scholarly journals ECCO Position Paper: Harmonization of the Approach to Ulcerative Colitis Histopathology

2020 ◽  
Vol 14 (11) ◽  
pp. 1503-1511 ◽  
Author(s):  
Fernando Magro ◽  
Glen Doherty ◽  
Laurent Peyrin-Biroulet ◽  
Magali Svrcek ◽  
Paula Borralho ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Remission ◽  
Scoring Systems ◽  
Processing Technique ◽  
Histological Changes ◽  
Minimum Requirement ◽  
Histological Activity ◽  
Histological Remission ◽  
Definition Of ◽  
Consensus Expert

Abstract Currently, the main targets of drug therapy for ulcerative colitis [UC] are endoscopic and clinical remission. However, there is active discussion about the additional advantages of including histological remission as a target. Accumulating evidence indicates that microscopic activity persists in endoscopically quiescent UC, that histological changes may lag behind clinical remission after treatment, and that absence of histological activity predicts lower rates of relapse, hospitalization, surgery and subsequent neoplasia. Obtaining useful information from mucosal biopsies in this setting depends on accurate and consistent evaluation of histological features. However, there is no standardization of biopsy procedures, histological sample processing technique or histological scoring systems, and there is no agreement on the definitions of histological remission, response or activity. Accordingly, a consensus expert panel convened by the European Crohn’s and Colitis Organisation [ECCO] reviewed the literature and agreed a number of position statements regarding harmonization of UC histopathology. The objective was to provide evidence-based guidance for the standardization and harmonization of procedures, definitions and scoring systems for histology in UC, and to reach expert consensus where possible. We propose the absence of intraepithelial neutrophils, erosion and ulceration as a minimum requirement for the definition of histological remission. For randomized control trials we recommend the use of the Robarts histopathology index [RHI] or the Nancy index [NI]. For observational studies or in clinical practice we recommend the use of the NI. To predict the risk of future neoplasia in UC, cumulative histological scores over time are more useful than single scores.

scholarly journals P545 Calprotectin at week 12 is a predictor for histological remission in ulcerative colitis patients treated with Vedolizumab

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S515-S516
Author(s):  
D Rubstov ◽  
P Kakkadasam Ramaswamy ◽  
J Edwards ◽  
D Shukla ◽  
L Willmann ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Remission ◽  
Real World Setting ◽  
Endoscopic Remission ◽  
Endoscopic Score ◽  
Histological Activity ◽  
Maintenance Of Remission ◽  
Histological Remission ◽  
Endoscopic Assessment

Abstract Background Vedolizumab (VDZ) is a gut-specific α4β7 integrin antagonist that has demonstrated efficacy for induction and maintenance of remission in moderate to severe ulcerative colitis (UC). The aim of this study was to assess the rates of histological remission (HR) in a real-world setting and to identify predictors for histological remission. Methods Retrospective cohort study of all UC patients (≥18 years) initiated on VDZ from 2016 to 2020 was completed. Clinical, biochemical, endoscopic and histologic data were collected. All patients received standard induction therapy with VDZ 300 mg IV at Weeks 0, 2, and 6 and maintained on an 8-weekly regimen. Dose was escalated to a every 4-weekly regimen as per physician’s discretion. A 52-week follow-up was completed on all patients. Endoscopic assessment was carried out between 24 and 52 weeks after commencing VDZ. Histological activity was graded as per Nancy index and histological remission was defined as Nancy grade 0. Endoscopic remission was defined as Mayo endoscopic score = 0. Clinical remission was defined as SCCAI ≤ 5. Results A total of 51 patients [55% female, median age 48 years (IQR 35–60)] were included. 16/51 (34%) were anti-TNF exposed. In 30/51 (59%) patients VDZ was combined with steroids at induction and by week 12 steroids were completely tapered in 14/30 (46.7%) patients. At weeks 12, 24 and 52, 89.6%, 87% and 97.5% of patients, respectively, were in clinical remission. 19/37 (51.3%) patients were in endoscopic remission at end of follow up. Median Nancy score prior to commencing VDZ was 3 (IQR: 2–4) and the median Nancy score at end of follow up was 1 (IQR: 0–2). 19/37 (51.3%) patients achieved HR; 3 patients who were in HR at the time of commencement of VDZ remained in HR at the end of follow up. Median baseline faeces calprotectin (FC) was 320 mcg/g (IQR 45–1000) and was similar in patients who achieved HR and those who did not. Median FC at 12 weeks was 155 mcg/g (45–720) and was significantly lower in patients who achieved HR when compared to patients who did not achieve histological remission (45 vs 420, p 0.028). FC at week 12 predicted histological remission (AUC =0.8667). FC ≥ 200mcg/g at week 12 predicted failure to achieve HR with sensitivity 70%, specificity 100%, PPV 100%, NPV 75%, accuracy 84%. Conclusion Vedolizumab is effective in achieving histological remission and FC ≥ 200 mcg/g at week 12 accurately predicts failure to achieve HR in patients treated with VDZ.

scholarly journals Can fecal calprotectin accurately identify histological activity of ulcerative colitis? A meta-analysis

2021 ◽  
Vol 14 ◽  
pp. 175628482199474
Author(s):  
Xiaoqi Ye ◽  
Ying Wang ◽  
Harry H. X. Wang ◽  
Rui Feng ◽  
Ziyin Ye ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Meta Analysis ◽  
Area Under The Curve ◽  
Fecal Calprotectin ◽  
Secondary Outcome ◽  
Histological Response ◽  
Summary Receiver Operating Characteristic ◽  
Histological Activity ◽  
Histological Remission ◽  
Sensitivity Specificity

Background and Aims: Elevated fecal calprotectin (FC) levels have been reported to correlate with histological activity in patients with ulcerative colitis (UC). However, the accuracy of FC for evaluating histological activity of UC remains to be determined. The aim of this study was to determine the accuracy of FC for evaluating histological activity of UC, based on updated definitions. Methods: Related studies were retrieved from the PubMed, Web of Science, Embase, and Cochrane databases. Adult participants diagnosed with UC were included when sufficient data could be extracted to calculate the accuracy of FC for evaluating histological activity. The primary outcome was histological response, and the secondary outcome was histological remission, defined according to a recently updated position paper of European Crohn’s and Colitis Organization. Statistics were pooled using bivariate mixed-effects models. The area under the curve was estimated by summary receiver-operating characteristic curves. Results: Nine studies were included, from which 1039 patients were included for the analysis of histological response and 591 patients for histological remission. For the evaluation of histological response, the pooled sensitivity, specificity, and the area under the curve were 0.69 [95% confidence interval (CI): 0.52–0.82], 0.77 (95% CI: 0.63–0.87), and 0.80 (95% CI: 0.76–0.83), respectively. For the evaluation of histological remission, the corresponding estimates were 0.76 (95% CI: 0.71–0.81), 0.71 (95% CI: 0.62–0.78), and 0.79 (95% CI: 0.75–0.82), respectively. FC had a higher accuracy in studies using Nancy Index. For histological response, the cut-off values of FC ranged from 50 to 172 µg/g, and the sensitivity was higher in studies with FC cut-off values >100 µg/g (0.77 versus 0.65). Conclusion: FC is a valuable biomarker for assessing histological activity in patients with UC. A cut-off value of 100–200 µg/g is more appropriate to spare patients from an unnecessary endoscopy and biopsy.

scholarly journals Is histological remission of ulcerative colitis achievable?

2021 ◽  
Vol 93 (8) ◽  
pp. 975-981
Author(s):  
Oleg V. Knyazev ◽  
Anna V. Kagramanova ◽  
Sergei G. Khomeriki ◽  
Asfold I. Parfenov
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Remission ◽  
Therapeutic Efficacy ◽  
Disease Recurrence ◽  
Mucosal Healing ◽  
Colon Mucosa ◽  
Normal Colon ◽  
Laboratory Markers ◽  
Important Challenge ◽  
Histological Remission

Current conception of deep remission in patients with ulcerative colitis (UC) consists of clinical remission, endoscopic mucosal healing and normalization of laboratory markers. Histological remission should not be used as a primary end point for therapeutic efficacy, but instead should be considered as a marker of deep remission. The main goal of UC treatment should be focused on endoscopic healing of colon mucosa, decrease of inflammation activity, prolonged remission, absence of disease recurrence, and also histologic remission. Nevertheless, the term histologic remission has not yet been fully validated and no histologic indexes have been standardized. We need single unified definition for remission, based on multicentral studies analysis. One of important challenge is restoration of normal colon mucosal and results of multiple studies showed contradictory tests for assessing histologic remission, thus remaining an issue for further discussion.

Comparison of the Nancy Index With Continuous Geboes Score: Histological Remission and Response in Ulcerative Colitis

2020 ◽  
Vol 14 (7) ◽  
pp. 1021-1025 ◽  
Author(s):  
Fernando Magro ◽  
Joanne Lopes ◽  
Paula Borralho ◽  
Cláudia Camila Dias ◽  
Joana Afonso ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Correlation Coefficient ◽  
Area Under The Curve ◽  
Clinical Relapse ◽  
Strongly Correlated ◽  
Histological Response ◽  
Faecal Calprotectin ◽  
Histological Activity ◽  
Histological Remission

Abstract Background and Aims Evidence has been supporting that histological activity of ulcerative colitis [UC] has relevance for the prediction of clinical outcomes in UC patients, such as clinical relapse. In this study, we aimed to compare two histological indexes—the continuous Geboes score [GS] and the Nancy index [NI] —regarding their definitions of histological remission and response, and to determine the ability of faecal calprotectin [FC] levels to discriminate between these histological statuses according to the NI. Methods A large cohort of UC patients [N = 422] who were previously enrolled in other studies was analysed. Results GS and NI were shown to be strongly correlated [correlation coefficient: 0.882, p <0.001], indicating high accordance in the classification of patients as having/not having histological remission and response. FC levels moderately correlated with NI regarding these histological statuses [correlation coefficient: 0.481, p <0.001], moderately predicted the absence of remission defined by NI >0 {area under the curve (AUC) 0.667 (95% confidence interval [CI] 0.609–0.724)}, and were good predictors of the absence of histological response defined by NI >1 (AUC 0.825 [95% CI 0.777–0.872]). The optimal FC cut-offs determined to predict the NI-defined histological remission and response were 91 μg/g and 106 μg/g, when maximising the negative predictive value [NPV]. Conclusions Due to the higher applicability of the NI, this study encourages the systematic use of this histological index to assess histological remission and response in UC patients.

Comparing the Continuous Geboes Score With the Robarts Histopathology Index: Definitions of Histological Remission and Response and their Relation to Faecal Calprotectin Levels

2019 ◽  
Vol 14 (2) ◽  
pp. 169-175 ◽  
Author(s):  
Fernando Magro ◽  
Joanne Lopes ◽  
Paula Borralho ◽  
Susana Lopes ◽  
Rosa Coelho ◽  
...  
Keyword(s):  
Healthy Population ◽  
Strongly Correlated ◽  
Histological Response ◽  
Faecal Calprotectin ◽  
Predictive Values ◽  
Endoscopic Remission ◽  
Prospective Cohorts ◽  
Histological Activity ◽  
Histological Remission ◽  
Definition Of

Abstract Background and Aims The histological status of ulcerative colitis [UC] patients in clinical and endoscopic remission has gained space as an important prognostic marker and a key component of disease monitoring. Our main aims were to compare two histological indexes—the continuous Geboes score [GS] and the Robarts Histopathology index [RHI]—regarding their definitions of histological remission and response, and the ability of faecal calprotectin [FC] levels to discriminate between these statuses. Methods This was an analysis of three prospective cohorts including 422 patients previously enrolled in other studies. Results The two continuous scores [GS and RHI] were shown to be significantly correlated [correlation coefficient of 0.806, p < 0.001] and particularly close regarding their definition of histological response: 95% and 88% of all patients classified as having/not having [respectively] histological response according to RHI also did so according to GS. Moreover, median FC levels in patients with histological response were lower than those in patients without histological response [GS: 73.00 vs 525.00, p < 0.001; RHI: 73.50 vs 510.00, p < 0.001]; a similar trend was observed when FC levels of patients in histological remission were compared to those of patients with histological activity [GS: 76.00 vs 228.00, p < 0.001; RHI: 73.50 vs 467.00, p < 0.001]. FC levels allowed us to exclude the absence of histological remission [according to RHI] and absence of histological response [according to RHI and GS], with negative predictive values varying from 82% to 96%. However, optimization of the FC cut-off to exclude the absence of histological remission, as for the continuous GS, falls within values that resemble those of the healthy population. Conclusion The continuous GS and RHI histological scores are strongly correlated in their definitions of histological response. An absence of histological remission could only be excluded at physiological levels of FC.

Role of Faecal Microbiota Transplantation for Maintenance of Remission in Patients With Ulcerative Colitis: A Pilot Study

2019 ◽  
Vol 13 (10) ◽  
pp. 1311-1317 ◽  
Author(s):  
Ajit Sood ◽  
Ramit Mahajan ◽  
Arshdeep Singh ◽  
Vandana Midha ◽  
Varun Mehta ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Pilot Study ◽  
Clinical Remission ◽  
Faecal Microbiota ◽  
Mayo Score ◽  
Endoscopic Remission ◽  
Secondary Endpoints ◽  
Maintenance Of Remission ◽  
Histological Remission

Abstract Objectives To study the role of faecal microbiota transplantation [FMT] in maintenance of remission in ulcerative colitis [UC]. Methods In this pilot study, patients with UC in clinical remission achieved after multi-session FMT were randomly allocated to either maintenance FMT or placebo colonoscopic infusion every 8 weeks, for 48 weeks. The standard of care [SOC] therapy was continued in all patients. The primary endpoint was maintenance of steroid-free clinical remission [Mayo score ≤2, all subscores ≤1] at Week 48. Secondary endpoints were achievement of endoscopic remission [endoscopic Mayo score 0] and histological remission [Nancy grade 0, 1] at Week 48. Results In all, 61 patients in clinical remission were randomised to receive either FMT [n = 31] or placebo [n = 30]. The primary outcome was achieved in 27/31 [87.1%] patients allocated FMT versus 20/30 [66.7%] patients assigned placebo [p = 0.111]. Secondary endpoints of endoscopic remission (FMT: 18/31 [58.1%] versus placebo: 8/30 [26.7%], p = 0.026) and histological remission (FMT: 14/31 [45.2%] versus placebo: 5/30 [16.7%], p = 0. 033) were achieved in a significantly higher number of patients with FMT. Three patients receiving FMT [9.7%] and 8 patients on placebo [26.7%] relapsed. There were no serious adverse events necessitating discontinuation in patients on FMT; one patient who relapsed on placebo required colectomy. Conclusions Maintenance FMT in patients who are in clinical remission may help sustain clinical, endoscopic and histological remission in patients with UC.

scholarly journals The prognostic value of histology in ulcerative colitis in clinical remission with mesalazine

2017 ◽  
Vol 10 (10) ◽  
pp. 749-759 ◽  
Author(s):  
Giuseppe Frieri ◽  
Brigida Galletti ◽  
Mirko Di Ruscio ◽  
Rachele Tittoni ◽  
Annalisa Capannolo ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Logistic Regression ◽  
Regression Analysis ◽  
Logistic Regression Analysis ◽  
Clinical Remission ◽  
Prognostic Value ◽  
Activity Index ◽  
Multivariate Logistic Regression Analysis ◽  
Histological Activity

Background: The aim of the study was to compare the prognostic value of histological and endoscopic activity in patients with ulcerative colitis (UC). Methods: Patients in clinical remission for 1 year under treatment with mesalazine underwent a planned colonoscopy with biopsies. Histological activity was scored using the histological activity index (HAI). Endoscopic activity was scored using the Mayo endoscopic subscore (MES). The clinical course was evaluated measuring relapses needing steroids during a follow up of 3 years. Results: A total of 52 patients were enrolled into the study and followed up for 3 years. At baseline 29 patients (55.77%) had no endoscopic lesions, and 17 patients (32.69%) showed no histological alteration. At 3 years of follow up, overall, 26 patients (50%) were still in steroid-free remission. Using univariate logistic regression analysis, both histological (HAI ⩾ 1) and endoscopic activity (MES ⩾ 1) were significantly associated with outcome, showing, respectively, a relapse risk (odds ratio [OR]) 16.4 times higher than histological remission (HAI 0) (96% confidence interval [CI]: 3.2–84.3) and 6.3 times higher with respect to endoscopic remission (MES 0) (96% CI: 1.9–21.3). After multivariate logistic regression analysis, histological activity was the only factor significantly associated with outcome (OR 10.2; 95% CI: 1.7–59.4). Conclusions: Histological activity has the most powerful prognostic value in predicting the need for steroids in patients with UC in stable clinical remission on mesalazine. It could be considered as a target of therapy in UC.

P111 CORRELATION OF FECAL CALPROTECTIN AND MUCOSAL BIOPSY IN IDENTIFYING SUBCLINICAL INFLAMMATION IN ULCERATIVE COLITIS PATIENTS: A PRELIMINARY STUDY

2020 ◽  
Vol 26 (Supplement_1) ◽  
pp. S16-S17
Author(s):  
Mahmoud Hashim ◽  
Courtney Perry ◽  
Kurt Schaberg ◽  
Ahmed Elkheshen ◽  
Mohamed Hussein ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Gold Standard ◽  
Scoring Systems ◽  
Fecal Calprotectin ◽  
Histological Evaluation ◽  
Subclinical Inflammation ◽  
University Of Kentucky ◽  
Reactive Protein ◽  
Endoscopic Remission ◽  
Histological Activity

Abstract Background For years, the gold standard for Ulcerative Colitis (UC) remission was mucosal appearance during endoscopy. However, recent literature suggests histological or “deep” remission is important for preventing flares and maintaining clinical remission. There are now validated histological scoring systems to identify subclinical inflammation, the simplest being the Nancy Histology Index (NHI). Colonoscopy with histological evaluation is the gold standard for UC monitoring, but frequent endoscopy is not always possible. Literature reporting the utility of fecal calprotectin (FC) in detecting subclinical inflammation is limited. We seek to evaluate the correlation of FC and C-reactive protein (CRP) with NHI scores to better assess their role in detecting subclinical UC. Methods We retrospectively evaluated clinical data and pathology slides of 69 UC patients that were collected over 6-months period at university of Kentucky. Pathology slides were scored according to NHI by a trained researcher and verified by an IBD pathologist. Presence of acute activity was defined as NHI>2. Mayo endoscopic scores (MES) were based on endoscopic reports from one expert endoscopist. Endoscopic remission was defined as MES <2. FC and CRP were recorded if collected within a month of endoscopy. FC was defined as elevated (≥120 mcg/g) or borderline (50.1–120 mcg/g). Elevated CRP was defined as (> 0.9 mg/dl). Results 33 of the 69 (47.8%) patients analyzed were in endoscopic remission. 17 of those 33 (51.5%) patients in endoscopic remission had acute histological activity (NHI >2). 7 (21.2%) patients with acute histological activity completed FC testing. Of the 7 who submitted FC, 4 were elevated, and 1 was borderline. 15 of the 17 NHI positive patients submitted CRP, 4 (26%) were elevated. Finally, among the 17 patients with NHI >2, four patients flared within a year (Table 1). In these 4 flared patients, FC was abnormal in 3 patients. CRP was negative in these three patients. One patient did not complete a FC or CRP. Conversely, of the 16 patients with quiescent UC and NHI <2 only 1 patient flared within a year. FC and CRP were not completed at the time of endoscopy. Conclusion We successfully identified an important subset of UC patients in clinical and endoscopic remission with active histological activity. Most patients in this subset had elevated fecal calprotectin levels. This suggests fecal calprotectin can be used for disease monitoring to proactively identify subclinical activity before disease flare. Our findings suggest that biopsies should be performed in all UC patients even in the absence of endoscopic abnormality, and fecal calprotectin should be ordered at regular intervals to pre-emptively detect and prevent UC flares.

scholarly journals Low Golimumab Trough Levels at Week 6 Are Associated With Poor Clinical, Endoscopic and Histological Outcomes in Ulcerative Colitis Patients: Pharmacokinetic and Pharmacodynamic Sub-analysis of the Evolution Study

2019 ◽  
Vol 13 (11) ◽  
pp. 1387-1393 ◽  
Author(s):  
F Magro ◽  
S Lopes ◽  
M Silva ◽  
R Coelho ◽  
F Portela ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Objective Response ◽  
Early Response ◽  
Induction Phase ◽  
Open Label ◽  
Faecal Calprotectin ◽  
Mayo Score ◽  
Histological Activity ◽  
Histological Remission ◽  
Trough Levels

Abstract Background and Aims Golimumab has an established exposure-response relationship in patients with ulcerative colitis [UC]. However, the association of serum golimumab trough levels [TL] with objective markers of disease activity, such as endoscopic and histological activity scores and concentrations of biomarkers, remains less understood. This report describes the relationship of serum golimumab TL at the end of the induction period [Week 6] with clinical, endoscopic, histological, and biomarker parameters. Methods This was an open-label, uncontrolled, prospective and interventional study. Moderate to severely active UC patients naïve to biologic therapy were treated with golimumab. Serum golimumab TL and faecal calprotectin levels were measured at baseline [Week 0 of induction] and Week 6. Results A total of 34 patients completed the induction phase [Week 6] and were included in this analysis. Overall, 47.1% and 14.7% of patients achieved clinical response and remission with significantly higher serum golimumab TL in patients with early response or remission [3.7 μg/mL vs 1.3 μg/mL, p = 0.0013; and 3.1 μg/mL vs 1.7 μg/mL, p = 0.0164, respectively]. In addition, golimumab TL were significantly higher in patients achieving histological remission [4.2 μg/mL vs 1.7 μg/mL, p = 0.0049]. Week 6 golimumab TL were inversely correlated with the total Mayo score [rs = -0.546; p = 0.0008], the Mayo endoscopic subscore [rs = -0.381; p = 0.0262], the Geboes histological activity score [rs = -0.464; p = 0.0057], and faecal calprotectin levels [rs = -0.497; p = 0.0044]. Conclusions A higher early exposure to golimumab is associated with a better objective response in active UC patients and appears to drive the outcome at Week 6.

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