Mayo Endoscopic Subscore Research Articles

Real-World Effectiveness and Safety of Carotegrast Methyl in Japanese Patients with Moderately Active Ulcerative Colitis

Introduction: Carotegrast methyl (CGM) is an oral, small-molecule α4-integrin antagonist, which became clinically available in Japan in May 2022. CGM is approved for remission induction treatment for moderately active ulcerative colitis (UC) with an inadequate response or intolerance to 5-aminosalicylates. Methods: We performed a single-center, retrospective, observational study of Japanese patients with moderately active UC to assess the real-world effectiveness and safety of CGM as remission induction treatment. Results: Of 14 patients, 71% (10/14) were women, and the median (range) age was 47 (20–68) years. Disease types were proctitis in 7% (1/14), left-sided colitis in 50% (7/14), and total colitis in 43% (6/14). With a median (range) treatment duration of 8 (2–26) weeks, the rate of endoscopic improvement (Mayo endoscopic subscore [MES] of 0 or 1) was 64% (9/14), and the rate of endoscopic remission (MES of 0) was 57% (8/14). After treatment with CGM, the median (range) MES decreased significantly from 3.0 (2–3) to 0.0 (0–3) (p = 0.008), the Mayo score decreased significantly from 7.0 (5–9) to 0.0 (0–9) (p = 0.006), and the clinical activity index decreased significantly from 6.0 (1–11) to 0.0 (0–9) (p = 0.015). Stool and diarrhea frequencies decreased significantly after initiating CGM, and the percentage of patients with bloody stool and abdominal pain tended to decrease. The cumulative relapse-free rate at week 26 among 9 patients who achieved endoscopic improvement with CGM was 77.8% (95% confidence interval, 36.5%–93.9%). No adverse drug reactions, including progressive multifocal leukoencephalopathy, were reported during the study period. Conclusion: This single-center, retrospective, observational study of 14 Japanese patients with UC showed that CGM was safe and effective as a remission induction treatment for moderately active UC with an inadequate response to 5-aminosalicylates in real-world settings.

The value of assessing deep disease healing by probe-based confocal laser endomicroscopy and histology for long-term prognosis of ulcerative colitis.

The benefits of deep disease healing need evaluation by long-term clinical research in different populations. Confocal laser endomicroscopy (CLE) is a superior method for evaluating deep disease healing. This prospective study enrolled ulcerative colitis (UC) patients in clinical remission who underwent colonoscopy, CLE, and histological assessment. Patients were monitored for relapse by patient-reported outcomes and colonoscopy evaluation of mucosal healing. The ability of different methods of mucosal healing to predict long-term disease recurrence was assessed using Kaplan-Meier estimation and Cox proportional hazard regression. Forty-two patients in clinical remission were assessed by colonoscopy. Those with Mayo endoscopic subscores (MES)≤1 were enrolled. The 48-month recurrence rates in present healing group, assessed by CLE (colonic barrier assessment and ENHANCE index) and by histological examination (Geboes scale), were 20.0%, 26.7%, and 11.1%, respectively, and were significantly lower than absent healing group (P<0.05). Univariate Cox proportional risk regression analysis in absent of healing disease, determined by the ENHANCE index and Geboes scale, indicated an increased risk of recurrent events, with hazard ratios (HR) of 3.87 (95% CI: 1.18, 12.62) and 8.20 (95% CI: 1.06, 63.30), respectively. Multivariate Cox proportional hazard regression analysis adjusted for the extent of inflammation (E3 or not) showed a significant difference only for the ENHANCE index, with an HR of 3.53 (95% CI: 1.03, 12.10), P=0.045. Deep disease healing has a lower recurrence rate. The colonic barrier healing assessment, ENHANCE index, and histological Geboes scale have superior long-term prognostic value for UC patients.

Mucosal cytokine expression associated with deep endoscopic mucosal healing in ulcerative colitis.

Ulcerative colitis (UC) is a chronic inflammatory disease of unknown cause for which no curative treatments have been developed. Cytokines play an important role in the pathogenesis of UC, and therapies targeting specific cytokines have been successful in treating refractory UC. The purpose of this study was to measure mucosal cytokines in UC and identify those that contribute to non-relapsing mucosal healing diagnosed by endoscopy. This prospective, observational study included 163 patients with UC. The mucosa was evaluated by Mayo Endoscopic Subscore (MES) and linked color imaging (LCI) at the time of endoscopy, and cytokine mRNA expression in biopsy tissue taken from the same site was quantified by real-time PCR and compared with endoscopic findings. The relationship between cytokine mRNA expression and endoscopic findings was investigated. Cytokines such as IFNγ, IL-1β, IL-8, IL-17A, and IL-23 were significantly elevated in proportion to endoscopic severity of MES and LCI classification.Interestingly, we found differences in the expression of cytokines (e.g., IL-22 and IL-33) between MES and LCI classification according to disease severity. Additionally, pathway analysis based on RNA sequencing compared between LCI-A and LCI-B in the patients diagnosed as MES 0 revealed that IL-5 and IL-6 are involved in the finer differences in endoscopic mucosal redness. This study is the first to report the correlation between mucosal cytokine expression and the pathogenesis of mucosal healing (MH) in UC and supports the contribution of specific cytokines as molecular markers of MH or in the pathogenesis of MH in UC.

Defining mucosal healing in randomized controlled trials of inflammatory bowel disease: A systematic review and future perspective.

Mucosal healing (MH) is an established treatment goal in inflammatory bowel disease (IBD). However, various definitions of MH exist. We aimed to identify how MH is defined in randomized controlled trials (RCTs) in ulcerative colitis (UC) and Crohn's disease (CD). We searched MEDLINE, EMBASE, and the Cochrane library from inception to December 2023 for phase 2 and 3 RCTs of advanced therapies in IBD. One hundred forty-four studies were included, 72 in UC and 72 in CD, published between 1997 and 2023. In UC, 64% (46/72) RCTs reported MH as an endpoint. 12 definitions of MH were found, from endoscopic assessment alone (35/46; 76%) to the more recent combination of histology and endoscopy (10/46; 22%). 96% (44/46) of studies used the Mayo Endoscopic Subscore. In CD, reporting of MH lagged behind UC, with only 12% (9/72) of trials specifically defining MH as an endpoint, 7 as "absence of ulceration," 2 as Simplified Endoscopic Score for CD score ≤2 or 0. Histological assessment was performed in 3 RCTs of CD. Centralized reading of endoscopy was used in 48% (35/72) of RCTs of UC and 22% (16/72) of CD. Only 1 RCT included transmural healing as an endpoint. A standard definition of MH in IBD is lacking. Definitions have evolved particularly in UC, which now includes the addition of histological evaluation. Transmural healing holds promise as a future target in CD. We support a greater standardization of definitions as we expect endpoints to become increasingly stringent and multimodal with computers automating the assessment.

Clinical profile and short-term outcomes of acute severe ulcerative colitis in Vietnam: insights from a resource-limited setting.

Acute severe ulcerative colitis (ASUC) is a significant complication of ulcerative colitis, affecting roughly 25% of patients and increasing the risk of colectomy and hospital mortality. While intravenous steroids are a primary treatment, only 67% of patients respond, necessitating rescue therapy for non-responders. Data on ASUC in the Vietnamese population are scarce. This study aims to provide insights into the clinical characteristics and short-term outcomes of Vietnamese patients with ASUC. We conducted a prospective case series on ASUC patients admitted to the University Medical Center in Ho Chi Minh City from January 2021 to June 2023. Steroid response was assessed using the Travis Oxford criteria. We evaluated clinical features, in-hospital steroid response rates, endoscopic remission, and colectomy rates 12 months post-hospitalization. Seventeen patients with a median age of 42 years (70.6% male) were included. The median time from symptom onset to diagnosis was six weeks, and 47.1% had a history of ulcerative colitis. Median CRP value was 75.8 mg/L, and 76.5% had fecal calprotectin concentrations above 800 µg/g. All patients had a Mayo endoscopic subscore of ≥2, with 12.5% showing deep ulcers. Eleven patients (64.7%) responded to in-hospital steroid treatment, while 6 (35.3%) required rescue therapy with infliximab or tofacitinib. After one year, 10 of 11 (90.1%) achieved mucosal healing, and no patients underwent colectomy. Corticosteroids remain the cornerstone for initial ASUC therapy, though many patients do not respond. Anti-TNF agents and tofacitinib show potential benefits for those unresponsive to steroids. This study highlights the effectiveness of corticosteroids and biologics in managing ASUC in Vietnam.

Predicting mucosal inflammation in IBD patients using patient-reported symptom scores and a faecal calprotectin home test: protocol for a multicentre prospective validation study

IntroductionCrohn’s disease and ulcerative colitis are chronic inflammatory bowel diseases (IBD) with a relapsing-remitting nature. With adequate non-invasive prediction of mucosal inflammation, endoscopies can be prevented and treatment optimised earlier...

Clinical Trial: A Pragmatic Randomised Controlled Study to Assess the Effectiveness of Two Patient Management Strategies in Mild to Moderate Ulcerative Colitis-The OPTIMISE Study.

Background: Current management of mild-to-moderate ulcerative colitis (UC) involves monitoring clinical markers of disease activity, such as stool frequency (SF) and rectal bleeding (RB), and adjusting treatment accordingly. Our aim was to assess whether targeting treatment based on faecal calprotectin (FC) levels (treat-to-target; T2T) provides greater UC disease control versus a symptom-based approach. Methods: This was a pragmatic, randomised (1:1) controlled study of patients with mild-to-moderate UC (global Mayo score 2-6) treated with ≤2.4 g/day 5-aminosalicylic acid that compared the effectiveness of two management strategies with (interventional arm) and without (reference arm) FC home monitoring over 12 months of follow-up. Treatment was optimised in the interventional arm using FC values and clinical symptoms (PRO-2), while the reference arm used only PRO-2. Results: 193 patients completed the study. No significant difference was found for the primary endpoint (Mayo Endoscopic Subscore [MES] = 0 at 12 months). A numerical advantage for the interventional arm over the reference arm for the primary endpoint (37.0% vs. 33.4%, respectively) and for MES ≤ 1, RB = 0, and SF ≤ 1 at 12 months was found following imputation for missing data. The composite endpoint of MES = 0, RB = 0, and SF ≤ 1 at 12 months was achieved at a significantly higher rate in the interventional arm than the reference arm (effect size [ES]: 0.17, 95% CI 0.02-0.32; p < 0.05). A similar result was obtained for MES ≤ 1, RB = 0 and SF ≤ 1 (ES: 0.22; 95% CI 0.07-0.37; p < 0.05). Conclusions: T2T using FC monitoring was effective in patients with mild-to-moderate UC at 12 months. Further longer-term studies are required to confirm the results.

Four intestinal ultrasound scores and bowel wall thickness alone correlated well with pediatric ulcerative colitis disease activity.

Intestinal ultrasound (IUS) is a noninvasive tool in ulcerative colitis (UC), but scoring systems have mostly been developed for adults, Crohn's disease, and flaring UC. Our aim was to evaluate the performance of bowel wall thickness (BWT) and four IUS scores in pediatric patients with newly diagnosed UC. Patients <18 years old with suspected UC were prospectively enrolled. Baseline IUS was done, and ulcerative colitis intestinal ultrasound score (UC-IUS), Milan criteria, simple pediatric activity ultrasound score (SPAUSS), and Civatelli index were calculated. Mayo endoscopic segment subscore, pediatric ulcerative colitis activity index (PUCAI), and biomarkers were correlated with IUS using nonparametric and receiver operating characteristic analyses. Fifty-two patients (56% male, median age 13.9 years, interquartile range [IQR] 11.2-16.3) with 206 colon segments were included. Patients who needed hospitalization (n = 27/52) had significantly worse IUS (BWT and all scores) compared to those not hospitalized. For all patients, IUS scores and BWT significantly correlated with baseline endoscopic, clinical, and biochemical disease activity (rho = 0.32-0.67, p < 0.05). BWT (τb = 0.53), UC-IUS (τb = 0.55), and Milan (τb = 0.52) had the strongest endoscopic correlations. For differentiating between endoscopic disease severity, BWT, UC-IUS, and Milan, had the highest areas under the curve (0.89-0.93). Using BWT alone, a thinner cut-off had improved sensitivity while maintaining high specificity: ≥2.5 mm for moderate/severe endoscopic inflammation (sensitivity 66%; specificity 94%) and ≥3.5 mm for severe endoscopic inflammation (sensitivity 92%; specificity 86%). BWT and all four IUS scores correlated well with endoscopic, clinical, and biochemical disease activity, and was another useful marker of severity in identifying patients needing hospitalization. Pediatric patients needed a thinner BWT cut-off, which should be accounted for when developing pediatric-specific scores. BWT alone may be just as clinically useful as composite US scores.

Histologic improvement predicts endoscopic remission in patients with ulcerative colitis

Limited research has been performed to determine if histologic improvement serves as a prognosticator for endoscopic remission, a key therapeutic target for ulcerative colitis (UC). The primary aim of the study was to evaluate if histological activity could predict endoscopic remission in UC patients with Mayo endoscopic subscores (MES) of 0 or 1. In addition, we compared the clinical outcomes between histologic improvement group and active group. This research encompassed 492 individuals with UC with MES of 0 or 1, who underwent histological assessment as per the established protocol of Samsung Medical Center between January 2018 and December 2020. Participants were categorized into two cohorts based on the degree of histological activity: those showing histologic improvement and those with ongoing histologic activity. The endoscopic activity was assessed during follow-up, and the primary outcome was endoscopic remission according to histologic activity. Out of the total participants, endoscopic activity was scrutinized in 435 patients during the colonoscopic follow-up and in 146 during the subsequent one. The histologic improvement group at the index colonoscopy was more likely achieve endoscopic remission than the histologic active group. Clinical relapse was more likely in the histologic active group than in the histologic improvement group.

Absence of Paneth Cell Metaplasia to Predict Clinical Relapse in Ulcerative Colitis with Endoscopically Quiescent Mucosa.

Paneth cells play multiple roles in maintaining intestinal homeostasis. However, the clinical role of Paneth cell metaplasia (PCM) in ulcerative colitis (UC) remains unclear. We aimed to investigate the relationship between PCM and relapse in patients with UC and compare the usefulness of PCM with other histological indexes, including mucin depletion (MD) and basal plasmacytosis (BP). Patients with UC in clinical remission (CR) who underwent colonoscopy to confirm a Mayo endoscopic subscore (MES) ≦1 with biopsies from the distal colon were enrolled into this retrospective cohort study. Biopsy samples were evaluated for histological findings of PCM, MD, and BP. Clinical relapse was defined as partial Mayo score ≧3 or medication escalation. Multivariate analysis was performed to determine independent predictors of relapse among the three histological findings, MES, and patient background, and relapse prediction models were generated. Eighty-three patients were enrolled in this study (MES 0, n = 47; MES 1, n = 36). The number of PCM cases was significantly higher in patients with prolonged CR than that in those with relapse (p = 0.01). Multivariate analysis showed that the absence of PCM and MD were related to relapse in all the patients. In patients with MES 1, the absence of PCM was the only risk factor significantly and independently associated with relapse (hazard ratio, 4.51 [1.15-17.7]; p = 0.03). The absence of PCM was a histological risk factor for relapse in patients with MES 1, implying a protective role for PCM in remission and a new index for mucosal healing.

A personalised algorithm predicting the risk of intravenous corticosteroid failure in acute ulcerative colitis.

An episode of acute ulcerative colitis (UC) represents an important watershed moment in a patient's disease course. To derive a personalised algorithm for identifying patients at high risk of corticosteroid non-response from variables available at hospital presentation using a large prospectively collected acute UC patient database and machine learning-based techniques. We analysed data from 682 consecutive presentations of acute UC. We used an Akaike information criterion-based elastic net model to select variables based on the 419 earliest presentations of acute UC (1996-2017). We constructed two risk-scoring algorithms, with and without utilising additional endoscopic variables, using logistic regression models. We validated these risk scores on separate cohorts of 181 (2018-2022) and 82 (2015-2022) acute UC presentations. The partial risk of rescue (ROR) score included the admission indices of oral corticosteroid treatment, bowel frequency ≥6/24 h, albumin, CRP ≥12 mg/mL and log10CRP. The full ROR score incorporates the same variables with the addition of the Mayo endoscopic subscore and disease extent. The AUCs in the main validation cohort were 0.76 (95% CI: 0.69-0.83) and 0.78 (95% CI: 0.71-0.85) for the partial and full ROR scores, respectively. These pragmatic personalised risk scores (available at www.severecolitis.com) have comparably strong performance characteristics and usability enabling the identification of individuals at high risk of corticosteroid non-response before or after endoscopic assessment. The ROR scores have the potential to challenge conventional acute UC treatment paradigms by identifying patients who may benefit from early rescue therapy or participation in relevant clinical trials.

Impact of completely histological remission on reducing flare-ups in moderate-to-severe, biologics-experienced ulcerative colitis patients with endoscopic remission

Background/purposeEndoscopic remission is presently recognized as the standard therapeutic target in the treatment of ulcerative colitis (UC). However, achieving histological remission is increasingly viewed as a pivotal objective. This study investigates the effects of attaining completely histological remission on the clinical outcomes for UC patients with a high disease burden who have already reached endoscopic remission. This is the inaugural study to concentrate on this specific patient demographic. MethodsThis retrospective cohort study enrolled moderate-to-severe, biologics-experienced UC patients with completely endoscopic remission (Mayo endoscopic subscore of 0) between June 2017 and October 2023 at Chang Gung Memorial Hospital, Linkou. Patients were classified into histological remission (HR) and non-histological remission (non-HR) groups based on the Nancy index (NI). HR was defined as an NI score of 0, with all other patients categorized as non-HR. The definition of flare-ups was based on both clinical and endoscopic evidence. Comparative analyses focused on baseline characteristics and clinical outcomes at follow-up. ResultsA total of 42 patients (HR group: 23, non-HR group: 19) were included. The average follow-up duration was 17.6 months. Baseline characteristics were comparable between the groups. At the end of follow-up, the HR group showed a significantly lower rate of acute flare-ups (26.1% vs. 68.4%, P = 0.006). Although not statistically significant, the HR group also experienced fewer emergency department visits and hospital admissions. ConclusionsFor moderate-to-severe, biologics-experienced UC patients in endoscopic remission, achieving completely histological remission is associated with a substantial reduction in flare-ups, suggesting its potential as a valuable therapeutic target.

Risk factors for clinical relapse in patients with ulcerative colitis who are in clinical remission but with endoscopic activity.

The treatment strategy for patients with ulcerative colitis (UC) in clinical remission who have not achieved mucosal healing is unclear. This study aimed to determine the risk factors of relapse in patients in clinical remission with endoscopic activity. This retrospective, single-center study included patients with UC who underwent colonoscopy (CS) and were in clinical remission with endoscopic activity. Characteristics were compared between patients who relapsed within 2 years after CS and those who did not. A Cox proportional hazards regression model was used to identify risk factors contributing to clinical relapse. Recent worsening in bowel symptoms was defined as increase in bowel frequency and/or increase in abdominal pain within approximately 1 month based on the descriptions in the medical charts. This study regarded 142 patients in clinical remission with an endoscopic activity of Mayo endoscopic subscore (MES) of ≥1 as eligible, and 33 (23%) patients relapsed during the observation period. Recent worsening of bowel symptoms was a significant risk factor for clinical relapse (hazard ratio [HR]: 3.02, 95% confidence interval [CI]: 1.34-6.84). This was particularly evident in patients with MES of 2 (HR: 5.16, 95% CI: 1.48-18.04), whereas no risk factors were identified in patients with MES of 1. The presence or absence of therapeutic intervention just after CS did not significantly affect clinical relapse. Recent worsening in bowel symptoms was a significant risk factor for clinical relapse in patients with UC who were in clinical remission with endoscopic activity.

Similar Efficacy of Mesalazine in Adult and Older Adult Ulcerative Colitis Patients: Post Hoc Analysis of a Randomized Noninferiority Trial of 1600mg vs 400mg Tablets.

The efficacy data on treatment in older adults are scarce, while the greatest increase in ulcerative colitis (UC) prevalence is observed in age groups of individuals 40 to 65 years of age and ≥65 years of age. We assessed the difference in rates of clinical and endoscopic response and remission in UC adults (≤60 years) and older adults (>60 years) treated with mesalazine. We performed a post hoc analysis of data from a phase 3 noninferiority trial of 817 UC patients treated with mesalazine for 8 and additional 26 weeks in a double-blind and open-label study, respectively. We used Wilcoxon rank sum or chi-square test to analyze differences between groups and multivariable logistic regression to determine the associations between endoscopic remission as outcome (Mayo endoscopic subscore [MES] = 0 or ≤1) and independent variables including disease duration, baseline MES, age, sex, comedications, and comorbidities. Older adults had a longer disease duration, a higher number of comorbidities, concomitant medications, and higher baseline MES (2.38 ± 0.486 in older adults vs 2.26 ± 0.439 in adults; P = .008) compared with adults. We observed no difference in rates of combined clinical and endoscopic remission, clinical remission and response, and endoscopic remission and response at week 8 and 38 post-treatment. In addition to other well-known predictors of worse outcome, patients with ≥3 comedications were less likely to achieve an MES = 0 at week 8 and 38 and an MES ≤1 at week 38. We observed similar efficacy of mesalazine in adult and older adult UC patients. The increased comedication number rather than age may decrease effectiveness of UC medications, highlighting the importance of healthy aging.

Early change in serum leucine-rich α-2-glycoprotein predicts clinical and endoscopic response in ulcerative colitis.

Leucine-rich α-2-glycoprotein (LRG) is a new serum biomarker reflecting the disease activity of ulcerative colitis (UC), but its change during the acute phase has not been enough investigated. Patients with UC who initiated the induction therapy with steroid or advanced therapy (biologics or Janus kinase inhibitors) were prospectively enrolled. Associations of LRG, C-reactive protein (CRP) and fecal calprotectin (FC) at baseline, week 1, and week 8 with clinical remission at week 8 and subsequent endoscopic improvement within 1 year (Mayo endoscopic subscore of 0 or 1) were assessed. A total of 143 patients with UC were included. LRG and CRP at week 1 were significantly lower in the clinical remission group than in the non-remission group (LRG, 20.6 μg/mL vs. 28.4 μg/mL, P< 0.001; CRP, 0.9 mg/dL vs. 2.3 mg/dL, P< 0.001) while FC demonstrated the difference between groups only at week 8. The area under the curves of week 1 LRG, CRP, and FC for week 8 clinical remission using the receiver operating characteristic curves analysis were 0.68, 0.71, and 0.57, respectively. Furthermore, LRG and CRP predicted subsequent endoscopic improvement as early as week 1, while FC was predictive only at week 8. LRG can be an early-phase biomarker predicting subsequent clinical and endoscopic response to induction therapy.

Artificial intelligence-assisted video colonoscopy for disease monitoring of ulcerative colitis: A prospective study.

The Mayo endoscopic subscore (MES) is the most popular endoscopic disease activity measure of ulcerative colitis (UC). Artificial intelligence (AI)-assisted colonoscopy is expected to reduce diagnostic variability among endoscopists. However, no study has been conducted to ascertain whether AI-based MES assignments can help predict clinical relapse, nor has AI been verified to improve the diagnostic performance of non-specialists. This open-label, prospective cohort study enrolled 110 patients with UC in clinical remission. The AI algorithm was developed using 74713 images from 898 patients who underwent colonoscopy at three centers. Patients were followed up after colonoscopy for 12 months, and clinical relapse was defined as a partial Mayo score >2. A multi-video, multi-reader analysis involving 124 videos was conducted to determine whether the AI system reduced the diagnostic variability among six non-specialists. The clinical relapse rate for patients with AI-based MES = 1 (24.5% [12/49]) was significantly higher (log-rank test, P = 0.01) than that for patients with AI-based MES = 0 (3.2% [1/31]). Relapse occurred during the 12-month follow-up period in 16.2% (13/80) of patients with AI-based MES = 0 or 1 and 50.0% (10/20) of those with AI-based MES = 2 or 3 (log-rank test, P = 0.03). Using AI resulted in better inter- and intra-observer reproducibility than endoscopists alone. Colonoscopy using the AI-based MES system can stratify the risk of clinical relapse in patients with UC and improve the diagnostic performance of non-specialists.

Magnetic Resonance Imaging Features Indicative of Permanent Colon Damage in Ulcerative Colitis: An Exploratory Study.

It is uncertain whether ulcerative colitis leads to accumulated bowel damage on cross-sectional image. We aimed to characterise bowel damage in patients with ulcerative colitis using magnetic resonance imaging [MRI], and to determine its relation with duration of disease and the impact on patients' quality of life. In this prospective study, patients with ulcerative colitis [UC] in endoscopic remission underwent MRI without bowel cleansing, and completed quality-of-life questionnaires. Participants' magnetic resonance findings were analysed considering normal values and thresholds determined in controls with no history of inflammatory bowel disease [n=40], and in patients with Crohn's disease with no history of colonic involvement [n = 12]. Subjects with UC were stratified according to disease duration [< 7 years vs 7‒14 years vs > 14 years]. We analysed 41 subjects with ulcerative colitis [20 women; Mayo endoscopic subscore 0 in 38 [92.7%] and 1 in three [7.3%]]. Paired segment-by-segment comparison of magnetic resonance findings in colonic segments documented as being affected by ulcerative colitis versus controls showed that patients with ulcerative colitis had decreased cross-sectional area [p ≤ 0.0034] and perimeter [p ≤ 0.0005] and increased wall thickness [p = 0.026] in all segments. Colon damage, defined as wall thickness ≥ 3 mm, was seen in 22 [53.7%] patients. Colon damage was not associated with disease duration or quality of life. Morphological abnormalities in the colon were highly prevalent in patients with ulcerative colitis in the absence of inflammation. Structural bowel damage was not associated with disease duration or quality of life.

Histologic Disease Persists beyond Mucosal Healing and Could Predict Reactivation in Ulcerative Colitis.

Mucosal healing (MH) is the main target in ulcerative colitis (UC) treatment. Even if MH lowers the risk of disease reactivation, some patients still relapse. Histologic activity (HA) beyond MH could explain these cases. This study aims to assess how many patients with MH have HA and which lesions are associated with relapse. We retrospectively enrolled UC patients showing MH, expressed as a Mayo Endoscopic Subscore (MES) of 0 and 1 upon colonoscopy. We reviewed the histological reports of biopsies evaluating the presence of typical lesions of UC and assessed the number of clinical relapses after 12 months. Among 100 enrolled patients, 2 showed no histological lesions. According to univariate analysis, patients with a higher number of histological lesions at the baseline had a higher risk of relapse (OR 1.25, p = 0.012), as well as patients with basal plasmacytosis (OR 4.33, p = 0.005), lamina propria eosinophils (OR 2.99, p = 0.047), and surface irregularity (OR 4.70, p = 0.010). However, in the multivariate analysis, only basal plasmacytosis (OR 2.98, p = 0.050) and surface irregularity (OR 4.50, p = 0.024) were confirmed as risk factors for disease reactivation. HA persists in a significant percentage of patients with MH. Despite the presence of MH, patients with basal plasmacytosis and surface irregularity have a higher risk of relapse.

Effects of Thiopurine Withdrawal on Vedolizumab-Treated Patients With Ulcerative Colitis: A Randomized Controlled Trial

Background and aimsThe impact of thiopurine de-escalation whilst on vedolizumab versus continuing thiopurine therapy in ulcerative colitis (UC) is unclear. We aimed to determine the effect of thiopurine withdrawal for patients with UC in remission on vedolizumab. MethodsThis multi-centre randomized controlled trial recruited UC patients on vedolizumab 300mg IV every 8 weeks and a thiopurine. Patients in steroid-free clinical remission for ≥6 months and endoscopic remission/improvement (Mayo endoscopic subscore[MES]≤1) were randomized 2:1 to withdraw or continue thiopurine. Primary outcome was comparing week 48 vedolizumab trough concentrations. Secondary outcomes were clinical relapse (partial Mayo score≥3 and fecal calprotectin>150μg/g or increase in MES≥1 from baseline), fecal calprotectin remission (<150μg/g), C-reactive protein remission (<5mg/L), centrally-read endoscopic remission (MES=0), histologic remission (Nancy index=0), histo-endoscopic remission and adverse events. ResultsIn total, 62 patients were randomized to continue (n=20) or withdraw (n=42) thiopurine. At week 48, vedolizumab trough concentrations were not significantly different between continue and withdrawal groups (14.7μg/mL [IQR:12.3-18.5μg/mL] versus 15.9μg/mL [IQR:10.1-22.7μg/mL] respectively, P=0.36). The continue group had significantly higher fecal calprotectin remission (95.0% [19/20] versus 71.4% [30/42], P=0.03), histologic remission (80.0% [16/20] versus 48.6% [18/37], P=0.02) and histo-endoscopic remission (75.0% [15/20] versus 32.4% [12/37], P=0.002) than the withdrawal group. Histological activity (HR:15.5 [95%CI:1.6-146.5],P=0.02) and prior anti-TNF exposure (HR:6.5 [95%CI:1.3-33.8],P=0.03) predicted clinical relapse after thiopurine withdrawal. ConclusionThiopurine withdrawal did not affect vedolizumab trough concentrations. However, it may increase fecal calprotectin, histologic and histo-endoscopic activity. Histological activity and prior anti-TNF exposure may predict disease relapse upon thiopurine withdrawal for patients using vedolizumab for UC; Australian and New Zealand Trial Registry, number ACTRN12618000812291.

Efficacy of Dose Escalation of Oral 5-Aminosalicylic Acid for Ulcerative Colitis With a Mayo Endoscopic Subscore of 1: An Open Label Randomized Controlled Trial.

Endoscopic healing is generally defined as Mayo endoscopic subscore (MES) ≤1 in ulcerative colitis (UC). However, patients with an MES of 1 are at higher relapse risk than those with an MES of 0. This study evaluated the therapeutic efficacy of proactive dose escalation of oral 5-aminosalicylic acid (5-ASA) in UC patients with an MES of 1. An open-label, randomized controlled trial was conducted in 5 hospitals between 2018 and 2022. Ulcerative colitis patients in clinical remission under oral 5-ASA therapy and diagnosed as having an MES of 1 were enrolled. Patients receiving maintenance therapy other than 5-ASA and immunomodulator were excluded. Patients were randomly assigned in a 1:1 ratio to receive either a dose-escalated (intervention) or constant dose (control) of 5-ASA. Concomitant immunomodulator was used as the stratification factor in the randomization. The primary end point was relapse within 1 year. The subgroup analysis was stratified for the use of immunomodulators. The full analysis set included 79 patients (39 intervention and 40 control). Immunomodulators were used in 20 (25.3%) patients. Relapse was less in the intervention group (15.4%) than the control group (37.5%; P = .026). In the subgroup with concomitant immunomodulators, relapse was also less in the intervention group (10.0%) than the control group (70.0%; P = .020). In patients without immunomodulators, the difference was not significant between 2 groups (intervention, 17.2%; control, 26.7%; P = .53). Dose escalation of 5-ASA reduced relapse within 1 year in UC patients in clinical remission with an MES of 1.