DOP68 Histological remission (NANCY index) is superior to endoscopic mucosal healing in predicting relapse-free survival in patients with ulcerative colitis in clinical and endoscopic remission

Abstract Background Fecal calprotectin (FC) is a common surrogate marker of mucosal healing (MH) in patients with ulcerative colitis (UC) and Crohn’s disease (CD). We investigated the optimum FC thresholds for defining endoscopic remission (ER) and histological remission (HR) using advanced endoscopic techniques. Patients and Methods In this cross-sectional study, we collected clinical, endoscopic, histological data, and FC from 76 UC and 41 CD patients. Receiver operating characteristic curves were created to evaluate the optimum cut-off of FC to predict ER evaluated by Mayo Endoscopic Score (MES), Ulcerative Colitis Endoscopic Index of Severity (UCEIS), and modified PICaSSO (Paddington International Virtual Chromoendoscopy Score) for UC patients and Simple Endoscopic Score (SES-CD) in CD patients; and HR was scored by the Robarts Histology Index (RHI) and Nancy Index for UC and modified Riley for CD. Results In UC patients, the best thresholds of FC to identify ER calculated with MES, UCEIS, and modified PICaSSO were 112, 148, and 161 mcg/g with accuracy of 86.9% 86.8%, and 81.6%, respectively. The best value of FC to predict HR was 112 mcg/g and 172 mcg/g with accuracy of 84.2% and 81.6% for RHI and Nancy Index, respectively. In CD patients, the best cut-off of FC to predict ER was 96 mcg/g with accuracy of 82.9%. The HR was best predicted by an FC value of 225 mcg/g with accuracy of 75.6%. Conclusions The FC value threshold between 112 and 172 mcg/g could identify ER and HR in UC patients, whereas a value under 225 mcg/g should be considered for CD patients.

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P383 Relationship between histo-endoscopic mucosal healing and baseline characteristics in patients with moderately to severely active Ulcerative Colitis receiving filgotinib in the phase 2b/3 SELECTION study

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjab076.507 ◽

2021 ◽

Vol 15 (Supplement_1) ◽

pp. S395-S396

Author(s):

L Peyrin-Biroulet ◽

E V Loftus Jr ◽

T Hibi ◽

C Birchwood ◽

C Yun ◽

...

Keyword(s):

Ulcerative Colitis ◽

Mucosal Healing ◽

Active Ulcerative Colitis ◽

Disease Characteristics ◽

Endoscopic Remission ◽

Remission Rates ◽

Baseline Characteristics ◽

Histological Remission ◽

To Receive ◽

Maintenance Study

Abstract Background Filgotinib (FIL), an oral preferential Janus kinase 1 inhibitor, was evaluated for the treatment of ulcerative colitis in the phase 2b/3 double-blind, placebo (PBO)-controlled SELECTION study (NCT02914522). Clinical, histological and endoscopic remission rates at week 58 were significantly greater with FIL 200 mg than with PBO (p < 0.025 for all comparisons). Here, we identify disease characteristics contributing to histo-endoscopic mucosal healing (HEMH; Geboes histological remission and endoscopic subscore ≤ 1) at week 58. FIL 100 mg data are excluded from by-treatment summaries because histological and endoscopic remission rates were not significantly different from PBO in SELECTION. Methods Eligible patients (18–75 years old) with moderately to severely active ulcerative colitis were enrolled in Induction Study A (biologic-naïve) or B (biologic-experienced) and randomized to receive FIL 200 mg, FIL 100 mg or PBO (2:2:1) once daily for up to 11 weeks, with response assessed at week 10. At week 11, FIL responders were re-randomized 2:1 to continue their induction FIL dose or to receive PBO for the 47-week maintenance study. PBO responders continued receiving PBO. For the maintenance study, univariate logistic regression was used to identify baseline and week 10 disease characteristics associated with HEMH (defined as achieving both Geboes histological remission [Grade 0 of ≤0.3, Grade 1 of ≤ 1.1, Grade 2a of ≤ 2A.3, Grade 2b of 2B.0, Grade 3 of 3.0, Grade 4 of 4.0, and Grade 5 of 5.0] and an endoscopic subscore of 0 or 1) at week 58 for patients receiving FIL 200 mg; variables with p < 0.05 in the univariate analysis were included in a multivariate analysis. Results Patients had similar characteristics across the treatment groups for both the induction (Table 1) and maintenance studies (Table 2). HEMH was achieved in a greater proportion of patients receiving FIL 200 mg than those receiving respective PBO at week 58 (32.7% vs 10.2%; p < 0.0001). No associations between disease characteristics (at baseline and week 11) and HEMH at week 58 were found (Table 3). Conclusion FIL 200 mg was effective at establishing HEMH compared with PBO at week 58; there were no baseline characteristics identified to be associated with HEMH at week 58.

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592 Histological Normalization Is Associated With Superior Relapse Free Survival Compared to Histological Activity and Histological Quiescence in Ulcerative Colitis

Gastroenterology ◽

10.1016/s0016-5085(15)30395-4 ◽

2015 ◽

Vol 148 (4) ◽

pp. S-115 ◽

Cited By ~ 2

Author(s):

Britt Christensen ◽

Olufemi Kassim ◽

Jonathan Erlich ◽

Stephen B. Hanauer ◽

David T. Rubin

Keyword(s):

Ulcerative Colitis ◽

Relapse Free Survival ◽

Free Survival ◽

Histological Activity

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Effectiveness of treatment of moderate ulcerative colitis with prolonged mesalazine in real clinical practice

Medical Council ◽

10.21518/2079-701x-2021-15-144-151 ◽

2021 ◽

pp. 144-151

Author(s):

O. V. Knyazev ◽

A. V. Kagramanova ◽

A. A. Lishchinskaya

Keyword(s):

Ulcerative Colitis ◽

Clinical Remission ◽

Topical Therapy ◽

Fecal Calprotectin ◽

Mucosal Healing ◽

Prolonged Release ◽

Mayo Score ◽

Endoscopic Remission ◽

Oral Mesalazine ◽

High Doses

Introduction. Ulcerative colitis (UC) is one of the severe therapeutic diseases. High doses of oral granular mesalazine are required to maintain clinical and endoscopic remission of UC, which may be sufficient and supposedly more acceptable for patients, as some studies showed that adherence to topical therapy is significantly lower than to oral 5-ASA drugs.Objective of the study. To evaluate the efficacy of therapy of patients with moderate left-sided ulcerative colitis (UC) and pancolitis receiving prolonged-release ethylcellulose-coated mesalazine.Materials and methods. The evaluation of the outcomes of treatment of UC patients who received prolonged-release mesalazine was carried out. We examined 87 patients with UC who received granular ethylcellulose-coated mesalazine, of those 38 (43.7%) men and 49 (56.3%) women. The average age of the enrolled patients was 38.3 ± 12.6 years.Results and discussion. After 2 weeks from the beginning of therapy with prolonged-release mesalazine, the majority of patients – 71 (81.6%) responded to the therapy. After 12 weeks, 71 (81.6%) of 87 UC patients, who responded to therapy with prolongedrelease mesalazine, remained in clinical remission. On average, the Mayo score in the group decreased from 7.6 ± 0.99 to 2.6 ± 0.25 points. There was a significant decrease in CRP, ESR, leukocytosis, and fecal calprotectin. After 26 weeks, Mayo score in the group of patients remained on average at the level of 2.2–2.3 points. The number of UC patients with colon mucosal healing was 32 (36.8%) patients. A year after the start of therapy with prolonged-release mesalazine, 69 (79.3%) UC patients who responded to therapy had a clinical remission, of those 32 (36.8%) patients had a clinical and endoscopic remission. During the year of observation, no case of surgical intervention or re-hospitalization due to exacerbation of the disease was recorded in patients with UC who achieved remission.Conclusions. Treatment of moderate active UC should begin with oral mesalazine ≥ 3 g per day in combination with topical mesalazine. The prolonged-release mesalazines are the most preferred

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Is histological remission of ulcerative colitis achievable?

Terapevticheskii arkhiv ◽

10.26442/00403660.2021.08.200981 ◽

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.

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Mucosal healing and histological remission in pediatric ulcerative colitis: Does the target change the outcomes?

Digestive and Liver Disease ◽

10.1016/j.dld.2017.09.055 ◽

2017 ◽

Vol 49 (4) ◽

pp. e262

Author(s):

M. Aloi ◽

G. D’Arcangelo ◽

S. Oliva ◽

M. Peresso ◽

F. Viola ◽

...

Keyword(s):

Ulcerative Colitis ◽

Mucosal Healing ◽

Histological Remission

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

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjab075.008 ◽

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<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<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<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.

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Molecular Signature of Persistent Histological Inflammation in Ulcerative Colitis with Mucosal Healing

Journal of Gastrointestinal and Liver Diseases ◽

10.15403/jgld-576 ◽

2020 ◽

Vol 29 (2) ◽

pp. 159-166

Author(s):

Mircea Manuc ◽

Elena Mirela Ionescu ◽

Elena Milanesi ◽

Maria Dobre ◽

Ioana Tieranu ◽

...

Keyword(s):

Gene Expression ◽

Ulcerative Colitis ◽

Pearson Correlation ◽

Mucosal Healing ◽

Formyl Peptide Receptor ◽

Molecular Signature ◽

Expression Levels ◽

Endoscopic Remission ◽

Formyl Peptide ◽

Gene Expression Levels

Background and Aims: Therapeutic targets in ulcerative colitis (UC) have evolved over time from clinical remission to biological and endoscopic remission. Histologic remission remains a debatable outcome due to lack of data regarding its impact on long-term evolution. The development of histologic activity scores has brought standardization. We aimed to identify mucosal markers differentiating histological inflammation from histological remission in UC patients. Methods: The gene expression levels of 84 genes associated with inflammatory bowel diseases have been analyzed in 43 colonic mucosa samples from 30 patients with UC. The gene expression levels have been correlated with histological inflammation score of Geboes. Patients with endoscopic remission were divided by histological activity into two groups and molecular results were compared in order to identify differences in the mucosal gene expression. Results: We found a significant Pearson correlation (p<0.001 and r>0.5) between the Geboes score and the expression of 29 genes, whereas negative correlation (p<0.001 and r<-0.50) was observed with two genes in the entire UC cohort. In the subgroup of patients with endoscopic remission three transcripts: formyl-peptide receptor 1 (FPR1), matrix metalloproteinases 1 (MMP1) and mucine 1 (MUC1) were significantly up-regulated in patients with histological inflammation compared to patients with histologic remission. Conclusion: Our study further emphasizes the importance of histological assessment when endoscopic mucosal healing is present, as FPR1, MMP-1 and MUC1 were all significantly upregulated in patients with histological alterations.

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Intravenous tacrolimus is a superior induction therapy for acute severe ulcerative colitis compared to oral tacrolimus

BMC Gastroenterology ◽

10.1186/s12876-021-02043-6 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Hiromichi Shimizu ◽

Toshimitsu Fujii ◽

Kenji Kinoshita ◽

Ami Kawamoto ◽

Shuji Hibiya ◽

...

Keyword(s):

Ulcerative Colitis ◽

Cohort Study ◽

Primary Outcome ◽

Remission Rate ◽

Survival Rates ◽

Efficacy And Safety ◽

Relapse Free Survival ◽

Free Survival ◽

Severe Ulcerative Colitis ◽

Intravenous Corticosteroid

Abstract Background Intravenous corticosteroid is the mainstay for managing acute severe ulcerative colitis, but one-third of patients do not respond to intravenous corticosteroid. Tacrolimus, a salvage therapy before colectomy, is usually orally administered, though its bioavailability is low compared intravenous administration. The efficacy of intravenous tacrolimus has not been widely studied. Aim To determine the efficacy and safety of intravenous tacrolimus for the treatment of acute severe ulcerative colitis. Methods Eighty-seven hospitalized acute severe ulcerative colitis patients were enrolled for a prospective cohort study between 2009 and 2017. Sixty-five patients received intravenous tacrolimus and 22 received oral tacrolimus. The primary outcome was the achievement of clinical remission within 2 weeks. Relapse and colectomy incidence and adverse events were assessed at 24 weeks. Results Response rates of both treatments exceeded 50% but were not significantly different. The remission rate was higher in intravenous tacrolimus compared with oral tacrolimus. At 24 weeks, oral and intravenous tacrolimus showed similar relapse-free survival rates; however, colectomy-free survival rates were higher in intravenous tacrolimus compared with oral tacrolimus. Conclusions Patients receiving intravenous tacrolimus achieved superior remission and colectomy-free survival rates compared with patients receiving oral tacrolimus. Safety was similar between the two treatments.

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