Fecal calprotectin-guided treatment escalation strategy enhances disease clearance in ulcerative colitis.

Background Disease clearance (DC), defined as combined clinical, endoscopic and histologic remission, has been proposed as the ultimate therapeutic target in ulcerative colitis (UC). However, the addition of faecal calprotectin (FC) remission to DC, now proposed as ‘extensive disease clearance (EDC)’, in predicting for relapse is unknown. We aimed to explore the use of composite therapeutic endpoints, including DC and EDC, in predicting long-term outcomes for UC patients on vedolizumab (VED). Methods The phase IV Vedolizumab Immunomodulator Enforced Withdrawal Study (VIEWS) prospectively recruited UC patients in steroid-free clinical remission on VED 300mg IV q8w. Baseline evaluation (week 0) included FC, endoscopy, histology and serum VED trough levels. Remission definitions were FC<150µg/g, centrally-read Mayo endoscopic score (MES)=0 and Nancy index (NI)=0. FC value differentiated DC and EDC. DC was defined as FC≥150µg/g, MES=0 and NI=0. EDC was defined as FC<150µg/g, MES=0 and NI=0. Clinical relapse, defined as partial Mayo score ≥3 and FC≥150µg/g or MES increase of ≥1, was evaluated for 2 years. Cox regression, Kaplan-Meier curves and log rank statistics were performed to assess the time to clinical relapse. Odds ratios (OR) and 95% confidence intervals (CI) were calculated for dichotomous categorial variables. Multivariate logistic regression models were performed to identify predictive factors of relapse. P<0.05 was deemed statistically significant (SPSS, IBM, USA). Results 62 consecutively recruited UC patients were followed over 24 months. Of 54 patients with endoscopic assessments at baseline, 80% were in endoscopic remission, 76% histologic remission, 68% had DC, and 63% had EDC. Baseline EDC was associated with significantly lower rates of clinical relapse compared with DC and clinical/endoscopic remission alone (log rank P<0.001; HR: 0.17 [95%CI:0.04-0.64], P=0.009) (Figure 1). Baseline EDC had an OR of 0.16 (95%CI:0.04-0.75, P=0.01) in predicting relapse, versus DC (OR: 0.20 [95%CI:0.05-0.89], P=0.03), endoscopic remission (OR:0.91 (95%CI:0.16-5.15), P=0.92), histologic remission (OR: 0.10 [95%CI:0.02-0.50], P=0.002), and neither endoscopic nor histologic remission (OR:4.44 [95%CI:0.55-35.90], P=0.13). Univariate predictors of EDC at baseline were female sex (P=0.03), UC disease duration < 5 years (P=0.01), smoking status (P=0.004) and serum VED concentrations (P=0.03). On multivariate analysis, only female sex (OR: 7.0 [95%CI: 1.17-42.33], P=0.03) predicted for EDC. Conclusion EDC, a novel composite endpoint, predicted for significantly lower rates of relapse compared with DC in UC patients on VED. Female sex was associated with baseline EDC. FC should be incorporated into composite endpoints with endoscopy and histology.

Background Current treatment goals in inflammatory bowel disease include clinical remission and endoscopic healing. A new concept of disease clearance (DC) is emerging as a new therapeutic target in ulcerative colitis (UC). Although not yet clearly defined, it reflects a combination of clinical, endoscopic, and histological remission1. Preliminary data suggest that DC is achievable with biologic therapy. Aim: to evaluate if patients treated with, 5-ASA with DC can maintain sustained remission and the incidence of negative disease outcomes. Methods We performed a retrospective cohort study including adult patients with confirmed UC treated with, 5-ASA. Patients performing colonoscopy with biopsies between, 2017 and, 2019, with at least, 1 year of follow-up were eligible for inclusion. DC was measured at baseline and was defined as clinical (partial Mayo score ≤2), endoscopic (endoscopic Mayo score ≤1) and histological remission (chronic inactive/quiescent colitis)1. Negative disease outcomes included need for systemic steroids, therapy escalation (immunomodulators and/or biologics) and UC-related hospitalization or surgery during follow-up. Kaplan-Meier analysis was performed. Results We included, 56 patients with UC treated with, 5-ASA and with DC at baseline. Mean age at diagnosis was, 41.2 ±, 15 years, 59% (n=33) were female and mean disease duration was, 6.9 ±, 7.3 months. History of smoking (current or former) was present in, 36% (n=20) of the patients. Most of the patients (54%) presented with left-sided colitis. Mean follow-up was, 34.6 ±, 10.7 months. During the follow-up, 14.3 % (n=8) had a negative outcome (flare requiring systemic corticosteroids (n=6), therapy escalation to immunomodulator or biologic treatment (n=6) or hospitalization (n=1)). None of the patients needed surgery. Negative outcomes were associated with shorter disease duration (3.4 vs, 7.4 years, p=0.003). No other factors were associated with the outcomes namely sex, UC extent, smoker status, age at diagnosis or previous use of corticosteroids. There was no difference on prognosis between patients with baseline endoscopic Mayo score, 0 or, 1 (p=, 0.066). In the survival analysis, the cumulative probability of maintaining remission was, 76% at, 3 years. Conclusion DC in UC patients treated with, 5-ASA was associated with a high cumulative probability of maintaining remission, suggesting that the benefits of such stringent endpoint may be independent of the therapy used. Reference 1. S Danese, S Schreiber, E Loftus, Jr., J F Colombel, L Peyrin-Biroulet, C Agboton, D Lindner, R Lirio, B Sands, P271 Evolving Targets in Ulcerative colitis: Defining Disease Clearance in the VARSITY Study, Journal of Crohn’s and Colitis,Volume, 15, Issue Supplement1, May, 2021, Page S305

Danese et al. described the association between early disease clearance and long-term outcomes in patients with ulcerative colitis (UC) treated with ustekinumab in the UNIFI study [1]. In this phase 3 study, participants were randomised to intravenous ustekinumab induction (130 mg or ~6 mg/kg) or placebo, and subcutaneous ustekinumab maintenance (90 mg every 8 or 12 weeks) or placebo, with the option to enrol in the long-term extension, remaining on maintenance therapy up to 220 weeks [2]. Danese et al. have described how disease clearance, defined here as combined symptomatic remission and histo-endoscopic mucosal improvement (HEMI), was associated with improved long-term clinical, endoscopic, and histologic outcomes. The term ‘disease clearance’ was coined in 2020 as an ambitious target in UC aimed at improving treatment outcomes, reducing complications, and potentially modifying the natural history of disease [3]. Current guidelines recommend endoscopic healing, normalised quality-of-life, and absence of disability as the long-term treatment goals, with histological healing considered an aspirational target, mainly due to a dearth of interventional trials assessing this endpoint [4]. Danese et al. demonstrated that disease clearance is feasible in UC as early as 8 weeks, with 15.2% and 15.1% of ustekinumab-treated patients (130 mg and 6 mg/kg, respectively) achieving this aspirational treatment target. Rates of disease clearance increased at Week 44 of maintenance treatment, with 36.6% (ustekinumab 130 mg) and 41.6% (ustekinumab 6 mg/kg) of participants achieving disease clearance. These data add to the evidence that disease clearance, beyond histological healing, is attainable in UC [5, 6]. Disease clearance has been associated with significantly lower risk of UC-related hospitalisation and surgery [7]. In the UNIFI study, disease clearance at Week 8 was associated with significantly higher rates of clinical remission, symptomatic remission, histological improvement, endoscopic improvement, and HEMI at Week 44 (p < 0.001 for all outcomes), when compared to those who did not achieve disease clearance. Patients who achieved disease clearance were less likely to have treatment failure than those who did not achieve either symptomatic remission or HEMI (p < 0.001), or those who achieved symptomatic remission but not HEMI (p = 0.043). While the UNIFI long-term data are encouraging for the merits of attaining disease clearance in UC, it is not presented whether disease clearance imparts prognostic benefit beyond endoscopic remission or histological improvement. Furthermore, while early disease clearance is associated with improved long-term outcomes in UC, this is vastly different to escalating therapy sequentially to achieve this target. VERDICT (NCT04259138), a randomised-controlled trial which aims to determine the optimal treatment target in moderate-to-severe UC, will shed light on whether disease clearance leads to better outcomes than corticosteroid-free histologic remission. UNIFI has established that aspirational treatment targets, including disease clearance, are achievable and associated with improved long-term outcomes in patients with UC. We await further evidence to better understand whether therapy should be escalated to achieve disease clearance, or whether this remains a stride too far. R. M. Mathias: conceptualization, writing – original draft, writing – review and editing. D. Bogatic: conceptualization, writing – original draft, writing – review and editing. R. V. Bryant: conceptualization, writing – original draft, writing – review and editing. R.M. Mathias has received honorarium travel support from Dr. Falk Pharmaceuticals. D. Bogatic has received research support from The Gutsy Group and BiomeBank. R.V. Bryant has received grant/research support/speaker honoraria/advisory board fees from AbbVie, Ferring, Janssen, Shire, Takeda, GlaxoSmithKline, Bristol Myers Squibb, and Emerge Health; and is a shareholder in BiomeBank. This article is linked to Danese et al. papers. To view this article, visit https://doi.org/10.1111/apt.70264. Data sharing not applicable to this article as no datasets were generated or analysed during the current study.

Background In VARSITY, the first head-to-head randomized controlled trial of biologics, vedolizumab (VDZ) was superior vs adalimumab (ADA) in achieving clinical remission (CR) at Week 52 in patients (pts) with moderate to severe ulcerative colitis (UC).1 Current treatment goals in UC are based on clinical symptoms and endoscopy, with histologic improvement considered an aspirational goal.2-4 In pts with CR in VARSITY, greater treatment differences between VDZ and ADA at Week 52 were seen in endoscopic improvement and histologic response. Here, data from VARSITY were used to define disease clearance: a novel composite outcome in UC comprising clinical and endoscopic remission plus minimal histologic disease activity. Methods VARSITY was a phase 3b, randomized, double-blind, double-dummy, active-control trial of treatment with VDZ (300mg IV Q8W) vs ADA (40mg SC Q2W) maintenance after induction. Pts were randomized in a treat through design, and no dose escalation was allowed. For these analyses, based on pts who completed the study until Week 52, disease clearance was defined as a composite outcome based on 1) CR: partial Mayo score ≤2 and no individual subscore &amp;gt;1 (excluding sigmoidoscopy subscore); 2) endoscopic improvement: endoscopic subscore ≤1; and 3) absence of active histologic disease (minimum histological disease activity [MHDA]): Robarts Histology Index (RHI) &amp;lt;5. Treatment failure was defined as discontinuation from treatment or completion of treatment but failure to achieve any of CR, endoscopic improvement, or MHDA. The rates of disease clearance and failures were compared between treatment groups and stratified by presence of inflammatory burden at baseline: C-reactive protein ≥5 mg/L and fecal calprotectin &amp;gt;100 µg/g. Results More pts in the VDZ treatment group than the ADA group achieved disease clearance at Week 52 (VDZ: 112/383, 29.2%, 95% CI 24.7-34.1 vs ADA: 63/386, 16.3%, 95% CI 12.8-20.4). Compared with treatment failures (VDZ: 92/383, 24.0% vs ADA: 134/386, 34.7%, Table 1), disease clearers had lower C-reactive protein (CRP) baseline mean values (7.4mg/L and 6.4mg/L vs 13.6mg/L and 9.4mg/L for disease clearers vs treatment failures, for VDZ and ADA, respectively). Fewer pts with inflammatory burden at baseline (CRP ≥5 mg/L and fecal calprotectin &amp;gt;100 µg/g) achieved disease clearance (Fig 1). Baseline corticosteroid use was more frequent in ADA disease clearers (42.9%) compared with VDZ disease clearers (32.1%). Conclusion Disease clearance is a novel and achievable composite outcome that is achieved by almost one third of pts in the VDZ treatment group in VARSITY. Analyses are ongoing to further characterize the trajectory leading to disease clearance as well as the role of baseline characteristics.

Background Symptom control and endoscopic endoscopic healing have been the main treatment targets in patients with ulcerative colitis (UC). Recently, the concept of disease clearance has been proposed as a potential target in UC. We aimed to evaluate the impact of disease clearance on long-term outcomes in patients with UC. Methods A multicenter retrospective cohort study was conducted at the Humanitas Research Hospital-IRCCS (Italy) and at the Nancy University Hospital (France) between January 2014 and February 2021. All consecutive adult patients with confirmed UC undergoing colonoscopy with biopsies and available histological reports and clinical data within one month of colonoscopy were eligible for inclusion. Disease clearance was defined as clinical (partial Mayo score ≤2 with no subscore &amp;gt;1), endoscopic (endoscopic Mayo score= 0), and histological (Nancy index= 0) remission of disease. The first available endoscopic procedure was considered as baseline. Disease clearance was measured at baseline and during follow-up by comparing the occurrence of negative disease outcomes in patients who achieved or not disease clearance. Results A total of 302 patients were included (46.4% female). Disease clearance was detected in 42 patients (13.9%) at baseline. Median follow-up was 32.2 ± 20.2 months. No patient achieving disease clearance underwent surgery during follow-up compared with 22 subjects in the non-disease clearance group (0.0% vs 8.5%, p=0.1). Similarly, a lower hospitalization rate was detected in patients with disease clearance at baseline compared with the control group (7.1% vs 25.4%, p=0.01). Interestingly, 51/302 patients (16.9%) achieved both endoscopic and histologic remission. This subgroup experienced a significantly lower rate of hospitalization (7.8% vs 25.9%, p=0.008) and surgery (0.0% vs 8.8%, p=0.05) compared with patients with endoscopic and/or histologic disease activity. The Kaplan Meier curves confirmed that patients with disease clearance at baseline had a lower risk for surgery (p=0.04) and hospitalization (hazard ratio (HR)= 0.49, 95% confidence interval (CI) 0.08–2.29, p=0.009) (Figures 1–2). Conclusion Disease clearance is a new outcome that simultaneously takes into account remission of symptoms, endoscopy and histology. Patients with disease clearance are at significant lower risk for hospitalization and surgery and could be the ultimate therapeutic target for full disease control.

Background Intestinal inflammation even without endoscopic evidence is associated with worse clinical outcomes in ulcerative colitis (UC) . However, recent advances in UC treatments have the potential to modify the disease’s natural history and improve clinical outcomes if inflammation is controlled. The emerging concept of "disease clearance" (DC) in UC aims to achieve combined clinical, endoscopic, and histological remission. Whether DC is associated with better outcomes remains unclear. Objective To evaluate the impact of DC during follow-up in UC patients. Methods A prospective longitudinal cohort study was conducted between 2012 and 2017. Consecutive UC patients undergoing colonoscopy were included, and those with clinical follow-up longer than 18 months were analyzed. At the time of colonoscopy, clinical condition (PRO: number of stools per day and presence of blood in the stool) and endoscopic index (Mayo endoscopic score, MES) were evaluated. Histological analysis (Geboes score, GS) of biopsies from the area with the greatest macroscopic inflammation was performed. Disease clearance was defined as simultaneous clinical (PRO2 = 0; normalized stool frequency without blood), endoscopic (MES = 0), and histological (GS ≤ 2) remission. Patients were monitored every 6 months to assess negative outcomes, defined as clinical relapse requiring therapy, treatment escalation, hospitalization, or colectomy. Results A total of 101 UC patients were included (50 females; 44.5 ± 15 years; UC extent: E3: 32.3%, E2: 52.5%, E1: 15.2%; median time since diagnosis: 103 ± 102 months; 13.3% on anti-TNF agents). DC was present in 52 patients (51.5%) at baseline colonoscopy. During follow-up, 40 patients (39.6%) experienced a negative outcome, most commonly requiring corticosteroids (57.6%). Patients who achieved DC had a significantly lower rate of negative outcomes compared to those without DC (21.2% vs. 59.2%, p &amp;lt; 0.0001). Kaplan-Meier curves confirmed a lower risk of clinical relapse in patients with DC (log-rank, p = 0.001) (Fig. 1). Among patients with endoscopic remission (MES = 0; n = 60), only those with DC (n = 52) had a lower risk of negative outcomes (21.2% vs. 75%, p = 0.005, log-rank, p = 0.0015) (Fig. 1A). Additionally, achieving DC reduced the risk of flare-ups even in patients with clinical remission (PRO2 = 0) (p = 0.044) (Fig.1B) or histological remission (GS ≤ 2) (p = 0.039) (Fig. 1C). Conclusion DC in UC patients reduces the risk of negative outcomes during follow-up, supporting its inclusion as a key composite treatment goal in UC management.

Background Managing inflammatory bowel disease (IBD) during pregnancy is challenging as pregnancy-related symptoms may overlap with symptoms of active IBD. Fecal calprotectin (FCP) is an optimal non-invasive measure of assessing disease activity during pregnancy. However, regular FCP during pregnancy may be impractical due to collection techniques. Rather, a home point-of care rapid lateral assay FCP test such as IBDoc® and a self-reported clinical disease activity program (IBD Dashboard) may be beneficial in routine monitoring of IBD activity during pregnancy. Aims To assess whether tight control of objective IBD disease activity using a point-of-care FCP (IBDoc®) monitoring is concordant with self-reported clinical symptoms (IBD Dashboard) in pregnant women with IBD. Methods Pregnant patients, aged ≥18 years, with IBD (Crohn’s Disease (CD) or Ulcerative colitis (UC)), in the 1st trimester (&amp;lt;13 weeks) with a singleton pregnancy were identified and enrolled. Patients were required to have access to a smartphone and internet to use the IBDoc® and IBD Dashboard. Patients completed a IBDoc® FCP and IBD Dashboard assessment at three study time points, 1) screening/baseline in 1st trimester, 2) 2nd trimester (14 to 18 weeks), and 3) 3rd trimester (28 to 32 weeks). Clinical disease activity was assessed by the modified HBI (Harvey Bradshaw Index) for CD and partial Mayo Index (pMayo) for UC. Elevated FCP (≥250 µg/g), mHBI ≥5 or pMayo ≥2 triggered an intervention to investigate or optimize therapy if required. A 5-point Likert scale questionnaire assessed patient satisfaction and feasibility of the IBDoc® and IBD Dashboard. Median values with interquartile ranges (IQR) were calculated for all continuous variables using SPSS. Results 29 patients (17 CD, 12 UC) were included. Median mHBI and pMayo were 2.0 (IQR 2.0) and 0.5 (IQR 1.25) respectively. A total of 17.6% (3/17) of CD patients, and 25.0% (3/12) of UC patients had active clinical disease. Median IBDoc® FCP was 73 µg/g (IQR 343) in the CD group and 267 µg/g (IQR 677) in the UC group. At baseline, disease activity was categorized into four groups: 1) clinical remission (CR) and normal FCP (n=16, no treatment Δ, 100% stayed in CR); 2) clinical disease and elevated FCP (n=5, treatment Δ in all five patients, 80% stayed in CR, 20% had a clinical flare); 3) clinical remission and elevated FCP (n=5, treatment Δ in three patients, 100% stayed in CR); 4) clinical disease and normal FCP (n=1, no treatment Δ, 100% stayed in CR). Median IBDoc® and IBD Dashboard feasibility scores were 5.0 (IQR 1.0). Conclusions A combination of both clinical scores and objective disease markers may better predict disease relapse compared to either clinical scores or objective markers in isolation. A home point-of-care FCP test is feasible among pregnant patients with IBD. Funding Agencies None

BACKGROUNDAlthough the usefulness of endoscopic scores, such as the Mayo Endoscopic Subscore (MES), Ulcerative Colitis Endoscopic Index of Severity (UCEIS), and Ulcerative Colitis Colonoscopic Index of Severity (UCCIS), and biomarkers such as fecal calprotectin (FC) for predicting relapse in ulcerative colitis (UC) has been reported, few studies have included endoscopic scores for evaluating the entire colon.AIMTo compare the usefulness of FC value and MES, UCEIS, and UCCIS for predicting relapse in patients with UC in clinical remission.METHODSIn total, 75 patients with UC in clinical and endoscopic remission who visited our institution between February 2019 and March 2022 were enrolled. The diagnosis of UC was confirmed based on the clinical presentation, endoscopic findings, and histology, according to the current established criteria for UC. Fecal samples were collected the day before or after the colonoscopy for measurement of FC. Endoscopic evaluations were performed using MES, UCEIS, and UCCIS. The primary outcome measure of this study was the assessment of the association between relapse within 12 mo and MES, UCEIS, UCCIS, and FC. The secondary outcome was the comparison between endoscopic scores and biomarkers in enrolled patients with UC with mucosal healing.RESULTSFC and UCCIS showed a significant correlation with UCEIS (r = 0.537, P < 0.001 and r = 0.957, P < 0.001, respectively). Receiver-operating characteristic analysis for predicting MES 0 showed that the area under the curve of UCCIS was significantly higher than that of FC (P < 0.01). During the 1-year observation period, 18 (24%) patients experienced a relapse, and both the FC and UCCIS of the relapse group were significantly higher than that of the remission group. The cut-off values for predicting relapse were set at FC = 323 mg/kg and UCCIS = 10.2. The area under the curve of the receiver-operating characteristic analysis for predicting relapse did not show a significant difference between FC and UCCIS. The accuracy of the endoscopic scores and biomarkers in predicting relapse was 86.7% for UCCIS, 85.3% for UCEIS, 76.0% for FC, and 73.3% for MES.CONCLUSIONThe three endoscopic scores and FC may predict UC relapse during clinical remission. Among these scores, UCEIS may be the most useful in terms of ease of evaluation and accuracy.

Background and aimsConcurrent achievement of symptomatic, endoscopic, and histologic remission, known as disease clearance, has been proposed as a treatment target in ulcerative colitis. Mirikizumab, an anti-interleukin-23p19 antibody, has demonstrated long-term efficacy and safety, as reported in the LUCENT Phase 3 trials (NCT03518086, NCT03524092, and NCT03519945). The current analysis evaluates the impact of mirikizumab on disease clearance and its association with other clinical and patient-reported outcomes (PROs).MethodsLUCENT methods have previously been reported. The proportion of patients achieving disease clearance was determined through week (W)104. Association analyses were assessed between disease clearance and PROs (IBDQ, SF-36, WPAI: UC, PGRS, and PGRC), and early disease clearance and subsequent clinical outcomes (clinical, corticosteroid-free, endoscopic, histological, histologic-endoscopic, bowel urgency, stool frequency, and rectal bleeding).ResultsThe proportions of patients achieving disease clearance with mirikizumab at W12, W52, and W104 were 16.0%, 36.4%, and 51.3%, respectively. Mirikizumab-treated patients with disease clearance showed greater PRO improvements through W52 than those without. Early clearance at W12 was associated with significantly better clinical outcomes at later time points, except for bowel urgency remission at W52. This trend was repeated for clinical outcomes at W104 in patients who achieved disease clearance at W52.ConclusionsMirikizumab consistently demonstrated disease clearance across induction, maintenance, and long-term studies. The attainment of disease clearance was associated with greater improvement in PROs, and early achievement of disease clearance was associated with better long-term outcomes, including clinical remission, corticosteroid-free remission, endoscopic and histological outcomes, reduced stool frequency, and rectal bleeding.

Background Histologic remission has emerged as a key therapeutic target in ulcerative colitis (UC). Endocytoscopy (EC), a real-time ultra-magnification imaging technique, may enable the evaluation of histologic healing without the need for biopsies. Our objective was to analyze the agreement between endocytoscopic assessment (ELECT index) and the histologic gold standard (Nancy index). Methods We included consecutive patients with UC undergoing surveillance colonoscopy. Endocytoscopy was performed during the procedure to evaluate the mucosa, focusing on the segment with the highest previously documented inflammatory activity and using 1% methylene blue staining. Histologic activity was estimated endocytoscopically using the ELECT index. Findings were compared with histology (Nancy index) from biopsies obtained from the same areas.Endoscopic activity was also evaluated using the Mayo endoscopic subscore and UCEIS, and clinical (PRO2) and biochemical activity (fecal calprotectin and C-reactive protein) were recorded. Results Twenty-seven patients with ulcerative colitis were included. Median age was 54 years (IQR 36–68), and 63% were women. Baseline characteristics and UC features are summarized in Table 1. Only three patients had demonstrated mucosal healing in prior endoscopies.Clinically, 63% reported one daily bowel movement without bleeding. Median fecal calprotectin was 38.9 µg/g (IQR 18.7–91.6), CRP 1.5 mg/L (IQR 0.5–4.75), hemoglobin 14.6 g/dL (IQR 13.6–15.4), and albumin 4.5 g/dL (IQR 4.4–4.7).Most patients were in endoscopic remission, with 92.5% scoring Mayo 0 and 89% UCEIS 0. Histologic remission based on the Nancy index was achieved in 84% (Nancy 0), while 16% showed activity (Nancy 2 or 3). The ELECT index showed a score of 0 in 66.7% of patients, and scores between 1 and 3 in the remainder.Regarding agreement between both indices, among the 21 patients with Nancy 0, 15 were classified as ELECT 0 and four as ELECT 1; only two had higher scores (2 and 3). Among the four patients with histologic activity (Nancy 2 or 3), three showed elevated ELECT scores (2 and 3), and one was classified as ELECT 0.The ELECT index demonstrated a sensitivity of 84%, specificity of 99%, positive predictive value (PPV) of 84.2%, and negative predictive value (NPV) of 98.9% compared with the Nancy index as the reference standard. Conclusion Endocytoscopy enables accurate assessment of histologic remission in patients with ulcerative colitis. The ELECT index demonstrated high concordance with the Nancy index, with an excellent negative predictive value, reinforcing its utility as a non-invasive tool in clinical practice. Conflict of interest: Dr. Suarez Ferrer, Cristina Julia: No conflict of interest Martin Arranz, Eduardo: No conflict of interest Rueda Garcia, Jose Luis: No conflict of interest Sanchez Azofra, Maria: No conflict of interest Amiama Roig, Clara: No conflict of interest García Ramírez, Laura: No conflict of interest Poza Cordon, Joaquin: No conflict of interest Martin Arranz, Maria Dolores: No conflict of interest

Baseline Disease Activity and Steroid Therapy Stratify Risk of COVID-19 in Patients With Inflammatory Bowel Disease

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 how strong patient reported outcomes, clinical scores and symptoms correlate with endoscopy for assessment of disease activity in UC patients. Methods 171 patients were included prospectively and consecutively (age: 49 (IQR: 38-61) years, duration 12 (4-19)years, 79 females (46.2%), 57.3% extensive disease, 42.7% on biologicals) at the time of the colonoscopy. The 2 item patient reported outcome (PRO), partial MAYO, Simple Clinical Colitis Activity Index (SCCAI), Mayo endoscopic subscore (MES), Baron and Ulcerative Colitis Endoscopic Index of Severity (UCEIS) scores were calculated. C reactive Protein (CRP) and fecal calprotectin (FCAL) was available in 83 and 45.6% of patients. 17.0% had clinical flare, treatment was escalated in 14.6% of patients. Sensitivity, specificity, PPV and NPV values were calculated, ROC analysis and K-statistics were performed. Results Rectal bleeding (RBS), stool frequency (SF) subscore of 0, or total PRO2 remission (RBS 0 and SF ≤1), partial MAYO (≤2) and SCCAI (≤2.5) remission were similarly associated to mucosal healing defined by MES (0 or ≤1) or Baron (0 or ≤1) scores (Table 1). PRO2 (AUCMES0/Baron0: 0.770/0.740, AUCMES0-1/Baron0-1: 0.868/0.858), SF (AUCMES0/Baron0:0.751/0.724, AUCMES0-1/Baron0-1:0842/0.820), RBS (AUCMES0/Baron0: 0.718/0.698, AUCMES0-1/Baron0-1: 0.814/0.845) partial Mayo (AUCMES0/Baron0: 0.823/0.788, AUCMES0-1/Baron0-1: 0.927/0.902) and SCCAI (AUCMES0/Baron0: 0.767/0.752, AUCMES0-1/Baron0-1:0.888/0.867) were similarly associated with mucosal healing in a ROC analysis. There was a strict association between MES 0 and Baron 0 (k=0.917) and UCEIS &amp;lt;4 and MES 0-1 (k=0.813), while moderate to fair agreement between UCEIS &amp;lt;4 and MES 0 (K=0.471) or Baron 0 (K=0.414)/Baron 0-1 (K=0.353), and between MES 0-1 and Baron 0-1 (K= 0.350) scores. Agreement between CRP and clinical remission or endoscopic healing (MES/Baron) was poor (K~0.2), while agreement between FCAL (&amp;gt;100 or &amp;gt;250) and RBS-PRO2 remission (K&amp;gt;100 or &amp;gt;250: 0.44-0.60) or pMAYO (K&amp;gt;100 or &amp;gt;250: 0.41-0.59) or MES/Baron 0 was moderate to good (K&amp;gt;100:0.53-0.52 and K&amp;gt;250:0.57-0.53). Conclusion We found no difference across accuracy of RBS, SF, PRO2, partial Mayo and SCCAI in predicting endoscopic healing. A strong association was found with high PPV for MES/Baron ≤1 and high NPV for MES/Baron 0. FCAL, but not CRP was associated to clinical and endoscopic remission.

Background: Resolution of clinical symptoms and mucosal healing constitute the therapeutic goals in ulcerative colitis (UC). Although a Mayo Endoscopic subscore (MSe) of 0 is the optimal target, there is insufficient information to recommend it for all patients and a MSe of 1 should be a minimum target. Moreover, histological healing is not a target in UC because of limited evidence for its clinical utility in UC. This study aims to determine the impact of the definition of endoscopic remission (MSe 0–1) and histological activity in the recurrence of UC and the time free of recurrence. Methods: Patients with UC in clinical remission (partial Mayo Score [MSp]≤1) and endoscopic remission (MSe≤1) who underwent colonoscopy with biopsies between 03/2010–12/2013 were included. The validated Nancy score was used to evaluate histological activity, which considers inactivity if 0–1 and activity if 2–4. The recurrence-free time was evaluated and recurrence was defined as MSp≥2, therapy to induce remission, hospitalisation or colectomy. Predictive factors associated with recurrence were determined. Statistical analysis: X2, Student's t-test, Kaplan-Meier survival curves, Log-rank test, logistic regression and Cox regression. Significance: p<0.05. Results: Sixty patients were included, 58.3% (n=35) were women, with a mean age of 52.7 years. MSe=0 was observed in 53.3% (n=32) and MSe=1 in 46.7% (n=28). Histological activity occurred in 61.7% (n=37). Clinical recurrence occurred in 31.7% (n=19) of patients, with a cumulative risk of 17.1%/24.5%/26.7%/40.1% at 12/24/36/48 months, respectively. MSe=1 (p=0.02) and histological activity (p=0.007) were significantly associated with recurrence. Of these, only histological activity (p=0.03) was an independent predictive factor of recurrence. Patients with MSe=1 (p=0.02) and with histological activity (p=0.01) had a significantly shorter recurrence-free time in univariate analysis. In multivariate analysis, only histological activity (p=0.02) was an independent predictive factor of lower recurrence-free time. Conclusions: Patients with UC in clinical and endoscopic remission experienced a global recurrence of 31.7% (n=19), reaching 40.1% in 48 months. The presence of histological activity represents an independent predictive factor of recurrence and time to recurrence, which was not verified with MSe 0–1.

Evaluation of Tofacitinib in Primary Sclerosing Cholangitis and Associated Colitis: A Multicenter, Retrospective Study

Objective: Non-invasive stool tests, including the fecal immunochemical test (FIT) and fecal calprotectin (FC), are reliable biomarkers for mucosal healing (MH) in ulcerative colitis (UC). However, which fecal test is superior for predicting MH in inactive UC patients requires evaluation. We aimed to compare the accuracy of FIT and FC results for predicting MH in quiescent UC patients.Methods: This prospective, multicenter study was conducted at three tertiary hospitals. UC patients in clinical remission for at least three months underwent colonoscopy and MH was evaluated using the Mayo endoscopic sub-score (MES). The receiver operating characteristic (ROC) curve and cutoff value with the best accuracy for predicting MH were assessed.Results: Among 127 patients, 65 (51.2%) showed MH (MES = 0). The area under the curve (AUC) for predicting MH (MES = 0) was significantly higher for FC than for FIT (AUC 0.858 (95% confidence interval (CI) 0.784–0.913) vs. 0.707 (95% CI 0.620–0.784), p < .001); there was no difference when MH included MES = 1 (MES ≤ 1) (AUC 0.820 (95% CI 0.742–0.883) vs. 0.813 (95% CI 0.734–0.877), p = .891). When the cutoff value was 70 μg/g for FC and 10 ng/mL for FIT, the sensitivity, specificity, positive predictive value and negative predictive value were 89.2, 71, 76.3, and 86.3, respectively, for FC and 92.3, 50, 65.9, and 86.1, respectively, for FIT.Conclusion: FC is more accurate than FIT for predicting MH in quiescent UC patients. The superiority of FC might be related to the distinctive performance of FC in differentiating inflammatory levels, particularly in low-grade mucosal activity.