bluuebunny/crossref_metadata_2025 huggingface dataset:
P085 Expression profiling of Wnt pathway genes in colon biopsies of patients with Ulcerative Colitis
Authors: Lu C , Shah D , Wijnands A , Oldenburg B , Yeh W C , Vanhove G , Li Y
Published: May 2021

Background

There is an increasing demand of agents that can promote mucosal healing in Inflammatory Bowel Disease (IBD). Wnt/β-catenin signaling plays a critical role in epithelial regeneration and repair, and stimulating regeneration in the damaged epithelium by modulating Wnt signaling has been suggested as a potential treatment option for IBD. To guide development of Wnt modulating therapeutic molecules for IBD, an understanding of how Wnt signaling may be altered in IBD tissues is required. While earlier work showed altered Wnt pathway gene expression in UC tissues, these studies failed to consider disease conditions (moderate vs severe) and patient treatment history on expression of the Wnt family genes. These previous studies utilized RT-qPCR or microarray and did not reveal how Wnt pathway gene expression might be affected specifically in the epithelium and in the adjacent stromal stem cell niche. Here we report our work investigating expression patterns of Wnt pathway genes in UC biopsies from 12 patients with moderate and severe disease. Patients had either received no anti-TNF treatment or had gone through anti-TNF treatment and partially responded to the treatment.

Methods

Expression of a set of Wnt pathway genes was assessed in UC colon and rectum biopsies by RNAscope in situ hybridization and compared to expression patterns in normal control colon. The genes included the Wnt target genes AXIN2, LGR5 and RNF43, Wnt ligands and the FZD5 and LRP6 receptors enriched in the intestinal epithelium as well as key Wnt signal modulators RSPO1-4.

Results

Expression of Wnt target genes were mildly reduced in the UC colon epithelium, while their expression in some crypts appeared much lower. Overall expression levels of Wnt pathway genes did not differ between moderate and severe UC colon and Wnt target gene expression was more affected in the anti-TNF treated colons, which may reflect more refractory disease. Expression of FZD5, LRP6 and the key niche factor RSPO2, was reduced in the UC colon. RSPOs are normally expressed in the stromal cells next to the crypt bottom stem cell compartment but this expression pattern was disrupted in the UC colon as a result of immune cell infiltration. Although expression of Wnts was induced in the UC colon tissues, the location of expression was altered due to tissue damage, potentially making the Wnts less accessible to the intestinal stem cells.

Conclusion

Reduced expression of Wnt receptors, RSPOs and Wnt target genes indicate insufficient Wnt signal induction in the damaged colon epithelium of UC patients. This suggests that repair of the damaged epithelium by Wnt agonist treatment may constitute a new mechanism of action and benefit patients with UC.
P093 COVID-19 lockdown and mental health burden in Inflammatory Bowel Disease paediatric patients: a case-control study
Authors: Milo F , Romeo E F , Rea F , Grimaldi Capitello T , De Angelis P , Tabarini P
Published: May 2021

Background

From March 10 to May 3, 2020, Coronavirus disease 2019 (COVID-19) and subsequent enforced lockdown in Italy has led to an increased general psychological distress1. In particular, people with both compromised immune function and pre-existing physical or psychiatric problems are at increased risk of adverse psychosocial outcomes2. The purpose of this study was to compare mental health burden in Inflammatory Bowel Disease (IBD) paediatric patients with and without COVID-19 lockdown exposure.

Methods

We conducted a retrospective case-control study comparing mental health outcomes of two matched 1:1 IBD paediatric groups: Group 1 - before the exposure (January 2019-September 2019) and Group 2 - after COVID-19 pandemic lockdown (April 2020-December 2020). Matching criteria included gender, age, disease duration, IBD subtype, Body Mass Index and disease activity (remission or active). This study included patients with Crohn Disease (CD) and Ulcerative Colitis (UC), >12 years, attending outpatient visits at Bambino Gesù Children Hospital. Data were collected using the Generalised Anxiety Disorder (GAD-7) for anxiety and the Patient Health Questionnaire (PHQ-9) for depression. We have estimated the prevalence of anxiety and depression between the two groups. Both groups were also compared with respect to the average score of anxiety and depression symptoms. Sociodemographic and clinical data were recorded from patients’ medical chart.

Results

A total of 108 IBD paediatric patients (62 males, 54 with CD and 54 with UC, mean age=16±2,5 years) was enrolled in this study. Out of these, 54 patients were enrolled in Group 1 and 54 in Group 2. Using a cut-off score ≥10, we found similar prevalence of anxiety (13.0% vs 22.2%, P=.206) and depression (13.0% vs 18.5%, P=.428) among the groups. Average scores were quite similar among the two groups, both for anxiety (5.78 vs 5.96, P=.924) and depression (5.89 vs 5.87, P=. 704). Symptom severity levels were mild (≃6) in both groups, according to standardized instrument cut-offs. No significant associations were found between disease activity and symptoms of anxiety and depression in both groups.

Conclusion

IBD-related symptoms (i.e. weight loss, persistent diarrhoea, abdominal pain and fatigue) lead to severe psychosocial impairment in paediatric IBD patients. COVID-19 pandemic outbreak and enforced isolation (i.e., lockdown, long distance learning, and social restrictions) limited patients’ stressful social situations engagement and paradoxically prevented a worsening of their mental health.

References
P100 Higher yield of serrated and adenomatous dysplasia detected with chromoendoscopy when compared with high-definition in patients with Primary Sclerosing Cholangitis and Inflammatory colitis
Authors: Gupta V , Hartery K , Bassett P , Culver E , East J
Published: May 2021

Background

There is an increased risk of colorectal dysplasia/cancer in patients with primary sclerosing cholangitis and inflammatory bowel disease (PSC-IBD); cumulative risk of 14% at 5 years and 17% at 10 years. SCENIC (2015) consensus guidelines recommend surveillance with chromoendoscopy (CE) and use of a high definition (HD) scope with white light colonoscopy. We aimed to assess the value of CE and HD scope in detection of dysplasia in PSC-IBD.

Methods

We analysed all colonoscopic surveillance performed for PSC-IBD between 2010–2020 at Oxford University Hospitals (n=422 procedures). Continuous variables were assessed by Kruskal-Wallis (three groups) and categorical variables by Chi-square test. Repeat measurements were accounted for by multilevel regression models with individual colonoscopies nested within patients. Multilevel ordinal logistic regression was used for assessment of bowel prep. Outcomes were adjusted for confounding variables (adj).

Results

359 colonoscopies were analysed in 91 patients with PSC-IBD (69/422 were excluded as prior dysplasia detected). CE and HD scope use increased in frequency over the 10-year period (p=0.02). HD were rarely used in those with bowel preparation deemed inadequate (p<0.001), but there was no association between CE and bowel prep quality. Dysplasia detection (adenomatous and serrated lesions) was higher with CE compared with white light examination; 14% vs 3% (p<0.001), and after adjusting for confounders (p<0.009) and use of HD scope (p<0.01), OR 5.02 (CI 1.43–17.7). Dysplasia detection was higher with HD compared with standard definition (SD); 14% vs 6% (p<0.04), but was non-significant after adjusting for confounders, OR 1.93 (CI 0.69–5.4). Dysplasia was more likely to be found on targeted than random colonic biopsies (p<0.001).

CE increased detection of serrated lesions (9% vs 2% (p=0.06) OR 3.5 adj) and more so adenomatous dysplasia (6% vs 1% (p=0.03) OR 12 adj) compared to white light. HD increased detection of serrated lesions (9% vs 3.5% (p=0.04) OR 2 adj) but not adenomatous dysplasia (6% vs 2.5% (p=0.19) compared to SD. (Table 1)

Conclusion

CE is superior to HD and SD white light examination for dysplasia detection in PSC-IBD after accounting for confounders and performed better for adenomatous than serrated lesions.
P132 Uncovering blood biomarkers of Inflammatory Bowel Diseases by Raman spectroscopy and FAP dosage: toward a noninvasive triage of patients in first care diagnostic
Authors: Truffi M , Morasso C , Albasini S , Malovini A , Bellazzi R , Piccotti F , Caldarone A , Sorrentino L , Mazzucchelli S , Sampietro G , Colombo F , Ardizzone S , Corsi F
Published: May 2021

Background

Currently, a major point of concern in the management of Inflammatory Bowel Diseases (IBD) is the absence of accurate and specific circulating biomarkers able to drive diagnosis in a timely and noninvasive manner. Aim of the present study was to explore blood biomarkers of IBD by coupling the targeted detection of circulating fibroblast activation protein (FAP), a recognized valuable marker of bowel lesion in IBD, and Raman spectroscopy (RS), a quick and label-free metabolomic technique that provides a real-time biochemical characterization of plasma samples without any previously known target.

Methods

Blood samples were collected from over 140 patients with IBD and 170 control subjects matched for gender and age. Isolated plasma was analysed by enzyme-linked immunosorbent assay for quantitative detection of circulating form of FAP. RS was performed on dry droplets of plasma, with the aim to decipher specific fingerprint of IBD in peripheral blood. A predictive model was built on FAP and Raman data separately, to determine specificity, sensitivity and accuracy of the two approaches in patients classification. Supervised multivariate model was applied on a subset of 203 patients to discriminate IBD and control subjects based on combined datasets.

Results

FAP levels were reduced in patients with IBD as compared to controls (p<0.0001). The sensitivity and specificity of FAP were 70% and 84% based on the optimal cutoff (57.6 ng mL-1, AUC=0.78). Raman spectra of IBD plasma revealed significant differences in peaks corresponding to carotenoids, proteins with β-sheet secondary structure, lipids and aromatic amino-acids. A machine learning model was applied on a subset of patients reaching an accuracy of 85% in classifying IBD and control subjects. No statistically significant differences were observed so far between the discriminative performance of the sole RS or the combination of RS and FAP.

Conclusion

RS and FAP dosage enable new discoveries in the biological fingerprint of IBD plasma and provide novel candidate biomarkers of IBD. Our preliminary results strongly suggest that novel blood-based approaches could represent a fast noninvasive way to triage patents with suspected IBD in first care diagnostic, to be applied prior to further specific evaluation.
P173 Subfertility in young women and men patients with Crohn′s disease
Authors: Rodríguez A , Herreros B , Muñoz R , Sempere L , Sirera P , González-Bueno V , Torregrosa M E , Alfayate R , Orts B , Zapater P , Tejedo D , Moreno-Pérez O , Gutiérrez A
Published: May 2021

Background

Crohn’s disease (CD) affects young adults on reproductive age. They are likely to desire pregnancy and are often concerned about the potential effects of inflammatory bowel disease on fertility. Aims to investigate the effect of CD in fertility, studying the ovarian reserve in women by serum anti-Müllerian hormone (AMH) and Sertoli cell function in men measured by serum Inhibine (IB).

Methods

Cross-sectional, prospective, case-control study, including CD patients, aged 18–40 yr, and healthy controls(HC) matched by gender and age(ratio 2:1). Morning IB was measured using ELISA. Serum AMH was measured by ECLIA. Sociodemographic and phenotypic features of CD patients and controls were collected. We defined impaired fertility potential as IB level < 89 pg/mL and AMH <1.66 ug/L 0–24 yr, <1. 18 ug/L 25–29 yr, <0.67 ug/L 30–34 yr, <0.77 ug/L 35–39 yr, <0.01 ug/L 40–44 yr. AMH < 2 ug/L under 40 yr was considered low.

Results

A total of 122 subjects were included:73 men(48 CD, 25 HC) and 49 women(21 CD, 28 HC). No statistical difference was found between mean serum AMH levels in CD and HC women(2,23±1,8 vs 2,86±1,9 ug/L, p=0,5). The rate of abnormal serum AMH levels according to age did not differ between groups (19% CD vs 25% HC, p=0,4). When classified according to age(<30 and >30 yr), the serum AMH levels remained comparable in <30 yr (3.3±2.06 CD vs 3,2±1.96 ug/L HC, P=0.9). However, a low AMH level(<2 ug/L) was measured in 13 CD women(61%) and in 9 HC(32%)(P < 0.03), especially in>30 yr, 9 CD(90%)vs 4 in HC(40%)(p=0.02). Serum IB levels were significantly lower in CD men vs HC (175.4 ±62.3 vs 234.12±75.56 ug/L, p=0.002). We did not find abnormal IB(<89 pg/mL) in HC vs 3(6%) among CD men.

Conclusion

Women with CD did not have severe ovarian reserve alterations compared to a control population. However higher proportion of CD women showed low AMH (< 2 ug/L), especially those > 30 years. These data could be helpful for female CD patients who want to have children. Inhibine levels, as biomarker of Sertoli cell function, were lower in CD men compared to healthy controls.
P174 Defining Crohn’s Disease Strictures Using Intestinal Ultrasound Compared to Histopathology
Authors: Cooper J , Danois K , Koro K , Wilson S , Medellin A , Ma C , Novak K , Seow C , Kaplan G , Panaccione R , Lu C
Published: May 2021

Background

Fibrostenotic Crohn’s Disease (CD) is a challenging phenotype often requiring surgical resection. MRE (magnetic resonance enterography) is commonly used to diagnose CD strictures, but is limited by access, cost, and long acquisition time. The CONSTRICT consensus criteria for defining CD strictures is based only on MRE or CT (computed tomography) and includes: increased bowel wall thickness (BWT), narrowed luminal apposition, and pre-stenotic dilation > 3cm. This definition has not been studied using intestinal US (IUS). IUS is a cost-effective, easily repeatable, and well-tolerated tool with similar sensitivity and specificity to MRE in diagnosing and monitoring CD. In patients with a confirmed CD stricture on ileal resection (gold standard for diagnosis), we aim to assess the applicability of CONSTRICT criteria in diagnosing strictures with IUS.

Methods

In this pilot study, thirty CD patients who underwent small bowel resection from 2015–2019 with IUS (fasting, no oral contrast) within 6 months prior to surgery (excluding fistulizing disease) were randomly identified for chart review Stricture was confirmed on resected ileum as microscopic presence of fibrosis, muscle hypertrophy, inflammation, and macroscopic localized luminal narrowing with decreased circumference on pathology. Student’s t-tests, sensitivities and specificities were calculated for IUS in detecting strictures.

Results

20 out of 30 patients had fibrostenosis on pathology and IUS. Only 40% (8/20) met CONSTRICT criteria for stricture diagnosis on IUS, despite having a stricture on pathology. All patients had elevated BWT and luminal narrowing, but 60% (12/20) of patients did not have prestenotic dilation > 3cm. Mean dilation was 2.9 cm (SD 1.38) and was significantly different from the mean stricture diameter of 1.3cm (SD 0.59 cm, p=0.0001, 95% CI: 0.9–2.2). Mean BWT was 8.7 mm (SD: 2.5, range 5–15), and mean luminal apposition was 2.3 mm (SD 1.2, range 0.2–5.8mm). IUS has a sensitivity of 95.2% (CI: 76.2 - 99.9%) and specificity of 66.7% (29.9 - 92.5%) in detecting strictures, when compared to the gold standard.

Conclusion

Diagnosis of fibrostenotic CD with CONSTRICT criteria using CT/MR may not be applicable to IUS. Only 40% of patients met criteria despite histologic-confirmed strictures. Unlike MR/CTE, IUS is not routinely performed with oral contrast, and as a result prestenotic dilation may be underestimated. Thus, perhaps additional criteria of stricture diameter < 50% of prestenotic dilation size is more appropriate for IUS. This pilot study provides the initial data to further delineate the definition of strictures on IUS for future validation and will inform both clinical practice and trial design.
P205 Influencing factors of Sleep quality in patients with Crohn’s Disease
Authors: Sabbah M , Jlassi H , Bellil N , Trad D , Ouakaa A , Bibani N , Gargouri D
Published: May 2021

Background

Sleep is considered vital for the health and quality of life of individuals. Recently, studies have suggested that sleep disturbances are common in people with Crohn’s disease (CD) and in the majority of cases are related to disease activity.The aim of our study was to determine the prevalence of insomnia in patients with CD and to identify the influencing factors.

Methods

A prospective cross-sectional study including patients with CD followed in the department between July and August 2020 was carried out. Epidemiological and clinical data have been collected. Self-report questionnaires were given to patients. Insomnia was assessed using the Insomnia Severity Index (ISI) which provides a valid index of the overall severity of insomnia. A score between 0 and 7 indicates the absence of insomnia; between 8 and 14 a mild infra-clinical insomnia; between 15 and 21 moderate clinical insomnia, and between 22 and 28 severe insomnia. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale (HADS) questionnaire which is a scale of 14 items rated from 0 to 3. Seven questions are related to anxiety and seven to depression. Fatigue was screened for using the Fatigue Severity Scale (FSS) which has 9 questions rated from one to seven. Significant fatigue was defined by a score greater than or equal to 5.5. Statistical analysis was performed by SPSS 21 software (p significant if less than 0.05).

Results

Thirty two patients with a mean age of 38.28 years [18–60 years] and a sex ratio equal to 1 were enrolled. Mean duration of the disease was 10.56 years [1–40 years]. At the time of inclusion, the average Harvey Bradshaw (HAB) score was 5.14 [1–14].

Mean insomnia score was 12.62 [0–26]. The insomnia severity index showed mild insomnia in 4 patients (12.5%), moderate insomnia in 7 patients (22%) and severe insomnia in 8 patients (25%).

The HADS score revealed obvious depression in 19% of patients, doubtful depression in 25% of patients. 56% of patients had no symptoms of depression. Likewise, anxiety was objectified in 22% of patients and doubtful anxiety in 37% of patients. 41% of patients had no symptoms of anxiety. The mean fatigue score was 3.75 ± 1.9 [range 1–9]. A fatigue score greater than or equal to 5.5 was observed in 3 cases (9%).

A significant positive correlation was found between the insomnia severity score and the depression score (r = 0.4, p = 0.035) as well as the fatigue severity score (r: 0.36, p = 0.04).

Conclusion

Our study shows that insomnia is very common in patients with CD. The factors associated with these sleep disturbances were depression and fatigue. Gastroenterologist and psychologist should join forces to evaluate emotional as well as sleep disturbances for a better global CD management.
P207 Clinical outcome of patients with Ulcerative colitis after anti-TNF discontinuation -\t10 years follow up
Authors: Johnsen K M , Mona D G , Florholmen J , Goll R
Published: May 2021

Background

Biological therapy for ulcerative colitis (UC) such as anti-TNF have shown high efficacy in achieving remission. There is a lack of information about the long-term outcomes after biologic withdrawal and validated clinical, immunologic, genetic or laboratory markers that can predict outcome after withdrawal accurately. The aims of this study were to describe the long-term outcomes after anti-TNF withdrawal and discover potential biomarkers to predict long-term remission as an approach to towards personalized medicine.

Methods

75 patients with moderate to severe UC treated to remission with anti-TNF were included in the study. These patients were categorized as either “Long term remission” (LTR) or “Relapse”. The “Relapse” group were divided in subgroups by the highest treatment level needed to obtain remission the last 3 years of observation: non-biological therapy, biological therapy or colectomy. LTR were divided in LTR + immunomodulating (imids) drugs and a new clinical phenotype “Near the Cure of disease” (NCD), defined as > 3 years in remission with no medication or 5ASA only.

Results

The median (IQR) observation time of all patients included were 121(111–137) months. Of the 75 patients 46 (61%) did not receive biological therapy including 23 (31%) in LTR + imids. Of the 23 patients 16 were defined as NCD with an observation time of median (IQR) 95(77–113) months. Fourteen patients underwent colectomy and 15 patients received biological therapy the last 3 years of the follow-up. Mucosal TNF copies/µg mRNA < 10 000 at anti-TNF discontinuation predicted long-term remission, biological free remission and lower risk of colectomy with a HR 0.36 (0.14–0.92) for long term remission, HR 0.17 (0.04–0.78) for biological free remission and HR 0.12 (0.01–0.91) for coelctomy.

Conclusion

This 10-year anti-TNF discontinuation follow up study of UC shows that 61% of patients experience an altered phenotype to a milder disease course without need of biological therapy. Normalized mucosal TNF transcript predict this mild disease course and lower risk of colectomy. Of special interest is that 21% of the patients defined as “Near the cure of disease” were in long-term remission without any medication or receiving 5ASA only.
P221 Crohn’s disease patients unable to complete preoperative mechanical bowel preparation have increased risk of anastomotic complications: results of a prospective observational study
Authors: Kunovsky L , Marek F , Kala Z , Ivanecka D , Iesalnieks I
Published: May 2021

Background

To assess the risk of postoperative anastomotic leak in Crohn’s disease patients unable to complete the preoperative mechanical bowel preparation (MBP): a prospective observational study from two referral centers in Germany and the Czech Republic.

Methods

Preoperative MBP was used routinely in all Crohn’s disease patients undergoing elective ileocolic or colorectal resections completed by formation of an anastomosis since 6/2016. The MBP consisted of 2 L Polyethyleneglycol (PEG) solution combined with two doses of oral antibiotics Metronidazole/Paramomycin or Metronidazole/Neomycine. The MBP was defined as incomplete when patients were not able to drink the whole amount of PEG solution due to side effects or complications. The primary endpoint was the occurrence of anastomotic leak. The secondary endpoint was the incidence of postoperative intra-abdominal septic complications (IASC) which were defined as anastomotic leak, intra-abdominal abscess, fistula or peritonitis.

Results

Between 6/2016 and 3/2021, 157 Crohn’s disease patients underwent elective ileocolic or colorectal resections after receiving preoperative MBP and oral antibiotics. Forty (26%) developed complications from the MBP, mostly vomiting; twenty-nine patients (18.5%) were not able to complete the MBP. Female sex (HR 4.2, p=0.016) was associated with an increased probability of not being able to complete the MBP. Postoperative anastomotic leak occurred in 5 patients (3%). In a multivariate analysis, the risk of anastomotic leak was significantly higher in patients unable to complete the MBP (10.5%), as compared to patients with complete MBP (1.6%, p=0.01, HR 21.0). Postoperative IASC occurred in 7 patients (7%). Patients unable to complete preoperative MBP were at higher risk of developing IASC. However, the difference was not statistically significant (14% vs. 5%, p=0.12).

Conclusion

The anastomotic leak rate was low when preoperative MBP and oral antibiotics were used. However, patients not able to complete MBP might be at an increased risk.
P231 Work productivity loss in perianal crohn’s disease
Authors: Jlassi H , Sabbah M , Bellil N , Trad D , Ouakaa A , Bibani N , Gargouri D
Published: May 2021

Background

Few data exist on the socio-professional impact in patients with perianal Crohn’s disease, probably because the patient-doctor relationship is mainly focused on obtaining clinical, biological and endoscopic remission of the Crohn’s disease (CD).

Our study aimed to evaluate the impacts of perianal Crohn’s disease on work productivity.

Methods

A prospective cross-sectional study including patients with CD followed in the Gastroenterology department between July and August 2020 was performed. Professional impact was assessed using Work Productivity and Activity Impairment questionnaire (WPAI) which is composed of 6 questions evaluating during the last seven days preceding the interview with the patient, the absenteeism, the presenteeism, the total decrease in productivity and the decrease in daily activities for health reasons. The results are multiplied by 100, expressed as a percentage of time lost. A higher percentage indicates greater depreciation and less productivity. Professional impact was compared in patients with perianal Crohn’s disease and controls without perianal symptoms.

Results

Thirty two patients were included. The mean age was 38.28 years [18–60] and the sex ratio was 1. Perianal manifestations were observed in 15 patients (44% of cases). Thirteen patients (41%) were in paid employment at the time of inclusion. CD was responsible for an average absenteeism of 30% ± 10.4% [0–80%] of the working time during the last seven days. An average percentage of work impairment defining the presenteeism was noted to be 52% ± 28% [0–80%] of working time. The overall average decline in productivity was estimated at 56% ± 22% [0–97%]. CD was responsible for an average restriction of 45% ± 33% [0–100%] of usual daily activities.

By comparing the professional impact according to the presence or not of anoperineal lesions (APL), an association between the mean rate of activity restriction and the presence of APL (p = 0.04) was objectified. However, no significant association was noted in the other dimensions of the WPAI questionnaire.

Conclusion

According to our study, it appears that Crohn’s disease is a source of reduced work productivity especially in case of perianal manifestation. These results should be confirmed by larger studies.
P255 Efficacy and safety of a restrictive ferric carboxymaltose infusion strategy for iron deficiency anemia in inflammatory bowel disease patients
Authors: Crispino F , Grova M , Maida M , Renna S , Casà A , Rizzo G , Macaluso F S , Orlando A
Published: May 2021

Background

Iron deficiency anemia (IDA) is a common condition in patients with inflammatory bowel disease (IBD) and ferric carboxymaltose (FCM) has shown fast correction of hemoglobin (Hb) levels and good tolerability. We evaluated the response to FCM in IBD patients with IDA. The primary outcome was the assessment of the rate of response to single or multiple FCM infusions after 12 months from the first infusion. Secondary outcomes were the response to a single FCM infusion after 3 months and the assessment of FCM safety.

Methods

We retrospectively included 185 consecutive patients from IBD Unit of “Villa Sofia-V. Cervello” Hospital who received at least a dose of 500 mg FCM infusion between 2015 and 2018. Complete response (CR) was defined as Hb ≥13 g/dL (men) or ≥12 g/dL (women) or Hb increase ≥2 g/dL; partial response (PR) was defined as Hb increase ≥1 and <2 g/dl, without anemia correction; response was considered either CR or PR. Failure was defined as Hb increase <1 g/dl. A univariate analysis was performed among complete responders, partial responders and failures at 3 and 12 months.

Results

After 12 months the mean number of FCM infusions was 1.7 ± 1.1 and the rate of response was 139/185 (75.1%; CR: 48.6%; PR: 26.4%). Concerning our secondary endpoint, 169/185 patients received a single infusion of FCM within 3 months, and 134/169 patients (79.2%) achieved response (CR: 56.8%; PR: 22.4%). At univariate analysis low ferritin was the only variable associated with failure at 12 months (p < 0.003). No adverse events were reported.

Conclusion

A restrictive FCM infusion strategy is effective in most IBD patients with IDA. Interestingly, no association was found with Hb and weight at baseline, so further studies are needed to assess their effective role in deciding dosage of FCM.
P257 Assessment of the nutritional status of pediatric Inflammatory Bowel Disease patients according to disease activity
Authors: Palomino Pérez L M , Velasco Rodríguez-Belvis M , Cañedo Villaroya E , Vazquez Gómez J A , Muñoz Codoceo R A
Published: May 2021

Background

To determine the nutritional status in patients with inflammatory bowel disease (IBD) and its possible relationship with the activity of the disease.

Methods

A cross-sectional and descriptive study of paediatric patients with previously diagnosed or suspected IBD who underwent upper endoscopy (EGD) and colonoscopy, blood tests, stool analysis and MR Enterography (MRE), from October 2018 to February 2020.

Results

We recruited 21 patients and 12 of them were males (57%). A total of 12 patients had Crohn ́s disease (CD) (57%), 3 had ulcerative colitis (UC) (14%), 6 had IBD unclassified (IBDu) (28%). The age at the time of the evaluation was 14.2 ± 0.7 years and the progression time of the disease was 3.9 ± 0.6 years. A total of 16 patients showed clinical remission (76%), and 6 of them (28%) also had endoscopic and histological remission. Eight patients were receiving biological treatment (38%).

Rotavirus, adenovirus, Clostridium difficile toxin analysis and stool culture were performed in 14 patients, all of them were negative. The weight was 55.7 ± 20.71 kg, the size was 159.1 ± 15.0 cm and the BMI was 21.5 ± 5.6. A total of 7 patients (58%) had malnutrition, 3 (14%) were overweight and 2 (10%) were obese. We found no significant differences in BMI according to the underlying diagnose.

The results of the blood analysis with nutritional profile were: folic acid 12.3 ± 7.2 ng/ml, vitamin B12 455.2 ± 200.6 pg/ml, ferritin 36.9 ± 16.7 ng/ml, total protein 7.6 ± 0.5 g/dl, albumin 4.4 ± 0.4, prealbumin 22.7 ± 7.0 mg/dl, retinol binding protein 2.2 ± 1.0 mg/dl, vitamin A 0.3 ± 0.1 mg/L, effective vitamin E 4.6 ± 0.7 mg/g, 25(OH) vitamin D 20.1 ± 6.2 ng/ml, vitamin B1 6.1 ± 1.2 mcg/dL, vitamin B6 28.3 ± 9.8 ug/L, IFG-1 312.1 ± 124.1 ng/ml, IGFBP-3 4.4 ± 0.6 μg/ml, PTH 54.9 ± 2.7, Selenium 88.7 ± 23.1, Zinc 99.4 ± 9.3, copper 96.0 ± 11.5 ug/dL.

We found a significant negative correlation between the IGF-1 levels and the SES-CD values, and between prealbumin levels and Mayo score values (p < 0.05). However, no significant correlations were found between other nutritional values and endoscopic scores. We found a significant negative correlation between the BMI values and the shPCDAI (p < 0.05), but no significant correlation was found with PUCAI. No differences in analytical markers or BMI were found between patients receiving biological treatment and those who were not.

Conclusion

More than half of the teenager patients with IBD showed some kind of nutritional disturbance. The analytical nutritional markers which related more closely to the endoscopic activity were IGF-1 and prealbumin. The alteration of the clinical score was related to alterations in the BMI in CD but not in the UC patients.
P259 Safety, tolerability and pharmacokinetics of BT051, an oral inhibitor of neutrophil migration and activation in clinical development for Inflammatory Bowel Disease
Authors: Murphy C , Stevens C , Hershberger E , Quintas M , Miller B , Ghahramani P
Published: May 2021

Background

BT051 is an oral, locally acting inhibitor of neutrophil trafficking and activation in clinical development for the treatment of patients with Inflammatory Bowel Disease (IBD). Herein we report the results of this first-in-human study of BT051 in healthy subjects.

Methods

This was a phase 1, randomised, double-blind, placebo-controlled, single-centre, single ascending dose (SAD) study. Healthy subjects (n=50) were randomised into 5 SAD cohorts to receive BT051 (100, 300, 700, 1500 or 3500 mg) or placebo (8 active:2 placebo in each cohort). A safety review committee evaluated any dose-limiting adverse events (AEs) through Day 3 before proceeding to the next cohort. Samples for pharmacokinetic (PK) analysis were collected from blood, stool and urine predose and up to 48 hours postdose; stool samples for PK analysis were also collected on Day 7. An exploratory endpoint of systemic immunosuppression was performed by assessing cytokine secretion induced from T-cells in subjects’ peripheral blood mononuclear cells (PBMC) at 4 and 24 hours postdose.

Results

Fifty healthy subjects were dosed with BT051 (n=40) or placebo (n=10). No dose-limiting toxicities, serious AEs or study discontinuations due to AEs were observed. Nine (22.5%) BT051 subjects and 2 (20%) placebo subjects experienced at least 1 mild or moderate AE with only vessel puncture site pain and constipation reported in more than 1 subject (n=2). Mean % of dose excreted in stool from partial collection ranged between 11.3–26.3%. At all doses tested, concentrations of BT051 in the large intestine were estimated to exceed >20x the threshold for inhibition of neutrophil transmigration and activation in vitro (1 μM) and continued to be detected out to 7 days postdose. Generally, blood concentrations of BT051 were undetectable except in two subjects at one time point each: one subject at 24 hours postdose who received 700 mg BT051 (70 ng/mL) and another subject at 12 hours postdose who received 1500 mg BT051 (8 ng/mL). Mean % of dose excreted in urine through 48 hours postdose ranged between 0.01–0.03%. No evidence of systemic T-cell immunosuppression was observed at any dose level.

Conclusion

Single ascending doses up to 3500 mg of BT051 were safe and well-tolerated in healthy subjects. Stool concentrations out to 7 days postdose that exceed the expected efficacious threshold, minimal to no systemic exposure and the lack of systemic immunosuppression support the continued development of BT051 as a gut-targeted therapy for patients with IBD.
P263 Influence of Crohn′s Disease phenotype in the retention rate of ustekinumab treatment: SUSTAIN Study
Authors: Chaparro M , Bastón Rey I , Fernández-Salgado E , González García J , Ramos L , Diz-Lois Palomares M T , Argüelles F , Iglesias Flores E , Cabelo M , Rubio Iturria S , Núñez Ortiz A , Charro M , Ginard D , Dueñas Sadornil C , Merino Ochoa O , David B , Iyo E , Gutiérrez Casbas A , Ramírez de la Piscina P , Boscá-Watts M M , Arroyo M , García M J , Hinojosa E , Gordillo J , Martínez Montiel P , Velayos Jiménez B , Quílez Ivorra C , Vázque morón J M , Huguet J M , González Lama Y , Muñagorri Santos A I , Amo V M , Martín Arranz M D , Bermejo F , Martínez Cadilla J , Fradejas Salazar P , Novella C , Vispo E , Barreiro-de Acosta M , Gisbert J P
Published: May 2021

Background

Crohn′s disease (CD) is a progressive inflammatory bowel disease that can lead to complications such as strictures or penetrating disease, and ultimately surgery, representing a complex clinical challenge in the care of patients. We aimed to evaluate the influence of CD phenotype in the retention rate of ustekinumab in the Sustain study.

Methods

Retrospective, multicentre study (>60 sites) including patients with active CD [(Harvey-Bradshaw (HBI)>4)] who received ≥1 dose of ustekinumab intravenously before July 2018. Clinical remission was defined as HBI≤4 and response as ≥3 points decrease from baseline. Loss of response (LoR) was defined as reappearance of symptoms that led to intensifying the treatment dose, adding another medication to control CD, switching or surgery in patients with short-term remission.

Disease characteristics were collected (date of diagnosis; location; behaviour: inflammatory, stenosing or penetrating; presence of perianal disease or extraintestinal manifestations; previous surgeries, etc.).

The retention rates in patients on ustekinumab depending of their disease phenotype were evaluated by descriptive analysis and Kaplan-Meier survival curves. Survival curves were compared using the log-rank test. Predictive factors were assessed by Cox-regression. Data quality was assured by remote monitoring.

Results

463 CD patients were included (Table 1).

87 patients (18.6%) had penetrating CD in our cohort.

The probability of maintaining UST treatment was 91% at 6, 83% at 12, 76% at 18 and 73% at 24 months.

Similar retention rates were observed in patients with inflammatory (77.6%), stricturing (76.4%) and penetrating (79%) disease behaviour (p>0.05). Figure 1.

Conclusion

Ustekinumab has shown to be equally effective in the treatment of inflammatory, stricturing and penetrating CD phenotype in Sustain, the largest study evaluating its use in CD in clinical practice, having the longest follow-up period reported to date.
P264 Impact of the HLA-DQ1*05 alelle on the initial response to infliximab in patients with Inflammatory Bowel Disease
Authors: Suris Marin G , Santacana E , Padullés N , Padró A , Serra K , Ruiz A , Blat R , Arajol C , Sanchez E , Berrozpe A , Rodríguez-Alonso L , Rodríguez-Moranta F , Guardiola J
Published: May 2021

Background

HLA-DQA1*05 Carriage is associated with development of anti-drug antibodies to infliximab in patients With Crohn’s Disease (Sazonovs et al. Gastroenterology 2019). Our group has shown that the presence of this allele is also an independent predictor of secondary loss of response to infliximab (Guardiola J, ECCO 2019) and adalimumab (Guardiola J ECCO 2020). However, the impact of the HLA-DQA1 * 05 allele on the initial response and persistence of IFX in the first months of treatment is unknown.

Methods

This is a retrospective cohort study from a prospectively maintained data base at the Hospital Universitari de Bellvitge (third level teaching hospital) Patients with Crohn’s Disease (CD) or Ulcerative Colitis (UC) who initiated IFX to induce remission and who had been followed up for failure or a minimum of 6 months were included. Failure at IFX was defined as the need of escalation or change treatment, surgery, or hospitalization for the first 6 months.

Results

99 patients (65 MC, 34 CU) were included. In 63 (63.63%) IFX failed. 39 (39%) were carriers of the HLA-DQA1 * 05 allele. In multivariate analysis, HLA-DQA1*05 carriage (HR 1.9, 95% CI 1.14–3.31 p=0.015), the use of immunomodulators (HR 0.38, 95% CI 0, 23–0.66 p = 0.001) and suffering a CU vs. MC (HR 1.72, 95% CI 1.02–2.89 p = 0.041) were independent predictors of IFX failure. HLA-DQA1 * 05 was also associated with non-persistence of treatment (HR 2,4,95% CI1.45–3.99 p = 0.001). Figure A

Conclusion

HLA-DQA1*05 carriage is common in patients with IBD and it’s associated with a marked increase in the risk of loss of response to infliximab. Testing for HLA-DQA1*05 would allow treatment to be tailored according to the risk of loss of response.
P277 Frequency and effectiveness of empirical anti-TNF dose intensification in Inflammatory Bowel Disease: systematic review with meta-analysis
Authors: Guberna Blanco L , Nyssen O P , Chaparro M , Gisbert J P
Published: May 2021

Background

Loss of response to anti-TNF (tumor necrosis factor) therapies in inflammatory bowel disease occurs in a high proportion of patients. However, the precise incidence of dose intensification (DI) and its effectiveness remains unclear. Our aims were: 1) To evaluate the need of DI of anti-TNF therapy either by increasing the dose or decreasing doses’ interval; 2) To evaluate possible variables influencing its requirement; 3) To assess the effectiveness of empirical DI.

Methods

Bibliographical searches were performed in Pubmed, Embase, the Cochrane Library and CINAHL. Selection: prospective and retrospective studies assessing loss of response to anti-TNF therapy, considered as the need of DI, in Crohn’s disease (CD) and ulcerative colitis (UC) patients treated for at least 12 weeks with an anti-TNF drug [infliximab (IFX), adalimumab (ADA), certolizumab or golimumab]. Exclusion criteria: studies using anti-TNF as prophylaxis for postoperative recurrence in CD or those where DI was based on therapeutic drug monitoring. Data synthesis: Effectiveness by intention-to-treat (random effects model). Data were stratified by medical condition (UC vs. CD), anti-TNF drug and follow-up. Subgroup analyses were performed to explore heterogeneity.

Results

In total, 174 studies (32,031 patients) were included. The overall rate of DI requirement after 12 months follow-up was 27% (95%CI 23-31, I2=96%, 51 studies) in naïve patients and 38% (95%CI 31-46, I2=87%, 18 studies) in non-naïve patients. The rate of DI requirement was higher in patients with prior anti-TNF exposure (c²=6.5, P=0.01) and in UC patients (c²=4.7, P=0.03). The rate of DI requirement in naïve patients after 36 months follow-up was 35% (95%CI 27-43%; I2=98%; 22 studies). The overall short-term response and remission rates to empirical DI in naïve patients were 66% (95%CI 61-71%; I2=81%; 35 studies) and 48% (95%CI 35-62%; I2=97%; 27 studies), respectively. Subgroup analyses are presented in the tables.

Conclusion

Loss of response to anti-TNF agents ―and consequent DI― occur frequently in IBD (approximately in 1/4 at one year and in 1/3 at 3 years). DI requirement is higher in UC patients and in those with prior anti-TNF exposure. Empirical DI is a relatively effective therapeutic option.
P314 TNF gene activation used as criterion to discontinue biologic therapy – A patient series introducing the NovaPrime TNF kit
Authors: Goll R , Kay-Martin J , Viola A , Paulssen E , Moe Ø K , Cui G , Fries W , Florholmen J
Published: May 2021

Background

Severe inflammatory bowel disease can be successfully treated with biologic drugs such as anti-TNF. However, there is no consensus on if and how to stop treatment. Our group has earlier shown that normalization of TNF gene expression may be a beneficial prognostic factor when attempting to discontinue biologic therapy. We here present data from a series of patients in endoscopic remission and with normalized TNF gene expression.

Methods

Severe inflammatory bowel disease can be successfully treated with biologic drugs such as anti-TNF. However, there is no consensus on if and how to stop treatment. Our group has earlier shown that normalization of TNF gene expression may be a beneficial prognostic factor when attempting to discontinue biologic therapy. We here present data from a series of patients in endoscopic remission and with normalized TNF gene expression.

A total of 91 patients were recruited at hospitals in Norway and Italy: 55 patients (32 UC, 23 CD) in remission (picked by normalization of TNF using our in-house TNF qPCR), and for comparison: 14 patients with active disease, and 22 normal controls. Mucosal samples taken prior to drug discontinuation from all patients were re-measured for TNF mRNA by the NovaPrime TNF kit.

Results

A clear difference could be seen between normal controls and patients with active disease, showing highly elevated TNF mRNA values in the active disease group. The patients in remission had values resembling the normal controls with values generally below a cut-off of 9060 copies/µg total RNA by the NovaPrime TNF kit.

The patients in remission were followed for up to 5 years noting two endpoints: relapse triggering any adjustment of medication, and relapse triggering restart of biologics. Median survival time before adjusting medication was 12 months for ulcerative colitis and 17 months for Crohn’s disease. Median time to restart of biologics was 21 months (2 – 40) overall, and after 3 years 43% still were not in need of biologic therapy.

Conclusion

We conclude that the NovaPrime TNF kit yields consistent readings comparable to our in-house assay, and that this industrial standard kit enables any PCR lab to perform TNF gene expression in samples from intestinal mucosa. A considerable proportion of patients with normalized TNF gene expression can maintain long term remission without biologic therapy, relieving health care costs and potential side effects of long-term therapy.
P480 Assessing primary response to biologic therapy in Inflammatory Bowel Disease - ‘the when and the how?’
Authors: Moore A C , Peake S
Published: May 2021

Background

ECCO guidelines state that patients started on biologic therapy for Inflammatory Bowel Disease (IBD) should be reviewed between week 10 and 16 depending on the biologic used and response assessed using predefined objective criteria. The study aim was to ascertain, the time point, and by which methods patients with IBD are being assessed for primary response.

Methods

A retrospective chart review was conducted of 50 consecutive patients with IBD who had been started on biological therapy between October 2018 and June 2019 at a tertiary referral university teaching hospital in London, UK.

Results

Patients were started on 5 biologics; infliximab (20 patients), adalimumab (11 patients), vedolizumab (6 patients), ustekinumab (9 patients) and tofacitinib (4 patients). Twenty two patients had Ulcerative Colitis and 28 patients had Crohn’s Disease. All 50 patients were still receiving biological therapy at the time of their first assessment in a consultant led IBD clinic.

On average, patients were assessed at week 13 for primary response. Figure 1 outlines the time to assessment of disease response, according to the biologic used. The most frequently used methods were clinical symptoms (49 patients, 98%) and blood tests (47 patients, 94%). Disease activity scores were rarely documented. Other methods of disease assessment were faecal calprotectin (13 patients, 26%), ileocolonoscopy (11 patients, 22%) and radiological studies (2 patients, 4%). Only 19 patients (38%) had either a faecal calprotectin or a colonoscopy ordered at their appointment. Thirteen patients (26%) had undergone an endoscopic assessment of their disease when the data was analysed in December 2019.

Conclusion

Patients are being assessed in a timely fashion for primary response to biological therapy, in line with current ECCO guidelines. Clinical symptoms and blood tests are being heavily relied on to assess for primary response to therapy. Patient-reported symptoms do not correlate well with mucosal inflammation in IBD1. Faecal Calprotectin, as a surrogate marker of mucosal inflammation, and colonoscopy are being underused. Potential reasons for the low rates of colonoscopy may include patient’s wishes and lack of endoscopy capacity. The importance of a mucosal healing assessment is imperative to be able to optimise treatment appropriately and improve long-term outcomes for our patients.

Reference