Introduction

Ulcerative colitis is a multifactorial immune-mediated inflammatory disease generally characterized by chronic recurrent mucosal inflammation and severe clinical symptoms which led to poor quality of life for patients. The methods for monitoring and follow-up of ulcerative colitis now are based on a combination of clinical and endoscopic findings but rarely involved serological and histological evaluation methods.

Aims & Methods

Aims: To investigate the consistency and correlation of endoscopic and histological scoring systems in assessing the disease activity of UC patients. Additionally, we explored the serological markers of endoscopic or histological activity of UC to achieve more accurate evaluation of disease activity.
Methods: A retrospective study was conducted in UC patients admitted from January 2014 to January 2020 at Renji Hospital, School of Medicine, Shanghai Jiao Tong University. The disease activity was examined endoscopically and histologically by Mayo Endoscopic Subscore and Simplified Geboes Score respectively. Blood samples were collected around the time of endoscopy.

Results

Altogether 143 UC patients were enrolled. Basal plasmacytosis is frequently seen in endoscopically active UC (OR=11.19， 95% CI: 4.80-26.09, P＜0.001). Approximately half of the patients ( 53.7% ) who achieved endoscopic remission still had inflammatory activity histologically. Kappa consistency test showed that the agreement between Mayo Endoscopic Subscore and Simplified Geboes Score for assessing disease activity was moderate ( κ = 0.4, P＜0.001). By Spearman correlation coefficient analysis, a moderate correlation between the two scoring systems was identified ( rs =0.533，P＜0.001). The histologically active group had lower hemoglobin (t=3.025, P＜0.01) and higher percent (t=-2.113, P＜0.05) neutrophils than the remission group.Blood biomarkers revealed a negative link to the Mayo score of UC patients, which includes large platelet ratio (ρ=-0.170, P<0.0001), hemoglobin (ρ=-0.275, P<0.0001) and albumin (ρ=-0.452, P<0.0001),while white blood cell count (ρ=0.205, P<0.01), neutrophil count (ρ=0.259, P<0.01), percentage of neutrophils (ρ=0.224, P<0.01), erythrocyte sedimentation rate (ρ=0.185, P< 0.05) and C-reactive protein (ρ=0.21, P<0.05) revealed a positive correlation.

Conclusion

In UC patients, the assessments of disease activities endoscopically and histologically are moderately correlated and are generally consistent. Basal plasmacytosis is predictive of endoscopically active UC. Decreased hemoglobin and elevated percentage of neutrophile granulocyte suggest endoscopic and histological activity.

Introduction

Intestinal ultrasound (IUS) is increasingly used as a point-of-care tool for patients with ulcerative colitis (UC). Non-invasive monitoring is essential for managing disease progression and therapeutic intervention in pediatric UC patients. The Milan Ultrasound criteria (MUC), ulcerative colitis intestinal ultrasound score (UC-IUS), and Civitelli score show promise as real-time disease activity assessment tools, potentially reducing the need for invasive procedures like endoscopy.

Aims & Methods

A prospective cohort of 34 pediatric UC patients underwent IUS and colonoscopy to assess disease activity using MUC, UCIUS, and Civitelli scores. Assessments were conducted within a 7-day interval, with no therapeutic changes between procedures. Diagnostic accuracy was determined using receiver operating characteristic (ROC) curves, with endoscopy as the reference
standard, and histological parameters assessed in a subset of patients using the Nancy Index.

Results

The study included 34 pediatric UC patients (median age: 14.7 years; 65% male) with varied disease severities and durations (median duration: 12.6 months; median PUCAI: 30; median fecal calprotectin: 1041 μg/g). Bowel wall thickness (BWT) correlated significantly with all IUS scores; however, no correlation was observed between BWT and baseline Mayo endoscopic disease activity. The area under the curve (AUC) was 0.528 (CI:0.348–0.704) for MUC, 0.602 (CI: 0.418–0.768) for UC-IUS, and 0.572 (CI: 0.388–0.742) for the Civitelli score, indicating moderate diagnostic accuracy. While differences among scores were not statistically significant, UC-IUS demonstrated the highest accuracy. In 16 patients with available Nancy Index data, the AUC values were 0.500 for MUC, 0.579 for Civitelli, and 0.563 for UC-IUS, further supporting moderate accuracy (Table 1).

Score	AUC (vs Endoscopic Findings)	AUC (vs Histological Parameters)
MUC	0. 528	0.500
UC-IUS	0.602	0.563
Civitelli	0.572	0.579

Table 1. Ultrasound characteristics and disease activity scores for the pediatric patients with UC.

Conclusion

Both MUC, Civitelli, and UC-IUS scores provide moderate diagnostic accuracy in assessing pediatric UC, though potentially less effective than in adult populations. UC-IUS, with its emphasis on vascularization, haustration and wall thickness, may offer enhanced sensitivity in pediatric patients. Lowering the cut-off for bowel wall thickness may improve accuracy in children, given their thinner, yet highly vascularized bowel walls, particularly in early disease stages.

References

1. van Wassenaer EA, van Rijn RR, Zwetsloot SLM, et al. Intestinal Ultrasound to Assess Ulcerative Colitis Disease Activity in Children: External Validation and Comparison of 2 Intestinal Ultrasound Activity Indices. Inflamm Bowel Dis. 2023;29:1217-1222.
2. Allocca M, Dell'Avalle C, Craviotto V, et al. Predictive value of Milan ultrasound criteria in ulcerative colitis: A prospective observational cohort study. United European Gastroenterol J. 2022;10:190-197

Introduction

Absence of neutrophils is the minimum standard to consider histological remission of ulcerative colitis (UC).1 The PICaSSO Histological Remission Index (PHRI) is a new simple index for UC disease assessment based only on the detection of neutrophils.2 We evaluate PHRI’s correlation with endoscopy and its prognostic value compared to other established indices.

Aims & Methods

Consecutive patients with UC underwent colonoscopy at 2 referral centers (Birmingham, UK and Milan, Italy) and were followed up for 2 years. Correlation between histology (PHRI, Nancy [NHI] and Robarts [RHI]) and endoscopy (Mayo Endoscopic Score [MES]; Ulcerative Colitis Severity Endoscopic Index of Severity [UCEIS], and PICaSSO score) was calculated as Spearman coefficients.
Cutoffs for remission were: MES = 0, UCEIS ≤ 1, PICaSSO ≤ 3, PHRI = 0, NHI ≤ 1, RHI ≤ 3 with no neutrophils in the lamina propria or epithelium.
Negative clinical outcomes were defined as: UC-related hospitalization, colectomy, use of steroids, increase in dose in UC therapy or medication change due to uncontrolled inflammation.
The diagnostic performance of endoscopy was assessed with ROC curves and outcome stratification with Kaplan-Meier curves and Cox proportional hazard model.

Results

192 patients with UC were enrolled, representing all grades of endoscopic severity. The correlation between histology and endoscopy did not differ significantly when using PHRI instead of NHI or RHI (Table 1). In particular, PHRI’s correlation with MES, UCEIS, and PICaSSO was 0.75, 0.72, and 0.69, respectively.

Table 1. Spearman correlation coefficients

Endoscopic score	Robarts	Nancy	PHRI
MES	0.779	0.730	0.745
UCEIS	0.769	0.725	0.718
PICaSSO	0.736	0.694	0.694

Analyzing the diagnostic performance of endoscopy scores to detect histological remission according to the different definitions we found no difference among endoscopy scores. Instead, all endoscopy measures captured with greater precision PHRI and NHI remission, as compared with RHI remission (p<0.005 for PHRI vs RHI, and NHI vs RHI). The areas under the ROC curve for PHRI were 0.91 (95% CI 0.864 – 0.947), 0.91 (95% CI 0.866 – 0.947), and 0.88 (0.828 – 0.926) for MES, UCEIS, and PICaSSO, respectively; for NHI 0.89 (95% CI 0.837 - 0.934), 0.89 (95% CI 0.842 - 0.938) and 0.87 (95% CI 0.814 - 0.921); and for RHI 0.63 (95% CI 0.553 - 0.711), 0.66 (95% CI 0.582 - 0.736), and 0.67 (95% CI 0.591 - 0.744).
We then stratified the risk of suffering any negative disease outcome, a proxy for flare, in the two years following endoscopy, in patients in remission and in activity according to the different histological definitions. The hazard ratios were statistically similar and numerically higher for PHRI (2.87 for PHRI, 2.75 for RHI, and 2.71 for NHI, respectively) proving that a neutrophil-only assessment predicts risk of flare at least as well as established scores.

Conclusion

PHRI correlates with endoscopy and stratifies the risk of relapse similarly to RHI and NHI. Neutrophil-only assessment of UC is a simple yet viable alternative to established histological scores.

References

1. Magro F, Doherty G, Peyrin-Biroulet L, et al. ECCO Position Paper: Harmonization of the Approach to Ulcerative Colitis Histopathology. J Crohns Colitis 2020;14:1503-1511.
2. Gui X, Bazarova A, Del Amor R, et al. PICaSSO Histologic Remission Index (PHRI) in ulcerative colitis: development of a novel simplified histological score for monitoring mucosal healing and predicting clinical outcomes and its applicability in an artificial intelligence system. Gut 2022;71:889-898.

Disclosure

OMN has served as a speaker for Janssen, Ferring, Takeda, Pfizer, Fresenius Kabi
FF ha received consulting fees from Janssen; speaker’s fees from Pfizer and Janssen
SD has served as a speaker, consultant and advisory board member for Schering Plough, Abbott (AbbVie) Laboratories, Merck and Co, UCB Pharma, Ferring, Cellerix, Millenium Takeda, Nycomed, Pharmacosmos, Actelion, Alfa Wasserman, Genentech, Grunenthal, Pfizer, AstraZeneca, Novo Nordisk, Vifor and Johnson and Johnson.
AA has received consulting fees from: AbbVie, Amgen, Arena, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Eli-Lilly, Ferring, Galapagos, Gilead, Janssen, MSD, Pfizer, Protagonist Therapeutics, Roche, Samsung Bioepis, Sandoz, Takeda; speaker’s fees from: AbbVie, Amgen, Arena, Biogen, Bristol-Myers Squibb, Eli-Lilly, Ferring, Galapagos, Gilead, Janssen, MSD, Novartis, Pfizer, Roche, Samsung Bioepis, Sandoz, Takeda; research support from: MSD, Takeda, Pfizer, Biogen.
SG has served as consultant, Steering committee member, Advisory Board Member and Drug Monitoring committee member for Janssen, Pfizer, Takeda, Abbvie, BMS, Gilead, Galapagos, Celltrion, Eli Lilly, Ferring.
MI has received research grants and equipment loans from Pentax USA, Olympus, and Fujifilm; is partially funded by NIHR Birmingham Biomedical Research Centre at the University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham.

The remaining authors declare no conflict of interest.

Introduction

Fecal immunochemical test (FIT), widely used in colorectal cancer screening, has emerged as a potential biomarker of endoscopic activity in inflammatory bowel disease (IBD). Compared to fecal calprotectin, FIT offers greater standardization, automation and availability, with simpler handling and potentially better adherence. Its implementation could streamline non-invasive monitoring, but its diagnostic accuracy in IBD remains unclear. We therefore conducted a systematic review and meta-analysis to evaluate its performance.

Aims & Methods

Selection of studies: assessing the accuracy of FIT to estimate endoscopic activity in IBD patients. Search strategy: electronic bibliographical searches. Data synthesis: meta-analyses of the FIT were performed combining the sensitivity (Se), specificity (Sp), likelihood ratios (LRs), and area under de curve (AUC) values of summary receiver operating characteristic (ROC) curves of the individual studies. Heterogeneity among the studies was assessed by the I-squared (I²) statistic.

Results

Eighteen studies (table 1) met the inclusion criteria: 12 focused on ulcerative colitis (UC), 4 on both UC and Crohn’s disease (CD), and 2 on CD alone. Twelve studies employed the standard cut-off for FIT provided by the manufacturer or used the same cut-off as for colorectal cancer screening (usually considered the common threshold), while 6 studies estimated their optimal cut-off values. When we considered all studies (including 1,812 patients and 2,137 assessments), the accuracy of FIT for the diagnosis of endoscopic activity was (pooled values): Se: 0.66, Sp: 0.83, LR+: 4.96, and LR-: 0.38, respectively, with an AUC of 0.86. Significant heterogeneity was found among the Se (I² 89%) and Sp (I² 86%) of different studies. Most of the available studies were based exclusively on patients with UC (including 1,554 patients and 1,904 assessments), so we performed a subgroup analysis including only this type of IBD, finding a pooled Se, Sp, LR+ and LR- of 0.69, 0.82, 5.35 and 0.31 respectively, with an AUC of 0.88. On the other hand, in patients with CD (327 patients, 302 assessments), the corresponding values were 0.55, 0.85, 3.2 and 0.58, with an AUC of 0.73. ROC curve analysis showed that FIT had a higher diagnostic performance in UC patients.

Table 1. Studies evaluating the accuracy of fecal immunochemical test (FIT) for estimating endoscopic activity in inflammatory bowel disease.
Author	Publication year	FIT cut-off	Endoscopic activity definition	Number of patients	Number of tests	Sensitivity	Specificity	TP	FP	FN	TN
Nakarai Takashima Ryu Inokuchi Nakarai Ma Shi Hiraoka Nakarai Iwamoto Hiraoka Ryu Mak Yen Kim Hijos-Mallada Latorre Takahara	2013 2015 2016 2016 2016 2017 2017 2018 2018 2018 2019 2019 2020 2020 2020 2021 2023 2024	Standard (>100 ng/mL) Standard (>100 ng/mL) Standard (>100 ng/mL) Optimal (>52 ng/mL) Standard (>100 ng/mL) Standard (>100 ng/mL) Standard (>50 ng/mL) Standard (>100 ng/mL) Standard (>100 ng/mL) Optimal (>13 ng/mL) Optimal (>78 ng/mL) Standard (>100 ng/mL) Optimal (>26 ng/mL) Optimal (>43 ng/mL) Optimal (>60 ng/mL) Standard (>5.1 μg/g) Standard (>100 ng/mL) Standard (>100 ng/mL)	MES >1 MES >1 MES >1 SES-CD >0 MES >0 UCEIS >3, SES-CD >0 MES >1 MES >0 MES >1 SES-CD >0 MES >1 MES >0 MES >1, SES-CD >3 MES >1 MES >1 MES >0, SES-CD >2 MES >0, SES-CD >0 MES >0	UC 152 UC 92 UC 63 CD 71 UC 194 UC 40 & CD 40 UC 140 UC 84 UC 113 CD 69 UC 152 UC 128 UC 62 & CD 51 UC 50 UC 127 UC 54 & CD 52 UC 40 & CD 44 UC 63	310 105 82 71 194 80 140 220 113 69 152 174 66 50 127 106 84 63	87% 68% 45% 48% 76% 57% 68% 63% 78% 71% 96% 37% 69% 100% 52% 59% 50% 93%	60% 81% 93% 96% 94% 90% 72% 95% 87% 73% 79% 98% 87% 81% 94% 87% 79% 100%	121 28 10 23 76 17 28 76 7 43 25 46 18 19 15 25 20 52	68 12 4 1 6 5 28 5 14 2 26 1 5 6 6 8 9 0	18 13 12 25 24 13 13 45 2 18 1 77 8 0 14 17 20 4	103 52 56 22 88 45 71 94 90 6 100 50 35 25 92 56 35 7
TP: True positives; FP: False positives; FN: False negatives; TN: True negatives; UC: Ulcerative colitis; CD: Crohn’s disease; MES: Mayo endoscopic score; SES-CD: Simple endoscopic score for Crohn's disease; UCEIS: Ulcerative colitis endoscopic index of severity.

Conclusion

FIT demonstrates moderate-to-high diagnostic accuracy for detecting endoscopic activity in IBD, particularly in UC. Therefore, FIT may represent a promising non-invasive tool for assessing IBD disease activity. However, significant heterogeneity among studies underscores the need for further research to optimize cut-off values and define the role of FIT in routine IBD monitoring.

Introduction

Recent delineations by experts from the IOIBD organization have emphasized disease clearance as a comprehensive outcome in ulcerative colitis (UC), incorporating concurrent clinical, endoscopic, and histologic remission [1]. However, real-world data regarding disease clearance following biologic therapy remain scarce.

Aims & Methods

We conducted a retrospective observational cohort study at our academic tertiary care institution in Padova, comprising 119 patients receiving treatment with biologic drugs, totaling 142 treatments. Patient data encompassed demographics, disease phenotype, treatment history, and concomitant medications. Categorical variables underwent comparison using the Chi-Squared exact test, Mann-Whitney U test, and McNemar test, while continuous variables were assessed via either the Student's t-test or the Wilcoxon test, based on their distribution. Propensity score matching was employed to analyze outcomes between patients administered Vedolizumab and Infliximab. Furthermore, conditional logistic regression was utilized to estimate the odds of outcomes. All data analyses were conducted using the JASP 0.18.3 statistical software package, DATAtab: Online Statistics Calculator (DATAtab e.U. Graz, Austria), and XLSTAT 2024 (Assinsoft, Paris, France).

Results

In total, 142 treatments were administered to 119 adult patients diagnosed with UC. Of these patients, 67 (47.1%) presented with pancolitis, 63 (44.4%) had left-sided colitis, and 12 (8.4%) had rectal involvement at the onset of biologic therapy. At initiation, 75 (52.8%) were biologic therapy naïve. The median duration of biologic therapy was 48 months (IQR 35-71). Following Infliximab therapy, disease clearance was achieved by 9 out of 43 patients (20.9%), by 4 out of 47 patients (8.5%) with Vedolizumab, 4 out of 25 patients (16.0%) with Adalimumab, 1 out of 7 patients (14.3%) with Ustekinumab, 4 out of 15 patients (26.7%) with Golimumab, and 1 out of 5 patients (20.0%) with Tofacitinib. Upon applying propensity score matching to the cohorts treated with Infliximab and Vedolizumab, Vedolizumab demonstrated an odds ratio of 0.26 (95% CI 0.04 - 1.56, p = 0.139) compared to Infliximab. Additionally, the log-rank test showed no significant difference in the time to event occurrence among various biologic therapies (p = 0.41).

Conclusion

Attaining disease clearance is an attainable goal for UC patients undergoing biologic therapy. Future data will shed light on whether specific medications facilitate reaching this target more effectively. Continued research endeavors are essential to validate and enhance these findings.

References

1. D’Amico, F.; Magro, F.; Siegmund, B.; Kobayashi, T.; Kotze, P.G.; Solitano, V.; Caron, B.; Al Awadhi, S.; Hart, A.; Jairath, V.; et al. Disease Clearance as a New Outcome in Ulcerative Colitis: A Systematic Review and Expert Consensus. Inflammatory Bowel Diseases 2023, izad159, doi:10.1093/ibd/izad159.