bluuebunny/crossref_metadata_2025_split huggingface dataset:
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
Authors: Peyrin-Biroulet L , Loftus Jr E V , Hibi T , Birchwood C , Yun C , Zhao S , Liu X , Rogler G , Danese S , Colombel J F , Feagan B 
Published: May 2021

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 &lt; 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 &lt; 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 &lt; 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.
P395 Impact of mirikizumab therapy on histologic measures of intestinal inflammation in a Phase 2 study of patients with moderately to severely active Crohn’s disease
Authors: Pai R , De Hertogh G , Reinisch W , Harpaz N , Feagan B , Agada N , Pollack P , Chan L S , Protic M , Magro F 
Published: May 2021

Abstract

Background
Mirikizumab (miri), a p19-directed IL-23 antibody, demonstrated efficacy and was well-tolerated in a phase 2 randomized clinical trial (NCT02891226) in patients with Crohn’s disease (CD). The histologic results at Week (W)12 induction and W52 maintenance are presented here.

Methods
Patients were randomized 2:1:1:2 across 4 treatment arms (PBO, 200, 600, 1000mg miri) administered intravenously (IV) every four weeks (Q4W) at Weeks 0, 4, and 8. Patients who received miri and achieved ≥1 point improvement from baseline (BL) at W12 in Simple Endoscopic Score for Crohn’s Disease (SES-CD) were re-randomized 1:1 into double-blind maintenance to continue their IV dose assignment Q4W (IV/IV) or to 300mg miri SC Q4W (IV/SC); maintenance IV arms were pooled for analysis. W12 non-improvers and all induction PBO patients received 1000mg miri Q4W from W12 through W52. Biopsies from terminal ileum and 4 colonic segments (ascending, transverse, descending, rectum) were obtained during endoscopy at W0, 12 and 52 and scored blind to treatment and response status. Ileum and colon scores were reported separately. Colon scores were derived from the sum of the 4 colonic segments, and total intestine scores from the 4 colonic segments plus ileum. Endpoints were defined post-hoc but prior to performing the analyses and only included patients with active histologic disease at BL (see Table). Histologic response was defined as: a) absence of neutrophils in lamina epithelialis, and absence of epithelial damage, erosions and ulceration or b) decrease of either RHI or GHAS ≥50% from BL. Histologic remission was defined as absence of mucosal neutrophils, epithelial damage, erosions, and ulceration. Deep histologic remission was defined as histologic remission combined with absence of chronic inflammatory cell infiltration of the lamina propria. For assessment of total intestine inflammation, the criteria for response, remission or deep remission must have been met in all 5 bowel segments.

Results
At W12, histologic response and remission were significantly higher in all segments of the 1000mg group versus PBO (response: ileum p&lt;0.01, total intestine p&lt;0.01, colon p&lt;0.05; remission: ileum p&lt;0.05, colon p&lt;0.05, total intestine p&lt;0.01). Among the W12 improvers, both histologic response and histologic remission at W52 were similar in ileum and colon in the IV/IV group, but lower in ileum than colon in the IV/SC group. All but 2 patients with remission at W52 were in deep histologic remission.

Conclusion
Patients treated with miri achieved and sustained histologic response and remission over 52 weeks of treatment. Among patients with W52 histologic remission, all but 2 patients achieved deep remission.
P397 Response to biologics in IBD patients assessed by Computerized image analysis of Probe Based Confocal Laser Endomicroscopy with molecular labeling
Authors: Iacucci M , Grisan E , Labarile N , Nardone O , Smith S C , Jeffery L , Ghosh S , Buda A 
Published: May 2021

Abstract

Background
The increase in therapeutic choices in inflammatory bowel diseases (IBD) imposed the identification of personalized therapeutic strategy. Confocal laser endomicroscopy (CLE) is a new endoscopic tool developed to obtain virtual in vivo histology. This study aimed to identify CLE in vivo and ex vivo features predictive of response for patients starting biologics.

Methods
We performed a prospective observational study at a single tertiary referral centre. 29 IBD patients (14 ulcerative colitis-UC and 15 Crohn’s Disease-CD) underwent colonoscopy with CLE before and 12-14 weeks after starting anti -TNF or 16 weeks after anti α4β7 integrin. CLE parameters analyzed were: crypt distribution along the mucosal surface, crypt area (CA), eccentricity, diameter, inter-cryptic distance (ICD), vessel tortuosity (VT), fluorescein leakage through the colonic mucosa (FLCM). Ex-vivo binding activity of fluorescein labelled biologics on corresponding biopsies was also assessed. Mosaicism reconstruction of CLE images were analyzed using a dedicated software algorithm (CellvizioViewer, Mauna Kea Technologies, ParisFrance). A dedicated Graphical User Interface was designed to enable a semiautomated analysis.

Results
After treatment, VT resulted significantly changed in overall IBD population (p&lt;0.05), FLCM were reduced in UC patients (p&lt;0.05), whilst CA, eccentricity and ICD decreased in CD patients (p&lt; 0.05). The univariate regression analysis identified FLCM as the most accurate parameter for predicting responsiveness (AUROC) 83%, accuracy 83%, positive predictive value-PPV 94% and negative predictive value-NPV 57%). FLCM and ICD were the best discriminants in responders Vs non responders in UC patients (AUROC 85%, accuracy 85%, PPV 100% and NPV 71%); whilst VT, CA and ICD in CD patients (AUROC 95%, 86% and 83%; accuracy 90%, 90% and 88%; PPV 100%, 100% and 86%; and NPV 75%, 75% and 100%, respectively). Ex vivo confocal imaging revealed that UC patients, especially those responders, had higher basal fluorescent intensity signals with a significant reduction after biological treatment (p&lt; 0.05), whereas in CD patients no significant change was found. An increased mucosal binding to the fluorescent labelled biological agent was associated to a higher likelihood of response to the treatment; this effect was higher in UC patients (AUROC 81%, accuracy 77%, PPV 100%, NPV 63%) compared to CD patients (AUROC 64%, accuracy 79%, PPV 80%, NPV 50%).

Conclusion
FLCM and ICD were the best discriminants of response in UC, while VT, CA and ICD in CD. A higher mucosal binding to a biological agent before treatment was observed in responders UC patients but not in CD patients.
P401 Risk of severe COVID-19 outcomes associated with inflammatory bowel disease medications: Reassuring insights from the United Kingdom PREPARE-IBD multicentre cohort study
Authors: Lamb C A , Sebastian S , Kent A J , Segal J P , Gonzalez H A , Brookes M J , Mehta S J , Subramanian S , Bhala N , Hicks L C , Conley T E , Patel K V , Walker G J , Kennedy N A 
Published: May 2021

Abstract

Background
During the early COVID-19 pandemic, the British Society of Gastroenterology (BSG) developed a risk stratification grid to inform the United Kingdom (UK) government regarding strict social isolation, termed “shielding”. This advised inflammatory bowel disease (IBD) patients thought to be most clinically vulnerable to SARS-CoV-2 infection or severe COVID-19 outcomes, to stay at home and minimize face to face contact, even with household members. Those considered at highest risk included recent commencement of combination biologic and immunomodulator therapy, prednisolone ≥20mg/day, presence of comorbidities, age ≥70 years or clinically active disease in those receiving immunosuppression. Mesalazine was not considered to increase risk. An acknowledged limitation was an absence of COVID-19 risk data. This study sought to identify patient or IBD medication-related factors associated with severe outcomes from COVID-19.

Methods
PREPARE-IBD was a multi-centre observational United Kingdom (UK) cohort study including adult IBD patients (≥18 years) diagnosed with COVID-19 by PCR between 1st March 2020 and 31st August 2020. The primary outcome was severe COVID-19 defined as requirement for intensive care admission, invasive ventilation or death. We tested associations of severe outcomes with medications and other covariates using multiple logistic regression.

Results
211 patients were included from 60 UK centres. 56 of 211 patients (26.5%) met the primary outcome. Severe COVID-19 was more common in ulcerative colitis relative to Crohn’s disease patients (33.9% [37/109] vs. 18.6% [16/86], p=0.018). Shortness of breath, nausea and vomiting were more common with severe COVID-19 (p&lt;0.001 and p=0.023 respectively). Multivariable analysis identified co-morbidities and age as associated with severe COVID-19 outcomes; odds ratio (OR [95% CI]) 1.68 (1.23-2.35) for each co-morbidity, and an OR 1.03 (1.00-1.05) with each successive year of age. Neither clinically active IBD (OR 0.58 [0.26-1.26]), non-white ethnicity (OR 1.98 [0.92-4.28]), nor prednisolone use (OR 2.42 [0.47-11.26]) were associated with increased risk. On multivariable analysis, mesalazine was associated with severe COVID-19 outcomes (OR 2.03 [1.01-4.12]). Univariable analysis identified biologics and thiopurines as protective (OR 0.38 [0.15-0.87] and 0.32 [0.092-0.86] respectively). On multivariable analysis no association of severe COVID-19 outcomes with thiopurine or biologic exposure was seen.

Conclusion
Our data provide reassurance for the continued evidence-based use of corticosteroids, immunomodulators and biologic therapies in IBD during the ongoing COVID-19 pandemic, and is consistent with an as yet unexplained association between mesalazine use and severe COVID-19 outcomes.
P473 Ustekinumab and vedolizumab influence on cardiovascular risk factors in patients with Inflammatory Bowel Disease
Authors: Amiama Roig C , Suárez Ferrer C , Poza Cordón J , Rueda García J L , Sánchez Azofra M , Martín Arranz E , González Díaz I , Amor Costa C , García Ramírez L , Martín Arranz M D 
Published: May 2021

Abstract

Background
Chronic inﬂammatory diseases, including the Inflammatory Bowel Disease (IBD), show an increased risk in the development of atherosclerotic cardiovascular disease and coronary microvascular dysfunction at an early age.
AntiTNF α have proven to be effective in reducing the cardiovascular risk in these malaises, nevertheless due to their mechanism of action, we cannot determine whether such efficacy is due to an adequate inflammation control or due to the specific cytokine blockade, which plays an important role in both the inflammation and the atherogenic process.
Taking this into account, our hypothesis assesses whether using other anti-inflammatory therapies, such as Ustekinumab and Vedolizumab, would achieve a decrease in cardiovascular risk.

Methods
In this observational and retrospective study, we collected cardiovascular risk factors(CVRFs) in 46 patients, immediately before starting Ustekinumab or Vedolizumab and a year after, taking into account if patients were in clinical remission or not.
The CVRFs included were: body mass index (BMI), arterial hypertension, triglycerides values, lipid profile, albumin and C-reactive protein.

Results
46 patients were included, 33(71.74%) with Crohn and 13(28.26%) with Ulcerative Colitis. Of the total number of patients 25(54.35%) were treated with Ustekinumab and 21(45.65%) with Vedolizumab. During the follow-up, only one patient(0.02%) presented a new cardiovascular event.
Paired student’s t-test were used for data analysis in both treatment groups, comparing the values of the different CVRFs at the baseline and after one year of treatment. When comparing these values according to clinical remission at one year, no statistically significant differences were observed for any of them.
BMI and weight values were |24.49(DE 4.58) vs 24.93(DE 4.74) p=0,71| and |70.76kg(DE 13.86) vs 71.38kg(DE 13.33) p=0,85| respectively. As for hypertension, no relevant changes were observed, representing 15.22% of the population at the beginning and 17.39% after one year of treatment.
The differences observed in blood glucose values were|86.23(81.87–90.6)mg/dL vs 89.87mg/dL(84.72–95.01) p=0,27|. Regarding the lipid profile, the total cholesterol values were 158.58mg/dL(DE 36.5) and 168.69mg/dL(DE 32.72) p=0.18. HDL at the beginning 44.67mg/dL(DE 11.69) and after one year 47.43mg/dL(DE 10.19) p=0.28 and triglycerides values of 126.65mg/dL(DE 56.38) and 133.5mg/dL(DE 60.95) p=0,61. Albumin levels|4.08g/dL(DE 0.39) vs 4.27g/dL(DE 0.27)|did show significant differences (p=0,01).

Conclusion
Patients treated with Vedolizumab or Ustekinumab do not present a significative reduction in the cardiovascular risk after one year regardless of clinical remission.
P494 Can Patients Monitor Response To Ustekinumab In The Real World?
Authors: Walsh A J , Matini L , Kormilitzin A , Wilson J , Lyden S , Al-Hillawi L , Kantschuster R , White L , Payton S , Brain O , Palmer R , Ambrose T , Satsangi J , Travis S P L 
Published: May 2021

Abstract

Background
Real time monitoring of patients with Crohn’s disease (CD) gives us the opportunity to examine disease trajectory. We have demonstrated the feasibility of using a monitoring platform with patient reported data, collected prospectively and routinely in clinical practice. The question is whether it can be used for specific drugs

Methods
TrueColours-IBD (TC-IBD)is a real time, web based platform that through email prompts linked to questionnaires, collects longitudinal patient reported outcome measures (for CD, symptoms measured by Harvey Bradshaw Index (HBI) and quality of life by IBD Control-8). It is routinely used by &gt;2000 patients in Oxford. This study examined 114 patients with Crohn’s: 45 males (median age 36, IQR 28–51) and 69 females (median age 34.8, IQR 28–47), treated with ustekinumab for a maximum of 16 months (range -2 months to 14 months). A linear mixed-effects model was used to approximate longitudinal trends of HBI and IBD Control-8. 3 individual items of the HBI scale (general well-being, abdominal pain & stool frequency) were also assessed. The TC-IBD platform has the capacity to analyse and show patients’ data automatically, using customised models and algorithms through the feedback loop (Fig 1). Model coefficients, intercept and slope were estimated using the restricted maximum likelihood (REML) approach. The intercept corresponds to the expected cohort mean value of the scale (e.g. HBI, IBD Control-8) at baseline (time zero) and the slope describes the rate of the change over time

Results
The models’ coefficients, the intercept and slope of both HBI and IBD Control-8 scales were statistically significant and are summarised in Table 1 with confidence intervals. Both linear trends (slopes) describing HBI (p&lt;0.001) and IBD Control-8 (p&lt;0.001) confirmed improvements for patients. The bowel movement component of the HBI dominated over general well-being and abdominal pain, while keeping a similar downward trend over time ( Fig 2 and Fig 3a,b)

Conclusion
Patient reported data through the TC-IBD platform can be used for statistical analyses and continuous monitoring of drug effect over time. This analysis is limited by a lack of comparator group, but the models may be used with the TrueColours platform as a decision support tool for other drugs
P497 The value of endoscopic healing index monitoring for guiding infliximab dosing in patients with Crohn’s disease
Authors: Kantasiripitak W , Mathôt R , Oldenburg B , Buisson A , Ferrante M , Laharie D , D’Haens G , Vermeire S , Dreesen E 
Published: May 2021

Abstract

Background
The endoscopic healing index (EHI) is a novel multi-protein serum biomarker test developed and validated to assess endoscopic disease activity in patients with Crohn’s disease (CD). Evidence for the use of EHI to guide decision-making during infliximab (IFX) treatment remains scarce. Therefore, we aimed to characterise the relationships between IFX dose, serum IFX concentrations, EHI, and endoscopic remission (ER).

Methods
Data were obtained from 118 biologic naïve adult patients with CD enrolled in the phase 4 TAILORIX trial (EudraCT 2011 003038 14). All patients had confirmed active CD at baseline based on clinical, biological, and endoscopic criteria. IFX and EHI (scores ranging from 0–100) were measured using a homogenous mobility shift assay (HMSA) and immunoassay, respectively (Prometheus Laboratories). First, the previously published population pharmacokinetic (popPK) model of the TAILORIX study population was revisited to describe the HMSA data. The effect of EHI, faecal calprotectin (FC), C-reactive protein (CRP), and serum albumin (ALB) on IFX clearance was evaluated. Next, a minimal continuous-time Markov model was developed to describe the time course of EHI within patients. EHI was considered as a three-stage ordinal variable (scores 0–19, 20–49, and 50–100) with the lowest score stage (0–19) indicative of ER. The course-modifying effect of IFX on EHI was assessed. Finally, a generalised linear model was used to describe the relationship between EHI and the probability of attaining ER (Simple Endoscopic Score for CD [SES-CD] ≤2). The predictive ability of EHI for ER was compared with that of FC, CRP, ALB, and IFX using a receiver operating characteristic (ROC) curve analysis.

Results
The revisited two-compartment popPK model described the IFX data with adequate descriptive and predictive accuracies. EHI, FC, CRP, and ALB at week (w)0 were not found to explain interpatient variability in IFX clearance. In contrast, higher IFX at w14 was associated with a higher probability of achieving EHI &lt;20 at w14 (Figure 1). The probability of attaining EHI &lt;20 at w14 was predicted to increase more than four-fold when IFX at w14 was targeted at 10 mg/L instead of 5 mg/L (Table 1). EHI and FC equally well predicted the probability of attaining ER at the same time point (Figure 2, Table 2).

Conclusion
EHI, FC, ALB, and CRP at w0 should not be considered for a priori IFX dose optimisation. Nevertheless, a posteriori IFX dose optimisation (based on IFX concentrations measurements) towards a predefined IFX concentration at w14 may lead to lower post-induction EHI scores and thus improved ER rates. An IFX target of 10 mg/L at w14 is associated with four-fold higher normalisation of EHI as compared to the commonly used target of 5 mg/L.
P504 Effectiveness and safety of ustekinumab maintenance therapy in 103 patients with real-world ulcerative colitis: A GETAID multicentre cohort study
Authors: Fumery M , Filippi J , Abitbol V , Biron A , Laharie D , Serrero M , Altwegg R , Bouhnik Y , Peyrinbiroulet L , Gilletta C , Roblin X , Pineton de Chambrun G , Vuitton L , Bourrier A , Nancey S , Gornet J M , Nahon S , Bouguen G , Viennot S , Pariente B , Amiot A 
Published: May 2021

Abstract

Background
Phase III trials have demonstrated the efficacy and safety of ustekinumab in moderate-to-severe ulcerative colitis (UC), but no real-life long-term data is currently available.

Methods
From January to September 2019, all consecutive patients with active UC treated with ustekinumab in a GETAID centre were included. Patients were evaluated at week 52. Remission was defined by a partial Mayo Clinic score ≤ 2. The aim of the present study was to assess long-term effectiveness and safety of ustekinumab in UC.

Results
103 UC patients (62 men; mean age: 41.2 ± 16.2 years; 52% pancolitis E3) were included in 21 centres. History of immunomodulator, anti-TNF and vedolizumab therapies was noted in 84.5%, 99.0% and 85.4% of the cases, respectively. At week 54, 44 (43%) patients discontinued ustekinumab, for lack of efficacy (n=41), pregnancy (n=1), persistence of eczematiform lesions (n=1) or personal decision (n=1). Cumulative probabilities of ustekinumab persistence were 96.1%, 81.6%, 71.7%, and 58.4% after 3, 6, 9, and 12 months, respectively. In multivariate analysis, a CRP&gt;5 mg/L at week 0 (OR=2.91, CI95%[1.15–7.36]; p=0.02) and concomitant steroids at week 0 (OR=3.05, CI95%[1.30–7.14]; p=0.01) were significantly associated with ustekinumab discontinuation within one year. The overall rate of steroid-free clinical remission at week 52 was 32% of whom 71% had null rectal bleeding and stool frequency subscores. Ten patients (9.7%) underwent colectomy within a median of 6.7 [4.3–10.6] months. Adverse events were observed in 15 (16.9%) patients, of whom 4 (4.5%) had severe adverse events including three patients with exacerbation of UC leading to hospitalization, and a 62 years-old men who died from a myocardial infarction four months after ustekinumab initiation.

Conclusion
In this real-world cohort study that included patients with refractory ulcerative colitis to multiple therapies, more than one-half of patients were still treated by ustekinumab and one-third were in steroid-free clinical remission, after 52 weeks.