, which may limit further research and clinical use of this drug. This review is a summary of published information on the biological and pharmacological effects of 5-ASA with the aim of identifying its anti-oxidant role and medicinal use. 5-ASA data have been collected from 1987 to February 2021 using major databases such as Web of Science, PubMed, Elsevier, Wiley Online Library, Springer, Google Scholar, etc. According to research, the pharmacological and biological effects of 5-ASA include treatment of inflammatory bowel disease, and anti-oxidant, anti-inflammatory, antibacterial, antifungal, anticancer, anti-amyloid, gastric protection (gastroprotective), and antidiverticulosis properties. Numerous pharmacological studies have shown that 5-ASA is an anti-oxidant and anti-ulcer compound with high therapeutic potential that, if the appropriate dose is discovered, its chemical structure changes and its effectiveness is optimized, 5-ASA has been used experimentally for other diseases. [ABSTRACT FROM AUTHOR]

[Display omitted] Ulcerative colitis (UC) is an idiopathic disease characterized by colonic mucosal tissue destruction secondary to an excessive immune response. We synthesized pH-sensitive cross-linked chitosan/Eudragit® S100 nanoparticles (EU S100/CS NPs) as carriers for 5-aminosalicylic acid (5-ASA) and hesperidin (HSP), then conducted in-vitro and in-vivo studies and evaluated the therapeutic effects. In-vitro analysis revealed that the 5-ASA-loaded EU S100/CS NPs and the HSP-loaded EU S100/CS NPs had smooth and curved surfaces and ranged in size between 250 and 300 nm, with a zeta potential of 32 to 34 mV. FTIR analysis demonstrated that the drugs were loaded on the nanoparticles without significant alterations. The loading capacity and encapsulation efficiency of loading 5-ASA onto EU S100/CS NPs were 25.13 % and 60.81 %, respectively. Regarding HSP, these values were 38.34 % and 77.84 %, respectively. Drug release did not occur in simulated gastric fluid (SGF), while a slow-release pattern was recorded for both drugs in simulated intestinal fluid (SIF). In-vivo macroscopic and histopathological examinations revealed that both NPs containing drugs significantly relieved the symptoms of acetic acid (AA)-induced UC in Wistar rats. We conclude that the synthesized pH-sensitive 5-ASA/EU S100/CS NPs and HSP/EU S100/CS NPs offer promise in treating UC. [ABSTRACT FROM AUTHOR]

Background: The drug 5-aminosalicylic acid (5-ASA) is the first-line therapy for the treatment of patients with mild-to-moderate ulcerative colitis (UC). However, in some cases, 5-ASA cannot achieve the desired therapeutic effects. Therefore, patients have to undergo therapies that include corticosteroids, monoclonal antibodies or immunosuppressants, which are expensive and may be accompanied by significant side effects. Synergistic drug combinations can achieve greater therapeutic effects than individual drugs while contributing to combating drug resistance and lessening toxic side effects. Thus, in this study, we sought to identify synergistic drugs that can act synergistically with 5-ASA.Methods: We started our study with protein-metabolite analysis based on peroxisome proliferator-activated receptor gamma (PPARG), the therapeutic target of 5-ASA, to identify more additional potential drug targets. Then, we further evaluated the possibility of their synergy with PPARG by integrating Kyoto Encyclopedia of Genes and Genome (KEGG) pathway enrichment analysis, pathway-pathway interaction analysis, and semantic similarity analysis. Finally, we validated the synergistic effects with in vitro and in vivo experiments.Results: The combination of 5-ASA and vorinostat (SAHA) showed lower toxicity and mRNA expression of p65 in human colonic epithelial cell lines (Caco-2 and HCT-116), and more efficiently alleviated the symptoms of dextran sulfate sodium (DSS)-induced colitis than treatment with 5-ASA and SAHA alone.Conclusion: SAHA can exert effective synergistic effects with 5-ASA in the treatment of UC. One possible mechanism of synergism may be synergistic inhibition of the nuclear factor kappa B (NF-kB) signaling pathway. Moreover, the metabolite-butyric acid may be involved.

Background: The drug 5 - aminosalicylic acid (5-ASA) is the first-line therapy for the treatment of patients with mild-to-moderate ulcerative colitis (UC). However, in some cases, 5-ASA cannot achieve the desired therapeutic effects. Therefore, patients have to undergo therapies that include corticosteroids, monoclonal antibodies or immunosuppressants, which are expensive and may be accompanied by significant side effects. Synergistic drug combinations can achieve greater therapeutic effects than individual drugs while contributing to combating drug resistance and lessening toxic side effects. Thus, in this study, we sought to identify synergistic drugs that can act synergistically with 5-ASA. Methods: We started our study with protein-metabolite analysis based on peroxisome proliferator-activated receptor gamma (PPARG), the therapeutic target of 5-ASA, to identify more additional potential drug targets. Then, we further evaluated the possibility of their synergy with PPARG by integrating Kyoto Encyclopedia of Genes and Genome (KEGG) pathway enrichment analysis, pathway-pathway interaction analysis, and semantic similarity analysis. Finally, we validated the synergistic effects with in vitro and in vivo experiments. Results: The combination of 5-ASA and vorinostat (SAHA) showed lower toxicity and mRNA expression of p65 in human colonic epithelial cell lines (Caco-2 and HCT-116), and more efficiently alleviated the symptoms of dextran sulfate sodium (DSS)-induced colitis than treatment with 5-ASA and SAHA alone. Conclusion: SAHA can exert effective synergistic effects with 5-ASA in the treatment of UC. One possible mechanism of synergism may be synergistic inhibition of the nuclear factor kappa B (NF-kB) signaling pathway. Moreover, the metabolite-butyric acid may be involved. [ABSTRACT FROM AUTHOR]

Background and aims: The evolution of inflammatory bowel diseases was significantly improved during the last decade by the new therapeutic options. Classical medications as corticosteroids and 5-aminosalycilates (5-ASA) are still highly used. In order to evaluate the pattern of corticosteroid usage we used a dedicated online tool-the steroid assessment tool. Our purpose was to evaluate if this tool can permit a change in the therapeutic habits and an improvement of quality of care. We succeeded to outline a therapeutic profile for a series of IBD patients in a tertiary centre from Romania. Methods: Two consecutive assessments were made using an online tool named Steroid Assessment Tool (SAT). Corticosteroid pattern of use and all previous and current treatments were registered and analyzed. Also the epidemiological and clinical data were collected and analyzed. The statistical analysis was performed using SPSS® software. Results: Results showed that most of our IBD patients (90%) had been treated with 5-ASA, with 29.2% of CD patients and 54.3% of UC patients currently using 5-ASA. Also, we had more CD patients (78%) than UC patients (56.5%) treated with anti-TNF inhibitors. The rate of thiopurine use was small (2.3%) and of anti-integrin therapy, interleukin 12/23 inhibitors as well. The rate of corticosteroid use was 34% in 2019 and in 2020 it dropped to 25% while the rate of corticosteroid excess was 20.4% in 2019 with a statistically significant decrease in 2020 (p=0,01) when it was 5.95%.Discussion: We managed to draw a therapeutic profile of IBD patients in a tertiary IBD centre from Romania using an online tool named SAT. We noticed that the majority of patients were treated with 5-ASA. Even though 5-ASA are not recommended by recent therapeutic guidelines as treatment for CD, we have 29.2% of CD patients treated with this class of drugs, a rate smaller than other reports but still outside guidelines. In the same time, we have a higher rate of anti-TNF agents use compared to other studies, but a lower rate of thiopurine use. Corticosteroid use was higher the other reports, but we succeeded to lower the rate of corticosteroid use and the rate of corticosteroid excess.Conclusions: The therapeutic profile and habits of prescription in a tertiary IBD centre were analyzed twice using an easy-to-use online tool. The results obtained in our first evaluation led to a change in the therapeutic management, improving our adherence to guideline’s recommendations. [ABSTRACT FROM AUTHOR]

Aims: Mesalamine is the first‐line therapy for treating mild‐to‐moderate ulcerative colitis. Multiple mesalamine formulations are available, with similar safety and efficacy profiles. Mesalamine is commonly administered as divided dosing, although once‐daily dosing may provide benefits for patients. We evaluated the pharmacokinetics of three dosing regimens of two oral delayed‐release mesalamine formulations in healthy adult volunteers. Methods: A randomised, open‐label, parallel‐group study of mesalamine pharmacokinetics following Lialda 2 × 1.2 g once daily (QD) (dose A), Asacol 6 × 400 mg QD (dose B), or Asacol 2 × 400 mg three times daily (TID) (dose C) over 7 days. Assessments included 5‐aminosalicylic acid (5‐ASA) and N‐acetyl 5‐aminosalicylic acid (N‐Ac‐5‐ASA, primary metabolite) pharmacokinetics (Ae(%), AUC0‐24 and Cmax), safety and tolerability. Results: All enrolled volunteers (n = 37) completed the study. Steady state was achieved for all treatments by day 4. Ratios (95% CI) of means for steady‐state AUC0‐24 (dose A vs B 90.3% [39.8, 204.8], dose A vs C 123.5% [55.3, 275.7], dose B vs C 136.8% [61.3, 305.5]) and Cmax (dose A vs B 106.0% [46.4, 242.2], dose A vs C 133.0% [59.1, 299.0], dose B vs C 125.5% [55.8, 282.1]) were similar for all 5‐ASA treatments. Mean urinary excretion of 5‐ASA plus N‐Ac‐5‐ASA was comparable between treatments (dose A 21.3%, dose B 20.2%, dose C 17.9%). All treatment regimens were well tolerated; no safety issues were observed. Conclusions: Plasma and urine pharmacokinetics for Asacol TID, Asacol QD, and Lialda QD are similar, suggesting similar daily systemic exposures can be obtained with either TID or QD dosing. NCT00751699. [ABSTRACT FROM AUTHOR]

The article discusses the possible relationships between intestinal microbiota and the therapeutic efficacy of 5-aminosalicylic acid (5-ASA) in inflammatory bowel diseases. Intestinal microbiota may be involved in 5-ASA enzymatic biotransformation, but the metabolism of drugs by the intestinal microbiota has been studied in less detail, and little is known about the relationships between anti-inflammatory efficacy of 5-ASA with bacterial viability, quantity and activity. It remains unclear whether 5-ASA affects the microbiota depending on the different segments of gastrointestinal tract. Drugs and diet can both improve and worsen the composition of the intestinal microbiota. However, it is not known whether drugs affect the intestinal microbiota regardless of diet. Further research is needed to answer these questions. [ABSTRACT FROM AUTHOR]