scholarly journals P233 Evaluating the association between faecal calprotectin and endoscopic outcomes in ulcerative colitis using the HICKORY open-label induction cohort

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S259-S259
Author(s):  
W Reinisch ◽  
B El Azzouzi ◽  
R Li ◽  
S Lacey ◽  
M Daperno ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Trials ◽  
Disease Activity ◽  
Clinical Remission ◽  
Area Under The Curve ◽  
Percentage Change ◽  
Open Label ◽  
Faecal Calprotectin ◽  
Using Data ◽  
Factor Α

Abstract Background In clinical practice, faecal calprotectin (FC) is used to monitor disease activity in ulcerative colitis (UC); however, there is no consensus on optimal cut-off values of FC for predicting endoscopic outcomes. FC performance has not been extensively assessed in the context of clinical trials using central endoscopy. This study aimed to evaluate the association between FC and endoscopic disease activity and to propose a meaningful cut-off FC value to predict endoscopic outcomes using data from the open-label induction (OLI) cohort of HICKORY (NCT02100696). Methods HICKORY is a Phase 3 study evaluating etrolizumab in anti-tumour necrosis factor α-experienced patients with moderate-to-severe UC. The study included patients who received ≥1 dose of etrolizumab 105 mg subcutaneously every 4 weeks during a 14-week induction period. Percentage change in FC was calculated at week 14. The endoscopic activity was measured by Mayo Clinic score (MCS) endoscopic subscore (ES) using a robust central-reading model. Endoscopic improvement was defined as ES=0/1; clinical remission as MCS ≤2 and no individual subscore >1. FC analysis was performed by Covance® (Bühlman FC ELISA assay). Receiver operator characteristic (ROC) curve analyses were used to calculate cut-off FC values. Results A total of 97 patients (mean age [standard deviation], 41.2 ± 13.4 years) were included in the analysis. Median (interquartile range [IQR]) baseline duration of disease was 6.3 (3.2–12.3) years with a median (IQR) MCS of 9 (8–10). Median (IQR) baseline FC and ES were 254 (156–455) µg/g and 3 (3-3). At week 14, median (IQR) FC percentage change was −13 (−57 to 112). A numerical association between changes in FC level and ES was observed (Table). A cut-off FC value of 159 µg/g was observed to predict endoscopic improvement with >70% sensitivity and specificity; ROC area under the curve was 0.78 (Figure). Similar results were observed for clinical remission. Conclusion In this exploratory analysis using HICKORY OLI cohort data, changes in FC appear to associate with changes in ES. A cut-off FC value of 159 µg/g predicted endoscopic improvement. In UC, FC may be a useful non-invasive biomarker for ascertaining endoscopic disease activity in clinical trials; however, further clinical studies validating FC cut-offs against centrally read endoscopy are needed.

scholarly journals P682 Faecal calprotectin and C-reactive protein levels are associated with long-term clinical and endoscopic outcomes: Analysis of the OASIS open-label extension trial of etrasimod for ulcerative colitis

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S555-S556
Author(s):  
A Yarur ◽  
M Chiorean ◽  
J Zhang ◽  
W Reinisch ◽  
S Vermeire ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Disease Activity ◽  
Clinical Response ◽  
Clinical Remission ◽  
C Reactive Protein ◽  
Open Label ◽  
Faecal Calprotectin ◽  
Reactive Protein ◽  
Open Label Extension

Abstract Background Reliable biomarkers of ulcerative colitis (UC) disease activity may be useful in clinical trials and practice. Etrasimod is an oral, selective, sphingosine 1-phosphate receptor modulator with efficacy in a 12-week, phase 2, double-blind (DB), randomised, controlled trial in adult patients with moderately-to-severely active UC (OASIS; NCT02447302). Patients who completed the DB study were eligible to enrol in an open-label extension (OLE; NCT02536404) and receive etrasimod 2 mg once daily for up to an additional 34 weeks. The aim of this post-hoc analysis was to assess the correlation of sequential faecal calprotectin (FC) and C-reactive protein (CRP) levels throughout the DB study and OLE with clinical and endoscopic outcomes at end of treatment (EOT) in the OLE. Methods In the DB study, patients received etrasimod 1 mg, etrasimod 2 mg or placebo. The OLE evaluable cohort comprised patients who received etrasimod 2 mg throughout the OLE. The modified intention-to-treat (mITT) population comprised patients with non-missing assessments. EOT was the last observation for each patient, occurring at week 46 (OLE week 34) for study completers or at last visit for patients who discontinued or had missing data. Endpoints were modified Mayo Clinic score (mMCS; range 0–9; including endoscopy, rectal bleeding [RB], and stool frequency [SF]); clinical remission (endoscopic subscore ≤1 [with absence of friability], RB ≤1, and SF score ≤1 with ≥1 point decrease from DB baseline); clinical response (clinical remission or decrease in mMCS of ≥2 points and ≥30% decrease from DB baseline, with either a RB decrease of ≥1 or RB score of ≤1); and endoscopic improvement (subscore ≤1). FC and CRP were measured longitudinally to EOT. Comparisons between subgroups were assessed with a Wilcoxon rank-sum test (2-sided P values). Analysis of correlation between variables was conducted using the Spearman’s rank coefficient. Results The evaluable cohort included 105 patients, 31 of whom received etrasimod 2 mg throughout both DB and OLE periods. At EOT 70%, 35% and 45% of patients in the mITT evaluable cohort had clinical response, clinical remission and endoscopic improvement, respectively. Differences in FC and CRP levels between patients with and without clinical remission at EOT are shown in Figures 1 and 2, respectively for patients who received etrasimod 2 mg throughout both the DB and OLE periods. Correlation analyses of FC and CRP with clinical (mMCS) and endoscopic disease activity and with each other are shown in Table 1. Conclusion FC and CRP appear to correlate with clinical and endoscopic outcomes over long-term treatment with etrasimod. Additional validation is needed to determine their utility in treat-to-target management strategies.

Faecal Calprotectin Predicts Endoscopic and Histological Activity in Clinically Quiescent Ulcerative Colitis

2019 ◽  
Vol 14 (1) ◽  
pp. 46-52 ◽  
Author(s):  
Lara Hart ◽  
Mallory Chavannes ◽  
Omar Kherad ◽  
Chelsea Maedler ◽  
Nathalie Mourad ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Disease Activity ◽  
Clinical Remission ◽  
Roc Analysis ◽  
Surrogate Marker ◽  
Area Under The Curve ◽  
Faecal Calprotectin ◽  
Mayo Score ◽  
Endoscopic Score ◽  
Histological Activity

Abstract Introduction Faecal calprotectin [FC] is a reliable surrogate marker for disease activity in ulcerative colitis [UC]; however, there are no consensus cut-off values for remission. The study aim was to correlate FC with Mayo Endoscopic Score [MES] and histological disease activity of UC patients in clinical remission. Methods Our study recruited adult UC patients at the McGill IBD Center between 2013 and 2017. Patients in clinical remission [partial Mayo score ≤2], undergoing endoscopy for disease activity or dysplasia surveillance, were enrolled. Before bowel preparation, FC was collected. MES was documented during colonoscopy. Biopsies were taken; histological activity was assessed using Geboes score and the presence of basal plasmacytosis. Results A total of 185 patients were recruited. The area under the curve [AUC] in receiver operating characteristic [ROC] analysis to predict MES 1–3 [from 0] was 0.743 [95% CI 0.67–0.82; p <0.001] with an FC cut-off value 170 µg/g [64% sensitivity, 74% specificity], and to predict MES 2–3 [from 0–1] was 0.722 [95% CI 0.61–0.83; p <0.001] with an FC cut-off value 170 µg/g [69% sensitivity, 65% specificity]. To differentiate MES 0 from MES 1, an FC value 130 µg/g yields a 70% sensitivity and 68% specificity. The AUC in ROC analysis to predict Geboes <3.1 was 0.627 [95% CI 0.55–0.71; p = 0.003], with an FC value 135 µg/g [54% sensitivity, 69% specificity]. Conclusions In this large study, FC ≥170 µg/g predicts endoscopic activity and FC ≥135 µg/g predicts histological activity. Therefore in clinical practice, lower faecal calprotectin thresholds can be chosen to optimise identification of patients with ongoing endoscopic and histological disease activity.

scholarly journals P471 What is the appropriate cut-off value of CRP to predict endoscopic remission in ulcerative colitis patients with clinical remission?

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S415-S415
Author(s):  
J Shin ◽  
G Seong ◽  
J H Song ◽  
S M Kong ◽  
T J Kim ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Sensitivity And Specificity ◽  
Clinical Remission ◽  
Activity Index ◽  
Area Under The Curve ◽  
Endoscopic Evaluation ◽  
Faecal Calprotectin ◽  
Reactive Protein ◽  
Endoscopic Remission ◽  
Low Sensitivity

Abstract Background A noninvasive and reliable markers for predicting endoscopic remission (ER) in ulcerative colitis (UC) patients with clinical remission (CR) provide important information in predicting disease progression and in determining treatment. Faecal calprotectin test is known to be the most accurate to predict ER, but patients are reluctant to handle faecal materials. C-reactive protein (CRP) is one of the surrogate markers for assessing disease activity, but it is known to have low sensitivity and specificity of normal CRP value (<0.3 mg/dl). The sensitivity of the CRP test has been improved, and even fine values within the normal range can be measured. The aim of this study was to determine appropriate CRP cut-off values for the prediction of ER in UC patients with CR even though within normal CRP range. Methods A total of 132 UC patients who underwent endoscopic evaluation in CR were retrospectively reviewed. Serum biomarkers including haemoglobin, leukocytes, platelets, erythrocyte sedimentation rate, and CRP were evaluated within 1 week period from endoscopic evaluation. The clinical and endoscopic activity was measured by simple clinical colitis activity index and endoscopic Mayo subscore. Results In UC patient with CR, CRP level was significantly lower in ER (median 0.05, 0.03–2.57) vs. non-ER (median 0.11 0.03-2.81). (p < 0.005) The proportion of males in non-ER was slightly higher than in ER (24, 72.7% vs. 52, 52.5 %; p = 0.042), and only gender and CRP showed statistical differences in baseline clinical characteristics. CRP had predictive value of ER [Area under the curve (AUC = 0.760)] and the sensitivity was 71.4%, specificity was 71.7 % at cut-off value of 0.09mg/dl. In contrast, the sensitivity and specificity of normal CRP (0.3mg/dl) were low. (sensitivity 27.3%, specificity 90.9%). Conclusion Norma CRP cut-off values are not sufficient to reflect ER. It may be helpful to change the CRP cut-off value that predicts ER in CR to value other than 0.3 mg/dl.

scholarly journals P712 Association of histologic-endoscopic mucosal healing after ustekinumab induction or maintenance therapy with 2-year outcomes in the UNIFI Phase 3 study in ulcerative colitis

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S574-S575
Author(s):  
K Li ◽  
F Yang ◽  
C Marano ◽  
H Zhang ◽  
W J Sandborn ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Maintenance Therapy ◽  
Disease Activity ◽  
Clinical Remission ◽  
Dose Adjustment ◽  
Mucosal Healing ◽  
Faecal Calprotectin ◽  
To Receive ◽  
Lower Disease Activity

Abstract Background Ustekinumab (UST) is an effective therapy for moderate-to-severe ulcerative colitis (UC). Histological and endoscopic improvement of mucosa after induction are associated with clinical remission and steroid-free clinical remission at maintenance Week 44. The association of histological-endoscopic mucosal healing after UST induction or maintenance therapy with 2-year outcomes in moderate-to-severe UC is not known. Methods In the UNIFI study of UST in moderate-to-severe UC, histological-endoscopic mucosal healing was defined as achieving both endoscopic improvement (Mayo endoscopy subscore ≤1) and histological improvement (i.e., neutrophil infiltration in <5% of crypts, no crypt destruction, and no erosions, ulcerations, or granulation tissue; based on the Geboes score). Associations of mucosal improvement after induction (irrespective of treatment) or UST maintenance with long-term efficacy of UST, disease severity, inflammation level, and dose adjustment were evaluated up to Week 92 in the long-term extension (LTE) phase of UNIFI. Analysis was conducted in patients who were randomised to receive UST maintenance therapy and continued with UST in LTE. Tests with p-value <0.05 were considered statistically significant. Results Patients with histological-endoscopic mucosal healing after induction had significantly lower disease activity (partial Mayo score and stool frequency) and a trend for lower inflammation measured by CRP and faecal calprotectin at maintenance Week 44 than those without induction mucosal healing (Table 1). These improvements in disease activity were retained through LTE Week 92, with patients with induction histological-endoscopic mucosal healing showing a continuous reduction of disease activity. Significantly lower disease activity, CRP, and faecal calprotectin were also observed through LTE among patients with histological-endoscopic mucosal healing after UST maintenance compared with those without (Table 1). Patients with histological-endoscopic mucosal healing after induction remained on treatment longer than those without (p < 0.05). In addition, patients with histological-endoscopic mucosal healing after induction or maintenance were less likely to receive dose adjustment during LTE, but this association was not statistically significant. Conclusion Early macroscopic and microscopic improvement of the mucosa is an indicator of positive long-term clinical outcomes and reductions in inflammatory burden.

scholarly journals Efficacy of 5-Aminosalicylic Acid Enemas in the Treatment of Distal Ulcerative Colitis

1990 ◽  
Vol 4 (7) ◽  
pp. 468-471 ◽  
Author(s):  
MG Robinson ◽  
DL Decktor
Keyword(s):  
Ulcerative Colitis ◽  
Disease Activity ◽  
Activity Index ◽  
Disease Activity Index ◽  
First Episode ◽  
High Dose ◽  
Aminosalicylic Acid ◽  
Open Label ◽  
Distal Ulcerative Colitis ◽  
The Mean

The efficacy of 4 g 5-aminosalicylic acid (5-ASA, mesalamine) enemas was assessed in 666 patients with distal ulcerative colitis. Patients were enrolled in an open-label compassionate use program. One 4 g 5-ASA enema was administered each night for a period of four weeks and the disease activity index was assessed at baseline and on days 14 and 28. On days 14 and 28, 78.0% and 88.1% of patients, respectively, demonstrated an improvement in disease activity index. The mean decline in disease activity index on day 14 was 40.7% (P=0.0001) and on day 28 it was 55.4% (P=0.0001). Efficacy was similar whether the disease was confined to or extended beyond 30 cm from the anus. There was no difference in efficacy in patients suffering their first episode of disease compared to patients suffering subsequent attacks. In conclusion, high dose 5-ASA enemas are a highly effective treatment for distal ulcerative colitis.

scholarly journals Automatic, computer-aided determination of endoscopic and histological inflammation in patients with mild to moderate ulcerative colitis based on red density

Gut ◽  
2020 ◽  
Vol 69 (10) ◽  
pp. 1778-1786 ◽  
Author(s):  
Peter Bossuyt ◽  
Hiroshi Nakase ◽  
Séverine Vermeire ◽  
Gert de Hertogh ◽  
Tom Eelbode ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Disease Activity ◽  
Objective Evaluation ◽  
Second Phase ◽  
Endoscopic Images ◽  
Severity Scores ◽  
Computer Based ◽  
Index Of Severity ◽  
Using Data ◽  
Histological Factors

BackgroundThe objective evaluation of endoscopic disease activity is key in ulcerative colitis (UC). A composite of endoscopic and histological factors is the goal in UC treatment. We aimed to develop an operator-independent computer-based tool to determine UC activity based on endoscopic images.MethodsFirst, we built a computer algorithm using data from 29 consecutive patients with UC and 6 healthy controls (construction cohort). The algorithm (red density: RD) was based on the red channel of the red-green-blue pixel values and pattern recognition from endoscopic images. The algorithm was refined in sequential steps to optimise correlation with endoscopic and histological disease activity. In a second phase, the operating properties were tested in patients with UC flares requiring treatment escalation. To validate the algorithm, we tested the correlation between RD score and clinical, endoscopic and histological features in a validation cohort.ResultsWe constructed the algorithm based on the integration of pixel colour data from the redness colour map along with vascular pattern detection. These data were linked with Robarts histological index (RHI) in a multiple regression analysis. In the construction cohort, RD correlated with RHI (r=0.74, p<0.0001), Mayo endoscopic subscores (r=0.76, p<0.0001) and UC Endoscopic Index of Severity scores (r=0.74, p<0.0001). The RD sensitivity to change had a standardised effect size of 1.16. In the validation set, RD correlated with RHI (r=0.65, p=0.00002).ConclusionsRD provides an objective computer-based score that accurately assesses disease activity in UC. In a validation study, RD correlated with endoscopic and histological disease activity.

scholarly journals Defining Faecal Calprotectin Thresholds as a Surrogate for Endoscopic and Histological Disease Activity in Ulcerative Colitis—a Prospective Analysis

2018 ◽  
Vol 13 (4) ◽  
pp. 424-430 ◽  
Author(s):  
Alissa Walsh ◽  
Andrey Kormilitzin ◽  
Christopher Hinds ◽  
Vanashree Sexton ◽  
Oliver Brain ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Disease Activity ◽  
Prospective Analysis ◽  
Faecal Calprotectin

scholarly journals P807 UCEIS is associated with PRO2, partial Mayo and SCCAI remission in UC: preliminary results from a prospective study

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S631-S631
Author(s):  
P A Golovics ◽  
L Gonczi ◽  
J Reinglass ◽  
C Verdon ◽  
W Afif ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Remission ◽  
Roc Analysis ◽  
Clinical Decision Making ◽  
Activity Index ◽  
Operating Characteristics ◽  
Faecal Calprotectin ◽  
Patient Reported ◽  
Index Of Severity ◽  
Active Disease

Abstract Background Optimal management of patients with ulcerative colitis (UC) requires the accurate assessment of disease activity. Endoscopic evaluation is considered the gold standard approach, but it is invasive. We aimed to determine the operating characteristics of the Ulcerative Colitis Endoscopic Index of Severity (UCEIS), to quantify the cut off most closely correlated with clinical remission or activity and determine agreement with the Mayo endoscopic subscore (MES), Baron score, clinical scores and biomarkers. Methods 136 patients were included prospectively (age: 48 (IQR38-61) years, duration 12 (4–19)years, 63 females, 53.7% extensive disease, 40.4% on biologicals) at the time of the colonoscopy. Ulcerative Colitis Endoscopic Index of Severity (UCEIS) Mayo endoscopic subscore (MES), Baron scores were calculated, as well as the2 item patient reported outcome (PRO), partial MAYO, Simple Clinical Colitis Activity Index (SCCAI). CRP and faecal calprotectin (FCAL) was available in 58.1 and 33.8% of patients. 20.7% had clinical flare, treatment was escalated in 17.8% of patients. ROC analysis and K-statistics were performed and Spearman’s correlation was calculated. Results UCEIS was strongly associated to PRO2 SF (AUC:0.866), RBS (AUC:0.921), PRO2 combined remission (AUC:0.905), partial MAYO (AUC:0.956) and SCCAI (AUC:0.907) remission in a ROC analysis. A UCEIS of ≤3 was identified as the best cut-off to identify RBS subscore of 0, or total PRO2 remission (RBS 0 and SF ≤1), partial MAYO (≤2) and SCCAI (≤2.5) remission, while a UCEIS≥4 identified active disease frequently needing change in medical therapy. A moderate agreement was found between UCEIS and MES (K=0.451) or Baron (K=0.499) scores. Correlation between FCAL and UCEIS (coeff:0.743, p &lt; 0.0001) was strong, while modest only with CRP (coeff:0.333, p = 0.01). Conclusion A UCEIS was strongly associated with clinical remission defined as PRO2, SF, RBS, partial Mayo or SCCAI with best agreement with RBS and partial Mayo remission. A UCEIS of ≤3 was identified as a cut-off for quiescent disease, while a UCEIS≥4 identified active disease, which can support clinical decision-making based on endoscopic findings. Agreement between UCEIS and FCAL was strong, while agreement with UCEIS and MES/Baron scores was moderate.

Predictors of Clinical Remission under Anti-tumor Necrosis Factor Treatment in Patients with Ankylosing Spondylitis: Pooled Analysis from Large Randomized Clinical Trials

2015 ◽  
Vol 42 (8) ◽  
pp. 1418-1426 ◽  
Author(s):  
Xenofon Baraliakos ◽  
Andrew S. Koenig ◽  
Heather Jones ◽  
Annette Szumski ◽  
David Collier ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Ankylosing Spondylitis ◽  
Tumor Necrosis Factor ◽  
Disease Activity ◽  
Clinical Remission ◽  
Partial Remission ◽  
Tumor Necrosis ◽  
Disease Duration ◽  
Hla B27 ◽  
Necrosis Factor

Objective.Investigate the role and relation of disease duration of different factors for achieving clinical remission with anti-tumor necrosis factor (TNF) treatment in patients with active ankylosing spondylitis (AS).Methods.Data pooled from 4 large (n = 1281) clinical trials were used to compare disease duration subgroups for placebo or sulfasalazine (SSZ) versus etanercept (ETN), which, in turn, were analyzed by age of diagnosis ≤ 40 versus > 40 years, HLA-B27 status, and baseline C-reactive protein (CRP) ≤ upper limit of normal (ULN) versus > ULN using chi-square tests, and ANCOVA. The primary efficacy measure was Assessments of SpondyloArthritis international Society (ASAS) partial remission (PR) after 12 weeks of treatment. Also analyzed were Bath AS Disease Activity Index and Functional Index, AS Disease Activity Scores, and ASAS response rates.Results.Overall, a larger percentage of patients achieved ASAS-PR with ETN versus SSZ or placebo. More patients with ≤ 2-year disease duration treated with ETN experienced partial remission (34%) versus longer disease duration (30%, 27%, and 22% for > 2–5, > 5–10, and > 10 yrs, respectively; all p < 0.05). In the subgroup of patients with both disease duration ≤ 2 years and aged ≤ 40 years at diagnosis, the treatment response was even more pronounced. Similar results were seen in HLA-B27–positive patients in the disease duration ≤ 2-year subgroup. Overall, patients with high CRP at baseline had better treatment responses compared with patients with normal CRP.Conclusion.Treatment response under anti-TNF treatment with ETN at 12 weeks was greatest among patients with disease duration ≤ 2 years and even more pronounced in subgroups of patients ≤ 40 years old or HLA-B27–positive at diagnosis.

Sign in / Sign up

Export Citation Format

Share Document