bluuebunny/crossref_metadata_2025 huggingface dataset:
P221 Association between Irritable Bowel Syndrome-type symptoms and Ulcerative Colitis: is it real?
Authors: Silva A P , Madeira J , Sant’Anna M , Temido M J , Fernandes A , Lopes S , Ferreira A M , Mendes S , Ferreira M , Silva M R , Cipriano M A , Figueiredo P , Portela F
Published: January 2022

Background

The origin of gastrointestinal symptoms compatible with irritable bowel syndrome (IBS) in patients with inflammatory bowel disease in remission is a challenge. Our aim was to prospectively determine the relation of IBS symptoms with calprotectin levels (FC), endoscopic Mayo score and histologic findings, in patients with ulcerative colitis (UC) in clinical remission.

Methods

Patient recruitment was between January – March of 2020 and November of 2020 - August of 2021 and included consecutive UC patients in clinical remission and scheduled for a colonoscopy. Clinical remission was defined by a stool frequency ≤3/day with no bleeding, ulcerative colitis activity index <4 and serum C-reactive protein lower than 1mg/dL. Exclusion criteria were therapeutic with corticosteroids over the prior 6 months or initiation of biological agents in the last 6 months. IBS diagnosis was evaluated by Roma IV criteria (IBS-like group). FC level was assessed before colonoscopy and during the exam Mayo endoscopy subscore was applied and random biopsies of all segments of colon and rectum were made to achieve histologic activity using Geboes index. This study was approved by Centro Hospitalar e Universitário de Coimbra Ethics Committee.

Results

A total of 106 patients (50% women; mean age 51 years ±14.8) were included. The mean of disease duration was 15.7 years (±9.06) and 13 of them (12.3%) had proctitis, 64 (60%) left-sided colitis and 29 (27.4%) extensive colitis. Regarding disease activity: mean FC was 189.48mg/Kg (±382), endoscopic Mayo score lower than 1 was found in 63 patients (59.4%) and Geboes index lower than 1.1 was found in 66 patients (62.3%). Rome IV criteria for IBS were fulfilled by 29 patients (27.4%). The IBS-like group showed FC levels significantly higher (303±483mg/Kg vs. 139±319mg/Kg; P<0.05), with greater histologic activity (Geboes index >1.1 in 65,5% vs. 27.3%, P<0.05). Besides, in the same group (IBS-like group), Mayo endoscopy subscore was numerical higher but with no statistical significancy (subscore ≥1: 55.2% vs. 36.4%; P>0.05).

Conclusion

IBS-like symptoms are common in patients with UC considered to be in clinical remission. Higher levels of FC and histological activity support the idea of the presence of subclinical inflammation rather than coexistent IBS.
P223 Neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in patient with intestinal Behçet’s disease as a marker of disease activity and prognosis
Authors: Jung B W , Kang E A , Park S J , Park J J , Cheon J H , Kim T I , Park J
Published: January 2022

Background

The neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) are used as a diagnostic marker, disease activity marker, and prognostic marker in patients with Crohn’s disease and ulcerative colitis. We aimed to investigate the NLR and PLR as a marker of inflammation and prognostic biomarker in intestinal Behçet’s disease (BD).

Methods

A total of 1712 diagnostic tests with 621 intestinal BD patients who underwent both blood examination and endoscopic examination at the Inflammatory Bowel Disease Clinic of Severance Hospital, Seoul, Korea between March 2005 to November 2020 were analyzed in our study. We analyzed to identify the independent risk factors of the clinical remission (CR) and endoscopic remission (ER). Moreover, for 435 patients who underwent a series of blood and endoscopic examination, we performed Kaplan-Meier (K-M) analyses to identify the NLR and PLR as a marker of prognosis in intestinal BD.

Results

The NLR levels were higher in non-CR group compared to CR group (3.3±2.7 vs. 2.0±1.2, p<0.001). The PLR levels were higher in non-CR group compared to CR group (192.9±113.8 vs. 139.6±63.757, p<0.001). The NLR levels were higher in non-ER group compared to ER group (2.8±2.2 vs. 2.0±1.3, p<0.001). The PLR levels were higher in non-ER group compared to CR group (171.5±171.5 vs. 136.3±54.4, p<0.001). In the CR group and the ER group, NLR and PLR were meaningful indicators for predicting each remission. We obtained the cut-off values of NLR(CR group 3.17, ER group 2.53) and PLR(CR group 187.28, ER group 124.27). There was a significant difference in the duration of CR/ER remission when the NLR/PLR high group and low NLR/PLR group were applied with the K-M curve based on cut-off.

Conclusion

The NLR and PLR were higher in patients with active intestinal BD compared to those with inactive intestinal BD. And the NLR and PLR showed a promising role as marker for prediction of disease prognosis. Therefore, the NLR and PLR might be effective, readily available, and low-cost biomarkers for inflammation in intestinal BD patients.
P234 Remission state in Inflammatory Bowel Disease patients on anti TNF or vedolizumab: a confocal endomicroscopy study
Authors: Loly J P , Vieujean S , Reenaers C , Van Kemseke C , Seidel L , Somja J , Louis E
Published: January 2022

Background

Confocal endomicroscopy is a technique allowing the in vivo assessment of the superficial layers of the mucosa, including the epithelium, the surrounding connective tissue and blood vessels. Some of the features observed by endomicroscopy can’t be assessed by classical histology. Preliminary studies have already suggested its added value in the assessment of endoscopic remission in IBD. However, most of these studies were performed on patients still having some endoscopic activity. Furthermore, to our knowledge, no study has used endomicroscopy to compare the state of remission in IBD patients under vedolizumab and anti TNF. Our aim was to disclose persisting endomicroscopy anomalies in patients with full endoscopic healing and to compare them between vedolizumab and anti-TNF.

Methods

we screened patients with CD or UC treated for more than 6 months by adalimumab, infliximab, or vedolizumab, and being in steroid-free clinical (PRO2) and biological remission (CRP<5 mg/l and F Cal <250 microg/g). Confocal endomicroscopy analysis was performed in the ileum, right colon, transverse colon, left colon and rectum. In each ileal segment, we recorded fluorescein leakage, the presence of epithelial erosions, gap junction anomalies and vessel diameter. In each colonic segment, we recorded the presence of fluorescein leakage, crypt dilatation, vessel diameter, and hypervascularization. Patients were prospectively follow-up and clinical relapses (PRO2 + one objective marker) were recorded.

Results

72 CD and UC patients treated by biologic therapy and in clinical remission were screened. 37 of them were also in endoscopic remission (eMayo=0 in UC and absence of ulcer or erosion in CD) and were included in our study. Their treatment were infliximab (n=5), adalimumab (n=16), vedolizumab (n=15) and ustekinumab (n=1). We found a persistence of residual endomicroscopy anomalies in the different segments in a substantial number of patients (table 1). These persisting abnormalities were not significantly associated with any demographic or clinical characteristics including the treatment (anti-TNF or vedolizumab), nor with histologic parameters (almost all patients were in histologic remission), levels of CRP or F Cal.

The average follow-up time was 33.4 (+/- 9.5) months. Among the 37 patients, 7 (18.9%) relapsed. The risk of relapse was not associated with any clinical, biological, histologic or endomicroscopy factor.

Conclusion

Despite endoscopic, biological and even histologic remission, we found a high prevalence of endomicroscopic abnormalities, which were not different between anti-TNF and vedolizumab treated patients. The clinical significance of these anomalies remains to be clarified.
P238 Symptom burden and indolent disease in newly diagnosed patients with ulcerative colitis and Crohn’s disease - a Copenhagen IBD Inception Cohort Study
Authors: Attauabi M , Madsen G R , Bendtsen F , Wilkens R , Ilvemark J F K F , Theede K , Boysen T , Bjerrum J T , Seidelin J B , Burisch J
Published: January 2022

Background

The early course of ulcerative colitis (UC) and Crohn’s disease (CD) is difficult to predict, particularly regarding identifying patients for whom an indolent course might be expected. Therefore, we aimed to investigate the initial course of UC and CD and clinical predictors hereof in a generalizable population-based inception cohort.

Methods

We initiated a prospective population-based inception cohort of newly diagnosed patients with UC and CD between May 1st, 2021 and November 1st, 2021, according to the Copenhagen IBD Criteria within the geographical uptake area of Hvidovre University Hospital and Herlev University Hospital. All patients were examined systematically by IBD specialists at diagnosis using endoscopy, magnetic resonance (MR) enterography, and patient-reported measures including Simple Clinical Colitis Index (SCCAI) and Harvey-Bradshaw Index (HBI) for UC and CD, respectively. Indolent disease presentation was defined as the absence of UC or CD-related hospitalization, surgery, or decision to start steroid, immunomodulator, or biologic therapy within three months of follow-up. In addition, well-recognized predictors of long-term disease course of UC and CD were a priori defined and implemented in a univariate logistic model, and factors with a p-value smaller than 0.10 were included in the multivariate model.

Results

The study included 63 adult patients with UC and 50 with CD. At diagnosis, 23 (36.5%) and 13 (26.0%) patients with UC and CD were in clinical remission according to their SCCAI or HBI score, respectively (Table 1). The symptomatic disease burden is outlined in Table 2–3. Interestingly, well-recognized risk factors for the long-term disease course of UC and CD, including disease extent, behavior, baseline endoscopy, MR enterography, and serologic data, did not predict the initial disease course in a multivariable analysis (Table 4). However, C-reactive protein <10 mg/L were associated with an indolent course of UC (adjusted odds ratio=6.2 (95% confidence interval 1.3–38.9), p=0.03).

Conclusion

The preliminary data from the ongoing prospective population-based cohort study indicate that very heterogenous disease course patterns might be experienced very early. As initial disease control is considered critical for long-term outcomes, this study highlights the inapplicability of long-term predictors for the short-term disease course. It emphasizes the need for further development of simple clinical tools or biomarkers for early patient stratification.
P239 Ulcerative Colitis Index of Severity is a better predictor of histologic activity than Mayo endoscopic subscore, an Asian cohort study in ulcerative colitis
Authors: Tay S , Teh K K J , Wang L M , Tan M
Published: January 2022

Background

Targets of therapy in ulcerative colitis (UC) have undergone a shift from clinical remission to endoscopic healing (EH). Recent STRIDE II guidelines1 have recommended stricter criteria for EH, Ulcerative Colitis Index of Severity (UCEIS) ≤1 or Mayo endoscopic subscore (MES)=0, with histologic healing (HH) as an adjunctive endpoint. We aim to ascertain the strength of correlations between EH and HH using validated indices in an Asian cohort.

Methods

A single-centre cohort study was performed in a tertiary centre. Patients with a diagnosis of UC were prospectively enrolled into a database from January 2017 to June 2020. Patient demographics, clinical classification, endoscopic and histological assessments were collected retrospectively and analysed. Endoscopic scores in the worst affected segments by two independent gastroenterologists. Histological activity was assessment by a single gastrointestinal histopathologist using the Nancy Histological Index (NHI). Analysis was done using SPSS v23. Spearman correlations between UCEIS, MES and NHI was performed.

Results

A total of 88 patients with UC were enrolled (Figure 1). Seven patients were excluded as no biopsies were done during endoscopy. Analysis was done for 163 pairs of endoscopy and histology. The distribution of UCEIS, MES and NHI scores for all endoscopies are shown in Figure 2. Both MES and UCEIS had modest correlations with NHI but UCEIS had a stronger correlation to NHI (r=0.640, p<0.01) than MES (r=0.538, p<0.01) (Figure 3). When evaluating patients in EH (UCEIS≤1 or MES=0), both endoscopic scores had similar distribution of NHI scores (Figure 4a & 4b). Despite appearing to be endoscopically inactive, more than half of patients had histologically active disease, with NHI≥2 (14/27 [51.8%] in the UCEIS≤1 group, 9/17 [52.9%] in the MES=0 group). When using the older definition of EH (MES≤1), 49 of 66 patients (74%) had histologically active disease with NHI≥2 (Figure 4c).

Conclusion

UCEIS ≤1 is slightly more predictive of HH than MES=0 but endoscopic correlation with HH is poor. Biopsies should still be performed if HH is a desired treatment outcome. The more stringent criteria change for EH in STRIDE II from MES≤1 to MES=0 results in higher rates of HH.

Reference

1. Turner D, et al.; International Organization for the Study of IBD. STRIDE-II: An Update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): Determining Therapeutic Goals for Treat-to-Target strategies in IBD. Gastroenterology. 2021 Apr;160(5):1570–1583.
P243 Relationship between intestinal ultrasound, fecal calprotectin and Harvey-Bradshaw Index in the assessment of infllamatory activity in Cronh′s Disease
Authors: Montero Moretón Á M , Bastón Rey I , Calvino Suarez C , De la Iglesia García D , Ferreiro Iglesias R , Maestro Antolín S , Santos Santamarta F , Pérez Millán A G , Dominguez-Munoz E , Barreiro-de Acosta M
Published: January 2022

Background

Crohn’s disease (CD) is an inflammatory bowel disease with chronic course and exacerbations. Diagnosis and follow-up are based on clinical activity, biomarkers, ileocolonoscopy and imaging techniques. Intestinal ultrasound (IUS) has been shown to have high sensitivity and specificity analyzing inflammatory activity in CD. The aim of our study is to correlate IUS parameters with clinical activity and biomarkers in CD.

Methods

Retrospective, observational, single-center study was designed. Adult patients with CD who underwent IUS between September 2020 and May 2021 were included. Exclusion criteria was exclusive colonic involvement. Examination was done by ultrasound machine (Hitachi Ascendus) with low frequency curved-array (1–5 MHz) and high-frequency linear-array (5–13 MHz) transducers. Examination assessed bowel wall thickness, mesenteric fat hypertrophy, lymph nodes, hyperemia on color Doppler flow measured as Limberg index and length of affected segment (cm). Clinical activity score for CD was assessed by Harvey Bradshaw index (HBI). Biomarkers parameters studied were C-reactive protein (CRP) and faecal calprotectin (FC). Results are shown as percentages, median and interquartile range (IQR). Data were analysed using Spearman′s correlation analysis

Results

121 patients were included (median age 45.6 years (IQR 33.4 – 59.6), 56.2% female). 78.5% had ileal disease and 21.5% ileocolonic involvement. At the time of IUS 17.4% of patients were not taking any maintenance treatment, 13.2% were on azathioprine, 48.8% on anti-TNF (61% adalimumab; 39% infliximab) and 8.3% on ustekinumab. 85.1% patients had HBI <6, 14.1% had moderate activity. Median CRP level was 0.334 mg/dl (IQR 0.06–1.12), FC was 141 µg/g (IQR 35–386). Median wall thickening was 4.7 mm (range 4.1–5.6), 68.6% of patients had mesenteric fat hypertrophy and 73.55% had lymph nodes. Limberg index was 0 in 20.7%, 1 in 23.1%, 2 in 37.2% and 3 in 19% of patients. IUS determined treatment modification in 60.3% of cases: 19% started biological therapy, 15.7% changed biological target, 14.9% underwent intensification or reinduction of biological treatment, in 1.7%, treatment reduction was decided. The Spearman′s correlation between IUS parameters, clinical and biochemical markers is presented in Table 1. IUS parameters were significantly associated with faecal calprotectin and CRP level, specially Limberg Index and faecal calprotectin (r=0.56, p<0.05) and Limberg Index and CRP level (r= 0.38, p<0.05) (Figure 1 and 2). No correlation was observed between HBI and IUS parameters.

Conclusion

Through this study, significant correlation between IUS and biomarkers was observed in CD. IUS has been shown to be useful for monitoring CD activity in order to optimize patients′ treatment.
P251 Endoscopic and pathologic findings of the esophago-gastroduodenal involvement of Crohn’s disease in Korea: a prospective cohort study
Authors: Kim G H , Kim J , Park S H , Ahn J Y , Ye B D , Jung H Y , Yang S K
Published: January 2022

Background

The characteristics and incidence of esophago-gastroduodenal involvement of Crohn’s disease (CD) are unclear in Korea. We aim to investigate the prevalence and clinicopathological characteristics of CD with esophago-gastroduodenal involvement.

Methods

A total of 115 patients with CD who underwent esophagogastroduodenoscopy (EGD) including esophageal, gastric and duodenal biopsies were enrolled prospectively between 2020 and 2021 at a tertiary care center. Total of five specimens obtained from the esophagus, gastric body and antrum, and duodenal bulb and second portion respectively during endoscopy were histologically reviewed. The presence of Helicobater pylori was evaluated by immunohistochemical analysis.

Results

The median age was 30.0 (interquartile range [IQR] 25.0–37.0) years and 74.8% were male. Of total, 32.2% had were symptoms including epigastric pain (29.7%), bloating (27.0%) and dyspepsia (13.5%). Based on histological features, 56 patients (48.7%) were identified as having UGI involvement (15 esophageal, 44 gastric, and 36 duodenal). Of 115 included patients, bamboo- joint-like appearance in the stomach was founded in 81 (70.4%) and their histologic findings were mostly revealed as non-specific feature. Notable histopathological findings included non-caseating granulomas in 8 cases (7.0%), focally enhanced gastritis in 38 cases (33.0%), and lymphocytic esophagitis in 13 cases (10.7%). Among 115 cases, 6 cases (5.2%) were H. pylori positive and 109 cases (94.8%) were H. pylori negative.

Conclusion

The prevalence of esophago-gastroduodenal involvement of CD was relatively high among CD patients who underwent EGD in Korea. A high suspicion of CD with esophago-gastroduodenal involvement with endoscopic biopsy is warranted when patients have abnormal endoscopic findings.
P259 Metabolic associated Liver Disease and sex as key factors of cardiovascular risk in Inflammatory Bowel Disease
Authors: García Mateo S , Martínez-Domínguez S J , Ballesta Martínez S , Espinosa Rueda J , Tejero Justes C , Aso Gonzalvo M C , Gallego Llera B , Alfambra Cabreja E , Baptista P M , Nocito Colón M M L , Gargallo-Puyuelo C J , Gomollón F
Published: January 2022

Background

Atherosclerosis is the main factor for the development of cardiovascular (CV) events. Patients with systemic inflammatory conditions such as inflammatory bowel disease (IBD) are supposed to be at risk of early atherosclerosis. However, data are still contentious. IBD patients are also at risk of other comorbidities such as metabolic associated fatty liver disease (MAFLD), a well-recognised entity associated with increased CV risk. The aim of this study is to demonstrate the impact of MAFLD on CV risk for IBD patients.

Methods

Prospective cohort study of consecutive IBD outpatients (Leonnard-Jones criteria, > 1 year) was performed from October 2020 to April 2021. Of 947 patients, 50 with IBD who met criteria for MAFLD and 50 with IBD and without MAFLD were matched by sex, age and IBD location. Patients with a previous diagnosis of CV disease, type II diabetes mellitus and under treatment for dyslipidaemia were excluded. Fatty liver disease (FLD) was diagnosed by ultrasonography, controlled attenuation parameter (CAP TM), fatty liver index (FLI), hepatic steatosis index (HSI) and lipid accumulation product (LAP). To assess early atherosclerosis, alterations in carotid artery intima-media thickness (CIMT) and SCORE as non-invasive CV risk test were performed in both groups. Statistical analysis was performed using SPSS, a binomial generalized linear model with logistic regression was performed, with CIMT alteration as dependent variable. For all tests a two-sided p value <0.05 was considered significant.

Results

Of 100 IBD patients included 51 (51%) were women with median age of 51.0 (41–59). There were 49 (49%) patients diagnosed of ulcerative colitis (UC) and 51 (51%) of Crohn’s disease (CD). Comorbidities and disease patient’s characteristics are shown in table 1. Most of the patients had an abnormal CIMT (58 (58%)). Of all the variables obtained, only female sex (OR (CI 95%) 3.322 (1.03–10); p=0.033) and MAFLD (OR (CI 95%) 5.05 (1.71–14.92); p=0.003)) were significatively associated with CIMT alterations. SCORE test did not associate with a significatively CIMT alteration. Among the different options to assess FLD, only ultrasonography and CAP were statisticaly associated with CIMT alterations (specificity 66%, sensibility 62%, p=0.005).

Conclusion

Female sex and MAFLD are associated with early atherosclerosis defined by CIMT alterations in IBD patients. Ultrasonography and CAP are better than biochemical test not only to predict FLD but also to assess CV risk.
P290 Therapeutic requirements in patients with Ulcerative Proctitis. Is it necessary immunosuppressive therapy in these patients?
Authors: Ferreiro Iglesias R , Porto Silva M S , Marín S , Casanova M J , Mañosa M , González-Muñoza C , de Francisco R , Caballol B , Arias L , Piqueras M , Zabana Y , Rivero M , Calvet X , Mesonero F , Varela Trastoy P , Busta Nistal R , Gomez Perosanz R , Vega P , Gonzalez Vivo M , Iborra M , Jimenez Marquez L , Madero L , Rodríguez-Lago I , Rodriguez Gonzalez M , Vera I , Ponferrada Diaz A , Vela M , Torrealba L , Van Domselaar M , Iglesias E , Gisbert J P , Calafat M , García-Planella E , Perez-Martinez I , Ricart E , Sicilia B , Mena R , Nieto L , Domenech E , Barreiro-de Acosta M
Published: January 2022

Background

Ulcerative proctitis may have a mild and less aggressive course, although evidence is scarce because these patients are excluded from participation in randomized controlled clinical trials. The aim is to identify clinical characteristics and complications associated with ulcerative proctitis refractory to conventional therapy.

Methods

Patients included in the prospectively maintained ENEIDA registry from GETECCU with ulcerative proctitis were included. Socio-demographic data were evaluated. We defined ulcerative proctitis based on ECCO guidelines and immunosuppression as the use of immunomodulators and/or biologics. Logistic regression was used to identify the independent factors associated with immunosuppressive therapy among the different socio-demographic data.

Results

From a total of 34.716 patients with ulcerative colitis, 6281 (18%) patients with ulcerative proctitis were identified. Mean age was 53 ±15 years and mean duration of illness was 12 ± 9 years. Surgery was necessary only in 2% of patients, 31 (0.5%) panprotocolectomy or subtotal colectomy. The clinical characteristics of the patients with and without immunosupressive therapy are summarized at table 1. A total of 3691 patients received oral 5-ASA (58.8%) and 4652 (74.1%) topic 5ASA. 636 (10.1%) were refractory to 5-ASA and corticosteroids, necessitating immunosuppression: 459 patients with azathioprine (7%), 28 with 6-mercaptopurine (0.4%), 49 with methothrexate (0.8%), 191 with infliximab (9%), 125 with adalimumab (2%), 50 with golimumab (0.8%), 57 with vedolizumab (0.9%), 6 with ustekinumab (0.1%) and 3 with tofacitinib (0.0). 316 (5%) patients needed one biologic therapy, 95 (1.5%) needed 2 biologics and 40 (0.6%) at least three different biologics. Longer duration of illness and use of corticosteroids were associated with higher risk of immunosuppression.

Conclusion

Good clinical outcomes were recorded in ulcerative proctitis, with only 10% of patients treated with immunosuppression therapy. The risk factors of immunosuppression were longer duration of illness and use of corticosteroids.
P296 vedolizumab Does Not Increase Risk of Clostridium Difficile Infection in Patients with Inflammatory Bowel Disease Using vedolizumab: a Retrospective Cohort Study
Authors: Alshahrani A
Published: January 2022

Background

Several studies have demonstrated that there is increased incidence, recurrence, and severity of Clostridium difficile (CDI) infection over the last decade. Patients with inflammatory bowel disease (IBD) who develop CDI are more prone to morbidity and mortality than CDI in patients without IBD. This study seeks to evaluate whether IBD patients who use vedolizumab are at increased risk of CDI compared to IBD patients using other therapies.

Methods

This was a retrospective cohort study, and 684 patients with confirmed IBD (228 on vedolizumab, 228 on anti-TNF, and 228 on 5-ASA therapy) were enrolled from January 2015 to August 2019 at a tertiary referral IBD center at McMaster University Medical Centre (MUMC) in Hamilton, Ontario, Canada. The primary outcome was time to the development of CDI in IBD patients using the three different classes of therapy. Secondary outcomes included rates of CDI and the association between baseline variables and risk of CDI. A Cox proportional hazards (PH) model was used to evaluate baseline factors and development of CDI.

Results

There was no difference in time to CDI between the three treatment groups (log rank p-value 0.37). No difference was seen in the number of patients with CDI; CDI occurred in 16 patients (2.3%), specifically four patients (1.75%) in the vedolizumab group, four patients (1.75%) in the anti-TNF group, and eight patients (3.5%) in the 5-ASA group (p=0.36). The Cox PH model revealed current smoking, older age, and concomitant immunomodulator use as risk factors for CDI, after adjustment for other covariates. Vedolizumab was not associated with increased risk of CDI in the model.

Conclusion

Biologic therapy with vedolizumab or anti-TNF did not impact risk of CDI. Risk factors for CDI in IBD patients included smoking, older age at the onset of medication, and immunomodulator therapy. Clinicians should have a high degree of suspicion for CDI in IBD patients presenting with diarrhea, particularly in those with risk factors identified in this study.
P299 Prediction model for steroid-free clinical remission with vedolizumab at week 22 in patients with Ulcerative Colitis: Machine learning using clinical data at baseline
Authors: Miyoshi J , Maeda T , Matsuoka K , Saito D , Morikubo H , Matsuura M , Tamura S , Hisamatsu T
Published: January 2022

Background

Predicting the response of patients with ulcerative colitis (UC) to a molecular targeted drug before administration is an unmet need for optimizing individual patient care. We hypothesized that a new machine-learning approach could identify predictors of therapeutic efficacy that have not been reported as statistically significant factors using the conventional statistical approaches. As a proof-of-concept study, we explored predictors and a prediction model for the efficacy of vedolizumab (VDZ) for UC.

Methods

The clinical data at baseline (week 0) of 34 UC patients who started VDZ at Kyorin University Hospital was collected (Cohort 1; training cohort). The collected data contained 49 clinical features; patient background (e.g. sex, age, disease phenotype, etc.), treatment history, clinical/endoscopic activity, and blood examination items. Random forest (RF) was employed to investigate clinical features that affect steroid-free clinical remission (SFCR) with VDZ at week 22 in UC. A prediction model was developed using logistic regression based on the results of RF. The prediction ability of the prediction model was evaluated with the data of 35 patients who started VDZ at Toho University Sakura Medical Center (Cohort 2; extra-facility test cohort). The prediction ability of the VDZ prediction model for ustekinumab (UST) was examined using the data of 22 patients who started UST at Kyorin University Hospital (Cohort 3).

Results

RF computed the contribution of each clinical feature to achievement/no-achievement of SFCR at week 22. When the top 8 features (partial Mayo score, MCH, BMI, BUN, concomitant use of AZA, lymphocyte fraction, height, and CRP) were employed for logistic regression, the prediction accuracy of the prediction model was 100% and 68.6% for Cohorts 1 and 2, respectively. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) in Cohort 2 were 92.3%, 54.5%, 54.5%, and 92.3%, respectively. Meanwhile, in Cohort 3 with UST, sensitivity, specificity, PPV and NPV were 70.0%, 45.5%, 53.4%, and 62.5%, respectively.

Conclusion

Our machine-learning approach detected clinical features at baseline that impact the achievement of SFCR at week 22 in patients who received VDZ for UC and developed a prediction model that appears to be useful to screen non-responders to VDZ. Given the low prediction ability in Cohort 3, our findings support the notion that a prediction model for each molecular targeted drug is needed for optimizing the drug selection for individual patients. This study provides the proof-of-concept that machine learning on clinical data could open a new era of personalized medicine for UC.
P316 Ozanimod is an efficacious oral therapy after, 5-ASA failure in immunomodulator- and biologic-naive patients with ulcerative colitis: post hoc analysis from True North
Authors: Sands B E , Dignass A , Irving P , Chiorean M , Long M , Eren D , Ahmad H A , Osterman M T , Petersen A , Elegbe A , Ritter T , Danese S
Published: January 2022

Background

Oral, 5-aminosalicylates (5-ASA) and corticosteroids (CS) are often the first-line treatment for ulcerative colitis (UC), and patients (pts) who fail these agents typically advance to chronic immunosuppressives. Ozanimod, an oral sphingosine, 1-phosphate receptor modulator, is approved for treating adults with moderately to severely active UC in the US. This post-hoc analysis from the pivotal phase, 3 True North randomised controlled trial evaluated the efficacy of ozanimod at week (wk), 10 (end of induction) in immunomodulator- and biologic-naive pts with moderate to severe UC who failed, 5-ASA with or without concomitant CS.

Methods

True North consisted of a, 10-wk induction period. Pts in Cohort, 1, stratified by CS use at screening, were randomised to either ozanimod, 0.92 mg (equivalent to ozanimod HCl, 1 mg; n=429) or placebo (n=216) once daily in a double-blind manner; pts in Cohort, 2 (n=367) received open-label daily ozanimod, 0.92 mg. At enrollment, pts were required to be on stable doses of oral, 5-ASA and/or CS for >2 wk and continued on the same dose throughout induction. Pts who received tofacitinib within, 2 wk of screening were excluded. This analysis focused on clinical remission, clinical response, endoscopic improvement, and mucosal healing efficacy outcomes in immunomodulator- and biologic-naive, 5-ASA exposed pts.

Results

Of, 464 pts treated with, 5-ASA and were immunomodulator- and biologic-naive, with or without CS, 205 were on ozanimod and, 105 were on placebo in Cohort, 1;, 158 received open-label ozanimod in Cohort, 2. Baseline characteristics were similar between groups in Cohort, 1. Compared with placebo at wk, 10, a higher proportion of ozanimod-treated patients achieved clinical remission (23.4% vs, 8.9%), clinical response (53.7% vs, 30.7%), endoscopic improvement (35.6% vs, 14.9%), and mucosal healing (18.0% vs, 5.0%; Figure, 1) in this subgroup. These results are consistent with previously published results of the overall study population,1 which demonstrated significantly greater proportions of patients receiving ozanimod vs placebo achieving clinical remission (18.4% vs, 6.0%), clinical response (47.8% vs, 25.9%), endoscopic improvement (27.3% vs, 11.6%), and mucosal healing (12.6% vs, 3.7%). Additionally, all efficacy endpoints were achieved by a greater proportion of patients on ozanimod vs placebo regardless of CS use at baseline (Figure, 2). Results were similar for open-label ozanimod-treated patients in Cohort 2.

Conclusion

Ozanimod demonstrated efficacy at wk, 10 in immunomodulator- and biologic-naive patients with UC who had failed, 5-ASA, regardless of CS use at baseline.

Reference

1. N Engl J Med, 2021;385:1280.
P317 Ustekinumab Trough Concentrations Associated with Biochemical Outcomes in Patients with Crohn’s Disease
Authors: Straatmijer T , Biemans V B C , Moes D J A R , Hoentjen F , ter Heine R , Maljaars P W J , Theeuwen R , Pierik M , Duijvestein M , van der Meulen A E
Published: January 2022

Background

Ustekinumab (UST) is a monoclonal antibody which binds to the p40 subunit of interleukins-12/23 and is an effective and safe treatment for patients with Crohn’s disease (CD). An association between serum drug concentrations and therapeutic outcomes is required to justify Therapeutic Drug Monitoring (TDM). However, it is currently unknown if TDM is of additional value in UST treatment. We assessed the exposure-biochemical response relationship of UST trough concentrations at week, 8 in a prospective, real-world setting.

Methods

We performed a prospective study in CD patients with biochemical, radiologic or endoscopic disease activity in four academic centers in the Netherlands. All patients (n=90) received weight adjusted intravenously (IV) UST induction. First subcutaneous (SC), 90 mg induction dose was administered at week, 8 followed by a maintenance dose of, 90 mg SC every, 8 or, 12 weeks, at the discretion of the physician. Blood for drug levels were drawn at different time points during follow up (median follow up was, 52 weeks (IQR, 50–52)) with a median amount of, 2 measurements (IQR, 1–4) per patient. Plasma concentrations of UST were determined by means of a validated enzyme-linked immune assay. A population pharmacokinetic (PK) model was developed based on these measurements and the UST FDA review documents. Subsequently, the individual UST concentration time course during treatment were predicted using the developed model. Corticosteroid-free clinical remission (HBI ≤, 4) and biochemical remission (C-reactive protein (CRP) ≤5 mg/L or faecal calprotectin (FC) ≤, 250) were assessed at week, 12 and, 24. Quartile analysis and logistic regression was performed to analyse if UST concentration at week, 8 was associated with biochemical remission rates at week, 24. An independent cohort of, 34 patients was used to validate the primary outcomes.

Results

Basis characteristics of all patients are shown in table 1. Median estimated trough concentrations of UST were, 4.23 µg/mL (IQR, 2.79–5.83) and, 7.19 µg/mL (IQR, 3.30–10.67) at week, 8 in the primary and validation cohort respectively. Patients achieving biochemical remission at week, 12 and, 24 had statistically significantly higher UST levels at week, 8 (P<0.01) compared to patients without biochemical remission (fig, 1). Also, higher UST levels at week, 8 were associated with better biochemical remission rates at week, 12 and, 24 in quartile analysis and logistic regression (fig, 2,3). Associations of UST levels at week, 8 and biochemical remission at week, 12 and, 24 were confirmed in the validation cohort. No UST antibodies were detected.

Conclusion

In this real-world cohort of CD patients, ustekinumab levels of ≥5.9 µg/mL at week, 8 were associated with higher biochemical remission rates at week, 12 and, 24.
P326 The effect of compliance during exclusive enteral nutrition on faecal calprotectin levels in children with Crohn’s disease
Authors: Mckirdy S , Russell R , Hansen R , Svolos V , Gkikas K , Logan M , Gerasimidis K
Published: January 2022

Background

It is yet unclear whether suboptimal response to exclusive enteral nutrition (EEN), in some children with Crohn’s disease (CD), is explained by poor compliance. All proprietary feeds used for EEN are gluten-free; hence patients’ compliance to EEN could be determined by detecting gluten immunogenic peptide (GIP), a biomarker of gluten intake, in faeces.

Methods

The concentration of GIP was measured in the faeces of, 45 children (3–17 years) with CD prior to and during (33 &, 54 days) treatment with EEN. Associations with GIP and faecal calprotectin (FCAL) levels were explored at, 33 and, 54 days of EEN.

Results

GIP was present in, 37 of the, 40 (93%) patients who provided stool samples prior to starting EEN, indicating typical gluten consumption in CD patients. In patients with undetectable GIP at both, 33 and, 54 days of EEN, FCAL significantly decreased from baseline (mean decrease, 33 days: -743mg/kg, 54 days: -1043mg/kg, p<0.001), but not in patients who had detectable GIP. At EEN completion, patients with undetectable GIP had a lower FCAL by, 763mg/kg than patients with a positive GIP result (p=0.041) and demonstrated a greater decline from baseline FCAL (-69% vs +5.%, p=0.021).

Conclusion

Poor response to EEN might be explained at least in part by diminished compliance and dietary transgressions. Faecal GIP might be useful as a proxy biomarker of EEN compliance.
P336 Can Mesenchymal Stem Cell (MSC) apoptosis be used as a biomarker for treatment success in perianal fistulising Crohn’s Disease (pCD)? Findings from a prospective pilot study
Authors: Iqbal N , Constable L , Tozer P , Lung P , Hart A , Powell N
Published: January 2022

Background

Mesenchymal Stem Cells (MSC) demonstrated promising results in patients with refractory perianal fistulising Crohn’s Disease (pCD) in the ADMIRE-CD trial, however their use is limited by treatment cost. Studies of Graft vs. Host Disease (GvHD) patients receiving MSCs for steroid refractory disease have shown that in vitro Peripheral Blood Mononuclear Cell (PBMC) induced MSC apoptosis correlates with clinical response. We conducted a pilot prospective study to investigate the clinical and radiological outcome of MSC treatment and determine whether in vitro MSC apoptosis correlates with clinical response in patients with pCD.

Methods

Patient eligibility and MSC administration mirrored that in ADMIRE-CD. Prior to treatment, patient PBMCs were isolated and co-cultured with MSCs and the proportion of apoptotic MSCs identified using flow cytometry (Annexin V+, 7AAD- MSCs). Patients were followed up at, 6-monthly intervals and clinical indices including the Perianal Disease Activity Index (PDAI) and Fistula Drainage Assessment (FDA) were recorded in addition to MRI response. Clinical response categories were determined according to ADMIRE-CD as well as new criteria accounting for radiological healing (Table 1).

Results

Ten patients underwent MSC treatment (M=4, median age, 35, range, 22–73 years). At final follow up (median, 24 months, range, 18–30 months), there was a significant improvement in mean FDA (baseline, 1.3, final follow up, 0.5, p<0.01) but not in PDAI. The apoptosis assay was performed in, 9 patients. A greater proportion of MSC apoptosis was demonstrated when co-cultured with pCD patient PBMCs than with PBMCs from healthy controls (Figure, 1). Patients with a percentage of apoptotic MSCs greater than the group median (22.3%) were classed as apoptosishigh. At final follow up, apoptosishigh patients were also those who demonstrated a response to MSC treatment according to both St Mark’s (Figure, 2) and ADMIRE CD criteria (Figure 3).

Conclusion

The ability of patient PBMCs to induce the highest proportions of MSC apoptosis correlates with clinical response to MSC treatment in this small sample of patients. An adequately powered prospective study is required to determine the potential use of MSC apoptosis as a biomarker of clinical response.
P338 Early proactive drug monitoring strategy of infliximab as monotherapy for inflammatory bowel disease in paediatric patients is associated with good sustained clinical remission
Authors: Girard C , Achkar S , Sassine S , Chapuy L , Jantchou P , Deslandres C
Published: January 2022

Background

Monotherapy with infliximab (IFX) could be as efficient as combotherapy with immunomodulators in the treatment and maintenance of remission for children with inflammatory bowel disease (IBD) if a proactive therapeutic drug monitoring strategy is adequately performed. This strategy may allow optimization of blood levels of IFX in order to obtain a sustained clinical response.

Methods

A retrospective study was conducted amongst children with IBD, aged from, 2 to, 18 years old and diagnosed between January, 2018 and June, 2020. All patients were treated with IFX less than, 30 days after diagnosis. Data concerning disease activity was collected at diagnosis, at one year after diagnosis. Close monitoring of IFX blood levels were collected before the third and fourth dose and regularly thereafter. Adjustments in IFX dose per infusion were made according to blood levels and clinical response. The primary outcome was clinical remission, defined by a PUCAI or shortPCDAI score <, 10 without the need of corticosteroid, at one year after diagnosis. The secondary outcomes measured were the median (interquartile range (IQR)) dose of IFX (in mg/kg) after a year of treatment, the median (IQR) number of changes of IFX dose, the time intervals between IFX infusions over a year, and the median (IQR) number of blood levels of IFX done in a year.

Results

A total of, 91 patients were included (81% Crohn’s disease; mean age at diagnosis was, 13.2 years (IQR = 11.3 to, 15.15)). After one year of treatment, 76 patients (83.5%) reached clinical remission. IFX was discontinued in, 13 patients:, 6 due to antibody occurrence, 5 because of treatment failure, 1 due to psoriasis and, 1 due to autoimmune hepatitis. In total, 61.5% of patients needed two or more IFX dose/interval optimization over the course of a year. At one year after diagnosis, the median IFX dose per infusion was, 8.78 mg/kg (IQR = 7.5 mg/kg to, 9.9 mg/kg) with infusions given, 6 weeks apart or less in, 82% of the patients. Patients who were diagnosed before the age of, 10 had a median IFX dose of, 9.43 mg/kg. The median number of IFX blood level dosage was, 4 per patient over a year (IQR=, 3.5 to 6).

Conclusion

Early treatment for IBD with IFX as monotherapy and a proactive optimization strategy is associated with a good sustained steroid free clinical remission. Most patients needed an increase of IFX dose during the first year of treatment. We therefore recommend to proactively monitor blood levels of IFX before the third and fourth dose of IFX and thereafter, in order to lower the risk of treatment failure and anti-infliximab antibodies occurrence.
P342 Trans-continental analysis of over, 2000 Inflammatory Bowel Disease patients implicates geography, disease type, and exposure to immunosuppression as drivers of SARS-CoV-2 seroprevalence: data from the ICARUS-IBD Consortium
Authors: Wong S Y , Helmus D , Marlow L , Martinez Pazos V , Brann S , Wellens J , Kedia S , Mak J W Y , Bergemalm D , Argollo M , Zaltman C , Steinwurz F , Rubin D , Allez M , Halfvarson J , Abreu M T , Lindsay J , Dutta U , Silverberg M S , Ng S C , Ahuja V , Watanabe K , Vermeire S , Colombel J F , Satsangi J
Published: January 2022

Background

IBD patients on immune-modulatory therapies are considered high-risk for SARS-CoV-2 infection. Direct comparisons of serological responses to SARS-CoV-2 infection in IBD patients across different continents and medications are lacking. We performed SARS-CoV-2 sero-surveillance of IBD patients prior to vaccination at seven large tertiary centres in Asia, Europe, and North America.

Methods

Clinical data and sera were collected from, 2,213 IBD patients receiving routine care at institutions in Belgium, Canada, Hong Kong, India, Japan, the United Kingdom, and the United States between, 26 May, 2020 and, 24 September, 2021 (Table, 1). Sera were taken prior to vaccination. Clinical data were collected through patient questionnaires and medical records. Antibody reactivity to the SARS-CoV-2 spike protein was assessed using the Roche SARS-CoV-2 anti-spike total antibody and/or Siemens Healthineers COV2T anti-spike total antibody assays, which showed, 99.4% concordance. Univariate analysis was performed to evaluate association between individual variables and sero-status.

Results

The pre-vaccination seroprevalence of antibodies to SARS-CoV-2 in IBD patient varied widely according to location from, 0% in Hong Kong to, 57.9% in New Delhi, India (p<0.001). Rates in Europe and North America were similar (range, 3.57%-8.94%). Overall, SARS-CoV-2 seroprevalence appears to be equal to or less than local populations (Table, 2). Seroprevalence rates were associated with IBD type (7.8% CD, 12.4% UC, 15% IBD-U, p<0.001), smoking status (p<0.001), and history of COVID diagnosis (p<0.001) or COVID hospitalization (p=0.001), and any IMM (p<0.001). (Table, 3). Whilst there were no significant differences in seroprevalence between patients receiving infliximab (IFX), vedolizumab (VDZ), and ustekinumab (UST), antibody levels were attenuated in patients on IFX monotherapy and combination therapy (both p=0.002) and VDZ (p=0.02), compared with no medications (Figure 1).

Conclusion

We confirm in diverse poulations that exposure to biologics or immunomodulators, type of disease, and smoking status are associated with seroprevalence and antibody levels. We show for the first time the dominant influence of geographical location on sero-status in these patients. These observations should be considered as we look towards post-vaccination data to help stratify patients for clinical guidelines on SARS-CoV-2 vaccination.