bluuebunny/crossref_metadata_2025 huggingface dataset:
P053 Overabundance of Lactobacillus species in gut microbiota of IBD patients
Authors: Khusnutdinova D , Markelova M , Siniagina M , Boulygina E , Abdulkhakov S , Grigoryeva T
Published: May 2021

Background

Changes in the composition of gut microbiota, and their metabolic pathways, are important factors in the pathogenesis of inflammatory bowel disease (IBD). Many clinical trials have shown that taking probiotics based on Lactobacillus has a positive effect on patients with IBD. However, Lactobacillus should be used more carefully during the active phase of IBD, since some strains can negatively affect the pathogenesis of the disease1,2. The aim of this study was to assess the diversity of Lactobacillus species in the gut microbiome of IBD patients and healthy volunteers.

Methods

In the study, 62 stool samples from healthy people, 31 from patients with Crohn’s disease (CD), and 34 - ulcerative colitis (UC) in active phase were analyzed. DNA was isolated using the QIAamp Fast DNA Stool Mini Kit (Qiagen, USA) following with shotgun metagenomic sequencing the NextSeq 500 (project #0671-2020-0058). Bioinformatic analysis was performed with the MetaPhlAn2 package.

Results

An increased relative abundance of Lactobacillus was found in patients with IBD (3.2% ± 6.6% in CD and 1.6% ± 2.8 in UC) compared to healthy individuals (0.3% ± 1.2%, p<0.05).

In the control group, Lactobacillus were absent in 41% of samples and 1–5 species were found in 58% of samples. Most CD and UC patients are characterized by the presence of 3 to 5 species of Lactobacillus (38% and 31%, respectively). For 23% of CD patients and 26% of UC patients, 6 to 9 types of Lactobacillus were found. Some patients with IBD have more than 10 different types of Lactobacillus in the gut microbiota (Fig.1).

The intestinal microbiota in IBD patients is characterized by an increased abundance of several species: L. salivarius, L. gasseri, L. mucosae, as well as L. casei paracasei in patients with CD and L. vaginalis in patients with UC (Fig.2).

Conclusion

The composition of the intestinal microbiota of IBD patients differs significantly in terms of Lactobacillus proportion and species diversity. Overabundance of five Lactobacillus species could be associated with the active phase of IBD.

References
P067 The effect of a probiotic mix on mucosal healing and fibrotic responses in healthy colonic subepithelial myofibroblasts
Authors: Tarapatzi G , Filidou E , Kandilogiannakis L , Arvanitidis K , Vradelis S , Kotzampassi K , Kolios G
Published: May 2021

Background

Various probiotic strains play a positive role in Inflammatory Bowel Disease and might support mucosal healing. Colonic Subepithelial Myofibroblasts (SEMFs) have a pivotal role in mucosal healing and fibrosis, by migrating to the trauma region and secreting collagen. Our study aimed to investigate whether different strains of probiotics can affect the migration capacity and the fibrotic phenotype of SEMFs isolated from healthy individuals.

Methods

The probiotic mix of Lactobacillus acidophilus, Lactobacillus plantarum, Bifidobacterium lactis and Saccharomyces boulardii was reconstituted in SEMFs culture medium, they were identified by Gram staining and their viability was assessed by Trypan Blue staining. Primary SEMFs were isolated from colonic biopsies from healthy individuals, and stimulated with 102, 104 or 108 cfu/ml of the mix for 6h or 48h; in 6h total RNA was collected and mRNA expression of collagen type I, III, fibronectin, tissue factor (TF) and α-SMA was measured by quantitative PCR, and in 48h their effect on migration rate through the Wound Healing Assay and collagen secretion via Sircol was assessed.

Results

Trypan Blue confirmed that the majority of the probiotic mix was alive, and all three bacterial strains and the yeast were stained Gram positive. Stimulation of SEMFs with the probiotic mix resulted in different effects depending on its concentration; 102 cfu/ml downregulated protein collagen secretion (3.4μg/ml, IQR: 2.7–5.0, p<0.01 vs control 6.3μg/ml, IQR: 5.2–6.7) and α-SMA mRNA production (0.7-fold, IQR: 0.7–0.8, p<0.01), 104 cfu/ml upregulated the Fibronectin mRNA expression (1.6-fold, IQR: 1.2–1.8, p<0.0001) and 108 cfu/ml downregulated collagen type I (0.2-fold, IQR: 0.1–0.8, p<0.01) and III mRNAs (0.3-fold, IQR: 0.1–0.8, p<0.01). In addition, all three concentrations resulted in the overall upregulation of TF mRNA expression. Regarding the effect of the probiotic mix on SEMFs migration capacity, 104 cfu/ml of the probiotic mix resulted in increased migration rate by 133.8% (IQR: 102.8–150.2, p<0.01) after 24h, while the use of 102 cfu/ml and 108 cfu/ml decreased it by 58.2% (IQR: 34.8–79.7, p<0.01) and by 46.8% (IQR: 34.3–72.1, p<0.01) respectively.

Conclusion

This study provides evidence that the probiotic strains L. plantarum, L. acidophillus, B. lactis and S. boulardii remain viable in SEMFs’ culture medium and have the ability to interact with and alter the behavior of SEMFs. Moreover, the effect of the probiotic mix on SEMFs fibrotic phenotype is dependent of the concentration of the probiotics used. Further preclinical research is needed in order to identify the effect of each strain, as well as the suitable dose and combinations in various pathological conditions.
P101 Fecal calprotectin is increased among patients with pouchitis and increases with increasing endoscopic subscores: Real-world data from a prospectively collected database
Authors: Ollech J , Bannon L , Maharshak N , Tulchinsky H , Yanai H , Dotan I
Published: May 2021

Background

An accurate and non-invasive surrogate marker of inflammation is needed for managing patients after Ileal pouch-anal anastomosis (IPAA). In this study, we evaluate the performance of fecal calprotectin (FC) in patients with ulcerative colitis (UC) who underwent IPAA and were assessed with clinical, endoscopic, and histologic examination of the pouch.

Methods

Medical records of patients who underwent IPAA with J-pouch formation registered in a prospectively collected database at the Tel Aviv Sourasky Medical Center, Israel, were evaluated. Clinical, endoscopic, histologic, and laboratory data were extracted. Each pouch evaluation was regarded separately. Pouchitis was defined as a Pouchitis Disease Activity Score (PDAI) of ≥7 (maximum score: 18).

Results

One hundred and fifty-six patients underwent 296 unique pouch evaluations. Fifty-two percent of patients were male, the median age at the time of evaluation was 43 years (IQR 35–58), and the median pouch age from the closure of the ileostomy was 10 years (IQR 2.5–15). The median [IQR] FC values were significantly lower in patients without pouchitis than in patients with pouchitis (208 [96–478] vs. 550 [250–1051] ug/g, p<0.0001). Mean FC values were lower in patients with lower endoscopic and histologic scores when compared to higher scores, with a significant linear trend for higher FC levels with increasing endoscopic and histologic disease activity. FC performed better than CRP as a predictor of pouchitis. A FC of over 400 ug/g had over 80% specificity for predicting significant endoscopic disease.

Conclusion

FC levels increase among patients with pouchitis and increase with increasing endoscopic and histologic inflammation. A FC of over 400 ug/g had good discriminative ability as a predictor of significant endoscopic disease. We suggest that in patients with symptoms of pouchitis and an FC level above 400 ug/g, antibiotic treatment can be initiated without awaiting pouchoscopy. Further research is needed to define FC concentrations more precisely among various outcome measures of interest in these patients.
P162 Microscopic inflammation in limited Ulcerative Colitis at diagnosis: can a single histological feature predict prognosis?
Authors: Revés J , Frias Gomes C , Ellul P , Callé C , Almeida A , Burisch J , Buhagiar T , Attard A , Lo B , Ungaro R , Morão B , Gouveia C , Branco J , Rodrigues J , Teixeira C , Castro F , Nunes G , Brito M , Antunes M , Torres J , Borralho P
Published: May 2021

Background

Histological assessment is becoming increasingly important in the management of Ulcerative Colitis (UC). The Nancy index (NI), a recently developed and validated score, has been shown to accurately represent histological inflammation and to correlate with prognosis. However, it is a composite score, involving the analysis of more than one histological feature, which may limit its applicability. Our aim was to evaluate if a single component of the NI could individually predict prognosis in limited UC (E1 and E2) patients.

Methods

Multi-centre retrospective cohort study of newly diagnosed, treatment-naïve proctitis and left-sided ulcerative colitis patients. Biopsies from inflamed rectal mucosa were reviewed by two pathologists. Histological features from the NI were selected for analysis, including presence of ulcers, acute inflammatory infiltrate (with separate evaluation of neutrophils in lamina propria and epithelium) and chronic inflammatory infiltrate. Mucin depletion and basal plasmacytosis were also evaluated. The primary outcome was a composite outcome intended to evaluate disease-related complications, including proximal disease extension, need for hospitalisation or colectomy. Survival analysis, including univariate and multivariate Cox-regression analysis was performed.

Results

A total of 91 patients were included (56.0% males, mean age 44±17 years, median follow-up 44 months [2–328]). Overall, 64.8% of the patients had proctitis (E1) and 35.2% left-sided colitis (E2). The most frequent histological features were the presence of chronic inflammatory infiltrate (93.4%), mucin depletion (81.3%) and basal plasmacytosis (78.0%). During the follow-up, 22.0% presented a disease-related complication. The NI was not able to predict prognosis (HR 3.09, 95% CI 0.71–13.36, p=0.132). In univariate analysis, the presence of neutrophils in the epithelium in more than 50% of the crypts was marginally significant for the primary outcome (HR 2.51, 95% CI 0.99–6.36, p=0.05). In multivariate analysis, after adjusting for gender, age at diagnosis, disease extent (E1 vs E2), Mayo endoscopic score (< 2 vs ≥ 2) and clinical severity at diagnosis (mild vs moderate to severe UC) this single component of the score was associated with the primary outcome (aHR 3.36, 95% IC 1.21–9.31, p=0.02). No other histological feature was able to individually predict prognosis (p>0.05).

Conclusion

The presence of neutrophils in the epithelium in more than 50% of the crypts in endoscopically inflamed mucosa at diagnosis was associated with higher disease complications in limited UC patients. The evaluation of a single feature could facilitate the use of histology in the prediction of prognosis in UC. Our results need to be prospectively validated.
P190 Ileo-caecal Crohn’s Disease; medical or surgical management. Cost and outcomes
Authors: Charan M , Maclaren L , Bryant C , Wade K , Johnson H , McLaughlin S
Published: May 2021

Background

An ileo-caecectomy is known to be an effective treatment for Crohn’s disease limited to the terminal ileum that can lead to a long term remission. ECCO guidelines recommend that patients with active inflammation should be treated medically. However the LIR!C trial suggested there are QOL benefits and reduced costs to performing primary surgery.

Methods

We aimed to compare the outcomes of patients treated with primary medical treatment to primary surgery for patients with Crohn’s disease limited to the terminal ileum. We reviewed our database to identify all these patients and analysed outcome data.

Results

49 patients were identified:

Mean age was 50 yrs (range 22 - 93). 23 were male.

Mean length of follow-up was 96 months (range 3 - 404).

1st line treatment was: medical; 33 (67.3%), surgery; 16 (32.6%).

Outcomes after medical treatment: 27 of 33 patients failed primary medical treatment, they required surgery at a mean of 38 months (range 1–900) after initiating medical treatment.

Colonoscopy after surgery to assess for disease recurrence: Colonoscopic assessment or calprotectin post was undertaken ileo-caecectomy in 4 of 16 patients at a mean of 6.2 months (range 1–10) who underwent primary surgery; and in 25 of 27 patients who underwent surgery following failure of medical treatment.

Outcomes after surgery: 4 of 16 patients who had primary surgical treatment had endoscopic recurrence, requiring medical treatment after a mean of 4.4 months (range 0–10). 8 of 27 patients who had surgery post-failure of medical treatment developed disease recurrence, requiring medical treatment after a mean of 40 months (range 7–136)

Bile acid malabsorption (BAM): BAM occurred after surgery in 10 of 43 patients. No medically managed patient developed BAM.

Conclusion

These data suggest that in our population the vast majority of patients with ileo-caecal Crohn’s disease will fail medical treatment and require surgery. 25% of those who undergo surgery will develop BAM (requiring medication), and 40% of those treated surgically will require immunosuppressant treatment in the medium term.

These outcomes should be discussed with patients so that they appreciate that ileo-caecectomy is unlikely to lead to long term drug free treatment, and medical treatment is unlikely to lead to the avoidance of surgery. From a health-economics point of view it could be argued there is little point in offering primary medical therapy and ileo-caecectomy should be the initial treatment of choice for patients with limited ileo-caecal Crohn’s disease.

Unfortunately endoscopic/calprotectin assessment following primary surgery was often not performed in the majority of patients, and changes in our local practice need to be undertaken to correct this.
P202 De novo Inflamatory Bowel Disease after solid organ transplantation
Authors: Luque Carmona A M , Rojas Feria M , De la Cruz Ramirez M D , Trigo Salado C , Herrera Justiniano J M , Leo Carnerero E
Published: May 2021

Background

The aim of this study was to determine the disease phenotype, evolution and therapeutic needs of de novo inflammatory bowel disease (IBD) in transplanted patients.

Methods

A retrospective single center study that included all patients who developed IBD after solid organ transplantation in a tertiary hospital. Data collected included transplant-related variables, IBD phenotype, course of the disease and its treatment. A control group of non-transplanted IBD patients was randomly selected.

Results

We included 17 post-transplanted IBD patients and 57 non-transplanted IBD patients. Post-trasplanted patients were older at diagnosis, had greater colonic involvement, with an inflammatory behaviour, absence of perianal involvement and extraintestinal manifestations compared to control group (Table 1).

The most common immunosuppression regimen was tacrolimus+mycophenolate mofetil (MMF)+prednisone and the most frequent change after diagnosis was the switch of MMF for azathioprine. De novo IBD patients required less biological therapy than the control group (11.8 vs 42.1% p 0.02) and none required surgical intervention compared to 35.1% in the control group (p 0.002).

Multivariate analysis carried out on the total population showed that active smoking, perianal disease and extraintestinal manifestations were associated with a greater need for biologics, while the only factor that influenced surgical risk was stricturing and penetrating behaviour of Crohn′s disease.

Conclusion

De novo IBD after solid organ transplantation has a favorable course, predominating the inflammatory behaviour and requiring less biological therapy and surgical interventions. The absence of extraintestinal manifestations and perianal disease stands out.
P248 Assessment of health-related quality of life of paediatric Inflammatory Bowel Disease patients through the IMPACT-III questionnaire
Authors: Vázquez Gómez J A , Velasco Rodríguez-Belvís M , Palomino Pérez L M , Sánchez Llorente P , Aguilar Ladrón de Guevara C , Muñoz Codoceo R A
Published: May 2021

Background

Health-related quality of life (HRQOL) is a multi-dimensional concept used to examine the impact of health status on their global well-being. The IMPACT-III is a 35-item questionnaire specifically designed to evaluate the quality of life of patients with paediatric Inflammatory Bowel Disease (pIBD). This questionnaire had its origin in 1999 in Canada (Otley et al.) and, since then, it has been adapted to many languages.

The objective of this study was to assess the quality of life of pIBD patients using the IMPACT-III questionnaire and to identify specific needs according to the patient’s profile.

Methods

An observational, descriptive, and retrospective study was carried out in November 2020, including the pIBD patients undergoing follow-up in a tertiary hospital that have previously completed the IMPACT-III questionnaire. Epidemiological and clinical data were anonymously retrieved from the electronic medical records. We established three blocks of IMPACT-III items according to physical, emotional and social well-being, or to the perception of body image. The results of each block and totals were compared according to gender, age, diagnosis, time of evolution, activity and treatment.

To make the comparison, the Mann-Whitney U test for independent samples for 2 groups and the Kruskal-Wallis test for 3 or more independent groups were used. The statistical analysis was performed using SPSS software and the results were considered statistically significant when reaching a bilateral critical level (p) ≤ 0.05, with a 95% confidence interval.

Results

We included a total of 40 patients. There were no significant differences according to gender, type of IBD or type of treatment. The group of adolescents obtained a higher score in the body image block (p = 0.009). Patients with over two years of evolution of the disease obtained statistically significantly higher scores in the physical well-being block (p = 0.027). In patients who filled out the questionnaire during a flare, the scores on questions of physical well-being (p = 0.007), emotional and social (p = 0.037), as well as total (p = 0.012) were significantly higher. Overall, 31 patients (77.5%) answered that IBD had negatively affected their family.

Conclusion

Our data suggest that patients with a longer evolution time, adolescents and patients suffering an active flare seem to report a worst HRQOL. Patients with the mentioned characteristics constitute a vulnerable population with special care needs that should be addressed from an interdisciplinary point of view. Despite the limitations of the retrospective design and the scarce number of patients, our results indicate that family-centered care should be a priority.
P251 Antiphospholipid antibodies in Crohn’s disease: Results of a prospective single-center study
Authors: Serghini M , Ben Youssef H , Baccouche H , Hafi M , Labidy A , Ben Mustapha N , Fekih M , Boubaker J
Published: May 2021

Background

Assess the prevalence of antiphospholipid antibodies (APL) and their association with disease phenotype and activity in patients with Crohn disease (CD).

Methods

This is a prospective study involving 30 patients with CD over a period of 2016 to 2020. Family and personal history of thromboembolic disease and fetal loss as well as their delay in relation to the date of the sample were taken from from the interrogation. Disease-related data such as age at the time of diagnosis, location and phenotype of the disease as well as treatment medical received were identified from the medical records. Disease activity was evaluated according to the CDAI (Crohn Disease Activity Index) score calculated time of inclusion. The serum of the patients was tested on anti-β2-glycoprotein-I (anti-β2-GPI Ig M / G), anti-cardiolipin (ACA Ig M / G) by method enzyme immunoassay (ELISA). This test was considered positive if the rate of anti-cardiolipin antibody was> 12U / mL and the level of anti-β2- glycoprotein-1> 8U / mL. The occurrence of thromboembolic events was noted during follow-up.

Results

The average age was 47.3 ± 10.8 years (29 men and 21 women). A family history of thromboembolic disease has been noted in 2 patients. A patient developed a pulmonary embolism 37 months before his inclusion in postoperative context. A history of fetal loss was reported in 7 women (16%) with a delay ranging from 5 to 432 months (in mean 181.6 ± 146) before their inclusion in the study. The average age at time of diagnosis was 37.9 ± 11.7 years. Colonic localization of the disease was noted in 12 patients (41.4%) and the inflammatory phenotype was the more common (62.1%). The disease was active in 13 patients (44.8%) with a mean CDAI score of 149.2 ± 111.7 (23–469). A patient has presented a mesenteric infarction during his follow-up 35 months after his inclusion. Positive anti-β2-glycoprotein-1 antibody levels IgG type with levels negative anti-cardiolipin antibodies were found in 2 patients (6%). No patient had positive anti-cardiolipin antibodies. No difference was found for the prevalence of anti-β2-GPI in patients patients in remission compared to those with active disease (p = 0.22) and in patients with severe acute colitis compared to the rest of the patients (p = 0.2). The frequency of β2-GP1 was not higher in patients with CRP greater than 6 mg / L compared to those with a normal CRP (p = 0.4). Anti-TNF treatment was started in 5 patients and no association was found between anti-TNF treatment and the prevalence of anti-β2-GP1 (p = 0.7). APL status was not associated with phenotype and localization of disease or thrombotic events.

Conclusion

The present study did not demonstrate an association between APL antibodies and disease phenotype or activity.
P258 Rates of admission of acute IBD flares during the COVID-19 pandemic in a tertiary healthcare setting
Authors: Hazel K , Glynn E , Boland K , O’Toole A
Published: May 2021

Background

Environmental tiggers are thought to contribute to Inflammatory Bowel Disease flares. The COVID-19 pandemic and resulting lockdown led to an emphasis on outpatient care, fewer presentations to hospital for non-COVID-19-related illnesses, changes in work practices and a reduction in air pollution. Our aim was to determine the impact of these changes on hospital admissions with acute IBD flares.

Methods

The hospital in-patient enquiry (HIPE) department provided records of all patients admitted with acute IBD flares during the first Irish lockdown from March to May 2020 and for the corresponding period in 2017, 2018 and 2019. Electronic patient records were used to assess patient demographics, biochemical markers, imaging, medication use and outcome.

Results

101 patients were admitted with an acute IBD flare. This was a marked reduction when compared to the corresponding period in the previous three years (p<0.0001). Despite the rates of admission decreasing in this period, rates of colectomy were significantly increased (p<0.0001). (Table 1).

Conclusion

We demonstrated a significant decrease in hospital admissions for acute IBD flares during the first wave of the pandemic. We postulate that changes in environmental triggers of IBD such as working from home and reduced stress levels in addition to reduced air pollution may account for this reduction. The increased rate of colectomy likely reflects a more severe presentation of IBD and patients’ reluctance to attend the hospital at an early stage in their disease flare as well as non-adherence to prescribed IBD therapies due to a perceived COVID-19-related risk.
P295 Comparative Assessment of Infliximab Trough Levels between Point-of-Care Testing and current Standard of Care (enzyme linked immunosorbent assay) in patients with Inflammatory Bowel Disease
Authors: Maniero D , Lorenzon G , Marsilio I , Rigo A , Cardin R , Facchin S , Barberio B , D’Incà R , Zingone F , Bahur B , Bray K R , Savarino E V
Published: May 2021

Background

Infliximab (IFX) is a monoclonal antibody that targets cytokine tumor necrosis factor; it is used for the treatment of patients with active inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC). IFX induces and maintains remission and mucosal healing in patients with IBD. Measurement of trough levels (TL) of IFX is important to assess if the drug is within its therapeutic concentrationand to explain lack/loss of response. Standard laboratory tests to assess IFX trough levels (enzyme linked immunosorbent assays, ELISA) present some downsides, related to the long turnaround (about 3 hours), and the need of specialized equipment and laboratory personnel. For this reason, point-of care testing (POCT) was developed to provide results within a few minutes from blood collection, leading to a decision-making approach.

Aim

To determine the degree of analytical correlation between a recently developed POCT (ProciseDx) IFX assay which analyze capillary whole blood and the comparative ELISA from serum.

Methods

From October 2020 to January 2021, patients (aged≥18 years) taking IFX were recruited at Gastroenterology Unit, Padua University Hospital. In each patient, IFX levels from capillary whole blood collected by finger stick were performed using the ProciseDx IFX assay with reportable range between 1.7-77.2 µg/mL; at the same time, a serum sample from venous blood was collected to carry out Grifols’ Promonitor ELISA test (range 0.035–14.4 µg/mL). A Deming regression test was used to identify the correlation between the two methods.

Results

Eighty-seven patients were enrolled (63% males; mean age of 44±16), with 52% of them having CD, 45% UC and 3% an undetermined-Inflammatory Bowel Disease. The assessment with ProciseDx POCT was feasible in each patient and only in three cases blood collection from finger prick was repeated. Moreover, from blood collection to results we needed about 3±0.5 minutes, while serum ELISA analysis required the collection of at least 40 samples (around three weeks at our centre) and 3 hours to be performed. 39 patients (59% males; mean age of 44±16) had TL as assessed by ProciseDx IFX assay lower than 1.7 or greater than 14.4 µg/mL, in accordance with ELISA assessment. Among the remaining 48 patients (67% males with mean age of 45±17), The correlation between the two tests was high (the total results showed an R squared of 0.691 (95% CI 0.717-0.902).

Conclusion

The ProciseDx POCT has good accuracy but was more rapid and easy to be performed in providing the results of Therapeutic Drug Monitoring in outpatients taking IFX. This could lead to a more effective optimization of the biological drug, thus avoiding treatment failure.
P346 Decreasing disparities in and use of systemic corticosteroid and disparities in use among paediatric patients with Crohn disease in a multicentre collaborative
Authors: Adler J , Kandavel P , Eder S , Saeed S
Published: May 2021

Background

Systemic corticosteroids (CS) have long been used to treat Crohn disease. However, cumulative CS exposure is associated with adverse effects, particularly among growing children. Steroid sparing therapies are increasingly available. It remains unknown to what extent CS use has decreased among children with Crohn disease.

Methods

This was an observational cohort study using data from ImproveCareNow Network, multi-centre international paediatric inflammatory bowel disease collaboration (2007-2018). Paediatric patients diagnosed with Crohn disease were included. We performed serial cross-sectional analyses of period prevalence for entire population. Patients enrolled <30 days from diagnosis were included in logistic multivariate regression to predict odds of CS use 120-365 days after diagnosis. All families provided consent/assent.

Results

The total population included 17,646 patients (82% white, 59% male). Systemic CS were used by 5,862 (33%), more commonly among black than white patients (37% vs 32%; p<0.001). Those with inflammatory phenotype had more CS use than stricturing or penetrating (34%, 28%, 22% respectively; p<0.001).

Overall, CS use decreased from 28% (2007) to 9% (2018). Excess CS use among blacks compared to whites reduced from mean 17% in first 3 years to 3% in last 3 years (Figure 1). Changes in other medications appear in Figure 2. Multivariate results are in Table 1. CS or 5-aminosalicylate use <120 days after diagnosis predicted later increased odds of CS use. Anti-tumour necrosis factor-α (anti-TNFα) use <120 days after diagnosis was associated with reduced odds of later CS use.

Conclusion

Corticosteroid use among paediatric patients with Crohn disease in the ImproveCareNow Network has decreased over time. Racial disparities in CS use were found, but gradually improved. Early 5-aminosalicylate or CS use predicted later CS use. Early anti-TNFα treatment is associated with reduction in later CS use.
P381 Fatigue is an independent disease manifestation largely independent of chronicity, comorbidity and disease activity in patients with Inflammatory Bowel Disease
Authors: Risager Christensen K , Steenholdt C , Buhl S , Skougaard M , Brynskov J , Ainsworth M A , Schjødt Jørgensen T , Kristensen L E
Published: May 2021

Background

Fatigue is a common reported symptom by patients with inflammatory bowel disease (IBD) and often with profound negative impact on quality of life including daily activities. The aim of this study was to encircle clusters of key components associated with fatigue to explore if fatigue is an independent IBD disease manifestation.

Methods

A cross-sectional study was conducted in patients with IBD receiving biologic therapies at the tertiary IBD Clinic at Herlev Hospital, Denmark, from March to May 2019. Consecutive patients were asked to participate in a questionnaire survey when visiting the clinic. The questionnaire included: FACIT-Fatigue, Harvey-Bradshaw Index/Simple Clinical Colitis Activity Index, short health scale, short IBD Questionnaire, and EQ-5D-5L. Additional disease-related information was retrieved from medical records. Principal component analysis (PCA) was used to identify factors associated with fatigue.

Results

Three hundred patients with IBD (Crohn’s disease n=190 (62%); ulcerative colitis n=110 (38%), mean age 44 years, SD 14) treated with biologics were included. The median FACIT F-score was 39 for the population, and scores ≤39 were considered moderate-to-severe fatigue. A high proportion of patients had moderate-to-severe fatigue (n=152 (51%)), these patients had significantly higher clinical disease activity (moderate-to-severe, n=56 (37%); remission, n=47 (31%)), compared to those with none-to-mild fatigue (n=148 (49%)) (moderate-to-severe, n=10 (7%); remission, n=105 (71%)) (p<0.005). Initial correlation analysis showed high clinical association between moderate-to-severe fatigue and patient reported outcomes, notably quality of life (rs=0.78), general well-being (rs=0.67), and disease worry (rs=0.52). The PCA subsequently reduced co-variables associated with fatigue into 3 main components, explaining 37% of fatigue (Figure). The first major component, explaining 15% of total fatigue, included ‘chronic disease related factors’, such as long disease duration, increasing age, previous use of biologics and corticosteroids, and previous surgery. The second component contributed to 13% of fatigue and comprised ‘comorbidity factors’, e.g., other chronic diseases, high body mass index (BMI), and self-reported disease activity. The third major component, explaining 11% of fatigue, comprised ‘disease activity and nutrition factors’ such as of high c-reactive protein, low iron, and low BMI.

Conclusion

Fatigue in IBD is only to a lesser extent driven by disease activity and nutritional deficits, chronicity, and co-morbidity. This indicates that fatigue is an independent disease manifestation in IBD.
P411 Baseline Hypertrophy of the Submucosa at intestinal ultrasound predicts Failure of Treatment in patients with ulcerative colitis
Authors: de Voogd F , Duijvestein M , Ponsioen C , Löwenberg M , D’Haens G , Gecse K
Published: May 2021

Background

Submucosal fibrosis in ulcerative colitis (UC) has been associated with disease severity in colectomy specimens. As intestinal ultrasound (IUS) visualizes all individual wall layers, we aimed to evaluate baseline IUS features to determine endoscopic response and investigate changes in wall layers during anti-inflammatory treatment in patients with UC

Methods

Moderate-severe UC patients (endoscopic Mayo score (EMS)≥2) extending beyond the rectum starting treatment were included. Simple Clinical Colitis Activity Index (SCCAI), fecal calprotectin (FCP), IUS and endoscopy were performed at baseline and at follow-up between week 8 and 26. BWT, individual wall layer thickness (WT) (mucosa (MC), submucosa (SM) and muscularis propria (MP)) and ratios among layers, Colour Doppler Signal, loss of haustrations, loss of stratification and hyperechogenicity of the submucosa (HoS) (Figure 1) were scored for the sigmoid colon (SC). EMS was assessed for the SC: endoscopic remission (ER) was defined as EMS=0 and endoscopic improvement (EI) as EMS≤1. For statistical analysis a paired t-test and X2-test were used.

Results

49 patients were included of whom 61% failed ≥1 biological. 59% started tofacitinib and 41% started a biological. At follow-up, 30% and 49% reached ER and EI, respectively. BWT decreased significantly when ER (2.32 ± 1.63 mm vs 1.00 ± 1.98 mm, p=0.034) or EI (2.53 ± 1.66 mm vs 0.30 ± 1.58 mm, p<0.0001) was reached. In patients with ER and EI, the SM thickness showed significantly more pronounced decrease compared to the other wall layers (Table 1 and Figure 2). Baseline presence of HoS (29% of patients) predicted failure of treatment (ER: OR: 0.10, 95% CI: 0.01-0.87, p=0.014, EI: OR: 0.16, 95% CI: 0.04-0.65, p=0.008,). Furthermore, when HoS was present, SCCAI (7.33 ± 3.62 vs 9.75 ± 3.23, p=0.023) and FCP (1249 ± 903 µg/g vs 2494 ± 2277 µg/g, p=0.008) were significantly lower at baseline. Also, patients with HoS more frequently failed one (OR: 4.44, 95% CI: 1.08-18.32, p=0.03) or multiple biologicals (OR: 5.63, 95% CI: 1.54-20.52, p=0.009). However, disease duration (p=0.950) or age at onset (p=0.853) did not differ between groups.

Conclusion

This is the first study showing that HoS on IUS is a predictor of endoscopic non-response to biologicals and tofacitinib in patients with UC. Additionally, changes in SM layer thickness is the most important component of the total bowel wall when evaluating mucosal healing on IUS.
P438 Maladaptive decision-making is associated with psychological morbidity in people with Inflammatory Bowel Disease
Authors: Grinsted Tate L , Johnson L , Jones G , Lobo A
Published: May 2021

Background

Inflammatory Bowel Disease (IBD) is a chronic relapsing-remitting inflammatory condition. Due to its long-term, multifaceted nature, patients will need to make many complex decisions during their treatment.

The Melbourne Decision Making Questionnaire (MDMQ) assesses the use of four decision-making styles. Vigilance is the only style considered adaptive, with a thorough, analytical approach. Buck-passing (avoiding responsibility), procrastination and hypervigilance (a hurried, anxious approach) are considered maladaptive.

This study aimed to assess the impact of psychological morbidity, health-related quality of life (HRQoL) and demographic/disease factors on decision-making in IBD.

Methods

People over the age of 16 with IBD completed the MDMQ. Psychological morbidity was assessed by the DASS-21 questionnaire, and HRQoL by the EQ-5D-3L/EQ-5D-Y. Demographic data included age, gender, ethnicity, Index of Multiple Deprivation quintile, educational level and employment status. Diagnosis, disease duration and age at diagnosis were also recorded.

Exploratory analysis of all variables against scores for each of the four decision-making styles was conducted. Significant results were used to perform multivariate analysis. All statistical analysis was performed using IBM SPSS Statistics software (v26).

Results

172 patients were studied (94 CD, 75 UC, 3 IBD-U, 68 (39.5%) male), median age 46.5 (16-83). Median MDMQ scores for vigilance, buck-passing, procrastination and hypervigilance were 10/12, 3/12, 2/10 and 3/10 respectively.

Multivariate analysis showed strong positive associations between psychological morbidity scores and all three maladaptive decision-making styles: buck-passing (F(1, 95)=12.512, p=0.001), procrastination (F(1, 115)=35.009, p<0.001) and hypervigilance (F(1, 114)=34.342, p<0.001). Age and duration of disease were not associated with decision making style.

Current employment and higher HRQoL scores were significantly associated with greater degrees of buck-passing (F(3,95)=5.100, p=0.003; and F(1, 95)=6.351, p=0.013 respectively). A diagnosis of CD was associated with lower vigilance score (F(2, 133)=3.224, p=0.043).

Conclusion

People with IBD are likely to have an adaptive decision-making style, demonstrated by a high median vigilance score. However, psychological morbidity is associated with maladaptive decision-making – an important consideration for clinicians and in shared decision making. Further studies are required to determine whether interventions for psychological morbidity can improve maladaptive decision-making.
P452 Oral ciclosporin is a convenient, effective and safe rescue therapy in steroid refractory Acute Severe Ulcerative Colitis: A single tertiary centre experience
Authors: Jiang C D , Thalagala T , Rosembert D , Parkes M , Lee J , Raine T
Published: May 2021

Background

Parenteral ciclosporin (CsA) is an effective rescue therapy for acute severe ulcerative colitis (ASUC) and has similar efficacy to infliximab (IFX). Although CsA is cheaper and can facilitate bridging to any IBD therapy, including newer biologics, its use is limited by variable pharmacokinetics and possibility of significant systemic toxicity particularly associated with the intravenous preparation. Despite favourable pharmacokinetics and bioavailability, the use of lipid-emulsified oral CsA in steroid-refractory ASUC is undefined.

Methods

All patients who received oral CsA (Neoral®) rescue therapy for ASUC at Addenbrooke’s Hospital, Cambridge, UK from Nov 2014 to May 2020 were identified from electronic healthcare records. Baseline data and outcomes were extracted and compared to patients who received IFX rescue therapy. Statistical significance was assessed using non-parametric tests. Survival estimates were computed using the Kaplan-Meier method.

Results

A total of 37 patients received oral CsA for refractory ASUC. Median time from admission to CsA initiation was 5 days (IQR 4–6 d) and median initial dose was 8 mg/kg/d (IQR 7–8 mg/kg/d). At admission, the median CRP was 26 (IQR 14–95) and Truelove and Witt’s severity criteria met in 21/37 (57%). 70% of patients (26/37) avoided colectomy during the index admission. No parameters were demonstrated to predict need for acute colectomy.

Median follow-up after hospital discharge was 3 years (IQR 2-5years). For those who avoided acute colectomy, median duration of therapy was 4 months (IQR 2.5-5months) with bridging to azathioprine (24/26, 92%), vedolizumab (1/26, 4%), or 5-ASA (1/26, 4%). Estimated colectomy-free survival in responders were 84%, 84% and 78% at 12, 24, and 60 months. No parameters were shown to predict colectomy-free survival. Comparable colectomy-free outcomes were obtained for contemporaneous IFX-treated ASUC patients in our hospital.

9 of 26 patients remained biologic-naïve and colectomy-free after a median of 3 years. Estimated colectomy and biologic-free survival were 51%, 47% and 18% at 12, 24, and 60 months.

15 patients experienced adverse events, which were all mild and self-limiting. There were 3 infective complications. No patients required drug cessation and no serious adverse events associated with parenteral CsA occurred.

Conclusion

In this cohort, oral CsA was a safe, well tolerated and effective rescue therapy for steroid-refractory ASUC. A proportion of patients remain biologic and colectomy-free for up to 5 years. Given the feasibility to bridge to effective maintenance therapies, including newer biologics, oral CsA should be considered as a rescue therapy in ASUC and avoids many of the side effects associated with intravenous CsA.
P457 Long-term follow-up of patients with IBD after switching from original adalimumab to adalimumab biosimilar during COVID 19 pandemic
Authors: Klimova K , Padilla Suarez C
Published: May 2021

Background

Studies have reported good efficacy outcomes for patients with inflammatory bowel disease (IBD) treated with biosimilars. There are limited long term data. We assessed the long-term efficacy data and safety after switching from adalimumab to adalimumab biosimilar Imraldi in patients with IBD.

Methods

A prospective single-centre observational study involving patients with Crohn’s disease or ulcerative colitis switched from adalimumab originator to adalimumab biosimilar and reviewed up to 24months. Efficacy and loss of response were measured using the Harvey–Bradshaw (HB) index and partial Mayo score for patients with Crohn’s disease and ulcerative colitis respectively. Blood tests including C-reactive protein, adalimumab drug levels and antidrug antibodies were monitored. We have recorded side effects and possible serious adverse effects including COVID 19 infection.

Results

113 patients were switched to Adalimumab biosimilar Imraldi from Adalimumab originator between January 2019 to March 2019. After 12 months of treatment, 25 patients interrupted treatment and 89 (78.8%) continued. These were analysed after 24 months of treatment - 57 (52.3%) continued on Imraldi. Of those who discontinued, 9 were switched back to Adalimumab originator due to side effects, and 34 stopped treatment - 16 patients due to loss of response, 11 patients developed antibodies, 5 underwent a surgery, 4 were in remission and 4 did not tolerate side effects. There was no statistical difference in CRP or Adalimumab levels prior to switch, at 12 months and at 24 months between the patients who continued or discontinued treatment.

Overall, 18 of the patients who completed 24 months of treatment reported side effects, most frequently pain after injection (9 patients), followed by skin rash and recurrent infections (in 3 patients each). No patient was diagnosed with COVID 19 during until now.

Conclusion

After 24 months of follow up, 52.3% patients continued on adalimumab biosimilar and no serious side effects were reported. In particular, none of our patients acquired COVID 19 infection.
P515 A 12-week tailored physical training program including dietary advice in children with Inflammatory Bowel Disease: a randomized crossover trial
Authors: Scheffers L , van den Berg L E , Pijnenburg M W , Utens E M , Dieleman G C , van der Ploeg A T , Helbing W A , Escher J C
Published: May 2021

Background

Inflammatory Bowel Disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract. Recently, physical activity has been suggested to improve the quality of life and course of disease in adult IBD patients. The aim of this study was to investigate physical functioning in paediatric IBD patients and to determine the effects of a tailored 12-week lifestyle intervention including a physical training program.

Methods

Figure 1 shows our study design and measurements. The tailored 12-week lifestyle intervention consisted of 3 strenuous physical training sessions a week and dietary advice. Effects on exercise capacity, endurance, physical activity levels, disease activity, quality of life, and fatigue were measured in paediatric IBD patients. Mild disease activity was defined as a PCDAI between 10 - 27.5 or PUCAI between 10 - 34.

Results

Sixteen paediatric IBD patients (median age 15 [9 - 17]) were included, 13 patients successfully completed the training program, 2 patients are still participating. At baseline, most patients had mild disease activity (n=9). Patients had reduced exercise capacity (76.8%±17.7% of predicted PeakVO2 , and reduced physical activity levels as shown by 80.3%±7.4% of measured time being spent in sedentary activity. PCDAI/PUCAI scores decreased significantly over the intervention period (13.8±11.7 vs. 3.65±4.5, P=0.002). Fecal calprotectin also decreased significantly (400 [18–3089] vs. 128 [20–2704], P=0.041). All patients but one had no changes in medical regimens before or during the lifestyle intervention that could have influenced disease activity. After the 12-week lifestyle intervention period, 9 out of 13 patients were in clinical remission. Maximum walked distance increased significantly (503±69 vs. 540±77 meters, P=0.001), although PeakVO2 and percentage of time spent in moderate-to-vigorous activity did not. Patients improved on overall quality of life measured by the Impact III questionnaire (+2.4 points, p=0.017). The Child Health Questionnaire showed a significant improvement on the child-reported physical functioning scale and on 5 parent-reported scales of quality of life. Child-reported fatigue measured by the PedsQol MFS did not improve significantly, parents-reported fatigue did. No changes were found on mentioned outcomes during the control period. After baseline measurements, the COVID-19 lock-down period started, possibly affecting normal daytime activities of the patients during the lifestyle intervention period.

Conclusion

A 12-week tailored physical training program including dietry advice is safe and beneficial for paediatric IBD patients and may contribute to better control of inflammation.
P586 Drug-induced lipid changes in patients with Inflammatory Bowel Disease: a single center, prospective study
Authors: Sleutjes J , de Vries A C , Roeters van Lennep J E , van der Woude C J
Published: May 2021

Background

Drug use in the treatment of inflammatory bowel disease (IBD) might negatively impact lipid levels. In this study, we assessed drug-induced changes in the lipid profile after IBD induction therapy.

Methods

In this single center, prospective study IBD patients aged ≥17 years who started systemic drug therapy (corticosteroids, thiopurines, methotrexate, infliximab, adalimumab, vedolizumab, ustekinumab and tofacitinib) for IBD were included. Exclusion criteria were pregnancy, history of liver transplantation and use of lipid lowering drugs. Data on cardiovascular risk profile, disease activity (HBI, SCCAI, CRP, FCP) and concomitant medication use were collected. To calculate mean lipid changes after induction therapy, nonfasting lipid levels (total cholesterol (TC), HDL-c, LDL-c, triglycerides (TG)) were measured before and 8–10 weeks after start of therapy. Pearson correlation test was performed to assess the association between lipid changes and CRP.

Results

A total of 183 patients (87 males (48%), median age 36 years (IQR 28–48), 128 Crohn’s disease (70%), 46 CU (3%), 9 IBD-U (7%)) were included. (Table 1) Fourty-nine patients were on concomitant steroids at baseline (31%). Relative increases in TC, HDL-c and LDL-c were significant after treatment with corticosteroids and tofacitinib (+9%, +17%, +8% and +19%, +29%, +24%, respectively) and decrease in TG after treatment with corticosteroids, thiopurines, infliximab, adalimumab, ustekinumab and tofacitinib (-9%, -14%, -10%, -8%, -11%, -8%, respectively). (Table 2, Figure 1) A significant inverse relationship was found between CRP and TC (R -.171), HDL-c (R -.202), LDL-c (R -.153) but not with TG.

Conclusion

Serum lipid levels increased most after start of corticosteroids and tofacitinib as compared to other drug therapies. Whether these changes are explained by the control of inflammation or by the mechanism of action of these agents remains undetermined.