Dose Of Mesalazine Research Articles

Modified Lichong decoction intervenes in colorectal cancer by modulating the intestinal flora and the Wnt/β-catenin signaling pathway

BackgroundThe pathogenesis and treatment of colorectal cancer (CRC) continue to be areas of ongoing research, especially the benefits of traditional Chinese medicine (TCM) in slowing the progression of CRC. This study was conducted to investigate the effectiveness and mechanism of action of modified Lichong decoction (MLCD) in inhibiting CRC progression.MethodsWe established CRC animal models using azoxymethane/dextran sodium sulfate (AOM/DSS) and administered high, medium, or low doses of MLCD or mesalazine (MS) for 9 weeks to observe MLCD alleviation of CRC. The optimal MLCD dose group was then subjected to metagenomic and RNA sequencing (RNA-seq) to explore the differentially abundant flora and genes in the control, model and MLCD groups. Finally, the mechanism of action was verified using WB, qRT‒PCR, immunohistochemistry and TUNEL staining.ResultsMLCD inhibited the progression of CRC, and the optimal effect was observed at high doses. MLCD regulated the structure and function of the intestinal flora by decreasing the abundance of harmful bacteria and increasing that of beneficial bacteria. The differentially expressed genes were mainly associated with the Wnt/β-catenin pathway and the cell cycle. Molecular biology analysis indicated that MLCD suppressed the Wnt/β-catenin pathway and the epithelial–mesenchymal transition (EMT), inhibited abnormal cell proliferation and promoted intestinal epithelial cell apoptosis.ConclusionMLCD mitigated the abnormal growth of intestinal epithelial cells and promoted apoptosis, thereby inhibiting the progression of CRC. This inhibition was accomplished by modifying the intestinal microbiota and disrupting the Wnt/β-catenin pathway and the EMT. Therefore, MLCD could serve as a potential component of TCM prescriptions for CRC treatment.

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

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

Modified-Release Phosphatidylcholine (LT-02) for Ulcerative Colitis: Two Double-Blind, Randomized, Placebo-Controlled Trials

The aim of this study was to evaluate the efficacy of LT-02, a novel modified-release phosphatidylcholine (PC) formulation, for induction and maintenance of remission in patients with mild to moderate ulcerative colitis (UC) and inadequate response to mesalamine. LT-02 was evaluated in a multicenter double-blind, randomized, placebo-controlled study comprising a 12-week induction trial (PCG-2), followed by a 48-week maintenance trial (PCG-4). In PCG-2, patients were randomized 1:1:1 to treatment with 0.8 g LT-02 4 times daily (QID), 1.6 g LT-02 twice daily (BID), or placebo, respectively. All patients continued to take a standard dose of oral mesalamine (≥2.4 g/day). The primary end point in PCG-2 was deep remission. Patients achieving remission at week 12 were randomly assigned 2:1:1 to 1.6 g LT-02 BID, placebo, or 500 mg mesalamine (3 times daily), respectively, in PCG-4; the primary end point was remission at 48 weeks. PCG-2 was terminated early for futility after a prespecified interim analysis; 466 patients (of 762 planned) were randomized. There was no statistically significant difference in deep remission at week 12 (placebo, 13.5%; LT-02 BID, 14.2%; LT-02 QID, 9.7%). In PCG-4, 150 patients (of approximately 400 planned) were randomized. There was no statistically significant difference in remission rates at week 48 (LT-02 BID, 49.3%; mesalamine, 50.0%; placebo, 43.2%). LT-02 was safe. Despite prior evidence of beneficial effects of PC in phase 2 trials, our induction study withLT-02 in patients with mild to moderate UC was terminated prematurely for futility. Signals of efficacy in maintenance therapy require confirmation in an adequately powered maintenance trial. LT-02 was safe and well-tolerated. gov: NCT02280629, NCT02142725.

Modificación de la dosis de mesalazina en función de los niveles de calprotectina fecal en pacientes con colitis ulcerosa en remisión clínica

BackgroundFaecal calprotectin (FC) shows an excellent correlation with endoscopic and histological activity of ulcerative colitis (UC) and it is the best predictor of clinical relapse. Our aim was to evaluate the usefulness of modifying the dose of mesalazine based on FC levels, in clinical practice. MethodsRetrospective, single-centre study in UC patients in clinical remission while treated with mesalazine which dosage was decreased (DOWN) or increased (UP) according to FC levels. The main endpoint was the long-term maintenance of clinical remission. ResultsA total of 56 patients were included (39 DOWN, 17 UP). In the DOWN group, the median baseline dose of mesalazine was 3.6g/day and the median baseline FC was 36μg/g. After a median follow-up of 22 months, 28% required rescue therapy. The cumulative relapse-free survival after tapering was 91% and 82% at 12 and 24 months, respectively. In the UP group, the median baseline dose of mesalazine was 2.4g/day, with a median baseline FC of 524μg/g. After a median follow-up of 12 months, 29% required rescue therapy. The cumulative relapse-free survival after dose increase was 86% and 72% at 12 and 24 months, respectively. ConclusionsMesalazine dose modification based on FC monitoring seems to be a safe strategy in patients with UC in clinical remission, with a probability of clinical relapse around 20% at two years.

The Efficacy of Cichorium intybus L., Trigonella foenum-graecum L. and Foeniculum vulgare Mill. in Improvement of Ulcerative Colitis Symptoms: A Randomized Clinical Trial

Due to the lack of favorable response to synthetic drugs, the tendency to use traditional medicine to treat inflammatory bowel disease has risen. We aimed to assess the effect of Cichorium intybus L., Trigonella foenum-graecum L., and Foeniculum vulgare L. on the control of recurrent ulcerative colitis (UC) symptoms. This randomized clinical trial was performed on 60 patients suffering from mild-to-moderate UC. Patients were randomly assigned to control and intervention groups. Patients in both groups were treated with a standard dose of oral mesalazine (3 g daily) for eight weeks. In addition, the intervention group was given a mixture of 200 mg C. intybus, 350 mg T. foenum-graecum, and 1.5 mg F. vulgare (three times a day). The disease activity was evaluated before and 60 days after the intervention using a simple clinical colitis activity index (SCCAI). The baseline mean SCCAI score was similar in both groups. Although the SCCAI score significantly reduced in both groups 60 days after the initial assessment, this reduction was significantly higher in the group receiving the herbal combination than in the control group. The intervention-related side effects, such as bloating and dyspepsia, were well tolerated. The use of C. intybus, T. foenum-graecum, and F. vulgare can effectively control UC symptoms and thus, can be used as an effective and safe medication for treating UC.

Insights into Mesalazine Use in Clinical Practice of Young Gastroenterologists.

Mesalazine is among the medications most prescribed by gastroenterologists, with variable and controversial use in different settings. We aimed to explore the use of mesalazine in the clinical practice of young gastroenterologists. A web-based electronic survey was distributed to all participants of the National Meeting of the Italian Young Gastroenterologist and Endoscopist Association. A total of 101 participants took part in the survey, with a majority (54.4%) being aged >30 years, 63.4% of whom were trainees in academic hospitals, and 69.3% of whom were involved in the clinical management of inflammatory bowel disease (IBD). While both non-dedicated and IBD physicians generally agreed on the appropriate dose of mesalazine for mild ulcerative colitis (UC), significant differences were observed between the two groups for moderate-severe ulcerative colitis (UC). Additionally, in IBD patients who were starting immuno-modulators and/or biologics, 80% of IBD-dedicated physicians continued to prescribe mesalazine, compared to 45.2% of non-dedicated physicians (p = 0.002). Indeed, 48.4% of non-dedicated IBD physicians did not acknowledge mesalazine for colorectal cancer chemoprevention. With regards to Crohn's disease, it is mainly used by 30.1% of IBD physicians for preventing postoperative recurrence of Crohn's disease. Finally, 57.4% used mesalazine for symptomatic uncomplicated diverticular disease, and 84.2% did not recommend its use for irritable bowel syndrome. This survey showed heterogeneous behaviors in the daily use of mesalazine, mainly in the management of IBD. Educational programs and novel studies are needed to clarify its use.

P430 Mesalazine dose modification based on fecal calprotectin levels in ulcerative colitis patients in clinical remission

Abstract Background Mesalazine is the most widely used maintenance therapy for ulcerative colitis (UC). The lowest effective dose recommended is 2g/day, although higher doses are often prescribed. Fecal calprotectin (FC) is a monitoring biomarker that correlates well with endoscopic remission and predicts clinical relapse. Our aim was to evaluate the suitability of mesalazine dose modification based on FC levels in asymptomatic UC patients. Methods Retrospective study in asymptomatic UC patients treated with oral mesalazine therapy which dose was modified in clinical practice according to FC levels between 2016-2022. Sustained clinical remission, clinical relapse and treatment escalation (increase in dose or introduction of rescue therapy) after dose change were assessed during follow-up. Results Mesalazine dose was reduced in 47 patients because of persistent low FC (mean 36ug/g; IQR 22-85); 51% extensive UC, median age of 55 years (IQR 43-63), median duration of clinical remission before dose-reduction 17 months (IQR 8-32) and mean baseline dose 3.2g/day (IQR 2-4). Mesalazine was reduced to 2g/day (IQR 0-2.4). A FC value >250 ug/g was observed at least once in 10% of subjects during follow-up. The cumulative probability of maintaining clinical remission after dose reduction was 90% and 82% at 12 and 24 months, respectively. Rescue therapy was used in 27%, 17% being corticosteroids. In 17 patients, mesalazine dose was increased due to high FC levels (mean 524ug/g; IQR 393-739); 47% extensive UC, median age 54 years (IQR 39-72), median duration of clinical remission before dose increase 16 months (IQR 11-33) and mean baseline dose 2.4g/day (IQR 1.5 -2.4). Dose was increased to 3.2g/day (IQR 3-4.4) and 58% presented FC <250 ug/g at least once during the follow-up. The cumulative probability of clinical recurrence after dose escalation was 14% and 28% at 12 and 24 months, respectively, and 29% needed rescue therapy (6% steroids). Conclusion Mesalazine dose modification based on CF levels in asymptomatic patients with UC appears to be a safe strategy and is followed by a low probability of clinical recurrence in the mid-term.

Assessing the Clinical and Endoscopic Efficacy of Extended Treatment Duration with Different Doses of Mesalazine for Mild-to-Moderate Ulcerative Colitis beyond 8 Weeks of Induction

Introduction: High-strength mesalazine formulations play an important role in providing a convenient option to increase the dose in ulcerative colitis (UC) patients and therefore avoiding the switch to another therapeutic class. Higher doses of mesalazine may be required during periods of remission in order to prevent relapse. Aim: The aim of the study was to investigate clinical outcomes of three mesalazine maintenance doses adapted for post induction response. Methods: In this post hoc analysis, 675 UC patients entered an open-label extension study for a total of 38 weeks (including 8–12 week induction period with 3.2 g/day mesalazine). After the induction period, they were separated into three groups: remitters (in clinical and endoscopic remission), responders (decrease in Partial Mayo Clinic Score of ≥2 points and ≥30% from week 0), and nonresponders (failed to achieve endoscopic or clinical response at week 8) and received 1.6 g/day, 3.2 g/day, or 4.8 g/day of mesalazine (using a new 1,600 mg mesalazine tablet), respectively. Results: 133/202 (65.8%), 108/274 (39.4%), and 59/199 (29.6%) patients achieved clinical and endoscopic remission at week 38 with 1.6 g/day, 3.2 g/day, and 4.8 g/day, respectively. At week 38, 142/202 (70.3%), 93/274 (33.9%), and 61/199 (30.7%) patients achieved clinical remission (stool score of 0 and rectal bleeding score of 0) with 1.6 g/day, 3.2 g/day, and 4.8 g/day, respectively. Conclusions: Patients partially responding or not responding to an initial induction dose of 3.2 g/day mesalazine could benefit from an extended treatment period at the same dose, or an increase to 4.8 g/day in an attempt to achieve combined clinical and endoscopic remission.

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

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

P577 Withdrawal of thiopurines in patients with Ulcerative Colitis in remission

Abstract Background Thiopurines (TP) are widely used in monotherapy in patients with ulcerative colitis (UC), mainly for the maintenance of remission in case of corticodependence or corticoresistance after cyclosporine use. However, these are drugs with significant side effects, especially in the long term. The optimal duration of treatment with TP remains unknown, so it is important to determine the risk factors for relapse in order to identify the group of patients in which treatment can be withdrawn. Methods A retrospective study was performed. Patients with UC in remission, in maintenance treatment with TP, who had discontinued the drug due to either maintained remission or the onset of adverse effects were included. Results 26 patients were included, 1 with proctitis, 9 with left colitis and 16 with pancolitis. 24 (92.31%) were treated with azathioprine and 2 (7.69%) with mercaptopurine. The mean treatment time with TP was 68.09 months (standard deviation 56.65). 11 patients (42.31%) discontinued TP due to adverse effects and the remaining patients (57.69%) discontinued it by medical decision because they were in prolonged remission. After withdrawal of TP, 92.34% of patients continued treatment with mesalazine and the remaining 7.69% without concomitant treatment. During follow-up, 10 patients (38.4%) relapsed and 16 patients (61.53%) had no relapse until the end of follow-up. The mean time from TP withdrawal to the onset of relapse was 69.15 months (standard deviation 52.53). Of the 10 patients who presented a flare, 5 (50%) were controlled by optimizing the dose of mesalazine, 4 (40%) required the addition of oral corticosteroids and 1 (10%) required biologics. No significant differences were found when comparing the time to relapse if the reason for discontinuation of TP was having had an adverse effect (65.05 months) or maintained remission (79.79 months) (p=0.42). No statistically significant differences were found in time to relapse when comparing time on TP treatment, presence of concomitant treatment with mesalazine or active smoking. Conclusion One third of patients relapsed after TP withdrawal. Discontinuation of TP in patients with UC in remission should be individualized according to the patient’s risk factors, the indication and the duration of treatment.

Maternal mesalazine-induced neonatal gastrointestinal bleeding.

Ulcerative colitis often develops in the reproductive age women and can cause exacerbation by pregnancy. Mesalazine (5-aminosalicylic acid) is recommended as a safe anti-inflammatory drug during pregnancy. However, maternal mesalazine is transferred to the fetus through the placenta and may cause allergic events. A pregnant woman with severe ulcerative colitis was treated with a dose of mesalazine 4,000 mg/day from early gestation to delivery. Immediately after birth, the preterm neonate vomited bloody contents and discharged massive gross haematochezia. Serum concentrations of mesalazine and its main metabolite were high in the mother and the umbilical cord. Faecal eosinophils and drug-induced lymphocyte stimulation test suggested possibility that sensitisation with mesalazine in utero caused allergic enterocolitis like food protein-induced allergic proctocolitis. Maternal mesalazine has a potential of fetal sensitisation and cause allergic disease.

Efficacy of Oral, Topical, or Combined Oral and Topical 5-Aminosalicylates, in Ulcerative Colitis: Systematic Review and Network Meta-analysis.

5-Aminosalicylates [5-ASAs] are the mainstay of treatment for ulcerative colitis [UC]. The optimum preparation, dose, and route of administration for UC remain unclear. We conducted a network meta-analysis to examine this issue. We searched MEDLINE, EMBASE, EMBASE Classic, and the Cochrane central register of controlled trials from inception to December 2020. We included randomised controlled trials [RCTs] comparing oral, topical, or combined oral and topical 5-ASAs, with each other or placebo for induction of remission or prevention of relapse of UC. Results were reported as pooled relative risks [RRs] with 95% confidence intervals [CIs] to summarise effect of each comparison tested, with treatments ranked according to P-score. We identified 40 RCTs for induction of remission and 23 for prevention of relapse. Topical mesalazine [P-score 0.99], or oral and topical mesalazine combined [P-score 0.87] ranked first and second for clinical and endoscopic remission combined. Combined therapy ranked first in trials where ≥50% of patients had left-sided/extensive disease, and topical mesalazine first in trials where ≥50% of patients had proctitis/proctosigmoiditis. High-dose [≥3.3 g/day] oral mesalazine ranked third in most analyses, with the most trials and most patients. For relapse of disease activity, combined therapy and high-dose oral mesalazine ranked first and second, with topical mesalazine third. 5-ASAs were safe and well tolerated, regardless of regimen. Our results support previous evidence; however, higher doses of oral mesalazine had more evidence for induction of remission than combined therapy and were significantly more efficacious than lower doses. Future RCTs should better establish the role of combined therapy for induction of remission, as well as optimal doses of oral 5-ASAs to prevent relapse.

Efficacy of Budesonide Foam in Patients with Mild-to-Moderate Ulcerative Colitis Treated with a Maximum Dose of Oral Mesalazine

Efficacy of Budesonide Foam in Patients with Mild-to-Moderate Ulcerative Colitis Treated with a Maximum Dose of Oral Mesalazine

P760 Differences in persistence of oral mesalazine preparations as monotherapy in patients with ulcerative colitis

Abstract Background Oral mesalazine is the mainstay treatment of ulcerative colitis (UC). Mesalazine exerts its anti-inflammatory effect locally in the colonic mucosa. The mucosal mesalazine concentration is inversely correlated with the degree of inflammation and previous studies have found that mucosal drug concentrations differ between various oral mesalazine preparations. In the current study we have examined the drug persistence of oral mesalazine preparations in a national cohort of UC patients. Methods Patients with newly diagnosed UC from 2010 to 2014 using oral mesalazine as anti-inflammatory monotherapy 3 months after the time of diagnosis were identified by combining data from the Norwegian Patient Registry and the Norwegian Prescription Database. The patients were retrospectively followed through 2017, median follow-up time was 1029 days. Treatment failure was defined as start of topical mesalazine or glucocorticoid preparations, systemic glucocorticoids, immunomodulators and biologic treatment or a change to another oral mesalazine preparation. Drug persistence was defined as duration of oral mesalazine preparation in monotherapy. Disease was categorised as more severe in patients who had dispensed systemic glucocorticoids the first three months after diagnosis. Drug persistence at national and regional level was stratified by mesalazine preparation (Mezavant (MEZ), Asacol (ASA), Pentasa (PEN), Salofalk (SAL)) and disease severity. Consumption was estimated based on defined daily doses (DDD = 1.5 g) of mesalazine dispensed from pharmacies. Results A total of 3421 patients were identified. Overall median mesalazine drug persistence was 311 days. The persistence differed between the preparations in descending order: MEZ (398 days), SAL (374 days), PEN (273 days), ASA (266 days), and the order was similar in the four regions. Patients with more severe disease at diagnosis had shorter drug persistence (193 vs. 407 days). Systemic glucocorticoids were given to similar proportion of patients for ASA (0.60) and PEN (0.61), while this proportion of MEZ users was lower (0.52) and even lower for SAL users (0.43). The number of prescribed DDD the first year after diagnosis was slightly higher in MEZ users (MEZ 1.75, ASA 1.36, PEN 1.42, SAL 1.40). Conclusion There were significant differences in drug persistence between oral preparations that were not explained by differences in prescription at regional level, but could partially be related to differences in disease severity. These differences could have clinical implications and bear further investigations.

Efficacy of Oral, Topical, or Combined Oral and Topical 5-Aminosalicylates, in Ulcerative Colitis: Systematic Review and Network Meta-Analysis

Background: 5-aminosalicylates (5-ASAs) are the mainstay of treatment for mild to moderately active ulcerative colitis (UC). The optimum 5-ASA preparation, dose, and route of administration for UC remains unclear. We conducted a network meta-analysis to compare and rank efficacy and safety of oral, topical, or combined oral and topical 5-ASAs for induction of remission of active UC and prevention of relapse of quiescent UC. Methods: We searched MEDLINE, EMBASE, EMBASE Classic, and the Cochrane central register of controlled trials from inception to July 2020. We included all available randomised controlled trials (RCTs) comparing oral 5-ASAs, topical 5-ASAs, or combined oral and topical 5-ASAs, with each other, or with placebo in induction of remission and prevention of relapse of UC. The efficacy and safety of all treatments were reported as a pooled relative risk (RR) with 95% confidence intervals (CIs) to summarise effect of each comparison tested, with treatments ranked according to their P-score. Findings: We identified 40 RCTs for induction of remission and 23 RCTs for prevention of relapse. Topical mesalazine alone (P-score 0.99), or a combination of oral and topical mesalazine (P-score 0.87) ranked first and second with regards to clinical and endoscopic remission combined. Findings were similar for clinical, endoscopic, and histological remission. Combined oral and topical mesalazine was ranked first for trials in which ≥50% of patients had left-sided or extensive disease, and topical mesalazine first in trials in which ≥50% of patients had proctitis or proctosigmoiditis. However, high-dose (≥3.3g/day) oral mesalazine ranked third in most analyses and had the most trials and most patients. For prevention of relapse, combined oral and topical mesalazine and high-dose oral mesalazine ranked first and second (P-scores 0.91 and 0.75 respectively), with topical mesalazine third. Only topical mesalazine was superior to placebo for prevention of relapse in trials in which ≥50% of patients had proctitis or proctosigmoiditis. 5-ASAs were safe and well tolerated, regardless of treatment regimen. Interpretation: In general, our results support current recommendations for use of 5-ASAs in induction of remission of UC, and prevention of relapse. However, higher doses of oral mesalazine (≥3.3g/day) had more evidence for efficacy in induction of remission than combined therapy and were significantly more efficacious than lower doses. Future RCTs should aim to better establish the role of combined oral and topical therapy for induction of remission, as well as optimal doses of oral 5-ASAs to prevent relapse of disease activity. The study protocol was published on the PROSPERO international prospective register of systematic reviews (registration number CRD42020185839). Funding Statement: None. Declaration of Interests: Brigida Barberio: none. Jonathan P. Segal: none. M. Nabil Quraishi: none. Christopher J. Black: none. Edoardo V. Savarino: none. Alexander C. Ford: none

Mesalazin-induced eosinophilic pneumonia in a 15-year-old boy with ulcerative colitis

One of the most difficult categories of patients is patients with inflammatory bowel disease. A clinical case of the development of mesalazine-induced eosinophilic pneumonia in a 15-year-old boy with ulcerative colitis is presented. The patient suffered an acute respiratory disease, which caused the aggravation of ulcerative colitis and, accordingly, an increase in the dose of mesalazine. Against this background, the child had active complaints of heaviness in the chest to the left. Eosinophilia was noted in the blood. Analysis of clinical symptoms, X-ray data, microscopic examination of the pleural fluid, the results of spiral computed tomography of the chest allowed a differential diagnosis of the main symptoms and associated identified pulmonary lesions with mesalazine.

P707 38 Weeks treatment of UC patients with different daily doses of mesalazine

P707 38 Weeks treatment of UC patients with different daily doses of mesalazine

Mesalazine for People with Diverticular Disease: A Systematic Review of Randomized Controlled Trials.

Background Diverticular disease treatment is limited to fibres, antibiotics, and surgery. There is conflicting evidence on mesalazine benefits and harms. Aim We systematically reviewed current evidence on benefits and harms of mesalazine versus all other treatments in people with diverticular disease. Methods We searched MEDLINE, EMBASE, CENTRAL, ClinicalTrials.gov for studies published to July 2018. We estimated risk ratios (RR) for dichotomous outcomes (disease remission/recurrence, acute diverticulitis in symptomatic uncomplicated diverticular disease, need for surgery/hospitalization, all-cause/disease-related mortality, adverse events), mean differences (MD) or standardized MD (SMD) for continuous outcomes (quality of life, symptoms score, time to recurrence/remission), and their 95% confidence intervals (CI) using random-effects models. We quantified heterogeneity by Chi2 and I2 tests. We performed subgroup analyses by disease subtype, comparator, follow-up duration, mesalazine dose, and mode of administration. Results We identified 13 randomized trials (n=3028 participants). There was a higher likelihood of disease remission with mesalazine than controls in acute uncomplicated diverticulitis (1 trial, 81 participants, RR=2.67, 95%CI=1.05-6.79), but not in symptomatic uncomplicated diverticular disease (1 trial, 123 participants, RR=1.04, 95%CI=0.81-1.34). There was a lower likelihood of disease recurrence with mesalazine than controls in symptomatic uncomplicated diverticular disease (2 trials, 216 participants, RR=0.52, 95%CI=0.28-0.97), but not in acute uncomplicated diverticulitis (7 trials, 2196 participants, RR=0.90, 95%CI=0.61-1.33). There was no difference in the likelihood of developing acute diverticulitis in symptomatic uncomplicated diverticular disease between the two groups (3 trials, 484 participants, RR=0.26, 95%CI=0.06-1.20). There was a higher global symptoms score reduction with mesalazine than controls in symptomatic uncomplicated diverticular disease (2 trials, 326 participants, SMD=-1.01, 95%CI=-1.51,-0.52) and acute uncomplicated diverticulitis (2 trials, 153 participants, SMD=-0.56, 95%CI=-0.88,-0.24). Conclusions Mesalazine may reduce recurrences in symptomatic uncomplicated diverticular disease. There is uncertainty on the effect of mesalazine in achieving diverticular disease remission. Mesalazine may not prevent acute diverticulitis in symptomatic uncomplicated diverticular disease.

Trisomy 8-Associated Intestinal Behcet’s Disease That Achieved Complete Remission With Mesalazine

A 39-year-old man was referred to our hospital because of ileocecal ulcer and pancytopenia. Past medical history included psoriatic arthritis and acne vulgaris. Physical examination findings showed recurrent oral ulcerations and acneiform eruptions on his body. Colonoscopy confirmed the presence of an ulcer at the ileocecal valve. Human leukocyte antigen was positive for B51. Based on the bone marrow findings of hypercellularity accompanied by trilineage dysplastic changes and cytogenetic findings of 47,XY,dup(1)(q21q32), idem+8, a definite diagnosis of intestinal Behcet’s disease (BD), incomplete type, associated with myelodysplastic syndrome (MDS) with positivity for trisomy 8 was finally confirmed. Treatment of intestinal BD with mesalazine at 3,000 mg daily induced complete ulcer healing after 4 months. Thereafter, two cycles of azacytidine was administered, followed by bone marrow transplantation. The patient has done well with continuous healing of the ulcer for a year. Differentiating episodic MDS with positivity for trisomy 8 from drug-induced MDS by examination of the bone marrow and the cytogenetic changes is indispensable. Intestinal BD patients who develop pancytopenia would probably need sufficient doses of mesalazine for treatment. J Med Cases. 2018;9(8):255-259 doi: https://doi.org/10.14740/jmc3082w

HYGIENIC RATIONING OF MESALAZINE AS SALICYLIC ACID DERIVATIVE

Introduction. Hygienic rationing of the content of adverse substances in the air on the basis of an experimental study of their toxicity is aimed at the elaboration and creation of safe working conditions. Material and methods. The toxic properties of the salicylic acid derivative (Mesalazine) have been studied in the experiments on out-bred and linear mice, rats, Guinea pigs, and rabbits kept in standard vivarium conditions and quarantined. In the experiments, various modes (single, repeated, chronic) and ways of exposure (intragastric, inhalation, epicutaneous) were simulated. The average lethal dose (LD50) of Mesalazine and the threshold of a single acute exposure (Limas) were determined; irritant effect on the skin and mucous membranes, cumulative and allergenic activity were estimated. In subacute and chronic intake, the main target organs were determined based on the results of biochemical and hematological studies. Results. By the value of the average lethal doses Mesalazine has been established to have to be classified as a substance of the 3rd hazard class (moderately hazardous). There were no significant differences in the species and the gender susceptibility of the animals to Mesalazine: the coefficient of species differences was 2.84; the coefficient of the gender susceptibility was 1.2, which was less than 3 units. In terms of the degree of specific blood damage, Mesalazine belongs to class V (no effect of the selective influence of the drug on the imbalance of various hemoglobin forms). Mesalazine has a weak ability to cumulate, have no irritating effects on the eyes and skin. Skin-resorptive and sensitizing effects were not revealed. Limas under the conditions of dynamic inhalation exposure is set at 30.4 mg/m3. Conclusion. Maximum allowable concentration (MAC) of Mesalazine in the air of the working area as 0.5 mg/m3 is recommended (hazard class II). Compliance with this standard will ensure the health preservation and will eliminate the risk of developing occupational diseases.