Effectiveness of treatment of moderate ulcerative colitis with prolonged mesalazine in real clinical practice

Introduction. Ulcerative colitis (UC) is one of the severe therapeutic diseases. High doses of oral granular mesalazine are required to maintain clinical and endoscopic remission of UC, which may be sufficient and supposedly more acceptable for patients, as some studies showed that adherence to topical therapy is significantly lower than to oral 5-ASA drugs.Objective of the study. To evaluate the efficacy of therapy of patients with moderate left-sided ulcerative colitis (UC) and pancolitis receiving prolonged-release ethylcellulose-coated mesalazine.Materials and methods. The evaluation of the outcomes of treatment of UC patients who received prolonged-release mesalazine was carried out. We examined 87 patients with UC who received granular ethylcellulose-coated mesalazine, of those 38 (43.7%) men and 49 (56.3%) women. The average age of the enrolled patients was 38.3 ± 12.6 years.Results and discussion. After 2 weeks from the beginning of therapy with prolonged-release mesalazine, the majority of patients – 71 (81.6%) responded to the therapy. After 12 weeks, 71 (81.6%) of 87 UC patients, who responded to therapy with prolongedrelease mesalazine, remained in clinical remission. On average, the Mayo score in the group decreased from 7.6 ± 0.99 to 2.6 ± 0.25 points. There was a significant decrease in CRP, ESR, leukocytosis, and fecal calprotectin. After 26 weeks, Mayo score in the group of patients remained on average at the level of 2.2–2.3 points. The number of UC patients with colon mucosal healing was 32 (36.8%) patients. A year after the start of therapy with prolonged-release mesalazine, 69 (79.3%) UC patients who responded to therapy had a clinical remission, of those 32 (36.8%) patients had a clinical and endoscopic remission. During the year of observation, no case of surgical intervention or re-hospitalization due to exacerbation of the disease was recorded in patients with UC who achieved remission.Conclusions. Treatment of moderate active UC should begin with oral mesalazine ≥ 3 g per day in combination with topical mesalazine. The prolonged-release mesalazines are the most preferred

Efficacy and safety of Qingre-Chushi therapies in active ulcerative colitis: A network meta-analysis

Background Ulcerative colitis (UC) is a chronic inflammatory disease with an increasing incidence in the world. Qingre-Chushi therapies (QC) can alleviate clinical symptoms. Therefore, a network meta-analysis was conducted to systematically evaluate the efficacy and safety of QC in the treatment of active UC patients. Methods 7 databases were screened and relevant randomized controlled trials were selected. The tools of Cochrane Handbook and the GRADE system were conducted to assess the quality of outcomes. Pooled risk ratio or standard mean difference was calculated with 95% credible interval for outcomes measurement using the random-effects model. The surface under the cumulative ranking curve (SUCRA) was performed to rank the treatments. The larger SUCRA scores, the more effective interventions. Results A total of 3560 articles were identified and 21 studies including 1829 participants were included for further analysis. Totally, 9 therapies regimens were compared: oral mesalazine, mesalazine enema, mesalazine suppository, oral mesalazine + mesalazine enema, oral QC, oral QC + oral mesalazine, QC enema, oral QC + QC enema, and oral mesalazine + QC enema. Based on the SUCRA plot, oral QC + oral mesalazine was the best treatment in inducing clinical response; oral QC + QC enema had the best efficacy in the improvement of Mayo scores and alleviating abdominal pain; oral mesalazine + mesalazine enema was the optimal therapy in the endoscopic improvement and reducing diarrhea; QC enema + oral mesalazine was the best option in preventing bloody stool. Conclusion This study confirmed the efficacy and safety of QC in treating active UC and suggested that the combination of oral medications with topical can achieve more benefits.

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

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

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

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

P572 The influence of beliefs about medication in therapeutic adherence among patients with inflammatory bowel disease

Background Medication nonadherence in inflammatory bowel disease (IBD) is common and has a negative impact on disease outcome. It is currently not clear whether in patients with IBD, the opinions, beliefs and attitudes towards medicines determine an adequate therapeutic adherence. Our aim was to assess what the real influence of medication opinions is on IBD patients adherence. Methods Patients attending a tertiary hospital IBD outpatient clinic were enrolled. They filled the BMQ (Beliefs about Medication Questionnaire): a 18-item standardized scale assessing specific opinions about medication that a person is taking and beliefs about the potential for harm and overuse of medication in general. Pharmacy refill data were checked for the previous 3 months and their medication possession ratios (MPR) were calculated. Nonadherence was defined as MPR<0.8.Ethical approval was obtained. Results We analyzed 193 IBD patients: 96 women and 97 men with average age 46.1 years. Ulcerative colitis 109 (56.6%) and 84 Crohn′s disease (43.5%). Oral mesalazine was used for IBD control in 48%, immunosuppressnat in 43.5% and targeted therapies, 28.5%. MPR detected non-adherence in 57 patients (29.5%). Patients with CD had a higher adherence than those with UC (78.6 vs 64.2% p=0.03). Non-adherence was higher in patients with mesalazine 41.3% (p=0.001) and lower with targeted therapies 15% (p=0.007). BMQ classified our IBD patients in 60% “ambivalent”, 36% “accepting”, 7% “indifferent” with no “sceptical”: Females had a higher puntuation in BMQ harm about medication scale (p= 0.006). Surgical patients scored higher about the necessity of their IBD medication (0.005) and patients with a low educational level showed many concerns about IBD medication (0.002). Nevertheless there were neither significant differences in BMQ general (abuse/harm) or specific (need/concern) scores nor in attitude profiles between patients with adequate adherence and non-adherent patients. Conclusion Non-adherence behaviour in IBD patients was not associated with beliefs about medication. Ulcerative colitis and oral mesalazine were related to lower adherence, meanwhile patients on directed therapies showed high adherence,

Lung disease/pneumonitis in a patient with ulcerative colitis due to mesalazine

Mesalazine is a main medicine for treatment of ulcerative colitis. Most patience of left-sides and total colitis receive oral mesalazine for many years. Currently, there is a little information about the tolerability and safety of long-term use of mesalazine. The eosinophilic pneumonia, organizing pneumonia, and nonspecific interstitial pneumonia are very rare adverse effects of ulcerative colitis treatment with mesalazine. The article presents case of the development interstitial lung disease induced by mesalazine under long-term maintenance treatment for three years in the young patient with ulcerative colitis. It shows the difficulties in diagnosing this disease due to the work-long low-grade fever in manifestation of pneumonitis, the similarity of clinical and radiological manifestations (diffuse bilateral pattern in chest imaging). The article demonstrates the limitations of modern laboratory and instrumental diagnostic methods for the differentiation of disseminated lesions of the lung tissue, and shows the importance of elimination treatment of mesalazine-induced pneumonitis.

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

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.

Switching between Three Types of Mesalazine Formulation and Sulfasalazine in Patients with Active Ulcerative Colitis Who Have Already Received High-Dose Treatment with These Agents

Background and aim: Oral mesalazine and sulfasalazine (SASP) are key drugs for treating ulcerative colitis (UC). The efficacy of switching from one of the several mesalazine formulations to another is largely unknown. This study assessed the efficacy of switching among three types of mesalazine formulation and SASP for UC therapy. Methods: UC patients receiving high-dose mesalazine/SASP who switched to other formulations due to disease activity were considered eligible. Efficacy was evaluated 2, 6, and 12 months after switching. Results: A total of 106 switches in 88 UC patients were analyzed. The efficacy at 2 months after switching was observed in 23/39 (59%) cases from any mesalazine formulation to SASP, in 18/55 (33%) cases from one mesalazine to another, and in 2/12 (17%) cases from SASP to any mesalazine formulation. Nine of 43 effective cases showed inefficacy or became intolerant post-switching. Delayed efficacy more than two months after switching was observed in four cases. Steroid-free remission was achieved in 42/106 (39%) cases—within 100 days in 35 of these cases (83%). Conclusions: Switching from mesalazine to SASP was effective in more than half of cases. The efficacy of switching between mesalazine formulations was lower but may be worth attempting in clinical practice from a safety perspective.

The effectiveness of mesalazine therapy of ulcerative colitis of moderate severity in real clinical practice

Aim of the study. To compare the efficacy of treatment of patients with moderate left-sided and overall affection ulcerative colitis (UC) receiving equivalent doses of mesalazines – Mesacol and Salofalk.Materials and methods. 90 UC patients of medium severity who received mesalazine Salofalk (group 1) were included, of which 41 (45.5%) were males and 49 (54.5%) females, mean age 35.8 ± 2.5 years, and 96 UC patients of medium severity who received mesalazine Mesacol (group 2), of whom 42 (43.75%) were males and 54 (56.25%) females, mean age 37.1 ± 3.1 years. Patient follow-up time was 12 weeks. The efficacy of the therapy was assessed taking into account 1) response to therapy in 2 weeks from the beginning of therapy; 2) achievement and maintenance of clinical remission (persistent remission) within 12 weeks after the beginning of therapy. Results and discussions. After 2 weeks 78 (86,7%) patients of the 1st group responded to the therapy with mesalazine Salofalc (stool frequency decreased to 4–6 t/day, presence of pathological impurities in the stool decreased, according to laboratory indices anemia and leukocytosis decreased, and the level of CRP and ESR decreased). Twelve patients (13.3%) did not have a proper response to therapy. In the 2nd group of patients receiving Mesacol mesalazine, 80 (83,4%) out of 96 patients responded to the therapy, and 16 patients (16,6%) did not respond. After 12 weeks, 78 (86.7%) of the 90 UC Group 1 patients who responded to mesalazine Salofalk treatment still had clinical remission. The Mayo index in the group decreased from an average of 7.98 ±0.11 to 2.9 ±0.24 points. After 12 weeks, in group 2 UC patients (n = 96), 80 patients (83.4%) who responded to Mesalazine Mesacol therapy also had clinical remission. The Mayo Index in Group 2 decreased on average from 7.8 ± 0.1 to 2.8 ± 0.25 points. One year after the start of Salofalk mesalazine therapy, clinical remission remained in 76 (84.4%) of the 90 UC patients who responded to therapy, of whom 32 (35.5%) had clinical endoscopic remission. In the second group of UC patients receiving Mesacol, clinical remission remained in 78 (82.0%) out of 96 patients who responded to therapy, clinical endoscopic remission in 32 (35.5%) patients with UC. When comparing the duration of remission among UC patients receiving mesalazine Salofalk and patients receiving mesalazine Mesacol, there was no statistically significant difference (p = 0.45).Conclusion. Mesalazines remain the first line of treatment for mild and moderate UC patients. Treatment of moderately active UC should start with oral mesalazine >2 g/day in combination with local mesalazine. Prolonged continuous use of Mesacol and Salofalk mesalazines for a year is comparable in efficacy.