Ulcerative Colitis Disease Activity Index Score Research Articles

COVID-19 pandemic and exacerbation of ulcerative colitis.

BACKGROUNDIn 2020, the world faced the unprecedented crisis of coronavirus disease 2019 (COVID-19). Besides the infection and its consequences, COVID-19 also resulted in anxiety and stress resulting from severe restrictions on economic and social activities, including for patients with ulcerative colitis (UC). Fresh acute stress exerts stronger influences than continuous stress on UC patients. We therefore hypothesized that the first wave of the COVID-19 pandemic would have serious effects on UC patients and performed this retrospective control study.AIMTo determine whether the first wave of the COVID-19 pandemic would have serious effects on UC patients included in a retrospective controlled study.METHODSA total of 289 consecutive UC outpatients seen in March and April 2020 were included in this study. Modified UC disease activity index (UC-DAI) scores on the day of entry and at the previous visit were compared. An increase of ≥ 2 was considered to indicate exacerbation. The exacerbation rate was also compared with that in 256 consecutive control patients independently included in the study from the same period of the previous year in the same manner.RESULTSNo significant differences in patient characteristics or pharmacotherapies before entry were seen between the groups. Mean UC-DAI score was significantly higher in subjects during the first wave of COVID-19 (0.67 + 0.07) compared to the previous visit (0.26 + 0.04; P = 0.0000). The exacerbation rate was significantly increased during the first wave of COVID-19, as compared with the previous year (15.9% [46/289] vs 8.9% [23/256]; P = 0.0151).CONCLUSIONThis study demonstrated that the COVID-19 pandemic caused exacerbations in UC patients, probably through psychological and physical stress.

Use of the ulcerative colitis endoscopic index of severity and Mayo endoscopic score for predicting the therapeutic effect of mesalazine in patients with ulcerative colitis

ObjectiveThe ulcerative colitis endoscopic index of severity (UCEIS) and the Mayo endoscopic score (MES) are developed as objective methods of evaluating endoscopic severity in patients with ulcerative colitis (UC). The aim of this study is to investigate the diagnostic accuracy of the UCEIS and MES in predicting the patient's response to mesalazine. MethodsConsecutive patients with UC who had undergone colonoscopy within 1 month before starting mesalazine between October 2011 and July 2016 were retrospectively collected at the Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine. The median follow-up was 81 months, and all the data were analyzed in January 2021. The primary outcome was the need for step-up treatment, which included the use of corticosteroids, immunomodulatory, or surgery during admission and follow-up. Data were analyzed using the χ2 or Fisher exact test, Spearman test, t-test, and Mann–Whitney U test. ResultsTotally, 65 patients were enrolled, of whom 12 (18.5%) needed step-up treatment due to nonresponse to mesalazine. The UCEIS score, MES, and the ulcerative colitis disease activity index (UCDAI) score were significantly higher in patients who had nonresponse to mesalazine (UCEIS score: 6.92 ± 0.69 vs. 4.45 ± 1.17, p < 0.001; MES: 2.67 ± 0.49 vs. 2.15 ± 0.69, p = 0.024; UCDAI score: 9.33 ± 1.87 vs. 6.70 ± 2.38, p = 0.002). In the multivariate analysis, the UCEIS score (OR = 25.65, 95% CI: 3.048–45.985, p = 0.003), UCDAI score (OR = 1.605, 95% CI: 1.144–2.254, p = 0.006), and C-reactive protein level (OR = 1.056, 95% CI: 1.006–1.108, p = 0.026) were independent risk factors of nonresponse. The area under the ROC curve of UCEIS was 0.95, with a sensitivity of 100% and specificity of 84.6%, a cut-off value of 6, which outperformed the MES with an area under the ROC curve of 0.70. When the UCEIS score ≥6, 60% of patients eventually needed step-up treatment. ConclusionsThe UCEIS is a useful instrument for predicting the therapeutic effect in patients with UC treated with mesalazine. The high probability of mesalazine treatment failure and benefits of other therapies should be discussed in patients with baseline UCEIS score ≥6.

Modulation of gut mucosal microbiota as a mechanism of probiotics-based adjunctive therapy for ulcerative colitis.

This was a pilot study aiming to evaluate the effects of probiotics as adjunctive treatment for ulcerative colitis (UC). Twenty-five active patients with UC were assigned to the probiotic (n=12) and placebo (n=13) groups. The probiotic group received mesalazine (60mgkg-1 day-1 ) and oral probiotics (containing Lactobacillus casei Zhang, Lactobacillus plantarum P-8 and Bifidobacterium animalis subsp. lactis V9) twice daily for 12weeks, while the placebo group received the same amounts of mesalazine and placebo. The clinical outcomes were assessed. The gut mucosal microbiota was profiled by PacBio single-molecule, real-time (SMRT) sequencing of the full-length 16S rRNA of biopsy samples obtained by colonoscopy. A significantly greater magnitude of reduction was observed in the UC disease activity index (UCDAI) in the probiotic group compared with the placebo group (P=0.043), accompanying by a higher remission rate (91.67% for probiotic-receivers versus 69.23% for placebo-receivers, P=0.034). The probiotics could protect from diminishing of the microbiota diversity and richness. Moreover, the gut mucosal microbiota of the probiotic-receivers had significantly more beneficial bacteria like Eubacterium ramulus (P<0.05), Pediococcus pentosaceus (P<0.05), Bacteroides fragilis (P=0.02) and Weissella cibaria (P=0.04). Additionally, the relative abundances of the beneficial bacteria correlated significantly but negatively with the UCDAI score, suggesting that the probiotics might alleviate UC symptoms by modulating the gut mucosal microbiota. Our research has provided new insights into the mechanism of symptom alleviation in UC by applying probiotic-based adjunctive treatment.

A Phase I Trial of Berberine in Chinese with Ulcerative Colitis

The Chinese natural product, berberine, has biological properties that support its potential efficacy as a colon cancer prevention agent. Its longstanding use in China to treat gastrointestinal tract and rheumatologic disorders is generally regarded as safe, supporting initial investigations in an at-risk population, such as individuals with ulcerative colitis. However, the safety of berberine in this population is not established. Individuals living in China with biopsy-proven ulcerative colitis, ≤grade 2 dysplasia, and with a ulcerative colitis disease activity index (UCDAI) score ≤1 on mesalamine, were randomized 3:1 in a double-blind phase I trial to berberine 900 mg/day or placebo for 3 months, with the primary objective of assessing safety. Blood samples and biopsies of the colorectum, from prespecified locations, were collected prior to and following therapy. Secondary endpoints included changes in UCDAI score, and in tissue and plasma markers of inflammation. Of toxicities at least possibly related, one episode of grade 3 elevation in transaminases and one episode of grade 1 nausea were observed among 12 individuals on berberine, and none were observed among 4 on placebo. The mean plasma berberine concentration was 3.5 nmol/L after berberine treatment, significantly higher than 0.5 nmol/L with placebo. Berberine significantly decreased the Geboes grade in colonic tissue, but had a nonsignificant effect on other tissue or blood biomarkers related to cell growth and inflammation. The combination of berberine and mesalamine is well tolerated in Chinese with ulcerative colitis and may enhance mesalamine's anti-inflammatory effects in colonic tissue.

Oral Nano Vitamin D Supplementation Reduces Disease Activity in Ulcerative Colitis: A Double-Blind Randomized Parallel Group Placebo-controlled Trial.

Vitamin D possesses anti-inflammatory properties and could be beneficial in ulcerative colitis (UC). We studied the effect of oral nano vitamin D3 supplementation on disease activity in active UC [ulcerative colitis disease activity index (UCDAI)≥3]. Patients with active UC and vitamin D <40 ng/mL were randomized to receive either oral nano vitamin D (60,000 IU/d×8 d) or placebo. They were evaluated for disease activity (UCDAI scores, C-reactive protein, erythrocyte sedimentation rate, and fecal calprotectin) at baseline and reassessed at 4 weeks. The response was defined as a 3-point reduction in UCDAI score at 4 weeks and reduction in inflammatory markers. The median vitamin D levels increased from 15.4 to 40.83 mg/dL in vitamin D group (P≤0.001) and marginally from 13.45 to 18.85 mg/dL (P=0.027) in controls. The 3-point reduction in UCDAI was seen more often in vitamin D group as compared with the control (53% vs. 13%; P=0.001). Increase in vitamin D levels correlated with reduction in UCDAI score (P≤0.001; ρ=-0.713), C-reactive protein (P≤0.001; ρ=-0.603), and calprotectin (P=0.004; ρ=-0.368). Patients who achieved target vitamin D of >40 ng/mL (n=17) more often had a 3-point reduction in UCDAI (80% vs. 20%; P≤0.001) and reduction in grade of severity from 60% to 35% (P=0.038). Vitamin D administration (odds ratio, 9.17; 95% confidence interval, 2.02-41.67) and baseline histologic activity (odds ratio, 1.92; 95% confidence intervals, 1.2-3.08) independently predicted response. Oral nano vitamin D supplementation in active UC is associated with a reduction in disease activity and severity grade and is seen more often in those who achieved a target vitamin D level of 40 ng/mL.

Role of fecal calprotectin as a biomarker of intestinal inflammation in ulcerative colitis: a prospective study

Abstract Background: The clinical utility of non-invasive markers in the diagnosis and monitoring of ulcerative colitis (UC) has been intensively studied. The aim of our study was to evaluate the value of fecal calprotectin (FC) in differentiating between UC and irritable bowel syndrome (IBS), and in estimating inflammatory activity in UC. Method: A total number of 140 patients were included in the study. All patients underwent ileocolonoscopy with biopsies, quantitative determination of FC, and blood tests (white blood cell count, CRP, ESR). The severity of UC was assessed by using the Ulcerative Colitis Disease Activity Index (UCDAI) and Mayo endoscopic score. Results: In patients with active UC the mean values of FC were 373.8 +/- 146.3 μg/g, significantly higher than those in the inactive UC (mean values 36.04 +/- 13.25 μg/g), and in IBS (42.9 +/- 16.00 μg/g). In univariate regression analysis, elevated FC levels strongly correlated with pancolitis (p=0.0001), UCDAI and Mayo scores (p=0.0001), and elevated CRP levels. In multivariate regression model, FC was positively associated with severe pancolitis, and elevated CRP. The optimal cutoff value of FC for the prediction of severe pancolitis (Mayo score˃ 3) was 540 μg/g. We obtained 71.4% sensitivity (CI95%: 41.95-91.6) and 96.1% specificity (CI95%: 89.2 -99.2) of FC in assessing the severity of inflammation in UC patients. Conclusion: FC is a promising marker that can be used in clinical practice to select patients with organic intestinal disorders, compared with those with functional disorders. It also correlates very well with the extent of lesions and the severity of clinical symptoms in UC, with increased sensitivity and specificity.

Comparison of efficacy of once daily multimatrix mesalazine 2.4 g/day and 4.8 g/day with other 5-aminosalicylic acid preparation in active ulcerative colitis: a randomized, double-blind study.

Background/AimsThis study compared the efficacy of multimatrix mesalazine 2.4 g/day and 4.8 g/day with controlled-release mesalazine 2.25 g/day.MethodsIn this multicenter, randomized, double-blind study, 251 patients with mildly to moderately active ulcerative colitis received multimatrix mesalazine 2.4 g/day once daily (Multimatrix-2.4), 4.8 g/day once daily (Multimatrix-4.8), or controlled-release (time-dependent) mesalazine 2.25 g/day 3 times daily (Time-2.25) for 8 weeks. The primary efficacy endpoint was the change in the ulcerative colitis-disease activity index (UC-DAI) score.ResultsThe mean change in the UC-DAI score and standard deviation in the per protocol set was −1.9±2.5 for Multimatrix-2.4 and −2.4±2.8 for Time-2.25. The difference between Multimatrix-2.4 and Time-2.25 was 0.3 (two-sided 95% confidence interval [CI], −0.5 to 1.1), thus non-inferiority was not demonstrated based on the pre-defined non-inferiority margin (1.0). In the full analysis set, the difference between Multimatrix-4.8 and Time-2.25 was −1.2 (two-sided 95% CI, −2.0 to −0.5), and the mean change in UC-DAI score in the FAS was −3.3 (two-sided 95% CI, −3.9 to −2.8) for Multimatrix-4.8 and −1.9 (two-sided 95% CI, −2.5 to −1.3) for Multimatrix-2.4, indicating that Multimatrix-4.8 was more effective than Time-2.25 and Multimatrix-2.4. There was no difference among the treatment groups in terms of safety.ConclusionsThis study showed that the efficacy of multimatrix mesalazine 2.4 g/day was comparable to controlled release mesalazine 2.25 g/day, although non-inferiority was not demonstrated. Importantly, this was the first study to indicate that multimatrix mesalazine 4.8 g/day was more effective than 2.4g/day with no associated safety concerns.

Golimumab Use in Bio-experienced Ulcerative Colitis Patients

Introduction: Golimumab is a human anti-tumor necrosis factor alpha (TNF- α) antibody approved for the treatment of moderate to severe ulcerative colitis (UC) in adults. It was found to be more efficacious compared to placebo in bio-naïve patients with ulcerative colitis. Due to the exclusion of patients with prior biologic experience in the PURSUIT trials, limited data exists in this population. The aim of our study is to evaluate the efficacy of golimumab in bio-experienced patients (as a second or third line anti-TNF agent) in comparison to bio-naive UC patients.Figure 1Figure 2Figure 3Methods: We performed a retrospective chart review of moderate to severe UC patients treated with golimumab at Fondren IBD clinic in Houston Methodist Hospital. Data for patient demographics, disease duration, location, severity, concomitant immunomodulator therapy and prior biologic use in these patients was collected. Clinical and biochemical parameters used to predict response (UC disease activity index(UCDAI), ESR, CRP, albumin levels) were obtained at first visit prior to initiation of golimumab and at subsequent visits post induction. Categorical and continuous variables were compared using chi square and t-test respectively. All p values calculated were two-tailed with 0.05 alpha level of significance. Results: 20 patients with an average age of 39.4 +/-13.4 years (mean +/- SD) were included in the study. See Table 1. The mean follow-up duration between the 1st and 2nd visit was 127.8 +/-83 days (mean +/- SD). Golimumab was used in 10 bio-experienced patients. Result details are shown in table 2. There was a definite drop in UCDAI scores in our patients (7.75 +/-5.2 to 3.9 +/- 4.6), regardless of them being bio-naïve or experienced. Interestingly, a paradoxical trend of ESR and CRP was noted. Patients receiving golimumab as first line biologic had decreased ESR and increased CRP whereas bio-experienced patients had reduced CRP and higher ESR. Mucosal healing was demonstrated in 3 patients who underwent endoscopy after initiation of golimumab (Mayo endoscopy score of 0). Conclusion: This is the first study which reports the endoscopic efficacy of golimumab in bio-experienced patients. Golimumab seems to be a promising therapy for patients with moderate to severe UC. Our results show that regardless of its use in bio-experienced patients as second or third line anti-TNF therapy, there is a significant improvement in UCDAI scores after treatment. Larger study designs will help better delineate this finding.

Effectiveness of budesonide MMX (Cortiment) for the treatment of mild-to-moderate active ulcerative colitis: study protocol for a prospective multicentre observational cohort study

IntroductionA study has been developed to assess the use and effectiveness of budesonide MMX for mild-to-moderate active ulcerative colitis (UC) in routine clinical practice.Methods and analysisA prospective, multicentre, observational, cohort...

P-096 YI Comparative Response of Combination Therapy vs. Mono Therapy in Steroid Dependent Ulcerative Colitis Patients

Ulcerative colitis (UC) is an idiopathic inflammatory bowel disease (IBD) characterized by a chronic relapsing/intermittent clinical course. Steroids offer efficient and prompt relief of symptoms in a high proportion of ulcerative colitis (UC). Although most patients initially respond to corticosteroids, after 1 year, approximately 25% become steroid-dependent. The aim of this prospective study was to assess whether the administration the efficacy of azathioprine (AZA) and mesalamine combination to AZA monotherapy in maintaining remission of steroid-dependent ulcerative colitis (UC). The present study was carried out in the Department of Gastroenterology, IMS, BHU, Varanasi, India. A total of 136 patients age sex matched were included in the study after written informed consent fulfilling inclusion and exclusion criteria's. Patients with steroid-dependent UC in remission were randomized to receive AZA alone (1.5 mg/kg) (group 1) or in combination with mesalamine (800 mg tid) (group 2). Each group had 59 patients. Patients were considered in remission when steroid was withdrawn, an Ulcerative Colitis Clinical Activity Index (UCCAI) score of <2, an Ulcerative Colitis Disease Activity Index (UCDAI) score of 0, and a negative colonoscopy and histology. Followup was carried out every monthly for 2 year. Clinical examination, hematological and biochemical test were carried out routinely. Sigmoidoscopy and completion of inflammatory bowel disease quality-of-life questionnaire (IBD-Q) and UCDAI every 3 months; and 3) total colonoscopy with biopsies at the end of the study. Out of 136 patients 110 patients were analysed and rest 18 (13.23%) were lost in followup and 4 patients in each group developed side effects or poor compliance with treatment and were withdrawn from the study. Five patients receiving monotherapy (group 1) relapsed after the first year of the study and 3 after the second year of the study (14.54%). In the combination group (group 2) 2 patients relapsed after the first year of study and 2 after the second year of the study (7.27%) having statistically significant when compared with group 1 (p<0.05). Relapse rates were significant whether analyzed by intention-to-treat or per protocol. There were no significant differences between groups in time to relapse or discontinuation of treatment, UCCAI, UCDAI, or IBD-Q scores. Adverse events were similar both the groups and statistically non significant. Patients with steroid-dependent UC successfully maintained in remission on AZA and mesalamine and however relapse rate were more common in patients on azathioprine alone.

Normalization of mucosal tumor necrosis factor-α: A new criterion for discontinuing infliximab therapy in ulcerative colitis

BackgroundBiological agents such as anti-tumor necrosis factor (TNF) induce remission in ulcerative colitis. There is however no consensus regarding the discontinuation of this treatment. AimThe aim of this study is to assess whether clinical parameters and mucosal cytokine mRNAs in healed colonic mucosa can predict long-term remission in ulcerative colitis following discontinuation of infliximab (IFX) therapy. MethodsThe prospective Tromsø Inflammatory Bowel Disease (IBD) Study is based on an intensified induction treatment algorithm with IFX to achieve disease remission. Following clinical and endoscopic remission, IFX treatment was discontinued, and follow-up until relapse was performed. Patients who achieved clinical and endoscopic remission following an induction course of IFX were included. Expression levels of TNF alpha (TNF), interferon gamma (IFNG), interleukin (IL) 6 (IL6), IL17A, IL23, and transforming growth factor beta (TGFB) were quantified by real-time PCR in mucosal biopsies obtained at colonoscopy. Remission was defined as Ulcerative Colitis Disease Activity Index (UCDAI) below 3, and an endoscopic sub-score of 0–1. Relapse was defined as UCDAI score >3 and endoscopic sub-score >1. Mucosal cytokine transcript levels from 20 non-IBD patients with a normal colonoscopy served as control group. ResultsOf the 45 patients included, twenty patients (44%) had normalized levels of mucosal TNF expression at the time of mucosal healing, whereas 35 of 42 (83%) had normalized IL17A expression levels, and 31 of 36 (86%) had normalized IFNG expression levels. The median time to relapse was 8months (range 4–12). Normalization of TNF gene expression predicted 20months (1–39) relapse-free survival after withdrawal of IFX compared to 5months (3–7) in the group with elevated TNF expression. Mucosal expression levels of IL17A, IL23, IFNG, TGFB, IL6 did not predict long-term remission (>12months) ConclusionNormalization of mucosal TNF predicts long-term remission after discontinuation of IFX.

Potential utility of a new ulcerative colitis segmental endoscopic index combining disease severity and the extent of inflammation.

To investigate the potential utility of a new scoring system, the Ulcerative Colitis Segmental Endoscopic Index (UCSEI), which combines measures of disease severity and extent of inflammation. Intestinal mucosal healing (MH) is a new therapeutic goal for ulcerative colitis (UC). Discontinuous lesions are common in UC and endoscopic observation of the entire colon is important. Patients with active mild-to-moderate UC received daily treatment with oral mesalazine (4 g/d) and mesalazine enemas (1 g/d) for 8 weeks. Endoscopic evaluations, using the UCSEI and Mayo Endoscopic Score (MES), were performed in 5 colonic segments at baseline and week 8. The UCSEI criteria included erythema, vascular pattern, friability, and erosion/ulcer. The sum of 5 subscores, determined for each segment, was calculated as the UCSEI. Disease activity was also assessed using the UC Disease Activity Index (UCDAI). MH was defined as MES=0 to 1. Of 58 patients, 51 completed the scheduled endoscopic evaluations. At week 8, the UCDAI score had significantly decreased from 6.63 (baseline) to 2.73 (P<0.001). The remission and MH rates were 35.3% and 55.3%, respectively. Segmental endoscopic evaluation, using UCSEI, showed that baseline inflammation tended to be more severe in the distal colon. The baseline UCSEI increased with the extent of disease, which was not seen in MES. Improvements in UCSEI were observed, even in the patients without decreases in the MES. UCSEI, reflecting disease severity and extent of inflammation, provides useful information for UC management that is not available with MES.

A Pilot Study to Evaluate the Safety and Efficacy of an Oral Dose of (−)-Epigallocatechin-3-Gallate–Rich Polyphenon E in Patients With Mild to Moderate Ulcerative Colitis

Green tea and its main polyphenolic component, (-)-epigallocatechin-3-gallate (EGCG), exert powerful anti-inflammatory effects that are protective against both inflammatory diseases and cancer. Research with animal and human cell lines provide plausible support for these claims. Poor absorption results in low systemic bioavailability of EGCG after oral administration but high colonic mucosal exposure. Patients with mild to moderate ulcerative colitis (UC) were randomized to daily doses of oral Polyphenon E (400 mg or 800 mg of total EGCG daily, administered in split doses) or placebo in a double-blinded, placebo-controlled pilot study. Response was measured by the UC disease activity index and the inflammatory bowel disease questionnaire on day 56. Twenty patients were randomized to active therapy or placebo in a 4:1 ratio. Nineteen subjects received >1 dose of study medication (15 Polyphenon E, 4 placebo). The mean UC disease activity index score at study entry was 6.5 ± 1.9 in the treatment group and 7.3 ± 1.7 in the placebo group. After 56 days of therapy, the response rate was 66.7% (10 of 15) in the Polyphenon E group and 0% (0 of 4) in the placebo group (P = 0.03). The active treatment remission rate was 53.3% (8 of 15) compared with 0% (0 of 4) for placebo (P = 0.10). Polyphenon E treatment resulted in only minor side effects. Administration of Polyphenon E resulted in a therapeutic benefit for patients who were refractory to 5-aminosalicylic and/or azathioprine. This agent holds promise as a novel option for the treatment of patients with UC with mild to moderately active disease.

The Role of Centralized Reading of Endoscopy in a Randomized Controlled Trial of Mesalamine for Ulcerative Colitis

Interobserver differences in endoscopic assessments contribute to variations in rates of response to placebo in ulcerative colitis (UC) trials. We investigated whether centralized review of images could reduce these variations. We performed a 10-week, randomized, double-blind, placebo-controlled study of 281 patients with mildly to moderately active UC, defined by an Ulcerative Colitis Disease Activity Index (UCDAI) sigmoidoscopy score ≥2, that evaluated the efficacy of delayed-release mesalamine (Asacol 800-mg tablet) 4.8 g/day. Endoscopic images were reviewed by a single expert central reader. The primary outcome was clinical remission (UCDAI, stool frequency and bleeding scores of 0, and no fecal urgency) at week6. The primary outcome was achieved by 30.0% of patients treated with mesalamine and 20.6% of those given placebo, a difference of 9.4% (95% confidence interval [CI],-0.7% to 19.4%; P= .069). Significant differences in results from secondary analyses indicated the efficacy of mesalamine. Thirty-one percent of participants, all of whom had a UCDAI sigmoidoscopy score ≥2 as read by the site investigator, were considered ineligible by the central reader. After exclusion of these patients, the remission rates were 29.0% and 13.8% in the mesalamine and placebo groups, respectively (difference of 15%; 95% CI, 3.5%-26.0%; P= .011). Although mesalamine 4.8 g/day was not statistically different from placebo for induction of remission in patients with mildly to moderately active UC, based on an intent-to-treat analysis, the totality of the data supports a benefit of treatment. Central review of endoscopic images is critical to the conduct of induction studies in UC; ClinicalTrials.gov Number, NCT01059344.

Randomised clinical trial: once‐ vs. twice‐daily prolonged‐release mesalazine for active ulcerative colitis

Aminosalicylates are first-choice treatment for mild-to-moderately active ulcerative colitis (UC); however, multi-dosing regimens are inconvenient. To compare the efficacy and safety of once- (OD) vs. twice- (BD) daily prolonged-release mesalazine (Pentasa, Ferring, Saint-Prex, Switzerland) for active mild-to-moderate UC in a non-inferiority study. Eligible patients (n = 206) were randomised to 8 weeks of mesalazine (4 g/day), either OD with two sachets of 2 g mesalazine granules in the morning (n = 102) or BD with one 2 g sachet in the morning and one in the evening (n = 104). Patients also received 4 weeks of mesalazine enema 1 g/day. Disease activity was assessed at randomisation, weeks 4, 8 and 12 using the UC Disease Activity Index (UC-DAI). Clinical and endoscopic remission (primary endpoint) was assessed after 8 weeks. Patients recorded stool frequency and rectal bleeding in a daily diary. The primary endpoint, non-inferiority in clinical and endoscopic remission with OD vs. BD mesalazine at 8 weeks, was met (intent-to-treat population: 52.1% vs. 41.8%, respectively, 95% confidence interval -3.4, 24.1; P = 0.14). Improvement of UC-DAI score (92% vs. 79%; P = 0.01) and mucosal healing (87.5% vs. 71.1%; P = 0.007) were significantly better, time to remission significantly shorter (26 vs. 28 days; P = 0.04) and safety similar with OD vs. BD dosing. When combined with mesalazine enema, prolonged-release mesalazine once-daily 4 g is as effective and well tolerated as 2 g twice-daily for inducing remission in patients with mild-to-moderately active ulcerative colitis (Clinicaltrials.gov: NCT00737789).

Once-daily budesonide MMX in active, mild-to-moderate ulcerative colitis: results from the randomised CORE II study

ObjectiveBudesonide MMX is a novel oral formulation of budesonide that uses Multi-Matrix System (MMX) technology to extend release to the colon. This study compared the efficacy of budesonide MMX with...

PMO-225 Use of infliximab for acute severe ulcerative colitis in a district general hospital

IntroductionThe prevalence of Ulcerative colitis (UC) in the UK is 243/100 000 and carries a high lifetime risk of surgery (20%–30%). Acute severe UC (ASUC) is potentially a life threatening...

Mo1673 Evaluation of Mucosal Healing of Ulcerative Colitis by Using a Quantitative Fecal Immunochemical Test

Background and Aim: Evidence has been accumulated to show that achievement of mucosal healing (MH) is associated with sustained clinical remission, and reduced rates of hospitalization and surgical resection. The combination of oral and topical mesalazine is thought to be more effective than alone in patients with mild-to-moderate disatal colitis and mild-tomoderate extensive colitis. However, endoscopic evaluation of the combined treatment on colonic mucosa is scarce. We conducted conventional endoscopic evaluation as well as segmental endoscopic evaluation in mild-to-moderate ulcerative colitis (UC) patients treated with oral Pentasa® and Pentasa® enema. Materials and Methods: Patients with active mildto-moderate UC were included and treated with 4 g/day of mesalazine combined with 1 g/ day mesalazine enema for 8 wks. At both baseline and 8 wks patients were endoscopically asseseed using Mayo Endoscopic Score and using Segmental Endoscopic Score. Segmental endoscopic evaluation was performed for each of 8 contiguous anatomic segments (rectum below/above the peritoneal reflection, rectosigmoid, sigmoid, left colon, transverse, right colon, cecum). The criteria of segmental endoscopy included erythema, vascular pattern, friability and erosion/ulcer (score range per segment: 0 10). MH was defined as Mayo Endoscopic Score = 0, 1. Disease activity was also assessed at baseline and 8 wks using the UC Disease Activity Index (UCDAI), with clinical and endoscopic signs. Remission and improvement were defined as a UCDAI score < 2 and as a decrease of UCDAI score by ≥ 2 points from baseline, respectively. Abbreviated UCDAI score (aUCDAI) obtained from stool frequency, rectal bleeding and physician's global assessment was assessed at baseline, 4 and 8 wks. Result: Of the 31 patients included, 29 completed endoscopic evaluations at both baseline and 8 wks. Median disease duration was 72.7 months and mean baseline UCDAI score was 6.72. The extents of disease were 10.3% in proctitis, 34.5% in left-sided colitis and 55.2% in extensive colitis. Mayo endscopic score significantly decreased from 2.14 to 1.45 (p < 0.001) and MH rate was 51.7%. The segmental endscopic scores of every assessed area at 8 wks decreased significantly compared to that at baseline (Table). UCDAI significantly decreased from 6.72 to 3.00 (p < 0.001). Remission and improvement rates were 31.0% and 79.3%, respectively. aUCDAI significantly decreased from 4.59 at baseline to 1.76 at 4 wks and 1.55 at 8 wks (p < 0.001). Conclusion: These results demonstrate that the combination of oral and topical mesalazine ameliorates mucosal appearances of the whole colon with fast clinical improvement. Therefore, combined mesalazine therapy is thought to be the optimum first line therapy for mild-to-moderate UC patients independent of the extent of disease. Segmental Endoscopic Score

Mo1670 Segmental Endoscopic Evaluation of Combined Oral and Topical Mesalazine (Pentasa(r)) in Patients With Mild-to-Moderate Ulcerative Colitis

Background and Aim: Evidence has been accumulated to show that achievement of mucosal healing (MH) is associated with sustained clinical remission, and reduced rates of hospitalization and surgical resection. The combination of oral and topical mesalazine is thought to be more effective than alone in patients with mild-to-moderate disatal colitis and mild-tomoderate extensive colitis. However, endoscopic evaluation of the combined treatment on colonic mucosa is scarce. We conducted conventional endoscopic evaluation as well as segmental endoscopic evaluation in mild-to-moderate ulcerative colitis (UC) patients treated with oral Pentasa® and Pentasa® enema. Materials and Methods: Patients with active mildto-moderate UC were included and treated with 4 g/day of mesalazine combined with 1 g/ day mesalazine enema for 8 wks. At both baseline and 8 wks patients were endoscopically asseseed using Mayo Endoscopic Score and using Segmental Endoscopic Score. Segmental endoscopic evaluation was performed for each of 8 contiguous anatomic segments (rectum below/above the peritoneal reflection, rectosigmoid, sigmoid, left colon, transverse, right colon, cecum). The criteria of segmental endoscopy included erythema, vascular pattern, friability and erosion/ulcer (score range per segment: 0 10). MH was defined as Mayo Endoscopic Score = 0, 1. Disease activity was also assessed at baseline and 8 wks using the UC Disease Activity Index (UCDAI), with clinical and endoscopic signs. Remission and improvement were defined as a UCDAI score < 2 and as a decrease of UCDAI score by ≥ 2 points from baseline, respectively. Abbreviated UCDAI score (aUCDAI) obtained from stool frequency, rectal bleeding and physician's global assessment was assessed at baseline, 4 and 8 wks. Result: Of the 31 patients included, 29 completed endoscopic evaluations at both baseline and 8 wks. Median disease duration was 72.7 months and mean baseline UCDAI score was 6.72. The extents of disease were 10.3% in proctitis, 34.5% in left-sided colitis and 55.2% in extensive colitis. Mayo endscopic score significantly decreased from 2.14 to 1.45 (p < 0.001) and MH rate was 51.7%. The segmental endscopic scores of every assessed area at 8 wks decreased significantly compared to that at baseline (Table). UCDAI significantly decreased from 6.72 to 3.00 (p < 0.001). Remission and improvement rates were 31.0% and 79.3%, respectively. aUCDAI significantly decreased from 4.59 at baseline to 1.76 at 4 wks and 1.55 at 8 wks (p < 0.001). Conclusion: These results demonstrate that the combination of oral and topical mesalazine ameliorates mucosal appearances of the whole colon with fast clinical improvement. Therefore, combined mesalazine therapy is thought to be the optimum first line therapy for mild-to-moderate UC patients independent of the extent of disease. Segmental Endoscopic Score

Clinical trial: effects of an oral preparation of mesalazine at 4 g/day on moderately active ulcerative colitis. A phase III parallel-dosing study

Oral mesalazine formulations are effective in the treatment of active ulcerative colitis (UC). It is not clear what induction dose of mesalazine is optimal for treating patients with active UC. We aimed to evaluate the efficacy and safety of 4 versus 2.25 g/day for selected patients with active UC. A multicenter, randomized, double-blind, parallel-group clinical study in 39 Japanese medical institutions. A total of 123 patients with moderately active UC received 4 g/day (two divided doses) versus 2.25 g/day (three divided doses) for 8 weeks. Primary endpoint was the ulcerative colitis-disease activity index (UC-DAI) score before and after 8 weeks of treatment. The improvement of each individual UC-DAI variable, remission, and efficacy rates were secondary endpoints. Safety was determined by laboratory data, vital signs, subjective symptoms, and objective findings. Patients receiving 4 g/day achieved a change in UC-DAI score significantly superior to those receiving 2.25 g/day [-3.0 (95% confidence intervals (CI) -3.8 to -2.3) vs. -0.8 (95% CI -1.8 to 0.1), respectively]. There were significant differences in all UC-DAI variables between the groups. Remission rates were 22.0% (4 g/day) and 15.3% (2.25 g/day). The efficacy rate was significantly better with 4 versus 2.25 g/day [76.3 vs. 45.8%, respectively (95% CI 13.8-47.2); P = 0.001]. No difference was seen in adverse events or adverse drug reactions. A dose of 4 g/day was significantly superior to 2.25 g/day in terms of UC-DAI score for patients with moderately active UC. Safety profiles were similar for both doses.