Mayo Endoscopic Score Research Articles

P1210 Gut microbiota profiling and disease course in patients with ulcerative colitis in clinical remission

Abstract Background The inflammatory bowel diseases, encompassing ulcerative colitis (UC) and Crohn’s disease (CD) are characterized by a relapsing-remitting disease course. Despite achieving remission, approximately one-third of the patients relapse annually and yet the microbiota associated with relapse remains elusive. We hypothesized that distinctions in gut microbial composition among patients in clinical remission could potentially influence the disease course. We aimed to discern a distinctive microbial signature in patients with UC in clinical remission, which could serve as a predictive marker for the sustained clinical remission. Methods This was a prospective observational cohort study conducted as a collaborative work between Dayanand Medical College and Hospital (DMCH), Ludhiana, and Institute of Microbial Technology (IMTECH), Chandigarh. Adult (≥18 years age) patients with an established diagnosis of mild UC (defined as no previous requirement of immune-modulators or biologics to induce or maintain remission) and in clinical remission, were included between January 2019 and December 2020 and followed for one year. The clinical remission was defined as partial Mayo score <2 for at least 6 months, with endoscopic Mayo score 0 and fecal calprotectin <100 µg/g within 4 weeks of enrolment. Utilizing using 16S rRNA metabarcoding based metagenome analysis, the bacterial composition of the collected stool samples were determined. Results During the study period, 34 patients (mean age 41.41±13.89 years, 20 [58.82%] males) meeting the eligibility criteria were included for analysis and followed up for one year. (Figure 1) The majority of the patients (21, 61.76%) had left sided colitis. On follow-up, 14 patients (41.17%) experienced a disease relapse (median time to relapse 6 [3-8.25] months). The phyla Firmicutes, Actinobacteria, Bacteroidetes and Proteobacteria were abundant in both the groups [sustained remission (n=20) and disease relapse (n=14)], but specific phyla were enriched in each cohort, Actinobacteria in remission and Proteobacteria in relapse groups. The genera Escherichia, Klebsiella, Enterobacter, Enterococcus, Streptococcus were enriched in relapse group. Interestingly the genus Clostridium was enriched in relapsed cohort whereas genera like Bifidobacterium, Prevotella, Bacteroides, Alistipes, Faecalibacterium were abundant in the remission cohorts. Conclusion There are inter-individual differences in the gut microbiota profile of patients with UC in clinical remission. These microbial differences can serve as determinants of the disease course.

P1175 Abdominal Pain is Associated with Poor Quality of Life in Quiescent Inflammatory Bowel Disease: A Cross-sectional Study of the SPARC Inflammatory Bowel Disease Cohort

Abstract Background Abdominal pain (AP) is common in patients with active inflammatory bowel disease (IBD) and has been associated with poor quality of life (QOL). Despite greater therapeutic options, symptoms persist in a subset of patients. Data is lacking regarding AP in patients with objectively documented quiescent disease. Among endoscopic quiescent disease: (1) estimate prevalence of AP, (2) assess predictors of worse AP, (3) describe its impact on validated QOL measures. Methods This cross-sectional study used prospectively collected data from SPARC (Study of a Prospective Adult Research Cohort) IBD, a multicenter longitudinal study of well-phenotyped adult IBD patients initiated by the Crohn’s & Colitis Foundation in 2016. Quiescent IBD was defined as Mayo endoscopy score <2 for ulcerative colitis (UC) and SES-CD score <3 for Crohn’s disease (CD). Patient reported outcomes (PROs) within 30 days of endoscopy were analyzed. Patients with ostomy or IPAA were excluded. Self-reported AP was categorized as none, mild, or moderate/severe. Univariate statistics used Pearson’s Chi-square and Kruskal-Wallis tests. Results A total of 973 patients with quiescent IBD (606 CD; 367 UC) were included in the study (Table 1). AP was more commonly reported in quiescent CD (31.2% mild, 15.5% moderate/severe) as compared to quiescent UC (23.4% mild, 10.1% moderate/severe) (p<0.001). In the entire quiescent cohort, those with mild or moderate/severe AP were more likely to be female sex (63.1% mild; 67.4% moderate/severe; p<0.001), higher BMI (28.4 mild; 30.0 moderate/severe; p=0.008) and have more recent tobacco use (p=0.004). Ileocolonic involvement was more commonly seen in moderate/severe AP. Mild and moderate/severe AP was associated with subjective fecal urgency, stool frequency, and bloody stool (all p<0.001). Disease behavior in CD was not associated with abdominal pain. General well-being was poorer for those with more severe AP (p<0.001), though this did not appear to result in more frequent recent ED visits or hospitalizations. Figure 1 depicts the PROMIS responses. Overall, worse AP was associated with universal worse scores on all PROMIS measures and subscales (all p<0.001). Data suggested that more severe AP had the greatest impacts on the "Fatigue" subscale. Conclusion In this study of patients in SPARC IBD with endoscopic quiescent IBD the overall prevalence of AP was 41.7% overall and more commonly reported in CD as compared to UC. AP was associated with a greater prevalence of other symptoms, worse general well-being, and poorer quality of life across all measures. Further research is needed to elucidate the pathophysiology for presence of AP in quiescent IBD and develop personalized management approaches.

P779 Long term efficacy of azathioprine monotherapy in patients with Inflammatory Bowel Disease

Abstract Background ECCO guidelines recommend monotherapy with azathioprine (AZA) as maintenance therapy of patients with inflammatory bowel disease (IBD) mainly in steroid-dependent disease. However, in the era of the new advanced treatments AZA is not considered as a preferable option, mainly because of the referred side effects and its use is limited in combination with biologic agents. Methods This is a retrospective observational study using data from the longitudinal, prospective IBD registry of University Hospital of Heraklion, Greece. Our aim was to study IBD patients who started on monotherapy with AZA, the profile of adverse effects they developed, the treatment persistence in monotherapy, as well as the possible related factors of treatment success [including age, gender, smoking status, body mass index, disease type, disease phenotype for Crohn’s disease (CD), history of IBD related surgery and the presence of extraintestinal manifestations]. Results Of 168 IBD patients treated with AZA, 89 (53%) were under AZA monotherapy [38 (43%) female, 67 (74%) CD, median age (IQR) 47 (32-56) years, mean (±SD) disease duration 17 (±8.4) years, median (IQR) time receiving AZA 72 (7-120) months]. Thirty (34%) patients continue their treatment till now (23 CD, 7 ulcerative colitis-UC), with a median time (IQR) of 108 (81-132) months. Of these, 18 (60%) (15 with CD and 3 with UC) present endoscopic remission and 11 (36%) (8 with CD, 3 with UC) mild endoscopic activity (based on SES-CD Score for CD and Mayo endoscopic score for UC). Of the 59 who discontinued, 33 (37%) experienced adverse events, 5 (5.5%) developed malignancy, 5 (5.5%) did not respond at baseline, 6 (6.5%) had loss of response (at a median of 91 months), 3 (3%) discontinued due to advanced age, 3 (3%) discontinued their medication on their own and 2 because of treatment de-escalation due to deep remission. Using logistic regression analysis, patients who responded to AZA monotherapy were patients without a history of IBD surgery or any extraintestinal manifestation, P=0.001 and 0.004, respectively. In the multivariate analysis, these associations remained statistically significant (P=0.01 and 0.006 respectively). Conclusion About one third of patients with IBD under AZA monotherapy experience long term response and about two thirds of them prolonged disease remission. Patients without either a history of IBD surgery or extraintestinal manifestations seem to respond better to AZA monotherapy.

Novel endoscopic scoring system for immune mediated colitis: a multicenter retrospective study of 674 patients

Background & AimsNo endoscopic scoring system has been established for immune-mediated colitis (IMC). This study aimed to establish such a system for IMC and explore its utility in guiding future selective immunosuppressive therapy (SIT) use compared to clinical symptoms. MethodsThis retrospective international 14-center study included 674 patients who developed IMC after immunotherapy and underwent endoscopic evaluation. Ten endoscopic features were selected by group consensus and assigned one point each to calculate an IMC endoscopic score (IMCES). IMCES cutoffs were chosen to maximize specificity for SIT use. This specificity was compared between IMCES, and clinical symptoms graded according to a standardized instrument. ResultsA total of 309 (45.8%) patients received SIT. IMCES specificity for SIT use was 82.8% with a cutoff of 4 . The inclusion of ulceration as a mandatory criterion resulted in higher specificity (85.0% for a cutoff of 4). In comparison, the specificity of a Mayo Endoscopy Score (MES) of 3 was 74.6% while specificity of clinical symptom grading was much lower at 27.4% and 12.3% respectively. Early endoscopy was associated with timely SIT use (p<0.001, r=0.4084). ConclusionsThis is the largest, multi-center study to devise an endoscopic scoring system to guide IMC management. An IMCES cutoff 4 has a higher specificity for SIT use than clinical symptoms, supporting early endoscopic evaluation for IMC.

Comparison of Endoscopic and Artificial Intelligence Diagnoses for Predicting the Histological Healing of Ulcerative Colitis in a Real-World Clinical Setting.

Artificial intelligence (AI)-assisted colonoscopy systems with contact microscopy capabilities have been reported previously; however, no studies regarding the clinical use of a commercially available system in patients with ulcerative colitis (UC) have been reported. In this study, the diagnostic performance of an AI-assisted ultra-magnifying colonoscopy system for histological healing was compared with that of conventional light non-magnifying endoscopic evaluation in patients with UC. The data of 52 patients with UC were retrospectively analyzed. The Mayo endoscopic score (MES) was determined by 3 endoscopists. Using the AI system, healing of the same spot assessed via MES was defined as a predicted Geboes score (GS) < 3.1. The GS was then determined using pathology specimens from the same site. A total of 191 sites were evaluated, including 159 with a GS < 3.1. The MES diagnosis identified 130 sites as MES0. A total of 120 sites were determined to have healed based on AI. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of MES0 for the diagnosis of GS < 3.1 were 79.2%, 90.6%, 97.7%, 46.8%, and 81.2%, respectively. The AI system performed similarly to MES for the diagnosis of GS < 3.1: sensitivity, 74.2%; specificity: 93.8%; PPV: 98.3%; NPV: 42.3%; and accuracy: 77.5%. The AI system also significantly identified a GS of < 3.1 in the setting of MES1 (P = .0169). The histological diagnostic yield the MES- and AI-assisted diagnoses was comparable. Healing decisions using AI may avoid the need for histological examinations.

The synergy of dual faecal immunochemical and faecal calprotectin testing for accurate assessment of endoscopic and histological activity in inflammatory bowel disease.

Faecal biomarkers are increasingly utilized for disease assessment in inflammatory bowel disease (IBD). To characterize the relative and combined accuracy of faecal calprotectin (FC) and faecal immunochemical testing (FIT) for detecting endoscopic and histologically active disease in Crohn's disease (CD) and ulcerative colitis (UC), subdivided by disease location. A prospective cohort study. Patients with confirmed IBD undergoing routine ileocolonoscopy for activity assessment were prospectively recruited and performed both FC and FIT ±30 days of ileocolonoscopy. Endoscopic activity was assessed via the simplified endoscopic score for CD, Mayo endoscopic score for UC and histological activity graded as nil/mild/moderate. Receiver-operator curve analyses were utilized to assess the performance of FC and FIT per disease subtype and location. In all, 137 (79 CD, 57 UC) patients were recruited. FC was more sensitive than FIT in detecting active endoscopic (CD: 91% versus 69%, UC: 94% versus 82%) and histological (CD: 86% versus 55%, UC 88% versus 56%) disease. However, FIT was more specific than FC in detecting active endoscopic (CD: 94% versus 56%, UC: 85% versus 69%) and histological (CD: 93% versus 55%, UC: 96% versus 70%) diseases. FIT was more sensitive and specific than FC in detecting active colonic CD (endoscopic activity: 94% versus 93%, histological activity: 92% versus 77%, respectively); however, it was poorly sensitive for active ileal CD (43% versus 89%). FC demonstrated higher sensitivity and FIT higher specificity for active IBD. Hence, dual testing was synergistic, displaying excellent performance characteristics across most IBD locations and subtypes, holding promise for future clinical application. Not applicable.

Comparison of Fecal Calprotectin with Different Endoscopic Scores in the Assessment of Ulcerative Colitis (UC) Activity and Its Utility in Differentiating IBS from IBD.

Ulcerative colitis (UC), a chronic inflammatory disease of gastrointestinal tract, can have initial presentation which is clinically difficult to differentiate from functional bowel disorders [irritable bowel syndrome (IBS) and irritable bowel disease (IBD)]. Conventional laboratory tests, such as erythrocyte sedimentation rate (ESR), C-reactive protein, and albumin express systemic patient responses instead of intestinal inflammation. In the last decade, fecal calprotectin, a calcium-binding protein, has been suggested as a sensitive marker of intestinal inflammation. However, only few studies have investigated its role in relation with the extent of the disease. To evaluate the usefulness of fecal calprotectin as a biomarker for disease activity in UC, its correlation with disease extent and its utility in differentiating IBS from IBD. A total of 75 patients (50 cases with colonoscopic evidence of inflammation and 25 cases with normal colonoscopic examination) were included in the study. Fecal calprotectin test was done on the day of colonoscopy. Severity of the disease was assessed by modified Mayo's endoscopy score (MMES). Age and baseline parameters were comparable in both the groups (UC and IBS). Patients in the ulcerative group had tachycardia (95 vs 74), high ESR (26 vs 20), high leukocytes count (9198 vs 8852), high fecal calprotectin (594 vs 29), low albumin (3.00 vs 3.80) and low hemoglobin (11 vs 13.40). Minimum and maximum MMES were 2 and 13.2. A significant correlation was observed between fecal calprotectin and MMES (p-value < 0.001). Fecal calprotectin is a simple, noninvasive, cost-effective marker that is strongly associated with colorectal inflammation; moreover, it has better role in the differentiation of IBD (UC) from IBS. Acharya K, Bhardwaj V, Chuahan I, et al. Comparison of Fecal Calprotectin with Different Endoscopic Scores in the Assessment of Ulcerative Colitis (UC) Activity and Its Utility in Differentiating IBS from IBD. Euroasian J Hepato-Gastroenterol 2023;13(2):120-123.

Development and validation of a blood routine-based extent and severity clinical decision support tool for ulcerative colitis

Monitoring extent and severity is vital in the ulcerative colitis (UC) follow-up, however, current assessment is complex and low cost-effectiveness. We aimed to develop a routine blood-based clinical decision support tool, Jin’s model, to investigate the extent and severity of UC. The multicentre retrospective cohort study recruited 975 adult UC inpatients and sub-grouped into training, internal validation and external validation set. Model was developed by logistics regression for the extent via Montreal classification and for the severity via Mayo score, Truelove and Witts score (TWS), Mayo endoscopic score (MES) and Degree of Ulcerative colitis Burden of Luminal Inflammation (DUBLIN) score. In Montreal classification, left-sided and extensive versus proctitis model achieved area under the receiver operating characteristic curve (AUROC) of 0.78 and 0.81 retrospectively. For severity, Mayo score model, TWS model, MES model and DUBLIN score model achieved an AUROC of 0.81, 0.70, 0.74 and 0.70 retrospectively. The models also were evaluated with satisfactory calibration and clinical unity. Jin’s model was free with open access at http://jinmodel.com:3000/. Jin’s model is a noninvasive, convenient, and efficient approach to assess the extent and severity of UC.

Early Intestinal Ultrasound Predicts Clinical and Endoscopic Treatment Response and Demonstrates Drug-Specific Kinetics in Moderate-to-Severe Ulcerative Colitis.

Intestinal ultrasound (IUS) is an emerging modality in monitoring disease activity in ulcerative colitis (UC). Here, we aimed to identify early IUS predictors of treatment response as evaluated by endoscopy and assessed the kinetics of IUS changes. This prospective, longitudinal study included UC patients with endoscopic disease activity (endoscopic Mayo score [EMS] ≥2) starting anti-inflammatory treatment. Clinical scores, biochemical parameters and IUS were assessed at baseline (W0), at week 2 (W2), at W6(W6), and at the time of second endoscopy (W8-W26). Per colonic segment, endoscopic remission (EMS = 0), improvement (EMS ≤1), response (decrease in EMS ≥1), and clinical remission (Lichtiger score ≤3) were assessed and correlated with common IUS parameters. Additionally, drug-specific responsiveness of bowel wall thickness (BWT) was assessed. A total of 51 patients were included and followed, and 33 patients underwent second endoscopy. BWT was lower from W6 onward for patients reaching endoscopic improvement (3.0 ± 1.2 mm vs 4.1 ± 1.3 mm; P = .026), remission (2.5 ± 1.2 mm vs 4.1 ± 1.1 mm; P = .002), and clinical remission (3.01 ± 1.34 mm vs 3.85 ± 1.20 mm; P = .035). Decrease in BWT was more pronounced in endoscopic responders (-40 ± 25% vs -4 ± 28%; P = .001) at W8 to W26. At W6, BWT ≤3.0 mm (odds ratio [OR], 25.13; 95% confidence interval, 2.01-3.14; P = .012) and color Doppler signal (OR, 0.35; 95% confidence interval, 0.14-0.88; P = .026) predicted endoscopic remission and improvement, respectively. Submucosal layer thickness at W6 predicted endoscopic remission (OR, 0.09; P = .018) and improvement (OR, 0.14; P = .02). Furthermore, BWT decreased significantly at W2 for infliximab and tofacitinib and at W6 for vedolizumab. BWT and color Doppler signal predicted endoscopic targets already after 6 weeks of treatment and response was drug specific. IUS allows close monitoring of treatment in UC and is a surrogate marker of endoscopy.

Evaluation of the diagnostic performance of estimated fecal calprotectin and serum intelectin-1 and C-reactive protein solo or in combination for differentiation between patients with query ulcerative colitis and irritable bowel syndrome

ObjectivesEvaluation of the ability of estimated levels of fecal calprotectin (FCP), serum intelectin-1 (ITLN1), and C-reactive protein (CRP) to differentiate between patients with ulcerative colitis (UC) and irritable bowel syndrome (IBS).PatientsThree-hundred forty-two patients were evaluated clinically for diagnostic criteria of UC and IBD and underwent colonoscopic examination and grading according to Mayo endoscopic scores (MES). Colorectal biopsies were taken for microscopic examination. Fecal and blood samples were obtained for ELISA estimation of levels of the studied variate. Patients were grouped according to microscopic examination of the obtained biopsies as UC and IBD groups. Study outcome is the ability of the laboratory variate for prediction of the microscopic diagnosis.ResultsIn UC patients, FCP and serum CRP levels were notably elevated compared to controls and IBS patients. Conversely, UC patients exhibited significantly reduced serum ITLN1 levels in comparison to controls and IBS patients with insignificantly lower levels in samples of IBS patients. Statistical analyses defined high FCP and low serum ITLN1 as the significant predictors for UC diagnosis with high specificity for FCP level > 150 µg/ml and high sensitivity for serum ITLN1 ≤ 30 and ≤ 18 ng/ml to predict colonoscopic and microscopic UC diagnosis, respectively.ConclusionThe combination of high FCP and low serum ITLN1 could accurately predict the colonoscopic and microscopic findings of UC and can differentiate UC from IBS and may spare the need for colonoscopy and biopsy especially for IBS patients.

The oral bacterial microbiota facilitates the stratification for ulcerative colitis patients with oral ulcers

BackgroundClinically, a large part of inflammatory bowel disease (IBD) patients is complicated by oral lesions. Although previous studies proved oral microbial dysbiosis in IBD patients, the bacterial community in the gastrointestinal (GI) tract of those IBD patients combined with oral ulcers has not been profiled yet.MethodsIn this study, we enrolled four groups of subjects, including healthy controls (CON), oral ulcer patients (OU), and ulcerative colitis patients with (UC_OU) and without (UC) oral ulcers. Bio-samples from three GI niches containing salivary, buccal, and fecal samples, were collected for 16S rRNA V3-V4 region sequencing. Bacterial abundance and related bio-functions were compared, and data showed that the fecal microbiota was more potent than salivary and buccal microbes in shaping the host immune system. ~ 22 UC and 10 UC_OU 5-aminosalicylate (5-ASA) routine treated patients were followed-up for six months; according to their treatment response (a decrease in the endoscopic Mayo score), they were further sub-grouped as responding and non-responding patients.ResultsWe found those UC patients complicated with oral ulcers presented weaker treatment response, and three oral bacterial genera, i.e., Fusobacterium, Oribacterium, and Campylobacter, might be connected with treatment responding. Additionally, the salivary microbiome could be an indicator of treatment responding in 5-ASA routine treatment rather than buccal or fecal ones.ConclusionsThe fecal microbiota had a strong effect on the host’s immune indices, while the oral bacterial microbiota could help stratification for ulcerative colitis patients with oral ulcers. Additionally, the oral microbiota had the potential role in reflecting the treatment response of UC patients. Three oral bacteria genera (Fusobacterium, Oribacterium, and Campylobacter) might be involved in UC patients with oral ulcers lacking treatment responses, and monitoring oral microbiota may be meaningful in assessing the therapeutic response in UC patients.

The ulcerative colitis endoscopic index of severity score is superior to reflecting long-term prognosis in ulcerative colitis patients treated with vedolizumab.

The scoring systems commonly used to assess endoscopic disease severity of ulcerative colitis (UC) in clinical research and practice include the Mayo endoscopic score (MES), ulcerative colitis endoscopic severity index (UCEIS), and degree of ulcerative colitis burden of luminal inflammation (DUBLIN). We aimed to assess and compare the predictive efficacy of the MES, DUBLIN score and UCEIS score for prognosis in UC patients treated with vedolizumab (VDZ). Seventy-four UC patients who treated with VDZ from September 2021 to February 2023 were retrospectively enrolled. We used the MES, DUBLIN and UCEIS score to evaluate endoscopic findings. The predictive capability of these 3 scores for surgery or therapeutic escalation was assessed using the receiver operating characteristic curve. The mean MES, DUBLIN and UCEIS score significantly improved from 2.83 ± 0.38, 7.80 ± 1.82 and 6.24 ± 1.51 to 2.07 ± 0.88, 5.57 ± 2.68, and 3.72 ± 2.12, respectively (P < .001). Lower pre-therapeutic UCEIS scores were associated with favorable short-term outcomes. Importantly, the post-therapeutic UCEIS score showed the best predictive capability with an area under curve of 0.871 (95% confidence interval: 0.767-0.976), specificity of 0.654, sensitivity of 0.900, and cutoff value of 3.5. A UCEIS score of ≥ 4 after treatment was correlated with surgical operation or treatment escalation. The UCEIS score is superior to the MES and DUBLIN score in reflecting short-term outcomes and long-term prognosis in UC patients treated with VDZ, and clinical remission could be defined as a UCEIS score ≤ 3.

Using Computer Vision to Improve Endoscopic Disease Quantification in Therapeutic Clinical Trials of Ulcerative Colitis

Endoscopic assessment of ulcerative colitis (UC) typically reports only the maximum severity observed. Computer vision methods may better quantify mucosal injury detail, which varies among patients. Endoscopic video from the UNIFI clinical trial (A Study to Evaluate the Safety and Efficacy of Ustekinumab Induction and Maintenance Therapy in Participants With Moderately to Severely Active Ulcerative Colitis) comparing ustekinumab and placebo for UC were processed in a computer vision analysis that spatially mapped Mayo Endoscopic Score (MES) to generate the Cumulative Disease Score (CDS). CDS was compared with the MES for differentiating ustekinumab vs placebo treatment response and agreement with symptomatic remission at week 44. Statistical power, effect, and estimated sample sizes for detecting endoscopic differences between treatments were calculated using both CDS and MES measures. Endoscopic video from a separate phase 2 clinical trial replication cohort was performed for validation of CDS performance. Among 748 induction and 348 maintenance patients, CDS was lower in ustekinumab vs placebo users at week 8 (141.9 vs 184.3; P < .0001) and week 44 (78.2 vs 151.5; P < .0001). CDS was correlated with the MES (P < .0001) and all clinical components of the partial Mayo score (P < .0001). Stratification by pretreatment CDS revealed ustekinumab was more effective than placebo (P < .0001) with increasing effect in severe vs mild disease (-85.0 vs -55.4; P < .0001). Compared with the MES, CDS was more sensitive to change, requiring 50% fewer participants to demonstrate endoscopic differences between ustekinumab and placebo (Hedges' g= 0.743 vs 0.460). CDS performance in the JAK-UC replication cohort was similar to UNIFI. As an automated and quantitative measure of global endoscopic disease severity, the CDS offers artificial intelligence enhancement of traditional MES capability to better evaluate UC in clinical trials and potentially practice.

Effectiveness of vedolizumab and ustekinumab as second biologic agent in achieving target outcomes in tumor necrosis factor antagonists experienced patients with inflammatory bowel disease (enroll-ex study).

Background: About a third of patients with inflammatory bowel disease (IBD) do not respond to anti-tumor necrosis factor (anti-TNF) therapy. In our study, we evaluated the effectiveness of vedolizumab and ustekinumab in achieving clinical and endoscopic outcomes in anti-TNF-experienced patients with IBD. Methods: We conducted a retrospective cohort study. Electronic medical records of patients with moderate to severe IBD, who were previously received anti-TNF therapies, were reviewed and evaluated retrospectively in a gastroenterology center. Outcomes of patients treated with ustekinumab or vedolizumab after failing one anti-TNF agent were evaluated. The primary outcomes were the percentage of hospitalization, surgery, mucosal healing and steroid-free remission. Mucosal healing was defined as a Mayo endoscopic score of 0 or 1 in ulcerative colitis (UC) and an SES-CD score of less than 3 in Crohn's disease (CD). Outcomes were quantified using descriptive analysis. Results: A total of 207 (130 CD: 77 UC) patients with IBD who had previously received one anti-TNF agent were included in the study. Of the total cohort, 62 (30.0%) patients were receiving vedolizumab, and 145 (70.0%) patients were on ustekinumab. 101 (77.6%) patients with CD who failed one anti-TNF therapy were on ustekinumab. Of these patients, 26 (19.7%) patients were hospitalized, and 12 (11.9%) patients had IBD-related surgery. 16 (16.1%) patients had at least one corticosteroid course. 60 (59.0%) patients with CD on ustekinumab achieved mucosal healing. 29 (22.3%) patients with CD who failed one anti-TNF therapy were receiving vedolizumab. Of those, 7 (25%) patients were hospitalized, and 11 (37.9%) patients had IBD-related surgery. 15 (51.0%) patients achieved mucosal healing. 44 (57.1%) patients with UC who failed one anti-TNF therapy were on ustekinumab. Of these 6 (14.1%) patients were hospitalized, 3 (7.0%) patients had IBD-related surgery and 13 (30%) patients had at least 1 corticosteroid course. 25 (57.0%) patients achieved mucosal healing. 33 (42.8%) patients with UC who failed one anti-TNF therapy were receiving vedolizumab. Of those, 6 (18.6%) patients were hospitalized, and 16 (49.6%) patients had at least 1 corticosteroid course. 17 (53.2%) patients achieved mucosal healing. Conclusion: Ustekinumab and vedolizumab were both effective in achieving clinical outcomes in patients with IBD after failing an anti-TNF agent. However, patients receiving ustekinumab had numerically higher percentages of reaching target outcomes than patients receiving vedolizumab. A prospective head-to-head trial is warranted to confirm these findings.

A systematic review and meta-analysis of artificial intelligence-diagnosed endoscopic remission in ulcerative colitis

Endoscopic remission is an important therapeutic goal in ulcerative colitis (UC). The Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and Mayo Endoscopic Score (MES) are the commonly used endoscopic scoring criteria. This systematic review and meta-analysis aimed to evaluate the accuracy of artificial intelligence (AI) in diagnosing endoscopic remission in UC. We also performed a meta-analysis of each of the four endoscopic remission criteria (UCEIS= 0, MES= 0, UCEIS= <1, MES= <1). Eighteen studies involving 13,687 patients were included. The combined sensitivity and specificity of AI for diagnosing endoscopic remission in UC was 87% (95% confidence interval [CI]:81-92%) and 92% (95% CI: 89-94%), respectively. The area under the curve (AUC) was 0.96 (95% CI: 0.94-0.97). The results showed that the AI model performed well regardless of which criteria were used to define endoscopic remission of UC.

Histologic Inflammation can Predict Future Clinical Relapse in Ulcerative Colitis Patients in Endoscopic Remission.

In ulcerative colitis (UC), endoscopic improvement, defined as a Mayo Endoscopic Score (MES) of 0 or 1, is a target of treatment. The aim of our study was to evaluate the risk of clinical relapse between patients with an MES of 0 or 1 and determine if histologic activity using the Robarts Histopathologic Index (RHI) was predictive of clinical relapse. UC patients with an MES score of 0 or 1, no prior colectomy, and at least 1 year of outpatient follow-up after colonoscopy were included. Demographic, clinical characteristics, and clinical relapse were retrospectively collected. Biopsy specimens were read by a gastrointestinal pathologist. Primary outcome was defined as a composite of relapse requiring change in medical therapy, new steroid use, UC-related hospitalization, and/or colectomy. Four hundred and forty-five UC patients were identified. Ninety-five percent of patients with MES 0 were in histologic remission by the RHI whereas only 35% of patients with MES 1 were in histologic remission. Twenty-six percent of patients experienced a clinical relapse; patients with MES 1 or RHI > 3 were significantly more likely to relapse (P < .01) compared to patients with MES 0 or RHI ≤ 3. When patients were stratified into 4 groups (MES 0, RHI ≤ 3; MES 0, RHI > 3; MES 1, RHI ≤ 3; MES 1, RHI > 3) and adjusted for age and sex, RHI > 3 was predictive of relapse (P = .008). UC patients with endoscopic improvement have a high rate of clinical relapse over time. Histologic activity is a predictor of clinical relapse.

Clinical significance of the C-reactive protein-to-bilirubin ratio in patients with ulcerative colitis.

Ulcerative colitis (UC) is a chronic relapsing remitting disease of the colon. Appropriate monitoring of the disease status is necessary for patients to adopt optimal therapy and obtain a better prognosis. Finding an ideal non-invasive biomarker, which is suitable for long-term monitoring in clinical settings will bring a significant benefit to the individualized management of patients with UC. The aim of this study is to determine the clinical significance of a novel optimizing serological biomarker by integrating C-reactive protein (CRP) and bilirubin levels in monitoring disease activity. A total of 182 patients with UC were retrospectively enrolled. Clinical characteristics and laboratory parameters of the subjects were retrieved from the electronic medical record database of our hospital. The CRP-to-bilirubin ratio (CBR) was computed for clinical activity of UC defined by the partial Mayo score and endoscopic activity by the Mayo endoscopic score (MES). CBR was significantly elevated in patients with UC than that in healthy controls. Patients with clinically or endoscopically active UC showed evidently higher CBR levels compared to those with inactive disease, even in a subset of patients with normal CRP levels. Receiver operating characteristic (ROC) analysis showed that the area under the curve (AUC) of CBR was higher than that of CRP or bilirubin alone for determining clinical remission and endoscopic mucosal improvement. Furthermore, CBR levels were significantly decreased when patients achieved mucosal improvement compared with when they had active endoscopic inflammation. CBR could be useful to reflect disease activity in patients with UC.

Factors Associated With Response to Rescue Therapy in Acute Severe Ulcerative Colitis.

Acute severe ulcerative colitis (ASUC) is a medical emergency for which colectomy is required in patients who do not respond to rescue therapy. While previous studies have predominantly focused on predicting outcome to first-line corticosteroid therapy, there is a need to understand the factors associated with response to rescue therapies in order to improve clinical outcomes. We reviewed the evidence regarding factors associated with response to rescue therapy in adults with ASUC and identified future directions for research. A systematic search of the literature was conducted, and 2 reviewers independently assessed studies for inclusion. Of 3509 records screened, 101 completed studies were eligible for inclusion. We identified 42 clinical, hematological, biochemical, endoscopic, or pharmacological factors associated with response to rescue therapy. Older age (≥50 years), thiopurine experience, and cytomegalovirus or Clostridioides difficile infection were associated with a higher risk of nonresponse to rescue therapy. Biochemical factors associated with poorer response included an elevated C-reactive protein (CRP) ≥30mg/L on admission, hypoalbuminemia and an elevated ratio of CRP to albumin. Severe endoscopic findings, including a Mayo endoscopic score of 3 or Ulcerative Colitis Endoscopic Index of Severity ≥5, portended poorer outcomes. The role of fecal calprotectin and therapeutic value of measuring infliximab drug levels in ASUC remain to be defined. Response to rescue therapy can be predicted by several specific factors, which would aid clinical decision-making. Existing and emerging factors should be integrated within predictive and prognostic models to help improve clinical outcomes.

Systemic immune-inflammation index as a potential biomarker to monitor ulcerative colitis

Objective The treat-to-target strategy is recommended by Selecting Therapeutic Targets in Inflammatory Bowel Disease II (STRIDE-II) for treating ulcerative colitis (UC), and monitoring remission status is crucial during this management. The systemic immune-inflammation index (SII), defined as platelet * neutrophil/lymphocyte, is a complete blood count-based index reflecting the balance of immune and inflammatory status. This study aims to investigate the feasibility of SII for diagnosing UC and monitoring UC disease activity. Methods This study retrospectively analyzed patients with UC and controls. Relationships between SII and Mayo clinical score, Mayo Endoscopic Score (MES), and Nancy Histological Index (NHI) were evaluated. Results 167 patients with UC and 106 controls were included. SII significantly increased in patients with UC and was closely correlated with the Mayo clinical score, MES, and NHI. SII diagnosed UC with a cut-off value of 619.1 × 109/L (area under the curve = 0.861, p < 0.0001, sensitivity 79.64%, specificity 77.36%), evaluated clinical remission status with a cut-off value of 1068 × 109/L (area under the curve = 0.691, p < 0.05, sensitivity 55.71%, specificity 81.48%), endoscopic improvement with a cut-off value of 981.3 × 109/L (area under the curve = 0.819, p < 0.0001, sensitivity 65.22%, specificity 89.66%), and histological healing with a cut-off value of 689.3 × 109/L (area under the curve = 0.898, p < 0.0001, sensitivity 88.89%, specificity 95.83%). Conclusion SII is a potential biomarker for diagnosing UC and monitoring UC disease severity, especially in evaluating mucosal and histological healing during the long-term management in treat-to-target strategy. However, further research is needed to confirm its usefulness and optimize its clinical application.

Alternative Endoscopy Reading Paradigms Determine Score Reliability and Effect Size in Ulcerative Colitis.

Central reading of endoscopy is advocated by regulatory agencies for clinical trials in ulcerative colitis [UC]. It is uncertain whether the local/site reader should be included in the reading paradigm. We explore whether using locally- and centrally-determined endoscopic Mayo subscores [eMS] provide a reliable final assessment and whether the paradigm used has an impact on effect size. eMS data from the TURANDOT [NCT01620255] study were used to retrospectively examine seven different reading paradigms (using the scores of local readers [LR], first central readers [CR1], second central readers [CR2], and various consensus reads [ConCR]) by assessing inter-rater reliabilities and their impact on the key study endpoint, endoscopic improvement. More than 40% of eMS scores between two trained central readers were discordant. Central readers had wide variability in scorings at baseline (intraclass correlation coefficient [ICC] of 0.475 [0.339, 0.610] for CR1 vs CR2). Centrally-read scores had variable concordance with LR (LR vs CR1 ICC 0.682 [0.575, 0.788], and LR vs CR2 ICC 0.526 [0.399, 0.653]). Reading paradigms with LR and CR which included a consensus, enhanced ICC estimates to >0.8. At Week 12, without the consensus reads, the CR1 vs CR2 ICC estimates were 0.775 [0.710, 0.841], and with consensus reads the ICC estimates were >0.9. Consensus-based approaches were most favourable to detect a treatment difference. The ICC between the eMS of two trained and experienced central readers is unexpectedly low, which reinforces that currently used central reading processes are still associated with several weaknesses.