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Background: Endoscopic healing (EH) is a therapeutic target in ulcerative colitis (UC). However, even patients who have achieved EH relapse frequently., Aims: To investigate the association between recent steroid use and relapse risk in UC patients with EH., Methods: This multi-centre cohort study included 1212 UC patients with confirmed EH (Mayo endoscopic subscore ≤1). We excluded patients with current systemic steroid use or history of advanced therapy. We divided patients into a recent steroid group (last systemic steroid use within 1 year; n = 59) and a non-recent or steroid-naïve group (n = 1153). We followed the patients for 2 years to evaluate relapse, defined as induction of systemic steroids or advanced therapy. We used logistic regression to estimate the odds ratio (OR) of relapse., Results: Relapse occurred in 28.8% of the recent steroid group and 5.6% of the non-recent/steroid-naïve group (multi-variable-adjusted OR 5.53 [95% CI 2.85-10.7]). The risk of relapse decreased with time since the last steroid use: 28.8% for less than 1 year after steroid therapy, 22.9% for 1 year, 16.0% for 2 years and 7.9% beyond 3 years, approaching 4.0% in steroid-naïve patients. (p trend  <0.001)., Conclusions: Even for patients with UC who achieved EH, the risk of relapse remains high following recent steroid therapy. Physicians need to consider the duration since last steroid use to stratify the relapse risk in UC patients with EH., (© 2024 John Wiley & Sons Ltd.)

Background: The increasing incidence of older-onset ulcerative colitis (UC), which has a higher risk of surgery, is a global health issue. However, data regarding intravenous steroid treatment, one of the important treatment options to avoid surgery, for older-onset UC is lacking., Aims: To evaluate the association between onset age and effectiveness of intravenous steroids in UC., Methods: This retrospective multicentre (27 facilities) cohort study included moderate-to-severe hospitalised UC patients who underwent their first intravenous steroids between April 2014 and July 2019. The primary outcome was clinical remission at day 30, using two-item patient-reported outcome scoring. The key secondary outcomes were risks of surgery and adverse events (death, infection and venous thrombosis) within 90 days. A modified Poisson regression model was used for analysis., Results: Overall, 467 UC patients (384 younger-onset and 83 older-onset) were enrolled. Clinical remission at day 30 was observed in 252 (65.6%) among younger-onset patients and 43 (51.8%) among older-onset patients (adjusted risk difference, -21.7% [95% CI, -36.1% to -7.2%]; adjusted risk ratio [ARR], 0.74 [95% CI, 0.59 to 0.93]). The risks of surgery and adverse events were higher in older-onset UC (20.5% vs. 3.1%; ARR, 8.92 [95% CI, 4.13 to 19.27], 25.3% vs. 9.1%; ARR, 2.19 [95% CI, 1.22 to 3.92], respectively). Four deaths occurred, all involving older-onset UC. The risks of infection and venous thrombosis were also higher in older-onset UC (18.1% vs. 8.6%, 7.2% vs. 0.5%, respectively)., Conclusions: Older-onset was associated with a lower effectiveness of intravenous steroids with higher risks of surgery and adverse events in UC., (© 2022 John Wiley & Sons Ltd.)

Background: Helicobacter pylori (H. pylori) prevalence is lower in patients with inflammatory bowel disease (IBD) than in those without IBD, suggesting that H. pylori plays a protective role in IBD. It has been reported that IBD may occur due to H. pylori eradication; however, it is unclear whether H. pylori eradication increases the incidence of IBD. Moreover, the effect of H. pylori eradication on IBD activity is unclear., Case Presentation: An 11-year-old boy diagnosed with ulcerative colitis (UC) was in clinical remission, with treatment involving 5-aminosalicylic acid. Fecal calprotectin (FC) level had decreased to 33.2 mg/kg, indicating mucosal healing. At age 12, he experienced epigastric pain on an empty stomach, which was relieved with dietary intake. His FC level was elevated without UC symptoms, such as diarrhea and bloody stools. He was diagnosed with H. pylori duodenal ulcer. H. pylori eradication (clarithromycin and amoxicillin for 7 days and a proton-pump inhibitor) led to symptom improvement the day after treatment initiation. However, he developed diarrhea and his FC level remained high despite improvement in duodenal ulcer symptoms and endoscopic findings of H. pylori eradication. Colonoscopy results indicated UC relapse., Conclusions: H. pylori eradication may worsen UC activity. However, further studies are required as this case report involved only one pediatric patient with increased UC activity after H. pylori eradication., (© 2021. The Author(s).)

A 26-year-old man was admitted to our institution for ulcerative colitis treatment. He used mesalamine, steroid, immunomodulators, and anti-TNFα anti-body, but it was difficult to maintain remission. We started induction therapy with tofacitinib (TOF) 10 mg twice daily. He maintained clinical remission but had chest pain 44 days after the start of TOF. Esophagogastroduodenoscopy showed multiple ulcers from middle to lower esophagus. Although rare, TOF induced esophageal ulcers were considered based on his clinical course and endoscopic findings.

While immunomodulators (IMs) are used as key drugs in remission maintenance treatment for ulcerative colitis (UC), there has been no evidence to date for determining monitoring methods and drug withdrawal. Therefore, we examined if a decrease in white blood cell count (WBC) and an elevation in mean cell volume (MCV) could be used as optimization indices and if mucosal healing (MH) could be a rationale for determining the time of IM withdrawal. Subjects were 89 UC patients who were using IMs and for whom clinical remission had been maintained. Those with a Rachmilewitz Clinical Activity Index score of 4 or lower and those with a Mayo endoscopic subscore (MES) of 0 or 1 were defined as MH. The remission maintenance rates of the following comparative groups were examined: an IM continuation group and an IM withdrawal group; an IM continuation group with a WBC of less than 3000 or a MCV of 100 or greater and an IM continuation group with a WBC of 3000 or greater and a MCV of 99 or lower; an IM continuation group of patients for whom MH had been achieved and an IM continuation group of patients for whom MH had not been achieved; and an IM withdrawal group with a MES of 0 and an IM withdrawal group with a MES of 1. A significantly higher remission maintenance rate was observed in the IM continuation group compared to the withdrawal group (p < 0.01). No significant difference was observed between the IM continuation group with a WBC of less than 3000 or a MCV of 100 or greater and the IM continuation group with a WBC of 3000 or greater and a MCV of 99 or lower (p = 0.08). Higher remission maintenance rates were observed in the IM continuation group of patients for whom MH had been achieved compared to the IM continuation group of patients for whom MH had not been achieved (p = 0.03). No significant difference was observed between the IM withdrawal group with MES 0 and the IM withdrawal group with MES 1. (p = 0.48). This retrospective study showed that remission maintenance could be firmly obtained by continuing IM administration in case of endoscopic MH; however, MH was not an indicator of IM withdrawal.

The patient was diagnosed with ulcerative colitis and received remission induction therapy with prednisolone. While they developed muscle pain in the lower extremities after starting prednisolone, they ultimately achieved clinical remission. After discharge, hematemesis and gastric discomfort developed. Esophagogastroduodenoscopy showed mucosal edema, redness, and oozing bleeding in the gastric body. In addition, the patient had bloody stool and was considered to have a relapse of ulcerative colitis. They therefore received remission induction therapy with tacrolimus. The patient achieved clinical remission again; however, gastric discomfort and muscle pain remained. A drug lymphocyte stimulation test revealed positivity for prednisolone; therefore, the patient was diagnosed with an allergy to prednisolone.

Objective: Although aminosalicylic acid (ASA) preparations have been used as first-line drugs for the treatment of ulcerative colitis (UC), no consistent view has been established regarding the ASA dose during the remission-maintenance phase of the disease. In this study, we examined whether the ASA dose should be reduced during the remission-maintenance phase., Materials and Methods: This study included 203 patients in the remission-maintenance phase of UC. The Mayo endoscopic subscore (MES) was used to evaluate mucosa. Comparison and analysis were performed between patients whose ASA dose had been unchanged and whose dose had been reduced, between patients with endoscopic healing (EH) group and those without endoscopic healing (WEH) group, and between patients with an MES of 0 and 1., Results: Comparison between the unchanged-ASA and reduced-ASA groups revealed that the remission-maintenance rate was higher in the unchanged-ASA group (p < 0.001). Next, the remission-maintenance rate was higher in the EH/unchanged-ASA group than in the EH/reduced-ASA group (p = 0.042). Comparison between the MES 0 and 1 groups revealed that the remission-maintenance rate was higher in the MES 0 group (p = 0.007). In addition, no significant difference in remission-maintenance rates was observed between the MES 0/unchanged-ASA group and the MES 0/reduced-ASA group (p = 0.108)., Conclusion: When the same ASA dose is maintained regardless of the presence or absence of EH, remission is more likely to be maintained. If the ASA dose must be reduced, dose reduction is more advantageous after an MES of 0 is achieved.

We herein report five cases of ulcerative colitis-associated cancer/dysplasia. Although clinical remission had been achieved in all patients, mucosal inflammation had been resolved in only one patient. Thus, in order to prevent cancer from developing, appropriate medical therapy aiming not only to relieve the clinical symptoms, but also to suppress chronic inflammation appears to be necessary. Moreover, cancer occurred as early as 4 years after the diagnosis in one patient. In patients without complete resolution of mucosal inflammation, careful surveillance colonoscopy should be initiated in the early phase.

Background & Aims: AJM300 is an orally active small-molecule antagonist of the α4 integrin subunit. We performed a randomized trial to investigate the efficacy and safety of AJM300 in patients with active ulcerative colitis (UC)., Methods: In a double-blind, placebo-controlled, phase 2a study, 102 patients with moderately active UC (Mayo Clinic scores of 6-10, endoscopic subscores ≥2, and rectal bleeding subscores ≥1) who had inadequate response or intolerance to mesalamine or corticosteroids were randomly assigned to receive AJM300 (960 mg) or placebo 3 times daily for 8 weeks. The primary end point was a clinical response at week 8, defined as a decrease in Mayo Clinic score of at least 3 points and a decrease of at least 30% from baseline, with a decrease in the rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of 0 or 1., Results: Clinical response rates were 62.7% and 25.5% at week 8 in the AJM300 group and placebo group, respectively (odds ratio [OR] = 5.35; 95% confidence interval [CI]: 2.23-12.82; P = .0002). Rates of clinical remission (Mayo Clinic score ≤2 and no subscore >1) were 23.5% and 3.9% in the AJM300 group and placebo groups, respectively (OR = 7.81; 95% CI: 1.64-37.24; P = .0099), and rates of mucosal healing (endoscopic subscores of 0 or 1) were 58.8% and 29.4% (OR = 4.65; 95% CI: 1.81-11.90; P = .0014). No serious adverse event, including progressive multifocal leukoencephalopathy, was observed, although more investigations are needed to confirm the safety profile of this drug., Conclusions: AJM300 was well tolerated and more effective than placebo in inducing clinical response, clinical remission, and mucosal healing in patients with moderately active UC. ClinicalTrials.jp no: JapicCTI-132293., (Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Patients with ulcerative colitis (UC) are treated with prednisolone (PSL), which causes adverse side effects. Extracorporeal granulocyte/monocyte adsorption (GMA) with an Adacolumn depletes elevated/activated myeloid lineage leucocytes as sources of inflammatory cytokines. We were interested to evaluate the efficacy, safety and the treatment cost for PSL and GMA., Methods: Forty-one patients with active UC had achieved remission with GMA, at 1 or 2 sessions/week, up to 10 sessions (n=24) or with orally administered PSL (1mg/kg bodyweight, n=17). Clinical activity index (CAI) ≤4 was considered clinical remission. Following remission, patients received 5-aminosalicylic acid (2250-3000mg/day) or sulphasalazine (4000-6000mg/day) as maintenance therapy and were followed for 600 days. The total treatment cost was assessed based on 1€=150JPY., Results: PSL was tapered after two weeks, and discontinued when a patient achieved remission. The average time to the disappearance of at least one major UC symptom (haematochezia, diarrhoea, or abdominal discomfort) was 15.3 days in the GMA group and 12.7 days in the PSL group, while time to remission was 27.9 days in the GMA group and 27.6 days in the PSL group, CAI 0.8 and 2.0, respectively. The Kaplan-Meier plots showed similar remission maintenance rates over the 600 days follow-up period. The average medical cost was 12739.4€/patient in the GMA group and 8751.3€ in the PSL group (P<0.05). In the GMA group, 5 transient adverse events were observed vs 10 steroid related adverse events in the PSL group (P<0.001)., Conclusions: In appropriately selected patients, GMA has significant efficacy with no safety concern. The higher cost of GMA vs PSL should be compromised by good safety profile of this non-pharmacological treatment intervention.

Background and Aim: Leukocytapheresis (LCAP) is an extracorporeal leukocyte removal therapy that removes immunocompetent leukocytes from the peripheral blood. Nafamostat mesilate (NM) is the most commonly used anticoagulant for LCAP due to various benefits associated with its use, such as a reduced likelihood of bleeding and minimization of adverse reactions caused by contact between blood and the LCAP device. However, adverse reactions have also been reported with NM administration. We reviewed the safety of anticoagulants other than NM, from the perspective of bradykinin production and the consequent drop in blood pressure during treatment., Methods: For each of 10 patients with ulcerative colitis, we used four types of anticoagulants sequentially [NM (30-50 mg), heparin, low-molecular-weight heparin (LMWH) and NM (1 mg), and LMWH] for LCAP. We then examined the changes in the blood bradykinin concentrations from the perspective of adverse reactions during LCAP., Results: The bradykinin production levels from Cellsorba EX varied, depending on the type of anticoagulant used. NM alone (30-50 mg) or LMWH + NM (1 mg) inhibited bradykinin production, whereas heparin alone or LMWH alone significantly accelerated it. However, an excessive fall of blood pressure was not noted in any of the cases. Use of LMWH alone was frequently associated with pressure elevations in the column., Conclusions: Given the significant benefits of minimized adverse reactions of LCAP and of continuation of LCAP, we suggest that an appropriate selection of the anticoagulant(s) may allow safer execution of LCAP., (Copyright 2007 S. Karger AG, Basel.)

Purpose: The incidence of colorectal neoplasia has increased among patients with longstanding and extensive ulcerative colitis (UC). Therefore, surveillance colonoscopy has been widely recommended. However, there is controversy about the impact of cancer surveillance, and ways to improve its effectiveness are being sought. The estrogen receptor (ER) gene shows age-related methylation in the colorectal epithelium and is frequently methylated in colorectal neoplasia, suggesting that ER methylation occurs early in the process of colorectal tumorigenesis., Experimental Design: To clarify whether methylation analysis of the ER gene in nonneoplastic epithelium can help predict an increased risk for UC-associated neoplasia, a total of 105 nonneoplastic colorectal epithelia from 18 patients with longstanding and extensive UC, including 8 patients with neoplasia and 10 patients without neoplasia, were analyzed. In all patients, multiple samples were taken from six regions of the colorectum. The combined bisulfite restriction analysis method was used to determine the methylation status of the ER gene., Results: The mean methylation level of the ER gene was 25.4% in the nonneoplastic epithelia from UC patients with neoplasia, whereas it was only 4.0% in those without neoplasia (P<0.001). The methylation level of the ER gene in UC patients with neoplasia was significantly higher than in UC patients without neoplasia throughout the colorectum except for the cecum. In UC patients with neoplasia, the mean ER methylation level in the distal colon (36.1%) was significantly higher than in the proximal colon (14.6%; P<0.001)., Conclusions: These results suggest that the analysis of ER gene methylation in nonneoplastic colorectal epithelium could have the potential to be a useful adjunct for identifying individuals with longstanding and extensive UC who are at increased risk of neoplasia and contribute to more effective cancer surveillance.