scholarly journals Assessment of Endoscopic Disease Activity in Ulcerative Colitis: Is Simplicity the Ultimate Sophistication?

2021 ◽  
pp. 1-6
Author(s):  
Ala I. Sharara ◽  
Maher Malaeb ◽  
Matthias Lenfant ◽  
Marc Ferrante
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Trials ◽  
Clinical Practice ◽  
Disease Activity ◽  
Incomplete Response ◽  
Endoscopic Remission ◽  
Endoscopic Score

<b><i>Background:</i></b> Endoscopic remission is an increasingly recognized important therapeutic endpoint in the management of patients with UC. <b><i>Summary:</i></b> The Mayo Endoscopic Score (MES) remains the most common endoscopic index recommended in guidelines and widely used in clinical trials and in clinical practice. The MES is easy, simple, and practical but is suboptimal at providing an accurate depiction of segmental healing and/or at measuring a substantial but incomplete response across the spectrum of endoscopic inflammation. Other endoscopic scores have been proposed but have not received wide recognition or adoption.

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 &gt;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 &gt;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 Evolution of psoriatic arthritis study patient population characteristics in the era of biological treatments

RMD Open ◽  
2019 ◽  
Vol 5 (1) ◽  
pp. e000779 ◽  
Author(s):  
Ann-Sophie Vandendorpe ◽  
Kurt de Vlam ◽  
Rik Lories
Keyword(s):  
Clinical Trials ◽  
Clinical Practice ◽  
Psoriatic Arthritis ◽  
Disease Activity ◽  
Patient Population ◽  
Patient Characteristics ◽  
Chronic Inflammatory Disease ◽  
Population Characteristics ◽  
Phase Iii ◽  
Study Patient

ObjectivesPsoriatic arthritis is a chronic inflammatory disease that affects the musculoskeletal system. It can include arthritis, spondylitis, dactylitis and enthesitis, and is strongly associated with the presence of psoriasis. The introduction of biological therapies as a treatment option has brought a significant improvement in disease control for patients with psoriatic arthritis. Here, we aimed to detect emerging differences in demographic and clinical characteristics of the psoriatic arthritis patient study population since the introduction of biologicals. We hypothesised that evolving views on control of disease activity and increased experience in the management of psoriatic arthritis have affected the patient population considered for clinical trials and that this may serve as a proxy for changes in clinical practice.MethodsWe systematically searched for and selected 12 phase II and phase III trials and divided them into three treatment periods based on different time periods and working mechanisms of the particular biologicals. We made a selection of patient and disease parameters for which data were available in all three periods, calculated those data per period and looked for statistically significant differences between the treatment periods.ResultsStatistical analysis showed significant differences in patient characteristics, disease characteristics, disease activity, disease effects and use of prior treatments between the patient populations of the three periods.ConclusionThis study shows a clear evolution of the patient population considered for clinical trials since the introduction of biologicals. Further research is needed to see if those changes can be detected in the daily clinical practice.

scholarly journals Thiopurine Treatment in Ulcerative Colitis: A Critical Review of the Evidence for Current Clinical Practice

2017 ◽  
Vol 24 (1) ◽  
pp. 67-77 ◽  
Author(s):  
Sara van Gennep ◽  
Nanne K de Boer ◽  
Geert R D’Haens ◽  
Mark Löwenberg
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Practice ◽  
Critical Review ◽  
Maintenance Treatment ◽  
Randomized Trials ◽  
Current Clinical Practice ◽  
Sufficient Power ◽  
Significant Difference ◽  
Endoscopic Remission ◽  
Remission Rates

Abstract Background Due to toxicity problems and controversial evidence, thiopurine use in ulcerative colitis (UC) has faced a lot of criticism. We present a critical review of the literature on efficacy of thiopurines in UC. Methods Studies evaluating therapeutic efficacy of thiopurine remission induction and/or maintenance treatment in UC were identified using the Cochrane Library, MEDLINE, and EMBASE. Results Out of 5 randomized trials on thiopurine induction treatment, 3 demonstrated a significant effect of thiopurine treatment vs mesalamine or placebo in steroid-dependent UC patients: (1) lower endoscopic activity scores, (2) higher clinical remission rates, and (3) more patients who discontinued steroids. Two found no significant difference in clinical and endoscopic remission of azathioprine compared with sulfasalazine or placebo in patients with active UC. Out of 7 randomized trials on thiopurine maintenance treatment, 4 demonstrated significant higher clinical and endoscopic remission rates in thiopurine-treated patients compared with placebo or mesalamine. Three found no significant difference in clinical and endoscopic remission of thiopurine maintenance treatment compared with sulfasalazine or placebo. Conclusions All studies that investigated thiopurine treatment in UC had shortcomings, such as lack of sufficient power, no use of blinding, allowed concomitant treatment with steroids, and no endoscopy to confirm active disease at study entry or to evaluate therapeutic efficacy. Hence, current clinical practice of thiopurine treatment in UC is based on minimal and controversial evidence. This underscores the need for clinical studies with sufficient power and objective end points in order to determine efficacy of thiopurines in UC. 10.1093/ibd/izx025_video1 izx025.video1 5732762967001

scholarly journals OP09 Patient reported outcomes reflect histologic disease activity in patients with Ulcerative Colitis: Interim analysis of the APOLLO study

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S008-S009
Author(s):  
B Verstockt ◽  
C Jorissen ◽  
E Hoefkens ◽  
N Lembrechts ◽  
L Pouillon ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Disease Activity ◽  
Patient Reported Outcomes ◽  
Activity Index ◽  
Remission Rate ◽  
Stool Frequency ◽  
Patient Reported ◽  
Endoscopic Remission ◽  
Histological Remission ◽  
General Wellbeing

Abstract Background Treating beyond endoscopic remission, aiming for histological remission, has shown to reduce relapse and hospitalization rates in patients with ulcerative colitis (UC). However, very little is known on how histological remission associates with patient reported outcomes (PROMs). Methods PROMs (Simple clinical colitis activity index [SCCAI], IBD disk and Visual Analogue Scales [VAS]) were prospectively collected through a digital questionnaire in all patients with UC undergoing colonoscopy between July 21st 2020-Jan 21st 2021. Mayo endoscopic sub score and UCEIS were determined, as well as the Nancy histologic index (NHI) of the most affected area. Endoscopic remission was defined as Mayo endoscopic sub score 0 and UCEIS 0; histologic remission as NHI 0, absence of active inflammation as NHI ≤ 1. PRO2 remission was defined as stool frequency ≤ 1 (absolute stool frequency ≤ 3 OR 1–2 stools more than usual) and rectal bleeding score of 0. Results Fifty-six paired assessments were collected in 48 unique patients (Table 1), with a histologic, endoscopic and PRO-2 remission rate of 23.2%, 28.6% and 38.2% respectively. Patients with histologic remission or absence of histologic inflammation had a significantly lower overall IBD disability (p=0.007, p=0.003) and disease activity score (p=0.003, p&lt;0.001), as compared to patients without. In line, NHI correlated with the overall IBD disk (r=0.40, p=0.002) and SCCAI score (r=0.50, p&lt;0.001). Many individual components of both scores (abdominal pain, arthralgia, impact on education and work/interpersonal interactions/sexual function, regulation of defecation, blood loss, general wellbeing, joint pain, numbers of stools during night/day, urgency) differed significantly between patients with and without histologic remission. VAS scores assessing general wellbeing (r=0.33, p=0.01), impact on daily activities (r=0.41, p=0.002), UC-related symptoms (r=0.42, p=0.001) and worries (r=0.40, p=0.002) correlated with histology. Quartile analysis of the overall IBD disk and SCCAI scores confirmed the highest likelihood for histologic remission in patients with the lowest scores (Q1-Q2 vs Q3-Q4 39.3% vs 7.1%, p=0.01; 40.0% vs 9.7%, p=0.01) (Figure 1). Nevertheless, the overall accuracy of the IBD disk (0.75) or SCCAI score (0.76) for histologic remission is lower (p&lt;0.05) than the accuracy of the Mayo endoscopic (0.90) or UCEIS (0.90) score. Table 1: Baseline features Abstract OP09 – Figure 1: Quartile analysis Conclusion In patients with UC, PROMs for disability and clinical disease activity reflect histologic disease activity and should therefore be further explored in (trial) endpoint discussions. However, they cannot fully replace endoscopic and histologic findings, and should be considered complementary.

scholarly journals P283 Decrease in bowel wall thickness at intestinal ultrasound accurately detects early endoscopic remission and improvement in ulcerative colitis patients on tofacitinib: a longitudinal prospective cohort study

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S315-S317
Author(s):  
F de Voogd ◽  
E Van Wassenaer ◽  
A Mookhoek ◽  
S Bots ◽  
S Van Gennep ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Disease Activity ◽  
Wall Thickness ◽  
Bowel Wall ◽  
Treatment Effectiveness ◽  
Observer Agreement ◽  
Close Monitoring ◽  
Bowel Wall Thickness ◽  
Endoscopic Remission

Abstract Background To assess disease activity in ulcerative colitis (UC) intestinal ultrasound (IUS) highly correlates with endoscopic outcomes. However, data on treatment response evaluated with IUS is limited. In this study we aim to evaluate bowel wall thickness (BWT) at follow-up to determine treatment effectiveness in moderate-severe UC patients treated with tofacitinib according to central read endoscopy and histology. Methods Patients with moderate-severe UC (endoscopic Mayo score (EMS)≥2) starting tofacitinib 10 mg bid were included. Disease activity was evaluated by recorded IUS cine-loops and video-taped endoscopies with biopsies from the sigmoid (SC) and descending colon (DC) at baseline and at 8 weeks. BWT and EMS were assessed per segment (SC and DC). Histology was scored for the SC with the Robarts Histology Index (RHI). BWT, EMS and RHI were centrally read and for IUS there was a second reader. Endoscopic remission (ERem) was defined as EMS=0, endoscopic improvement (EI) as EMS≤1 and endoscopic response (ERes) as a decrease of EMS≥1. For statistical analysis a Wilcoxon signed-rank and Spearman’s test were used. Area under the ROC was used to determine optimal cut-off values. Inter-observer agreement was analyzed by intra-class correlation coefficient (ICC). Results 29 patients were included and started tofacitinib. 10% reached complete ERem after 8 weeks, respectively. Per-segment analysis for EMS showed 22% and 53% reaching ER and 40% and 60% having EI in the SC and DC, respectively. BWT in SC and DC correlated highly with the EMS (rho=0.68, rho=0.75, both p&lt;0.0001) and moderately with RHI (rho=0.49, p=0.002). Patients with EMS≥2 after 8 weeks had an increased BWT (SC: 4.32 ± 1.57 mm, DC: 4.38 ± 1.58 mm) when compared to ERem (SC: 2.10 ± 0.67 mm, DC: mean: 2.00 ± 1.18 mm, both p&lt;0.0001) and EI (SC: 2.29 ± 0.76 mm, DC: 2.56 ± 1.38 mm, both p&lt;0.0001) in the similar segment (Figure 1 and 2). BWT decreased after 8 weeks when there was ERes (SC: mean: -2.59 ± 1.44 mm, DC: -1.82 ± 1.01 mm, both p=0.007) and did not when there was no ERes (Figure 3). BWT cut-off values for ERem are reported in Figure 4. Furthermore, agreement for BWT in the SC and DC was excellent (ICC: 0.92 and ICC: 0.89), respectively. Conclusion BWT reduction showed early endoscopic remission, improvement and response after 8 weeks of tofacitinib treatment and correlated with histology in this central read cohort. Furthermore, accurate and reliable cut-off values for BWT in SC and DC were found for endoscopic remission and improvement. Therefore, IUS should be incorporated in the standard follow-up and close monitoring of UC patients.

scholarly journals P198 Practical deep learning tool for the scoring of ulcerative colitis disease activity in central reading

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S263-S264
Author(s):  
M Byrne ◽  
J East ◽  
M Iacucci ◽  
S Travis ◽  
R Kalapala ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Trials ◽  
Disease Activity ◽  
Video Quality ◽  
Opinion Leaders ◽  
Subject Matter Experts ◽  
Web Based ◽  
Software Interface ◽  
Index Of Severity

Abstract Background Central Reading Org.& the pharma industry employ subject matter experts(SMEs)to score videos from sites participating in clinical trials for Ulcerative Colitis(UC).As we are developing Artificial Intelligence(AI)models for scoring purposes,we need to build a new software interface that can incorporate these AI models to aid SMEs,making their determination of the scores for each segment of the video & for the video as a whole.We propose a system that reduces the time for SMEs to review & score videos,improving the accuracy of scoring,with the help of our AI models. Methods We built a web-based interface supported by our AI models which can read,write multiple databases & data stores to read & display videos to be scored by a central reader, as well as the associated metadata required to improve the process.User interface shows a timeline with markers for the segments of the colon,with sections that are blurry,poorly prepped,or unscorable highlighted in different colours.While we could also highlight sections of the video with the precise score assigned to it by the AI,this would bias the central reader’s opinion.We hide the precise score generated by our AI models & instead display 3 colours for low,medium or high disease activity.When a video is loaded to be read by the user,the playback marker is set to the first high disease activity section based on known medical indexes such as the Mayo Endoscopic Subscore(MES) & UCEIS(Ulcerative Colitis Endoscopic Index of Severity),usually consists of a few seconds of video & that video is played back continuously in a loop until the reader selects the appropriate score for that section.When the reader saves the section,the software immediately moves the video cursor to the highest scored section of the video.That way the central reader can review only the relevant portions of the video to confirm the score assigned to each segment.If the central reader’s scores do not align well with the AI scores then the software continues to show more sections of the video to the user,including sections it may have labeled as unscorable,that may be scorable. Results The review of the system by 3 key opinion leaders,user experience was positive.Not only does the system allow the reader’s attention to be more efficiently used,but the interface allows both AI & central reader scores to be saved,allowing for the latter to be used iteratively to re-train & improve the underlying AI model(s).Our tool was also used by a gastroenterologist specialist in order to perform video quality assessment & colon sections scoring. Conclusion We developed an AI tool that can be used to improve the efficiency & accuracy of the central reading process in clinical trials for UC.Further work is ongoing to improve the interface.

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 Milan Ultrasound Criteria are accurate in assessing disease activity in ulcerative colitis: External validation

2020 ◽  
pp. 205064062098020
Author(s):  
Mariangela Allocca ◽  
Elisabetta Filippi ◽  
Andrea Costantino ◽  
Stefanos Bonovas ◽  
Gionata Fiorino ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Disease Activity ◽  
External Validation ◽  
Area Under The Curve ◽  
Complete Agreement ◽  
Tertiary Referral ◽  
Endoscopic Remission ◽  
Inflammatory Bowel ◽  
Disease Unit ◽  
Bowel Ultrasound

Introduction The aim of this study was to provide an external validation of bowel ultrasound (US) predictors of activity in ulcerative colitis (UC) and quantitative Milan Ultrasound Criteria (MUC). Methods Forty-three consecutive patients with UC (16 in endoscopic remission and 27 with endoscopic activity) underwent bowel US and colonoscopy in a tertiary referral inflammatory bowel disease unit. Results A MUC score >6.2 discriminated patients with active versus non-active UC with a sensitivity of 0.85 (95% confidence interval (CI) 0.66‒0.96), specificity of 0.94 (95% CI 0.70‒0.99) and an area under the curve of 0.902 (95% CI 0.772‒0.971) in complete agreement with the derivation study. Conclusion The external validation of MUC confirms that it is an accurate tool for assessing disease activity in patients with UC.

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