BACKGROUND: The benefits and risks of Xileisan (XLS) in the treatment of ulcerative colitis (UC) remain unclear.
OBJECTIVE: The present study aimed to evaluate the efficacy and safety of the combination of XLS and mesalazine when treating UC.
METHODS: We searched eight databases for clinical trials evaluating the combination of XLS and mesalazine in the treatment of UC, up to January 2024. Meta-analysis and trial sequential analysis (TSA) were performed using Revman 5.3 and TSA 0.9.5.10 beta, respectively.
RESULTS: The present study included 13 clinical studies involving 990 patients, of which 501 patients received XLS combined with mesalazine while 489 patients received mesalazine alone. The meta-analysis showed that, in terms of efficacy, the combination of XLS and mesalazine significantly improved the clinical efficacy rate by 22% [risk ratio (RR) = 1.22; 95%CI: 1.15-1.28; P < 0.00001] and mucosal improvement rate by 25% (RR = 1.25; 95%CI: 1.12-1.39; P = 0.0001), while significantly reducing the duration of abdominal pain by 2.25 days [mean difference (MD) = -2.25; 95%CI: -3.35 to -1.14; P < 0.0001], diarrhea by 2.06 days (MD = -2.06; 95%CI: -3.92 to -0.20; P = 0.03), hematochezia by 2.32 days (MD = -2.32; 95%CI: -4.02 to -0.62; P = 0.008), tumor necrosis factor alpha by 16.25 ng/mL (MD = -16.25; 95%CI: -20.48 to -12.01; P < 0.00001), and interleukin-6 by 14.14 ng/mL (MD = -14.14; 95%CI: -24.89 to -3.39; P = 0.01). The TSA indicated conclusiveness in the meta-analysis of the efficacy endpoints. In terms of safety, the meta-analysis revealed that the combination of XLS and mesalazine did not increase the occurrence of total and gastrointestinal adverse events, abdominal distension, and erythema (P > 0.05). The TSA showed non conclusive findings in the meta-analysis of the safety endpoints. Harbord\'s test showed no publication bias (P = 0.734).
CONCLUSIONS: Treatment with XLS alleviated the clinical symptoms, intestinal mucosal injury, and inflammatory response in patients with UC, while demonstrating good safety.

BACKGROUND: The efficacy data on treatment in older adults are scarce, while the greatest increase in ulcerative colitis (UC) prevalence is observed in age groups of individuals 40 to 65 years of age and ≥65 years of age.
OBJECTIVE: We assessed the difference in rates of clinical and endoscopic response and remission in UC adults (≤60 years) and older adults (>60 years) treated with mesalazine.
METHODS: We performed a post hoc analysis of data from a phase 3 noninferiority trial of 817 UC patients treated with mesalazine for 8 and additional 26 weeks in a double-blind and open-label study, respectively. We used Wilcoxon rank sum or chi-square test to analyze differences between groups and multivariable logistic regression to determine the associations between endoscopic remission as outcome (Mayo endoscopic subscore [MES] = 0 or ≤1) and independent variables including disease duration, baseline MES, age, sex, comedications, and comorbidities.
RESULTS: Older adults had a longer disease duration, a higher number of comorbidities, concomitant medications, and higher baseline MES (2.38 ± 0.486 in older adults vs 2.26 ± 0.439 in adults; P = .008) compared with adults. We observed no difference in rates of combined clinical and endoscopic remission, clinical remission and response, and endoscopic remission and response at week 8 and 38 post-treatment. In addition to other well-known predictors of worse outcome, patients with ≥3 comedications were less likely to achieve an MES = 0 at week 8 and 38 and an MES ≤1 at week 38.
CONCLUSIONS: We observed similar efficacy of mesalazine in adult and older adult UC patients. The increased comedication number rather than age may decrease effectiveness of UC medications, highlighting the importance of healthy aging.
We investigated the rates of clinical and endoscopic response in adult (≤60 years) and older adult (>60 years) ulcerative colitis patients treated with oral mesalazine; our results demonstrated that age did not influence the efficacy and safety.

Chronic rhinosinusitis (CRS) is a disease characterised by the inflammation of the nasal and paranasal cavities. It is a widespread condition with considerable morbidity for patients. Current treatment for chronic rhinosinusitis consists of appropriate medical therapy followed by surgery in medically resistant patients. Although oral steroids are effective, they are associated with significant morbidity, and disease recurrence is common when discontinued. The development of additional steroid sparing therapies is therefore needed. Mesalazine is a commonly used therapeutic in inflammatory bowel disease, which shares a similar disease profile with chronic rhinosinusitis. This exploratory in vitro study aims to investigate whether mesalazine could be repurposed to a nasal wash, which is safe on human nasoepithelial cells, and retains its anti-inflammatory effects. CRS patients\' human nasal epithelial cells (HNECs) were collected. HNECs were grown at an air-liquid interface (ALIs) and in a monolayer and challenged with mesalazine or a non-medicated control. Transepithelial electrical resistance, paracellular permeability, and toxicity were measured to assess epithelial integrity and safety. The anti-inflammatory effects of mesalazine on the release of interleukin (IL)-6 and tumour necrosis factor alpha (TNF-α) were analysed using human leukemia monocytic cell line (THP-1). mesalazine did not impact the barrier function of HNEC-ALIs and was not toxic when applied to HNECs or THP-1 cells at concentrations up to 20 mM. mesalazine at 0.5 and 1 mM concentrations significantly inhibited TNF-α release by THP-1 cells. mesalazine effectively decreases TNF-α secretion from THP-1 cells, indicating the possibility of its anti-inflammatory properties. The safety profile of mesalazine at doses up to 20 mM suggests that it is safe when applied topically on HNECs.

OBJECTIVE: The recommendations of the Spanish Ministry of Health on vaccination in risk groups include mesalazine among the treatments with a possible negative effect on its effectiveness. However, this is not the recommendation of most experts. Our objective was to evaluate the effect of mesalazine on the humoral response to the SARS-CoV-2 vaccine in patients with inflammatory bowel disease (IBD).
METHODS: VACOVEII is a Spanish, prospective, multicenter study promoted by GETECCU, which evaluates the effectiveness of the SARS-CoV-2 vaccine in patients with IBD. This study includes IBD patients who have recieved the full vaccination schedule and without previous COVID-19 infection. Seroconversion was set at 260BAU/mL (centralized determination) and was assessed 6 months after full vaccination. In this subanalysis of the study, we compare the effectiveness of the vaccine between patients treated with mesalazine and patients without treatment.
RESULTS: A total of 124 patients without immunosuppressive therapy were included, of which 32 did not receive any treatment and 92 received only mesalazine. Six months after full vaccination, no significant differences are observed in the mean concentrations of IgG anti-S between both groups. In the multivariate analysis, antibody titers were independently associated with the use of mRNA vaccines and with SARS-CoV-2 infection.
CONCLUSIONS: Mesalazine does not have a negative effect on the response to SARS-CoV-2 vaccines in IBD patients.

BACKGROUND: The introduction of biological drugs has led to great expectations and growing optimism in the possibility that this new therapeutic strategy could favourably change the natural history of Inflammatory Bowel Disease (IBD) and, in particular, that it could lead to a significant reduction in surgery in the short and long term. This study aims to assess the impact of biological versus conventional therapy on surgery-free survival time (from the diagnosis to the first bowel resection) and on the overall risk of surgery in patients with Crohn\'s disease (CD) who were never with the surgical option.
METHODS: This is a retrospective, double-arm study including CD patients treated with either biological or conventional therapy (mesalamine, immunomodulators, antibiotics, or steroids). All CD patients admitted at the GI Unit of the S. Salvatore Hospital (L\'Aquila. Italy) and treated with biological therapy since 1998 were included in the biological arm. Data concerning the CD patients receiving a conventional therapy were retrospectively collected from our database. These patients were divided into a pre-1998 and post-1998 group. Our primary outcome was the evaluation of the surgery-free survival since CD diagnosis to the first bowel resection. Surgery-free time and event incidence rates were calculated and compared among all groups, both in the original population and in the propensity-matched population.
RESULTS: Two hundred three CD patients (49 biological, 93 conventional post-1998, 61 conventional pre-1998) were included in the study. Kaplan-Meier survivorship estimate shows that patients in the biological arm had a longer surgery-free survival compared to those in the conventional arm (p = 0.03). However, after propensity matching analysis, conducted on 143 patients, no significant difference was found in surgery-free survival (p = 0.3). A sub-group analysis showed shorter surgery-free survival in patients on conventional therapy in the pre-biologic era only (p = 0.02; Hazard Ratio 2.9; CI 1.01-8.54) while no significant difference was found between the biologic and conventional post-biologic groups (p = 0.15; Hazard Ratio 2.1; CI 0.69-6.44).
CONCLUSIONS: This study shows that the introduction of biological therapy has only a slight impact on the eventual occurrence of surgery in CD patients over a long observation period. Nevertheless, biological therapy appears to delay the first intestinal resection.

Background: Nonspecific terminal ileal ulcers are one of the common ulcerative diseases in terminal ileum. However, the studies about treatment efficacy are scarce. We aimed to investigate the efficacy of mesalazine in the treatment of this disease. Methods: Eighty-two patients with nonspecific terminal ileal ulcers who sought outpatient medical treatment in the Division of Gastroenterology, Wuhan Union Hospital, from April 2016 to January 2019 were enrolled and randomly divided into two groups. The experimental group took mesalazine orally, 4.0 g/d, once a day for 3 months. The control group was followed up without special intervention. The primary endpoint was the endoscopic remission rate at the 6th and 12th month. Secondary endpoints included the clinical remission rate at the 1st, 6th and 12th month and adverse events (ChiCTR1900027503). Results: About the endoscopic efficacy, the remission rate of the experimental group and control group was 73.2 versus 61.0% at the 6th month (RR = 1.20, 95%CI 0.88∼1.63, p = 0.24) and 87.8 versus 78.0% at the 12th month (RR = 1.13, 95%CI 0.92∼1.37, p = 0.24). About the clinical efficacy, the remission rate was 70.3 versus 43.8% at the 1st month (RR = 1.61, 95%CI 1.03∼2.51, p = 0.03), 83.8 versus 68.8% at the 6th month (RR = 1.22, 95%CI 0.93∼1.60, p = 0.14) and 91.9 versus 81.3% at the 12th month (RR = 1.13, 95%CI 0.93∼1.37, p = 0.34). During follow-up, no patients were diagnosed with Crohn\'s disease or intestinal tuberculosis, and no patients developed significant complications. Conclusion: For patients with nonspecific terminal ileal ulcers, there is no disease progression over a short term. In addition, there is no significant difference in clinical or endoscopic efficacy between patients who received mesalazine and patients who are followed up without special intervention.

Mesalazine is a low-permeable and low-soluble drug, which makes it a class IV drug in the Biopharmaceutics Classification System. Hence, its solubilization can be helpful for various stages of formulation development. The purpose of this study was to investigate the solubilization manner and thermodynamics of mesalazine in ternary solvent combinations of {ethanol (1) + propylene glycol (2) + water (3)} using the shake-flask technique at (298.2-313.2) K. In the following, the mathematical representation of the acquired solubility data using some popular models was evaluated. The accuracies of the applied models were described by percentages of mean relative deviation (MRD%). Based on obtained results (MRD% < 10.0), it can be concluded that the trained models can adequately predict the solubility of mesalazine in the investigated ternary solvent combinations. The findings also revealed that the solution composition and temperatures greatly influence the solubility of mesalazine. In addition, the thermodynamic characteristics of the mesalazine dissolution process indicate that the mesalazine dissolution process is endothermic and entropy-driven. The generating data in the current work also expands the available solubility database for mesalazine in the solvent mixtures.

BACKGROUND: Various systemic agents have been assessed for treatment of alopecia areata; however, there is a paucity of comparative studies.
OBJECTIVE: To compare the efficacy of azathioprine versus mesalazine in the treatment of severe alopecia areata.
METHODS: Our study was carried out in 30 patients with severe alopecia areata divided into two groups, group A: fifteen patients were treated by azathioprine in an oral dose of 1-2 mg/kg/day and group B: fifteen patients were treated by mesalazine in an oral dose of 15-30 mg/kg/day in two divided doses. The treatment was considered effective if percentage regrowth of hair was determined by change in SALT score >50 from base line after 6 months of treatment. The treatment was continued for 3-6 months after complete remission to minimize the risk of relapse. The dose was gradually tapered during this time.
RESULTS: The study found that there is statistically significant difference between mean SALT scores before treatment and after 6 months of treatment in both groups. In group A, SALT score at base line was 84.42 ± 17.41, after 6 months it was 35.95 ± 35.79 (p value 0.04). In group B, SALT score at base line was 73.06 ± 22.10, after 6 months it was 23.04± 12.27 (p value 0.037). Changes in SALT score after 6 months were -27.74 ± 20.66 in group A and -60.42±38.41 in group B (p value 0.055).
CONCLUSIONS: Mesalazine may be considered as effective as azathioprine with lesser side effects. Azathioprine is also considered safe. However, a large group study should be performed to confirm these findings.

In this study, a new, fast and sensitive HPLC method with fluorometric detection was developed for the determination of mesalazine in human plasma and applied to a pharmacokinetic study. Mesalazine was precolumn derivatized with NBD-Cl and the fluorescent derivative was separated on a C18 (150 × 4.6 mm × 2.6 μm) analytical column at 30 ºC using a mobile phase composed of acetonitrile-0.1% o-phosphoric acid in water (70:30, v/v) by isocratic elution with flow rate of 1.0 mL min-1. The method was based on the measurement of the derivative using fluorescence detection (λex = 280 nm, λem = 325 nm). The retention time of mesalazine is 3.08 ± 0.06 min. Nortriptiline was used as internal standard. This currently developed method was validated according to ICH criteria by evaluating the specificity, linearity, precision, accuracy and robustness. The method was determined to be linear in a concentration range of 0.25-1.5 μg mL-1 with the correlation coefficient of 0.9997. LOD and LOQ were found to be 0.075 and 0.25 μg mL-1, respectively. Intraday and interday RSD values were less than 5.92%. The plasma concentration-time profile and pharmacokinetic parameters such as AUC0-t, AUC0-∞, Cmax, tmax, t1/2, were calculated according to the assays. The presented method can certainly be used for bioequivalence and bioavailability investigations and routine analysis of the drug in plasma.

Several compounds based on short chain fatty acids and/or probiotics/prebiotics have shown promising results in the therapy of ulcerative colitis (UC), possibly due to its key role in restoring gut homeostasis as well as intestinal barrier integrity. Here, we investigated the efficacy of a patented preparation based on calcium butyrate, Bifidobacterium bifidum, Bifidobacterium lactis, and fructooligosaccharides (FEEDColon®, Princeps, Cuneo, Italy) in maintaining remission and improving subjective symptoms and inflammatory indices in patients with UC receiving 5-ASA therapy. A total of 42 patients were prospectively recruited and randomized in 21 patients receiving combination therapy with mesalamine (5-ASA) plus FEEDColon® and 21 patients treated with standard 5-ASA therapy. Patients were assessed at baseline, at 6-month, and 12-month follow-up (FU). Therapeutic success (defined as Mayo partial score ≤ 2 and faecal calprotectin (FC) < 250 µg/g at 12-month FU) was reached by 32 (76%) patients: 20 (95%) among those treated with 5-ASA + FeedColon®, and 12 (57%) among those treated with 5-ASA only (p = 0.009). Consistently, patients treated with combination therapy improved subjective symptoms (quality of life, abdominal pain, and stool consistency) and reduced FC values, while those treated with 5-ASA alone, improved neither subjective symptoms nor FC during the FU. In conclusion, FEEDColon® supplementation appears to be a valid add-on therapy for the maintenance of remission in patients with UC. Further multicentre, placebo-controlled, double-blind clinical trials are needed to validate our results on larger cohorts of patients with UC.