Mesalazine Treatment Research Articles

Intestinal anti-inflammatory activity of the seeds of Raphanus sativus L. in experimental ulcerative colitis models

Ethnopharmacological relevanceWater extract of Raphanus sativus L. (RSL) seeds was traditionally used to treat digestive inflammatory complaints in Korean culture. RSL seeds exerted antioxidant, anti-inflammatory, and anti-septic functions, suggesting their pharmacological potential for the treatment of inflammatory pathologies associated with oxidative stress such as inflammatory bowel disease. Aim of this studyWe evaluated the intestinal anti-inflammatory effects of RSL seed water extract (RWE) in experimental rat models of trinitrobenzenesulphonic acid (TNBS)- or dextran sodium sulfate (DSS)-induced colitis. Materials and methodsRWE was characterized by determining the content of sinapic acid as a reference material and then assayed in the DSS and TNBS models of rat colitis. Male Sprague–Dawley rats were divided into 10 groups (n=7/group): non-colitic control, DSS or TNBS control, DSS colitis groups treated with RWE (100mg/kg) or mesalazine (25mg/kg), and TNBS colitis groups treated with various doses (10, 40, 70, and 100mg/kg) of RWE or mesalazine (25mg/kg). RWE or mesalazine treatment started the same day of colitis induction and rats were sacrificed 24h after the last treatment followed by histological and biochemical analyses. ResultsOral administration with RWE suppressed intestinal inflammatory damages in both DSS- and TNBS-induced colitic rats. The treatment with 100mg/kg RWE recovered intestinal damages caused by TNBS or DSS to levels similar to that of mesalazine, decreasing the activity of myeloperoxidase activity and the secretion of tumor necrosis factor (TNF)-α and interleukin (IL)-1β. RWE treatment inhibited malondialdehyde production and glutathione reduction in colon of colitis rats. The administration of RWE at dose of 100mg/kg also suppressed the TNBS- or DSS-stimulated expression of TNF-α, IL-1β, monocyte chemotactic protein-1, inducible nitric oxide, and intercellular adhesion molecule-1. Furthermore, RWE inhibited p38 kinase and DNA–nuclear factor-κB binding activities, both of which were stimulated in the colitic rats. ConclusionsThe current findings show that RWE ameliorates intestinal oxidative and inflammatory damages in DSS and TNBS models of rat colitis, suggesting its beneficial use for the treatment of intestinal inflammatory disorders.

Detection of intestinal epithelial tight junction proteins ZO1 for evaluating efficacy of drug treating in rats with ulcerative colitis

Objective To detect the efficacy of intestinal epithelial tight junction protein ZO1 detection on evaluating the effects of single Mesalazine or Montmorillonite powder or both on treating rats with ulcerative colitis(UC) in order to explore potential mechanisms for the damages and the recovery of intestinal mucosa of rats with UC. Methods Male SD rats were randomized into 5 groups: normal control group, model control group, Mesalazine treatment group, Montmorillonite powder treatment group, and Mesalazine plus Montmorillonite powder treatment group.The acute colitis was induced in rats by 2-4-6 trinitrobenzene sulfonic acid/ethanol after adaptive feeding for 3 days.Then, the amount of drug was administered in each treatment group respectively.The expression of ZO1 proteins in intestinal mucosal epithelium in each group was detected by immunohistochemistry and real-time PCR(RT-PCR) on the 12th day after intervention respectively. Results Colon tissues by light microscope and electron microscope observation showed that models were made successfully 24 hours after 2-4-6 trinitrobenzene sulfonic acid was given to the mice by clystering.Disease activity index outcomes of Montmorillonite powder group[(0.72±0.29)scores], Mesalazine group[(0.95±0.38)scores], Mesalazine plus Montmorillonite powder group [(0.60±0.00)scores] were lower than those of the model control group[(1.18±0.53)scores], and there was a statistical significance(F=3.172, P=0.047). The expressions of ZO1 protein showed Montmorillonite powder group(0.52±0.28), Mesalazine group(0.35±0.17), Mesalazine plus Montmorillonite powder group(0.78±0.13) were higher than model control group(0.25±0.21) , and there was a statistical significance(F=7.025, P=0.001). The expressions of ZO1-mRNA showed Montmorillonite powder group[(49.53±13.32)×10-4], Mesalazine group[(43.50±18.60)×10-4], Mesalazine plus Montmorillonite powder group[(78.12±21.81)×10-4]were higher than those of the model control group[(16.60±23.23)×10-4], and there was a statistical significance(F=10.660, P=0.000). Conclusions Intestinal epithelial tight junction protein ZO1 is involved in the pathogenesis of UC.The expression of tight junction protein ZO1 in UC treated with Mesalazine plus Montmorillonite powder increased more.It is suggested that the Mesalazine plus Montmorillonite powder is helpful in improving the recovery of the damaged intestinal mucosa. Key words: Ulcerative colitis; Tight junction protein; ZO1; Mesalazine; Montmorillonite powder; Rat

Efficacy of a pH-dependent controlled-release mesalazine based on clinical and endoscopic assessment for ulcerative colitis: a retrospective cohort study.

BackgroundWe conducted a retrospective cohort study to clinically and endoscopically assess the efficacy of delayed-release mesalazine for ulcerative colitis.MethodsThe study included 104 ulcerative colitis patients (52 men, 52 women) initiated on treatment with delayed-release mesalazine between 2009 and 2012. The clinical symptoms at months 0, 1, and 12 were scored using the clinical activity index. An endoscopic index was also used to determine disease activity in 72 patients who underwent total colonoscopy before and after mesalazine treatment.ResultsThe clinical activity index at months 0, 1, and 12 were 4.6±2.8, 3.4±1.8, and 2.8±1.4, respectively, decreasing with time after the start of mesalazine treatment (P<0.001). The endoscopic index decreased significantly from 4.5±3.2 before to 3.1±2.8 after the start of delayed-release mesalazine treatment in the mean follow-up period of 1.0±0.4 years (P<0.001).ConclusionDelayed-release mesalazine was confirmed to be effective both clinically and endoscopically.

Novaferon ameliorates dextran sulfate sodium-induced colitis and downregulates expression of TNF-α in mice

To explore the effects of novaferon on dextran sulfate sodium (DSS)-induced colitis and expression of TNF-α in mice and to evaluate the efficacy of novaferon on ulcerative colitis and the possible mechanisms. A total of 70 BALB/C mice [weight (20.0±2.0) g, 8-week years old, female, pathogen free] were randomly divided into 7 groups: a normal group, a model group, a mesalazine treatment group, a prednisone treatment group, a low-dose novaferon group, a middle-dose novaferon group and a high-dose novaferon group (10 mice per group). The normal group-mice were given distilled water. The ulcerative colitis model was established by treated the mice with 4% DSS for 7 continuous days. At the 8th day, the mice in the all of drug treatment groups were injected corresponding drugs (i.p.). During the experiment, the general situation, daily weight, stool trait and occult blood were recorded, and the mice were killed on the 14th day. The disease activity index (DAI), colon length, histological scores were assessed. Immunohistochemistry was used to measure the expression of TNF-α in colonic mucosa. 1) The mice treated with DSS solution showed diarrhea, mucous stool and bloody stool, and the DAI score increased gradually. The mesalazine, predinison and nofaferon could ameliorate the general situation of the mice, reduce the DAI and histological scores, and reverse the decrease in the colon length. 2) Compared with the model group, the DAI scores were significantly decreased in the novaferon groups (at low, middle or high dose), the mesalazine group or the prednisone group (all P<0.01), but there was no difference among the mesalazine group, the prednisone group and the low-dose novaferon group (all P>0.05). The efficacy of novaferon in the middle-dose group and the high-dose group are better than that in the mesalazine group, the prednisone group and the low-dose novaferon group (all P<0.01). The efficacy of novaferon showed a dose-dependent manner. 3) The injury of colonic mucosa was relatively mild in the novaferon groups (at low-dose, middle-dose or high-dose), the mesalazine group and the prednisone group, and there were partial glands and less inflammatory cells. Compared with the model group, there was statistics difference (all P<0.05). The tissue injury was significantly alleviated, and the DAI score was decreased in the high-dose novaferon group compared the middle-dose novaferon group (P<0.05), but there was no significant difference between the low-dose novaferon group and the middle-dose novaferon group or between the mesalazine group and the prednisone group (both P>0.05). 4) The TNF-α expression was significantly down-regulated in the novaferon groups (at low-dose, middle-dose or high-dose), the mesalazine group and the prednisone group compared with model group (all P<0.01); but there was no significant difference between the mesalazine group and the prednisone group (P>0.05); the decrease of TNF-α expression by novaferon displayed a dose-dependent manner. Compared with the mesalazine group or the prednisone group, the TNF-α expression in novaferon groups at all dosages was dramatically reduced (all P<0.01). Novaferon can improve the DAI scores and colonic tissue injury in ulcerative colitis induced by DSS in mice, and down-regulate the TNF-α expression in dose-dependent manner.

Combined diosmectite and mesalazine treatment for mild-to-moderate ulcerative colitis: a randomized, placebo-controlled study.

BackgroundThe relapse rate of ulcerative colitis (UC) is high. The efficacy of combined diosmectite and mesalazine treatment for active mild-to-moderate UC was investigated.Material/MethodsA total of 120 patients with UC were enrolled in this randomized, single-blind, placebo-controlled study. Sixty patients were assigned to the Diosmectite group (diosmectite and mesalazine) and 60 were assigned to Placebo group (placebo and mesalazine). In the induction phase, the primary end point was the clinical remission rate at 8 weeks; secondary end points were clinical response, endothelial mucosal healing, Mayo score, erythrocyte sedimentation rate, C-reactive protein levels, and defecation frequency. In the maintenance phase, the primary end point was clinical remission at 52 weeks; secondary end points were clinical response, endothelial mucosal healing, Mayo score, erythrocyte sedimentation rate, and defecation frequency.ResultsAt 8 weeks, the Diosmectite group had a significantly higher clinical remission rate (68.3% vs. 50%) and mucosal healing rate (66.7% vs. 48.3%) compared with the Placebo group. There were no significant differences in clinical response rates, Mayo score, erythrocyte sedimentation rate, C-reactive protein, or defecation frequency. At 52 weeks, the Diosmectite group had a significantly higher clinical remission rate (61.7% vs. 40%) and mucosal healing rate (60% vs. 38.3%) compared with the Placebo group. Defecation frequency was lower, but this was not significant.ConclusionsCombined diosmectite and mesalazine treatment successfully induced and maintained the treatment of active mild-to-moderate UC as indicated by higher rates of clinical remission and mucosal healing.

Gastroenterology case report of mesalazine-induced cardiopulmonary hypersensitivity

Mesalazine is a 5-aminosalicylic acid derivative that has been widely used to treat patients with inflammatory bowel disease. Accumulating evidence indicates that mesalazine has a very low rate of adverse drug reactions and is well tolerated by patients. However, a few cases of pulmonary and cardiac disease related to mesalazine have been reported in the past, though infrequently, preventing clinicians from diagnosing the conditions early. We describe the case of a 32-year-old man with ulcerative colitis who was admitted with a two-month history of persistent fever following mesalazine treatment initiated 14 mo earlier. At the time of admission, mesalazine dose was increased from 1.5 to 3.0 g/d, and antibiotic therapy was started with no improvement. Three weeks after admission, the patient developed dyspnea, non-productive cough, and chest pain. Severe eosinophilia was detected in laboratory tests, and a computed tomography scan revealed interstitial infiltrates in both lungs, as well as a large pericardial effusion. The bronchoalveolar lavage reported a CD4/CD8 ratio of 0.5, and an increased eosinophil count. Transbronchial biopsy examination showed a severe eosinophilic infiltrate of the lung tissue. Mesalazine-induced cardiopulmonary hypersensitivity was suspected after excluding other possible etiologies. Consequently, mesalazine treatment was suspended, and corticosteroid therapy was initiated, resulting in resolution of symptoms and radiologic abnormalities. We conclude that mesalazine-induced pulmonary and cardiac hypersensitivity should always be considered in the differential diagnosis of unexplained cardiopulmonary symptoms and radiographic abnormalities in patients with inflammatory bowel disease.

Multiple Masses in the Colon of a Patient With Ulcerative Colitis

Question: A 43-year-old woman who had been followed for ulcerative colitis (UC) was admitted to the gastroenterology department with a complaint of abdominal pain, rectal bleeding, and diarrhea for the previous 2 months. She had left-sided UC for 8 years and had never used steroids or any other immunosuppressive drugs. Previous and current medication included systemic and local mesalazine treatment. Physical examination was normal. Laboratory findings were normal other than mild anemia (hemoglobin, 10.3 g/dL) and high sedimentation rate (57 mm/h).

Su2086 A Pilot Study of Mesalazine Treatment in IBS, Evaluating the Tolerance and Usefulness of the Mucosal Patch Technique for Measurement of Rectal Inflammatory Markers

Su2086 A Pilot Study of Mesalazine Treatment in IBS, Evaluating the Tolerance and Usefulness of the Mucosal Patch Technique for Measurement of Rectal Inflammatory Markers

P394 Pooled clinical trial analysis of MMX mesalazine safety: Focus on 4.8 g/d dose long-term exposure

Background: Mesalazine (5-aminosalicylic acid) is standard first-line treatment for mild-to-moderate ulcerative colitis (UC), and has been studied for the treatment of diverticulitis (DV). Although there is some evidence of improved efficacy in induction of remission in UC with high-dose treatment, data are limited on the safety of long-term high-dose mesalazine treatment. This analysis examines the safety profile of highdose (4.8 g/d) MMX mesalazine administered for 2 years to patients with DV, pooled from 2 studies. Methods: Two Phase 3, randomized, double-blind, placebocontrolled, multicenter studies (PREVENT1, NCT00545740; PREVENT2, NCT00545103; sponsor, Shire Development LLC) evaluated the efficacy and safety of 3 dose regimens of oncedaily MMX mesalazine (1.2 g, 2.4 g, or 4.8 g) versus placebo in the prevention of recurrent DV in adult patients over a period of 104 wks. Results: A total of 1,182 total patients were enrolled in PREVENT1 and PREVENT2, and 301 were randomized to receive 4.8 g/d MMX mesalazine. Of these, 299 were administered 1 dose of MMX mesalazine (mean [SD] age, 55.6 [11.9] y; 46.8% male). Mean (SD) treatment exposure was 64.4 (42.7)wks. Among patients who received 1 dose of MMX mesalazine, 211 (70.6%) reported 1 treatment-emergent adverse event (TEAE; 1006 events reported); 59 (19.7%) patients experienced only mild TEAEs, 114 (38.1%) experienced TEAEs with a maximum severity of moderate, and 38 (12.7%) experienced severe TEAEs. Serious TEAEs were reported by 32 (10.7%) patients (38 events). A total of 51 (17.1%) patients experienced TEAEs determined to be related to study treatment (102 events), and 4 (1.3%) patients reported serious TEAEs related to study treatment (4 events). A total of 36 (12.0%) patients experienced TEAEs that led to withdrawal from their respective studies. The most frequently reported TEAEs (>5%) were abdominal pain (11.0%), diarrhoea (10.0%), headache (9.3%), back pain (6.3%), urinary tract infection (6.0%), nausea (5.3%), and upper respiratory tract infection (5.3%). Conclusions: Pooled analysis of adverse event data from longterm exposure to MMX mesalazine 4.8 g/d in patients with a history of DV showed that high-dose MMX mesalazine was welltolerated for 2 years.

Pancreatic lymphoma presenting with acute pancreatitis

oral mesalazine, ursodeoxycholic acid, and prednisone treatment was started. There was no diarrhea during follow-up, proteinuria decreased, and renal function improved at third month. There were no significant changes in the liver function tests. The patient presented to emergency room with complaints of fever (39oC) and shortness of breath. His chest X-ray showed diffuse interstitial pulmonary infiltrates. The patient died from an opportunistic infection (pneumonia) ten days after hospitalization.

Randomised clinical trial: a herbal preparation of myrrh, chamomile and coffee charcoal compared with mesalazine in maintaining remission in ulcerative colitis - a double-blind, double-dummy study

The herbal treatment with myrrh, dry extract of chamomile flowers and coffee charcoal has anti-inflammatory and antidiarrhoeal potential and might benefit patients with UC. Aminosalicylates are used as standard treatment for maintaining remission in ulcerative colitis (UC). To compare the efficacy of the two treatments in maintaining remission in patients with ulcerative colitis. We performed a randomised, double-blind, double-dummy study over a 12-month period in patients with UC. Primary endpoint was non-inferiority of the herbal preparation as defined by mean Clinical Colitis Activity Index (CAI-Rachmilewitz). Secondary endpoints were relapse rates, safety profile, relapse-free times, endoscopic activity and faecal biomarkers. A total of 96 patients (51 female) with inactive UC were included. Mean CAI demonstrated no significant difference between the two treatment groups in the intention-to-treat (P=0.121) or per-protocol (P=0.251) analysis. Relapse rates in total were 22/49 patients (45%) in the mesalazine treatment group and 25/47 patients (53%) in the herbal treatment group (P=0.540). Safety profile and tolerability were good and no significant differences were shown in relapse-free time, endoscopy and faecal biomarkers. The herbal preparation of myrrh, chamomile extract and coffee charcoal is well tolerated and shows a good safety profile. We found first evidence for a potential efficacy non-inferior to the gold standard therapy mesalazine, which merits further study of its clinical usefulness in maintenance therapy of patients with ulcerative colitis. EudraCT-Number 2007-007928-18.

Tumor necrosis factor inhibitors and acute leukemia in two cases.

e18010 Background: Inhibitors of tumor necrosis factor alpha (anti-TNF agents) are commonly used in Crohn’s disease and rheumatoid arthritis. Relationship between TNF inhibitors and development of malignancy, e.g., lymphoma and solid tumors, is defined recently. However, a few authors reported leukemia. Crohn’s disease and also azothioprine may also be associated with leukemia. Here, we are presenting two acute myeloid leukemia (AML) cases using azothioprine and anti-TNF inhibitors for Crohn’s disease. Methods: Observational case report. Results: Case 1: A 56-year-old male patient with active Crohn’s disease for 4 years was refractory to first line mesalazine, corticosteroid and azothioprine treatment. So, anti-TNF monoclonal antibody (moAb) (Adalimumab) had been given. After second dose of adalimumab treatment AML (AML-M2 as FAB) developed. Case 2: A 38-year-old male had been diagnosed with ankylosing spondylitis for 7 years and Crohn’s disease for 2 years. He had been treated with salazopyrin and indomethacin. Anti-TNF etanercept (50 mg/wk) was started 30 months ago due to severe active pulmonary disease. After 1 year, he developed active Crohn’s disease. So, the treatment changed to infliximab. Also, mesalazine and azothioprine were added to treatment. On the 18th month of the infliximab t(15;17) positive acute promyelocytic leukemia were developed in the patient. Conclusions: Blocking TNF with anti TNF agents may cause blocking apoptosis and inhibit natural killer activity. So, antitumoral activity of natural killer cells is blocked by these agents. TNF alpha gene mutation has been associated with CLL, lymphoma, myelodysplastic syndrome and secondary AML. Azothioprine may also increase leukemia, lymphoma and solid tumors risk at patient on anti TNF treatment. Following the diagnosis of Crohn’s disease without immunomodulator treatment a case had developed acute leukemia in the literature. In our patients, anti-TNF, azothioprine and inflammatory bowel disease may be cause acute leukemia cumulatively. Physicians should be careful and regularly check the patients using anti-TNF agents in considering of malignancy development. In conclusion, the pathogenesis of leukemia development after TNF blockage should be clarified.

Tu1181 Intermittent Versus Every-Day Mesalazine Therapy in Preventing Complications of Diverticular Disease: A Long-Term Follow-up Study

Mesalazine seems to be effective in preventing recurrence of acute uncomplicated diverticulitis (AUD), but the optimal mesalazine scheme to achieve these results is still debated. To assess the effectiveness of two different mesalazine-based treatments in preventing recurrence of AUD and the occurrence of other complications of diverticular disease (DD) during a long-term follow-up. We reviewed 311 patients suffer from recent episode of AUD and undergoing to mesalazine treatment: 207 (group A, 105 males, median age 63 years, range 47-74 years) were treated with mesalazine 1.6 g for 10 days each month, whilst 104 (group B, 55 males, median age 65 years, range 50-72 years) were treated with mesalazine 1.6 g every day. Patients were followed-up every 6 months (median 7.5 months, range 5-13 months). Patients were followed-up for a mean time of 3 years (range 12-72 months). Overall, occurrence of complication recurred more frequently in group A than in group B (p = 0.030, log-rank test). Acute diverticulitis recurred in 17 (8.2%) patients in group A and in 3 (2.9%) in group B; diverticular bleeding occurred in 4 (1.9%) patients in group A and in 1 (0.96%) patient in group B; surgery was required in 3 (1.4%) patients in group A and in no (0%) patient in group B. This is the first study showing that long-term mesalazine treatment is significantly better that intermittent mesalazine treatment in preventing occurrence of DD complications after an attack of acute diverticulitis.

Tu1182 Gender Difference in Acute Colonic Diverticulitis: Large Retrospective Multicenter Study in Japan

from recent episode of AUD and undergoing to mesalazine treatment: 207 (group A, 105 males, median age 63 years, range 47-74 years) were treated with mesalazine 1.6 grams for 10 days each month, whilst 104 (group B, 55 males, median age 65 years, range 50-72 years) were treated with mesalazine 1.6 grams every day. Patients were followed-up every 6 months (median 7.5 months, range 5-13 months). Results: Patients were followed-up for a mean time of 3 years (range 12-72 months). Overall, occurrence of complication recurred more frequently in group A than in group B (p=0.030, log-rank test). Acute diverticulitis recurred in 17 (8.2%) patients in group A and in 3 (2.9%) in group B; diverticular bleeding occurred in 4 (1.9%) patients in group A and in 1 (0.96%) patient in group B; surgery was required in 3 (1.4%) patients in group A and in no (0%) patient in group B. Conclusions: This is the first study showing that long-term mesalazine treatment is significantly better that intermittent mesalazine treatment in preventing occurrence of DD complications after an attack of acute diverticulitis.

Acute eosinophilic pneumonia related to a mesalazine suppository

It has been well known that mesalazine can cause the interstitial lung disease, such as Bronchiolitis obliterans with organizing pneumonia (BOOP), Non-Specific Interstitial Pneumonia (NSIP), or eosinophilic pneumonia. 5-Aminosalicylic acid (5-ASA), mesalazine, and sulfasalazine are important drugs for treating inflammatory bowel disease. Topical products of these limited systemic absorption and have less frequent side effects, therefore suppository form of these drugs have been used more than systemic drug. Most cases of measalzine-induced lung toxicity develop from systemic use of the drug. A 30-year-old woman had an interstitial lung disease after using mesalazine suppository because of ulcerative colitis. The lung biopsy demonstrated eosinophilic pneumonia combined with BOOP. She was recovered after stopping of mesalazine suppository and treatment with systemic steroid.

P353 The economics of 4 grams once daily mesalazine dosing compared with 4 grams twice daily in active ulcerative colitis

Background: Dosing frequency is an important treatment consideration that has been shown to influence adherence and outcomes when treating ulcerative colitis (UC). In this analysis we evaluate the economic consequences of outcome differences observed in the study comparing mesalazine 4g per day once daily (OD) versus 4g per day in twice daily (BD) doses in combination with 1g mesalazine enema in patients with active ulcerative colitis (MOTUS). Methods: Cost-effectiveness analysis comparing costs and outcomes based on data obtained from the multicenter, randomized, controlled MOTUS trial were used. Medical costs were based on treatment guidelines in the Netherlands and applying published cost data to resources consumed. Outcomes generated in the model were quality-adjusted life years (QALYs) based on active UC health state utilities derived from ulcerative disease activity index (UCDAI) and changes in active UC status. The defined health states based on accepted treatment practices applied in the Markov model were as follows: (1) active UC with 4g mesalazine (OD or BD); (2) mesalazinerefractory active UC; (3) steroid-refractory active UC; (4) infliximab-responsive active UC; and (5) remission. The health service perspective of the Netherlands was reflected in the model and considered a 32 week time horizon with 4 weekly Markov cycles. Results: After 32 weeks the mean per patient costs were € 2,943 and € 3,444 for those treated with OD and BD mesalazine, respectively, with an average per person savings of € 501 per patient treated with OD. Within 8 weeks 82% and 78% of patients achieved remission in the OD and BD cycles. At 32 weeks the accumulated QALYs were 0.57 and 0.56 for OD and BD mesalazine, respectively, resulting in a cost per QALY of € 5,518 and € 6,485, respectively. Mesalazine treatment costs, including 4 g mesalazine for maintenance and 2 g mesalazine for those that achieve remission represented 23% (€ 668) and 20% (€ 680) of all treatment costs. Conclusions: The OD daily dosing regimen was found to be cost-saving compared with BD dosing in active UC. The major cost driver for achieving remission was ancillary treatment escalation costs which included intravenous prednisolone and high cost biological agents. The precise mechanism why OD may improve outcomes is undetermined. However, the team posits that the OD dosing could lead to higher peak luminal concentration and higher mucosal concentration of mesalazine compared with divided dosing with similar daily dose.

Commentary: impact of MMX mesalazine on health‐related quality of life in ulcerative colitis

Solomon et al. present evidence that daily MMX mesalazine therapy is associated with improvement in disease-specific, health-related quality of life (HRQL), as measured by the short inflammatory bowel disease questionnaire (SIBDQ), in patients with mild-moderate active ulcerative colitis (UC) and that this HRQL is maintained in patients with quiescent UC, when treatment is continued.1 In addition to its central finding, this study adds evidence of the previously suggested relationship between HRQL and patient-reported measures of disease activity – including stool frequency (SF) and rectal bleeding score (RBS).2, 3 Ulcerative colitis carries a significant psychological and social burden.4, 5 Maintaining HRQL is therefore important in long-term management and increasingly recognised as a critical end-point in randomised controlled trials in UC. Patient-reported measures are non-invasive and may be simple, capturing features of importance to patients. The authors stressed the correlation between changes in the SIBDQ and the SF and RBS, suggesting that the improvements in HRQL are mediated through improvements in bowel symptoms. However, there were significant improvements in all domains of the SIBDQ over the acute phase, although more patients showed an improvement in the bowel symptoms domain than the other domains, implying a smaller effect size for these latter items. Interpretation of the data is limited by the lack of a comparator arm, variable treatment dose in the acute phase and incomplete data availability (only 103/137 had interpretable data at the beginning and end of the acute phase). Multiple statistical comparisons were made and it is not clear whether appropriate adjustments were made. Despite its limitations, this study helpfully documents improvement or maintenance of HRQL with MMX mesalazine treatment, but cannot confirm that the effect is due to treatment or its size. This - as the authors indicate - would require a randomised, controlled study. Declaration of personal and funding interests: None.

Comparison of the effect of mesalazine and sulfasalazine on laboratory parameters: a retrospective observational study

Mesalazine and sulfasalazine are commonly used drugs for the treatment of inflammatory bowel disease. However, there have been few reports with a strict statistical analysis comparing the effects of mesalazine and sulfasalazine on laboratory test results. Therefore, we designed a retrospective cohort study to investigate whether or not differences in clinical laboratory parameters exist between mesalazine and sulfasalazine users. We used data from the Clinical Data Warehouse of Nihon University School of Medicine to identify cohorts of new mesalazine users (n = 303) and sulfasalazine users (n = 67). We used a multivariate regression model and regression adjustment with the propensity score to adjust for differences in baseline covariates between mesalazine and sulfasalazine users, and compared serum levels of creatinine, urea nitrogen, aspartate aminotransferase, alanine aminotransferase, and hematological parameters including red and white blood cell counts and platelet count. After adjustment, in sulfasalazine users, the mean values for all tests showed no significant change between baseline and during the exposure period. In contrast, in mesalazine users, the mean WBC and platelet counts during the exposure period were significantly lower than those at baseline. Furthermore, mean serum urea nitrogen level during the exposure period was significantly higher than that at baseline. In terms of mean changes in laboratory test values during the exposure period compared with baseline, the reduction of platelet count in mesalazine users was significant in comparison to that in sulfasalazine users. Our findings suggested that the hematological adverse effects of mesalazine treatment might be greater than those of sulfasalazine treatment.

Recurrence of Myocarditis After Mesalazine Treatment for Ulcerative Colitis

Recurrence of Myocarditis After Mesalazine Treatment for Ulcerative Colitis

Questions about mesalazine and the irritable bowel syndrome

Sirs, Andrews et al. reported the effect of mesalazine (mesalamine) on symptoms and faecal bacterial profiles in patients with IBS.1 Fourteen patients were included and treated with mesalazine, two dropped out due to worsening diarrhoea, and eight reported satisfactory relief from symptoms. Data analyses were performed only on patients without worsening symptoms. The summary states that 8 of 12 (67%) responded favourably to mesalazine, which is not correct; 8 of 14 (57%) responded favourably and 2 of 14 (14%) unfavourably. Correspondingly, the conclusion that mesalazine treatment is associated with a decrease in faecal bacteria abundance was based on analyses of patients without worsening symptoms. Correct handling of missing data is challenging, but to report the treatment effect without mentioning that all patients with aggravation of symptoms were excluded from the analyses is unacceptable.2 Inclusion of patients, irrespective of response to treatment could have changed the conclusions. Authors and editors are responsible for conscientious and correct data analyses and reporting. Declaration of personal and funding interests: None.