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 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.

Novel Leucocyte/Thrombocyte Apheresis for Induction of Steroid-Free Remission in Ulcerative Colitis: A Controlled Randomized Pilot Study

2019 ◽  
Vol 13 (7) ◽  
pp. 949-953 ◽  
Author(s):  
Wolfgang Kruis ◽  
Phuong Nguyen ◽  
Julia Morgenstern ◽  
Wolfgang Ramlow ◽  
Axel Dignaß ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Pilot Study ◽  
Clinical Remission ◽  
Activity Index ◽  
Disease Activity Index ◽  
Oral Prednisolone ◽  
Serious Adverse Events ◽  
Symptomatic Infection ◽  
Reactive Protein ◽  
Group A

Abstract Background and Aims In active ulcerative colitis [UC] refractory to mesalazine, escalation to either steroids or immunosuppression is common practice. The efficacy and safety of alternative escalation therapy with a novel leukocyte apheresis device were studied. Methods This was a prospective, randomized, controlled multicentre pilot study comparing leukocyte apheresis with prednisolone in refractory UC (disease activity index [DAI] ≥ 4 and ≤8). Group A received weekly apheresis over five consecutive weeks. Group P received oral prednisolone 40 mg/day tapered to 0 mg at week 6. The primary end point was steroid-free clinical remission [DAI ≤ 2] at week 12. Clinical response was also analysed. Results Twenty-four patients were enrolled, 13 of whom were randomized into group A and 11 into group P. Clinical remission off steroids at week 12 was achieved in 3/12 patients [25.0%] with apheresis and 2/10 [20.0%] with prednisolone [p = 1.0]. The response rate after 12 weeks was 75.0% in group A and 50.0% in group P. Mean DAI scores improved in both treatment groups [p = 0.008]. C-reactive protein decreased from 6.0 ± 5.3 to 3.8 ± 3.7 mg/L at 12 weeks in group A and increased from 5.2 ± 6.0 to 6.3 ± 7.9 mg/mL in group P. Both treatments were well tolerated. No unexpected serious adverse events were seen in group A. In group P one symptomatic infection with Clostridium difficile occurred. Conclusions In patients with active UC refractory to mesalazine a novel leukocyte apheresis showed promising results. A comparison with prednisolone revealed similar therapeutic effectivity and excellent safety, providing the chance to escalate without systemic steroids.

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 < 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.

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.

scholarly journals Faecal Calprotectin Is a Very Reliable Tool to Predict and Monitor the Risk of Relapse After Therapeutic De-escalation in Patients With Inflammatory Bowel Diseases

2019 ◽  
Vol 13 (8) ◽  
pp. 1012-1024 ◽  
Author(s):  
Anthony Buisson ◽  
Wing Yan Mak ◽  
Michael J Andersen ◽  
Donald Lei ◽  
Stacy A Kahn ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Roc Curve ◽  
Clinical Remission ◽  
Activity Index ◽  
Area Under The Curve ◽  
Daily Practice ◽  
Clinical Relapse ◽  
Faecal Calprotectin ◽  
Inflammatory Bowel ◽  
Risk Of Relapse

AbstractAimsTo assess faecal calprotectin [Fcal] levels before and after therapeutic de-escalation, to predict clinical relapse in patients with inflammatory bowel disease [IBD].MethodsFrom a prospectively maintained database, we enrolled 160 IBD patients [112 Crohn’s disease/48 ulcerative colitis] in clinical remission, with Fcal measured within 8 weeks before therapeutic de-escalation. Clinical relapse was defined using the Harvey-Bradshaw index or Simple Clinical Colitis Activity Index.ResultsUsing a receiver operating characteristic [ROC] curve, Fcal >100 µg/g was the best threshold to predict clinical relapse after therapeutic de-escalation (area under the curve [AUC] = 0.84). In multivariate analysis, clinical remission >6 months before therapeutic de-escalation (hazard ratio [HR] = 0.57 [0.33–0.99]; p = 0.044) was associated with decreased risk of relapse, whereas current steroid medication ( = 1.67[1.00–2.79]; p <0.0001) was a risk factor. Fcal >100 µg/g was predictive of clinical relapse (HR = 3.96 [2.47–6.35]; p < 0.0001) in the whole cohort but also in patients receiving anti-tumour necrosis factor [TNF] agents [n = 85 patients; p <0.0001], anti-integrins [n = 32; p = 0.003], or no biologics [n = 43; p = 0.049], or attempting to discontinue steroids [n = 37; p = 0.001]. One patient [1/98] and seven patients [7/88, 8.0%] with baseline Fcal <100 µg/g relapsed within 3 months and 6 months after therapeutic de-escalation, respectively. A total of 74 Fcal measurements were performed in 52 patients after therapeutic de-escalation. Monitoring Fcal >200 µg/g [ROC curve with AUC = 0.96] was highly predictive of clinical relapse in multivariate analysis ([HR = 31.8 [3.5–289.4], p = 0.002). Only two relapses [2/45, 4.4%] occurred within 6 months while Fcal <200 µg/g.ConclusionsFcal level is highly accurate to predict and monitor the risk of relapse after therapeutic de-escalation in IBD patients and could be used in daily practice.

scholarly journals P537 Real-world long-term effectiveness of ustekinumab in Crohn’s disease: Results from the ENEIDA registry

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S458-S460
Author(s):  
M I Iborra Colomino ◽  
B Beltrán ◽  
A Fernández-Clotet ◽  
E Iglesias Flores ◽  
P Navarro ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Real World ◽  
Clinical Remission ◽  
Poor Response ◽  
Faecal Calprotectin ◽  
The Real ◽  
Reactive Protein ◽  
Endoscopic Remission

Abstract Background There are limited data of long-term ustekinumab administered according to the doses recommended in the UNITI studies. The objective of this study was to assess the real-world, long-term effectiveness of ustekinumab in refractory Crohn’s disease (CD) (LONG-CROHNUSK Study). Methods Multicentre study of CD patients starting ustekinumab at the recommended dose based on weight ~6 mg/kg IV week 0, 90 mg SC week 8 and maintenance 90 mg SC every 8 or 12 weeks and with 1 year of follow-up. Values for Harvey-Bradshaw Index (HBI), endoscopic activity, C reactive protein (CRP) and faecal calprotectin (FC) were recorded at baseline and at weeks 26 and 52. Demographic and clinical data, previous treatments, adverse events (AEs), surgeries and hospitalisations were documented. Potential predictors of clinical and endoscopic remission were examined. Results Four hundred and seven patients were analysed (Table 1). For the maintenance dose, ustekinumab 90 mg was administered SC every 12, 8 and 4 weeks in 56 (14%), 318 (84.5%) and 7 (1.5%) patients, respectively. An interval reduction was applied for 118 patients (29%). Before 52 weeks, treatment discontinuation occurred in 71 patients (17%). At baseline, 295 (72%) had an HBI >4 points. Of these, 169 (57%) and 190 (64%) achieved clinical remission at weeks 26 and 52, respectively. FC levels returned to normal (<250 μg/g) in the 44% and 54% of the patients at weeks 26 and 52, respectively. CRP returned to normal (<3 mg/l) in 36% and 37% of the patients at weeks 26 and 52 respectively. HBI, FC, and CRP values over time are shown in Figure 1. Of the 159 patients with endoscopy at 52 weeks, 25 (16%) were in remission and 58 (36%) presented mild activity. Thirty-eight (9.3%) patients worsened extra-intestinal manifestations and 33 (8%) their perianal disease. AEs were recorded in 54 patients, 73 were hospitalised and 53 had surgery. An association was shown for fewer previous anti-TNF agents and ileal localisation with clinical remission, and for endoscopic severity at baseline with poor response. No factors correlated with endoscopic remission. Conclusion This is the first study to show the real-world long-term effectiveness, endoscopic improvement and safety of ustekinumab administered according to the recommended induction regimen in a cohort of highly refractory CD patients.

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 P291 Diagnostic utility of the neutrophil-platelet rate (NeuPla) as a marker of activity in patients with ulcerative colitis

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S298-S298
Author(s):  
J K Yamamoto-Furusho ◽  
E A Mendieta-Escalante
Keyword(s):  
Ulcerative Colitis ◽  
Complete Blood Count ◽  
Area Under The Curve ◽  
Easy Access ◽  
Differential Count ◽  
Diagnostic Utility ◽  
Moderate Activity ◽  
C Reactive Protein ◽  
Faecal Calprotectin ◽  
Reactive Protein

Abstract Background Ulcerative colitis (UC) is a chronic disease characterised by periods of activity and remission. There are biomarkers such as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and faecal calprotectin that are elevated in patients with active UC. The platelet, one of the main activators of neutrophils, contains IL-8, a potent neutrophil chemo-attractant and P-selectin that induces excretion of superoxide in the neutrophils, forming platelet-neutrophil aggregates that are increased in individuals with UC activity. No previous studies have evaluated the neutrophil-platelet (NeuPla) rate as a tool for evaluating disease activity. The aim of this study was to evaluate the clinical utility of NeuPla rate in patients with UC. Methods A total of 158 patients with a definitive diagnosis of UC were included and NeuPla index was calculated on the ratio between neutrophil differential count and platelets from complete blood count (CBC) at least 1 day after the colonoscopy and colon biopsies. The activity was classified according to Mayo endoscopic sub-score, Riley score, Truelove-Witts, Montreal, full Mayo, and Yamamoto-Furusho indexes. Results The correlation of the NeuPla index with all activity indexes was statistical significant (p <0.001) as well as faecal calprotectin (rho: 0.532, p = .0001). The ROC curve was used to determine the cut off level of NeuPla according to moderate activity (optimal cut off 14.63 with a sensibility of a 79.5% and specificity of 51.3% with an Area Under the Curve (AUC) of .635 and severe activity (optimal cut off 18.7 with a sensibility of 80% and specificity of 81.8% AUC of .749) considering as a gold standard the endoscopy findings as shown in Figure 1. Conclusion The NeuPla index has a good diagnostic utility in order to distinguish patients with clinical and endoscopic activity without the need to perform invasive studies such as colonoscopy. This index is a cheap and easy access monitoring tool and a better diagnostic performance in comparison with other serum biomarkers CPR, ESR and serum albumin.

scholarly journals P348 Clinical outcomes and response predictors of vedolizumab treatment for anti-TNF-failed patients with IBD in Korea: A prospective multicenter cohort study

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S333-S334
Author(s):  
J Kim ◽  
H Yoon ◽  
K M Lee ◽  
S A Jung ◽  
D I Park ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Response ◽  
Clinical Outcomes ◽  
Induction Therapy ◽  
Clinical Remission ◽  
Response Rates ◽  
Faecal Calprotectin ◽  
Korean Patients ◽  
Response Predictors ◽  
Endoscopic Remission

Abstract Background Vedolizumab (VDZ) inhibits gut lymphocyte trafficking by binding to α4β7 integrin, which can be effective for patients with Crohn’s disease (CD) or ulcerative colitis (UC). We aimed to investigate the clinical outcomes and response predictors of VDZ treatment for Korean patients with CD or UC, who were previously failed to anti-tumour necrosis factor (TNF) therapy. Methods Between August 2017 and November 2019, a total of 159 patients with CD (n = 81) or UC (n = 78) received a VDZ induction therapy from 16 centres and were prospectively enrolled. Of those, patients who were evaluated at week 14 after three induction doses of VDZ (week 0, 2, and 6) were analysed. The co-primary endpoints were corticosteroid-free clinical remission and endoscopic remission/response (for UC) at week 14. We also analysed predictors of corticosteroid-free clinical remission, persistence of vedolizumab and safety. Results A total of 153 patients were analysed (CD, 77 [50.3%]; male, 94 [61.4%]; median age, 40 years [range, 17–80]; median disease duration, 8.0 years [range, 0.1–38.0]). All patients had previously experienced failures to at least one anti-TNF agent (one, 105 [68.6%]; two, 44 [28.8%]; three, 4 [2.6%]). Corticosteroid-free clinical remission/response rates in CD and UC patients were 44.6%/51.8% and 39.4%/62.0%, respectively. In patients with UC, endoscopic remission and response rates defined by Mayo endoscopic subscore/ulcerative colitis endoscopic index of severity were 33.8%/14.1% and 55.4%/39.1%, respectively. Multivariate analysis revealed that a clinical response at week 6 were associated with a corticosteroid-free clinical remission at week 14 in both CD (Odds ratio [OR] 33.84, 95% confidence interval [CI] 6.25–183.31, p < 0.001) and UC (OR 12.22, 95% CI 1.30–115.28, p = 0.029). In addition, UC patients with higher baseline levels of C-reactive protein (CRP) and faecal calprotectin were less likely to be in corticosteroid-free clinical remission (CRP > 0.31 mg/dl: OR 0.05, 95% CI 0.00–0.60, p = 0.019; faecal calprotectin > 2,000 μg/g: OR 0.04, 95% CI 0.00–0.93, p = 0.045). The cumulative probabilities of continuing VDZ after one year were 48.7% for CD and 65.7% for UC, respectively. During median 10 months of follow-up periods (range, 3–26 months), disease exacerbation was the most common adverse event (n = 73, 47.7%), followed by nasopharyngitis (n = 23, 15.0%) and arthralgia (n = 19, 12.4%). Conclusion In anti-TNF-failed Korean patients with CD and UC, VDZ induction therapy was effective with an acceptable safety profile. Early clinical response and higher inflammatory burden at baseline were associated with corticosteroid-free clinical remission after VDZ induction therapy.

scholarly journals A15 EFFICACY AND SAFETY OF FILGOTINIB AS INDUCTION THERAPY FOR PATIENTS WITH MODERATELY TO SEVERELY ACTIVE ULCERATIVE COLITIS: RESULTS FROM THE PHASE 2B/3 SELECTION STUDY

2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 18-20
Author(s):  
B G Feagan ◽  
E V Loftus ◽  
S Danese ◽  
S Vermeire ◽  
W J Sandborn ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Induction Therapy ◽  
Clinical Remission ◽  
Active Ulcerative Colitis ◽  
Treatment Groups ◽  
Disease Characteristics ◽  
Serious Infections ◽  
Endoscopic Remission ◽  
Induction Study ◽  
Secondary Endpoints

Abstract Aims The SELECTION (NCT02914522) Induction Studies evaluated the efficacy/safety of filgotinib (FIL), a preferential JAK1 inhibitor, as induction therapy for patients (pts) with moderately to severely active ulcerative colitis (UC) who were biologic-naïve but failed conventional therapy (Induction Study A) or failed prior biologics (Induction Study B). Methods Pts were randomized 2:2:1 to once–daily FIL 200mg, FIL 100mg or placebo (PBO). The primary (clinical remission), key secondary (Mayo Clinic Score [MCS] remission, endoscopic remission, and histologic remission), and exploratory endpoints (MCS response and endoscopic improvement) were assessed at Week 10. Results In both studies, baseline demographics and disease characteristics were similar across treatment groups. In Study A, 659 pts were randomized and treated. Baseline mean MCS was 8.6 and 56% had a Mayo endoscopic subscore (ES)=3. A significantly higher proportion of biologic-naïve pts on FIL 200mg achieved clinical remission vs PBO and all key secondary endpoints (Table). In Study B, 689 pts were randomized and treated. Baseline mean MCS was 9.3 and 78% had ES=3. Prior treatment failures were: anti-TNF (86%), vedolizumab (52%) and both (dual-refractory; 43%). A significantly higher proportion of biologic-experienced pts on FIL 200mg achieved clinical remission vs PBO. In Studies A and B, a greater proportion of pts on FIL 200 mg achieved an MCS response and endoscopic improvement vs PBO. The rates of AEs, serious AEs and discontinuations due to AEs were similar across FIL and PBO groups during induction. In the PBO, FIL 100mg and FIL 200mg groups, serious infections occurred in 0.7%, 0.7% and 0.4% pts in Study A and 1.4%, 1.4% and 0.8% pts in Study B; H Zoster occurred in <1% in both groups for both cohorts. Conclusions SELECTION included a high proportion of dual-refractory pts, and pts with severe endoscopic disease. Both doses of FIL were well tolerated. Filgotinib 200mg was effective induction therapy for both biologic-naïve/-experienced pts with moderately to severely active UC. Funding Agencies None

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