bluuebunny/crossref_metadata_2025 huggingface dataset:
P111 Gut barrier markers in Inflammatory Bowel Disease
Authors: Nguyen A , Sparrow M P , Moore G , Gibson P R
Published: January 2022

Background

Blood monitoring for disease activity in inflammatory bowel disease (IBD) is largely limited to C-reactive protein (CRP), but this may be raised in other inflammatory conditions and normal in active disease. Aims were to: (a) compare plasma levels of putative gut barrier markers, lipoprotein polysaccharide-binding protein (LBP), soluble CD14 (sCD14), syndecan-1 and intestinal fatty acid-binding protein 2 (IFABP2) in patients with IBD with those in controls; (b) define association with inflammatory activity; (c) examine responsiveness to change after biologic induction therapy.

Methods

Plasma was prospectively collected from patients with IBD and matched healthy controls. IBD was considered active with faecal calprotectin (FCP) ≥150 μg/g and/or an intestinal ultrasound showing a Limberg score ≥2. Gut barrier markers were compared to FCP and CRP. In a subset of patients who commenced on biologic therapy, they were measured at baseline and at least 14 weeks later. Biomarker concentrations were described as medians and spearman correlation was used for comparison with traditional biomarkers.

Results

101 patients with IBD and 51 controls were matched in age (33 vs 34 years) and gender (males 54% vs 47%). Treatment for IBD included aminosalicylates (38%), immunomodulators (47%), biologics (58%) and steroids (20%). In Crohn’s disease (n=60), distribution was ileal (45%), ileocolonic (30%) and colonic (25%); 31 had active disease. In ulcerative colitis (n=41), distribution was pancolitis (63%), left-sided (29%) and proctitis (7%); 18 had active disease. Compared with controls, patients with IBD had higher levels for LBP (13.6 vs 10.1 μg/ml; p<0.0001), sCD14 (1.3 vs 1.2 μg/ml; p<0.001) and LBP:sCD14 ratio (11 vs 8.8; p=0.002), but lower levels for syndecan-1 (19.4 vs 30 ng/ml; p=0.006) and IFABP2 (1452 vs 1696 pg/ml; p=0.015).

Only LBP differentiated between active and inactive disease in Crohn’s disease (16.1 vs 13.5 μg/ml; p=0.045) and ulcerative colitis (16.7 vs 10 μg/ml; p=0.012). LBP, and not other markers, correlated with FCP in all patients with IBD (r=0.46; p<0.001). LBP and sCD14 correlated with CRP (r=0.7 and r=0.46; p<0.001). The best cut-off value for LBP in detecting active disease was >15.9 μg/ml (AUC 0.71, sensitivity 57%, specificity 82%). In 18 patients who underwent biologic induction, LBP (17.1 to 13.8 μg/ml; p=0.094) and sCD14 (1.5 to 1.3 μg/ml; p=0.064) tended to fall.

Conclusion

Of putative barrier markers, only those associated with bacterial translocation (LBP, sCD14) were elevated in IBD with epithelial markers (syndecan-1, IFABP2) paradoxically reduced. Only LBP was associated with active disease though its responsiveness to therapy is uncertain and requires further prospective study.
P115 Implementation of a vaccination tool in the electronic patient health record significantly increases vaccination coverage
Authors: Fierens L , De Dycker E , Joly J , Vanhoutvin T , Verschueren P , De Haes P , Sabino J , Vermeire S , Ferrante M
Published: January 2022

Background

Patients with immune-mediated inflammatory diseases (IMID) are at higher risk for infectious diseases. Despite this increased risk and the available guidelines1, we reported a sub-optimal vaccination rate of 27.4% of IMID patients in 2018. In the meantime, a vaccination module was introduced in the electronic patient health record of our hospital to accurately document and monitor vaccination status of patients. The impact of this new module on vaccination coverage was re-evaluated in the same IMID patients in 2021.

Methods

Between Aug and Oct 2021, the vaccination status of 1448 (out of the original 1488) IMID patients (44.8% male, median age 53.6 years) was collected (798 patients with IBD, 612 with rheumatological, and 38 with dermatological inflammatory conditions) and compared to that of 2018. The vaccination status was obtained mainly through the patients’ electronic medical records. Missing data were added after contacting patients or their general practitioner.

Results

From 2018 to 2021, the overall vaccination coverage of all IMID patients significantly increased from 27.4% to 51.9% (p<0.001, Figure 1).

The vaccination coverage in IBD patients increased significantly from 75.9% to 86.3% for influenza (p<0.001), from 72.9% to 88.7% for pneumococci (p<0.001), from 66.0% to 80.2% for hepatitis B (p<0.001), from 79.9% to 85.7% for tetanus (p=0.041) and from 42.2% to 60.4% overall (p<0.001) (Figure 1 and Table 1).

Similarly, the vaccination coverage significantly increased for rheumatology patients, namely from 69.3% to 78.3% for influenza (p<0.001), from 34.5% to 85.0% for pneumococci (p<0.001), from 32.8% to 36.5% for hepatitis B (p<0.001) and from 7.8% to 32.6% overall (p<0.001) (Figure 1 and Table 1).

For patients with dermatological inflammatory conditions, vaccination coverage significantly increased from 60.5% to 81.6% for pneumococci (p=0.031) and from 47.1% to 55.3% for hepatitis B (p=0.002) (Table 1).

Conclusion

The suboptimal vaccination rate measured in 2018 and the COVID-19 pandemic stressed the importance of vaccination recommendations to patients and healthcare professionals. We here show that the implementation of a vaccination tool integrated in the electronic medical record of patients is correlated with a significant increase in specific vaccination rates and also in the total amount of IMID patients that were fully vaccinated according to guidelines.

Reference

1. Rahier JF, Magro F, Abreu C, et al. Second European evidence-based consensus on the prevention, diagnosis and management of opportunistic infections in inflammatory bowel disease. J Crohns Colitis. 2014;8:443–468.
P129 Hepcidin and ferritin index can help to differentiate between different types of anaemia: an exploratory study
Authors: Bevers MD N , Adriaans G M C , Aliu A , Rezazadeh Ardabili A , Vreugdenhil A C E , de Almeida R , van Rheenen P F , Pierik M J
Published: January 2022

Background

Anaemia is frequent in patients with IBD. Iron deficiency anaemia [IDA] and anaemia of chronic disease [ACD] are the most common subtypes and warrant a different treatment approach.

The ESPGHAN/ NASHGAN position paper on Anaemia in Children with IBD describes cut-off values on ferritin, transferrin saturation [TSAT] and ferritin index (soluble transferrin receptor/log10(ferritin)) [sTfR-F], to distinguish between IDA and ACD. However, cut-off values for sTfR-F and hepcidin are based on adult data.

In this exploratory study we used a data driven approach to define different anaemia groups, using hepcidin and sTfR-F and studied differences between groups and their response to iron suppletion therapy. Insights contribute to a better description of ACD and IDA in a pediatric population.

Methods

Data from the multi-centre prospective POPEYE study (NTR4487) consisting of a paediatric IBD population was used. Subjects with anaemia (haemoglobin [Hb] < 2 standard deviations [SD] below the mean of a healthy age reference group) with baseline ferritin, TSAT, hepcidin, sTfR-F and erythrocyte sedimentation rate [ESR] values were selected. Summary statistics of these biomarkers were generated for the data-driven groups and compared with existing characteristics for IDA and ACD groups. At baseline subjects received oral or intravenous iron repletion therapy, Hb was determined at baseline and 1 month after iron therapy. Kmeans was used, an unsupervised clustering algorithm using Euclidean distance, to divide data points into k clusters based on sTfR-F and hepcidin.

Results

Mean age was 13.6 (2.5 SD) years, and mean standardized Hb value -3.2 at baseline for 47 subjects. Data driven groupings using Kmeans (k=3) were based on baseline hepcidin and sTfR-F (figure 1).

Group 1 shows characteristics indicative for IDA, with mean ferritin <15µg/l, TSAT < 20% and sTfR-F > 2. Group 2 shows signs suggestive for inflammation since ferritin, hepcidin and ESR were increased (mean ESR 28,5 mm/h [23,2 SD]); this group could be characterized as ACD. Group 3 could not be related to a specific anaemia type.

Mean standardized Hb increase 1 month after iron repletion for 37 patients, was 2,9 (SD 0,8), 0,8 (0,7 SD), 1,3 (1,1 SD), for group 1, 2 and 3 respectively.

Conclusion

Explorative data-driven analysis of a real-world data set showed that hepcidin and sTfR-F can be used to characterize groups that relate to ACD and IDA in a paediatric population. Children with high sTfR-F and low hepcidin possibly benefit more from iron repletion therapy (group 1), compared to when hepcidin is high (group 2). If validated in a larger patient population this determination could contribute to the development of diagnostic algorithms that support targeted therapy.
P136 Risk of polyps and colorectal cancer in patients with microscopic colitis: case-control study with long-term follow-up
Authors: Fajardo I , Zabana Y , Salas A , Aceituno M , Ruiz L , Esteve M , Fernández-Bañares F
Published: January 2022

Background

A previous study (Fernandez-Bañares et al, UEGJ 2016;4s: A434) showed that in microscopic colitis (MC) there is a low frequency of polyps and colorectal cancer (CRC) compared to the general population at medium risk, without observing differences with a group of chronic diarrhoea and normal colonic histology. The aim of the present study is to assess whether this low incidence of adenomas in patients with MC and chronic diarrhoea persists in the long term.

Methods

Patients with follow-up colonoscopies for control of colonic polyps or for diarrhoea recurrence after index colonoscopy were included in two groups: patients in the MC group (32/100 patients, Group A) and in the chronic diarrhoea group (68/200 patients, Group B). Colonic polyps were recorded, collecting adenomas, advanced adenomas (AA; high-grade dysplasia -HGD-, villous component and size > 1cm) and CRC. A conditional logistic regression analysis was performed (COXREG: 1 case-2 controls, matched by age and sex).

Results

With a median follow-up of 9 years (IQR =7–12 years), 2 CRC were diagnosed in Group B (2/200). A total of 44 colonoscopies were performed in Group A and 105 in Group B, with no significant differences between groups (p=0.35). Recurrent diarrhoea was present in 25% of Group A and 38% of Group B (p=0.19). In these endoscopies, the total frequency of adenomas was: Group A 28% and Group B 56% (p=0.009). The frequency of AA was: Group A 12.5% and Group B 14.7% (p=1). The frequency of HGD/CRC was 0% in Group A and 5.8% in Group B (p=0.30). For adenomas, the COXREG OR was 0.2 (CI=0.05–0.75; p=0.017) and for AA (with CRC included) 0.8 (CI 0.26–2.9; p=0.8).

Conclusion

After long-term follow-up, patients with MC have a decreased frequency of adenomas and a trend to have less HGD/CRC compared with patients with chronic diarrhoea and normal colonic histology. These differences, therefore, are probably due to the MC itself and not to a protective effect of diarrhoea, as had been previously suggested. These results support the recommendation of not doing specific screening for CRC prevention in patients with MC.
P139 Body composition and Crohn’s disease behavior: Is adiposity the main game changer?
Authors: Morão B , Velho S , Agostinho L , Torres J , Cravo M
Published: January 2022

Background

Introduction: Visceral fat has been associated with unfavorable outcomes in Crohn’s disease (CD) patients. We investigated the association between body composition upon diagnosis and complicated phenotypes and time until surgery in patients with CD.

Methods

retrospective cohort study including patients with CD who had a computed tomography enterography (CT) or an entero magnetic resonance (MR) performed within 6 months of diagnosis. Skeletal muscle, visceral and subcutaneous adipose tissue cross-sectional areas were determined with CT or MR images at L3 vertebrae level, after being processed with Slice-o-Matic (Tomovison) and ABCS module (applicable only to CT scan images). Logistic regression was used to assess predictors of disease behaviourand time until abdominal urgery was modeled with proportional hazards Cox models.

Results

We included 63 patients: 33(52%) men with median age of 35 years. Disease location and behaviour according to Montreal classification was as follows: L1=28(44%), L2=13(21%), L3=18(28%), L1+L4=1(2%), L3+L4=3(5%); B1=39(62%), B2=11(17%), B3=13(21%); 20(32%) patients had perianal disease. At diagnosis, 17(27%) patients were treated with corticosteroids. Anti-TNF agents were started in 8(13%) patients, azathioprine in 23(36%), combination therapy in 15(24%); 17(27%) patients did not start any medical therapy. Visceral obesity was present in 12(19%) patients at diagnosis. Visceral obesity was associated with higher age of CD onset (median 60 vs 34 years, p=0.002) and complicated disease behaviour(B2/B3) at diagnosis (66.7% vs 31.7%, p=0.021), with an approximately 4 times higher risk of complicated behaviour(OR=4.37, 95%IC=1.19–18.44, p=0.03).After adjusting for age and perianal disease, total adipose tissue (visceral and subcutaneous fat) remained statistically significant and was associated with a 4% increase in the odds of complicated behaviourat diagnosis per 10 cm2of total adipose tissue (OR 1.004,95%CI 1.00–1.008, p=0.043). Median follow-up time was 3.35 years, during which 15 (24%) of patients underwent abdominal surgery. Visceral obesity was associated with a 5.10 times higher risk of abdominal surgery during follow-up (95%CI 1.52–17.09, p=0.008); after adjusting to disease behaviour, visceral obesity maintained a near significant association with a 2.90 times higher risk of surgery (95%CI 0.83–10.08, p=0.09).

Conclusion

In our cohort of patients with newly diagnosed CD, total fat upon diagnosis seems to be associated with B2 and B3 disease phenotypes. Furthermore, visceral obesity was associated with a 5.10 times higher risk of abdominal surgery during follow-up and with a shorter time until surgery.
P150 Increased risk of ibd flare after sars-cov-2 infection. who’s the more guilty: viral infection or therapy withdrawal?
Authors: Bezzio C , Guarino A D , Fiorino G , Armuzzi A , Ribaldone D G , Furfaro F , Pugliese D , Vernero M , Variola A , Gerardi V , Scucchi L , Viganò C , Caprioli F A , Roselli J , Coppini F , Ardizzone S , Onali S , Zingone F , Daperno M , Cortellezzi C , Carparelli S , Soriano A , Manes G , Saibeni S
Published: January 2022

Background

In the last year, the severe adult respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic has spread rapidly around the world. The interactions between SARS-CoV-2 and inflammatory bowel disease (IBD) are so far not fully understood. In particular, no studies evaluated the potential role of SARS-CoV-2 on IBD course. Indeed, it is known that viral infections can be act as triggers for IBD flare and it is reasonable that the possible drug discontinuation during SARS-CoV-2 infection could in turn lead to an IBD flare.

Methods

This was a prospective, observational case-control study. From March 11th 2020 to June 30th 2020 we enrolled IBD patients with proven SARS-Cov-2 infection (“cases”) and IBD patients without SARS-CoV-2 infection matched for sex, age, diagnosis, therapy and clinical activity (“controls”). Cases and controls were followed-up at least for 6 months. Differences between case and control group were tested for significance using the Student’s t test and Fisher’s test, as appropriate. A two-tailed p value < 0.05 was indicative of statistical significance.

Results

219 IBD patients (127 UC, 58.0%) with SARS-CoV-2 infection and 219 IBD patients without SARS-CoV-2 infection were enrolled. Table 1 shows baseline features of the population. Among the 122 cases in clinical remission at the time of viral infection, 28 (22.9%) showed a disease flare; this percentage was significantly higher than that observed in controls: 12/137 (8.8%)(p=0.0018). Among patients with disease flare, there were no significant differences between cases and controls group in terms of age (42.3 ± 16.0 vs. 43.1 ± 15.4 years, p=0.44), gender (female 45.7% vs. 48.2%, p= 0.54), use of biologic therapies (p=0.83) and UC or CD diagnosis (p=0.06). Biologic therapy was temporary withdrawn more significantly in cases than in controls (68/202, 33.6% vs. 14/204, 6.9%) (p<0.001) and overall biologic therapy discontinuation was significantly associated with disease flare (OR 2.56, 95% CI 1.02–6.41, p=0.04).

Conclusion

IBD patients with SARS-CoV-2 infection have an increased risk to have a clinical recurrence in short-term in comparison with IBD patients without SARS-CoV-2 infection. This increased risk could be due to the viral infection and/or to the temporary discontinuation of biologic therapies, because of infection.
P168 Matrix Gla protein, a potential marker of tissue remodelling and physiological ageing of the gut in Crohn’s Disease
Authors: Vieujean S , Delanaye P , Seidel L , Cavalier E , Pierre N , Louis E
Published: January 2022

Background

Matrix Gla protein (MGP) is an extracellular matrix protein. The inactive dephosphorylated and uncarboxylated form of this protein, called dp-ucMGP, has been shown to be increased in plasma of Crohn’s disease (CD) patients compared to non IBD patients (Brnic et al., 2020). Our aim was to assess if the plasmatic level of dp-ucMGP could reflect disease endoscopic activity and could be a potential marker of mucosal healing in CD.

Methods

The plasmatic level of dp-ucMGP was measured in a blood sample collected the same day as the ileocolonoscopy by CLIA method using IDS-iSYS InaKtif MGP. In addition to classical clinical data (gender, age, body mass index or BMI, disease duration, IBD treatment), endoscopic (disease localisation, Crohn’s Disease endoscopic index or CDEIS, as well as the presence of erythema, ulcer, oedema, pseudopolyp, stricture) and biological (C-reactive protein or CRP) parameters were collected as well as faecal calprotectin to assess CD activity.

Results

A total of 82 colonoscopies and dp-ucMGP assays were performed in 75 CD patients (44 females and 31 males; 43 colonic diseases, 22 ileal diseases and 19 ileocolic diseases) between October 2012 and November 2019. Out of the 82 performed colonoscopies, 22 showed a mucosal healing. Although MGP level was significantly correlated with CDEIS (r=0.21, p=0.040), it was neither associated with endoscopic remission (737 ± 205 pmol/L for patients in endoscopic remission vs 809 ± 332 pmol/L for those who were not, p=0.37), nor correlated with faecal calprotectin (r=0.074, p=0.51) or with CRP (r=0.12, p=0.27) levels. Plasma MGP levels increased significantly with age (r=0.38, p=0.0004) and disease duration (r=0.37, p=0.0006) but not with the BMI (r=0.045, p=0.69). Patients on corticosteroids at the time of colonoscopy had a higher level of MGP (1065 ± 531 pmol/L vs 729 ± 179 pmol/L, p=0.0003). There was no association with other treatments (5-ASA, immunomodulators, anti-TNF, anti-α4β7 integrin or anti-IL-12/IL-23 p40 monoclonal antibody). Regarding endoscopic CD lesions, MGP values were significantly higher in cases of oedema (1153 ± 628 pmol/L vs 766 ± 261 pmol/L, p=0.019) and pseudopolyps (1099 ± 569 pmol/L vs 766 ± 264 pmol/L, p=0.018) but there was no association with the presence of other lesions.

Conclusion

The significant increase of plasmatic MGP levels with age, disease duration but also in patients with pseudopolyps suggests that this extracellular matrix protein could rather be a marker of tissue remodelling (not necessarily stricturing) and physiological ageing of the gut in CD than a marker of disease activity. The relevance of the plasmatic dosage of this protein to assess CD bowel damages deserves to be further investigated.
P179 Distinct ultrasound characteristics of the appendix in patients with ulcerative colitis: a prospective, cross-sectional cohort study
Authors: Reijntjes M , de Voogd F , Bemelman W , d’Haens G , Buskens C , Gecse K
Published: January 2022

Background

Increasing evidence suggests a role for the vermiform appendix in onset and relapse of ulcerative colitis (UC). Consequently, appendectomy is increasingly being seen as a potential alternative treatment. As a recent study suggests that patients with histological appendiceal inflammation are most likely to respond, pre-operative identification of ulcerative appendicitis could be beneficial1. Intestinal ultrasound (IUS) is increasingly utilized in the diagnosis and follow-up of patients with UC. The objective of this study was to characterize the appendix by IUS in UC patients with active and quiescent disease and healthy controls.

Methods

In this cross-sectional prospective observational cohort study, we performed appendiceal IUS on UC patients with active (A) disease (FCP>250 and SCCAI>5) and quiescent (Q) disease (FCP<150 and SCCAI<5), followed by age-, body mass index- and gender- matched healthy (H) controls. During IUS, the appendix was identified as a bowel structure with cecal origin and a blind-ending tip. IUS still images and cineloops were centrally and blindly read by an IUS expert (>1000 examinations). Primary outcomes were signs of appendicitis on IUS, defined as a <6 mm transverse appendiceal diameter3 (average of a cross-sectional and longitudinal measurement), hyperaemia (using the modified Limberg score2), presence of peri-appendiceal fat and fluid, and compressibility.

Results

Out of 95 (A n=35, Q n=30, H n=30) included patients, the majority (n=58, 61.1%) had a visible appendix on IUS, which was similar among cohorts (p=0.56). The appendiceal diameter measured >6.0mm in a significantly higher proportion of active UC patients (A: 45.5%, Q: 5.6%, H: 0.0%, p=0.01). An increased diameter occurred irrespective of disease extent (42.9% of E1/E2 endoscopic active patients). Although the appendiceal diameter was higher for UC patients (Q-H p= 0.02, A-H p< 0.01), no significant difference between A and Q patients was found (p=0.15, Fig. 1). A higher proportion of UC patients had incompressibility when compared to healthy controls (Fig. 2a, p= 0.02). Hypervascularity was present in 54.5% of active UC (Fig. 2b, p= 0.02).

Fig 1. Box plot of appendiceal diameter (mm) among cohorts

Fig 2 (a, b). Bar charts of incompressibility (a) and hypervascularity (b) among cohorts

a

b

Conclusion

Appendiceal IUS was feasible in UC patients. Characteristics of appendiceal inflammation of IUS were reported for UC patients, as both the transverse appendiceal diameter and incompressibility rates were significantly higher in UC patients when compared to healthy controls. Correlating appendiceal IUS findings to histological inflammation could contribute to identifying UC patients most likely to benefit from appendectomy.
P184 Relationship Between Patient Sex and Serum Tumor Necrosis Factor Antagonist Drug and Anti-Drug Antibody Concentrations in Inflammatory Bowel Disease; A Nationwide Cohort Study
Authors: Shehab M , Alasfour H , Abdullah I , Alhendi G , Alhadab A , Alfadhli A , Ziyab A , Battat R
Published: January 2022

Background

Anti-drug antibodies to infliximab (ATI) and adalimumab (ATA) are associated with loss of response to tumor necrosis factor antagonist (anti-TNF) therapy in inflammatory bowel disease (IBD). We evaluated the relationship between patient sex and serum TNF antagonist drug and antibody concentrations in inflammatory bowel disease

Methods

A nationwide multicenter retrospective cohort study was conducted by evaluating patients’ charts from July 2018 until September 2021. The effect of patient sex on anti-drug antibodies and serum drug concentration in patients with IBD across 7 hospitals was investigated. A subgroup analysis also investigated the effect of anti-TNF combination therapy. Geometric means were calculated, and multiple linear regression was used to estimate the adjusted ratio of geometric means (RoGM) and their 95% confidence intervals (CI).

Results

In the total study sample (n = 1093), males receiving infliximab had higher anti-drug antibody concentrations (38.3 vs. 22.3 AU/ml; aRoGM = 1.72, 95% CI: 1.30–2.27, p-value <0.001) compared to females. Additionally, infliximab serum drug concentrations among males were lower compared to females (2.6 vs. 4.1 ug/ml; aRoGM = 0.62, 95% CI: 0.44–0.88, p-value = 0.007). In the subgroup analysis (n = 359), male compared to female patients on combination therapy with infliximab and immunomodulators had similar anti-drug antibody concentrations (30.2 vs. 21.9 AU/ml; aRoGM = 1.38, 95% CI: 0.79–2.40, p-value = 0.254). There was no difference in the anti-drug antibody and serum drug concentrations among males and females on adalimumab.

Conclusion

In patients receiving infliximab, anti-drug antibodies were higher in males than females. Consistent with this, serum drug concentrations were lower in males than females on infliximab. There was no difference in anti-drug antibody and serum drug concentrations among males and females on adalimumab. In addition, no difference in anti-drug antibodies between males and females receiving anti-TNF combination therapy was observed
P196 Pre-treatment antibodies to infliximab and adalimumab are common but are not associated with anti-TNF treatment failure
Authors: Nice R , Goodhand J R , Kennedy N , Ahmad T , Winyard P , McDonald T J
Published: January 2022

Background

Anti-TNF treatment failure is common. Primary non-response and loss of response are frequently caused by low anti-TNF drug levels mediated, principally, by the formation of anti-drug antibodies which can be mitigated by concomitant immunomodulator use.

Previous small studies in patients with IBD suggest that antibodies formed prior to treatment can bind drug and impair the pharmacokinetics, efficacy and safety of the anti-TNF drugs.

We sought to determine the prevalence, neutralising capacity and clinical relevance of pre-treatment antibodies to infliximab and adalimumab in in anti-TNF-naïve patients with active luminal Crohn’s disease.

Methods

The Personalised Anti-TNF Therapy in Crohn’s Disease study (PANTS) is a UK-wide, multicentre, prospective observational cohort reporting treatment failure rates of the anti-TNF drugs infliximab and adalimumab in Crohn’s disease.

The prevalence of antibodies to infliximab and adalimumab at baseline in all patients were measured using IDKmonitor ELISA assays and neutralising capacity in positive cases was determined using the iLite™ cell-based assays. Associations between baseline antibody status, subsequent immunogenicity and drug levels, and response status were assessed using Mann-Whitney U tests and chi-squared analyses, respectively.

Results

In the PANTS cohort, at baseline, pre-treatment anti-TNF antibodies were detected in 7.3% (112/1525) patients. Pre-treatment antibodies to infliximab were more common (6.3% 96/1525 vs 2.4% 36/1525, p<0.01) and of higher levels (median (IQR) infliximab: 23.9 (14.2 – 55.2) AU/ml vs adalimumab: 7.2 (6.3 – 10.4) AU/ml, p<0.0001) than adalimumab. A minority (1.3% (20/1525)) of patients had anti-drug antibody reactivity to both drugs. None of the detected anti-drug antibodies had demonstrable anti-TNF neutralising capacity detected by our iLite™ cell-based assay. No associations were seen between baseline antibody reactivity, subsequent immunogenicity, drug levels or response status at week 14 or week 52.

Conclusion

Pre-treatment anti-drug antibodies are common. However, they do not neutralise anti-TNF drug activity invitro, promote drug clearance or influence clinical response to anti-TNF drugs. Further work is required to understand this cross-reactivity and to determine the exact nature of the antibodies detected in drug naïve individuals.
P214 Plasma fatty acid binding protein 2, interleukin-10 and lipopolysaccharides as biomarkers for microscopic colitis
Authors: Vytautas K , Varkalaite G , Vaitkeviciute E , Arstikyte J , Skieceviciene J , Kupcinskas J
Published: January 2022

Background

The pathogenesis of microscopic colitis (MC) is still poorly understood and there are no non-invasive diagnostic markers to aid in disease diagnosis. Fatty acid binding protein 2 (FABP2) is expressed in enterocytes and colonocytes (although to a lesser extent) and is released after intestinal injury. Interleukin-10 (IL-10) is an anti-inflammatory cytokine that is reduced in inflammatory bowel diseases. Lipopolysaccharides (LPS) are bacterial endotoxins that promote inflammation and their presence in systemic circulation represents impaired intestinal barrier function. Our aim was to investigate these compounds as possible non-invasive diagnostic biomarkers for MC and compare their profile between MC and ulcerative colitis (UC).

Methods

63 patients with active MC, 52 healthy controls (HCs), 43 patients with active and 43 with inactive UC were recruited for the study. The presence of active disease was assessed using the Hjortswang criteria in MC and Mayo score in UC patients. Plasma concentrations of FABP2, IL-10 and LPS were measured using Human FABP2/I-FABP Quantikine ELISA Kit (DFBP20; R&D systems, MN, USA), Human IL-10 Quantikine ELISA KIT (D1000B; R&D systems, MN, USA), and Human Lipopolysaccharides (LPS) ELISA Kit (CSB-E09945h; Cusabio, China). Statistical significance of concentration differences between groups was determined using the Mann-Whitney U test.

Results

No significant difference was discovered when comparing the plasma FABP2, IL-10 and LPS concentrations between MC patients and HCs. However, FABP2 concentrations were significantly lower in the plasma of UC patients, both active (median 1272 pg/ml, p = 0,004) and inactive (median 1334 pg/ml, p = 0,001) when compared with MC patients (median 1680 pg/ml). The difference in FABP2 concentration between HCs (median 1365 mg/ml) and active or inactive UC patients did not reach statistical significance.

IL-10 concentrations were significantly lower in patients with active UC (median 2,58 pg/ml) than in MC patients (3,89 pg/ml, p = 0,006) and HCs (median 4,79 pg/ml, p = 0,005). There was no significant difference between MC patients or HCs when compared with inactive UC patients (median 3,04 pg/ml).

The plasma concentrations of LPS were similar across all the patient groups and no significant difference was observed.

Conclusion

Plasma FABP2, IL-10 and LPS did not distinguish MC patients from HCs in our study and did not show potential as biomarkers. Our results of lower plasma IL-10 concentration in patients with active UC show that it could be a useful biomarker for disease activity. It is unclear whether the lower plasma concentration of FABP2 in active UC patients compared to MC patients is important since neither group differed significantly from HCs.
P217 Prevalence of COVID-19 in IBD patients treated with infliximab and vedolizumab in Croatian tertiary center – clinical observation of a case series
Authors: Domislović V , Brinar M , Čukovic-Čavka S , Turk N , Grgić D , Barišić A , Jelaković M , Krznarić Ž
Published: January 2022

Background

The risk of COVID-19 in patients with IBD is considered comparable to general population. However, it has been hypothesized that patients on immunosuppressive therapy could be more susceptible to SARS-CoV-2, mainly due to well-known association of immunosuppressive therapy and increased risk of viral infections. Our aim was to examine the frequency of COVID-19 infection among tertiary center IBD patients treated with biological therapy.

Methods

These are descriptive data including IBD patients on biological therapy which are regularly followed in Croatian referral IBD center at the University Hospital Centre Zagreb, Croatia. Patients on adalimumab were excluded since they are not regularly followed and are receiving therapy at home. SARS-CoV-2 infection was identified as RNA positive nasopharyngeal swab. Disease activity was measured using Harvey-Bradshaw Index (HBI) in CD, partial Mayo score (pMayo) in UC, and CRP. COVID-19 was defined as mild as any of the symptoms consistent with COVID-19 without shortness of breath, dyspnea, abnormal chest imaging and room SpO2>=97%.

Results

Out of total 234 patients on infliximab 15 (6.4%) had COVID-19, which was the case for 3 out of 48 (6.2%) patients on vedolizumab. We have not documented COVID-19 among 67 patients on ustekinumab and 10 on golimumab. Among infected there were 9 patients with CD, 8 UC and 1 IBD unclassified, 61.1% were male and average age was 37 (SD 12). All patients had mild clinical picture with symptoms lasting around 3 days. Overall, 3 UC patients on infliximab had worsening of IBD symptoms (bloody stools and diarrhea) in approximate time to and after COVID infection (increase of pMayo by >=2 points) with only 1 patient requiring glucocorticoid therapy. One male patient had prolonged post-COVID syndrome in terms of fatigue and mild dyspnea over 4 months, but suffered from bronchial asthma. There was no difference in HB index, pMayo or CRP before and after COVID-19 infection (p>0.05). Loss of smell and taste was present 3 patients.

Conclusion

Our analysis was limited to IBD patients scheduled to receive a visit; hence it could not represent general IBD population. However, according to the results of other studies, we did not gain the impression of increased risk of infection or poorer clinical outcome in IBD patients on biological therapy. In addition, study from Singh AK et al. reported worse outcomes of COVID-19 IBD patients in UC, but not on biological therapy, which is also in line with our observation (1).

Reference

1. Singh AK et al. Risk and outcomes of coronavirus disease in patients with inflammatory bowel disease: A systematic review and meta-analysis. United European Gastroenterol J. 2021;9:159–176.
P226 Nuclear magnetic resonance spectroscopy measure of protein glycosylation is a biomarker of activity and metabolic complications in Inflammatory Bowel Disease
Authors: García Mateo S , Martínez-Dominguez S J , Aso Gonzalvo M C , Refaie E , Gallego Llera B , Alfambra Cabrejas E , Sanz B , Amigó Grau N , Ribalta J , Martínez-Micaelo N , Gargallo-Puyuelo C J , Gomollón F
Published: January 2022

Background

Plasma glycoproteins are acute-phase proteins, which can contribute to the development of many complex inflammatory diseases as Inflammatory Bowel Disease (IBD). Glycoprotein concentration as measured by nuclear magnetic resonance (NMR) spectroscopy has been proposed as a biomarker for monitoring activity of IBD, but has been also related to metabolic syndrome. Our goal is to further define the role of this new biomarker in IBD patients with MAFLD.

Methods

Prospective cohort study of consecutive IBD outpatients (Leonnard-Jones criteria, > 1 year) seen at reference centre, was performed from October 2020 to April 2021. Of 947 outpatients, 50 patients with IBD who met criteria for MAFLD and 50 patients with IBD and without MAFLD were matched by sex, age and IBD severity. Every IBD patient was also matched with 4 controls without IBD. Patients and controls with a previous diagnosis of CV disease, type II diabetes mellitus and under treatment for dyslipidaemia were excluded. Serum samples were analysed by NRM Spectroscopy with glycoprotein (Glyc-B, Glyc-F and Glyc-A) analysis by Biosfer Teslab, Spain. Demographic, clinical, biochemical and anthropomorphic variables were obtained prospectively in all cases. Wilcoxon Rank-sum test was used for comparison between groups with R (v 4.1.1).

Results

A total of 100 IBD patients and 400 controls were included. The median age were 51.0 (41–59) years old for each group. There were no differences in body mass index (BMI) between groups (26.4 (23.1–29.9) for IBD and 27.1 (24.4–30.4) for controls p=0.130). Regarding IBD patients, 49 (49%) had ulcerative colitis (UC) and 51(51%) Crohn’s disease (CD). Both IBD groups (with or without MAFLD) were well-matched excepting BMI as expected (table 1). Glycoprotein concentrations were significatively higher in IBD when compared to controls (table 2, p<0.001). In IBD patients with MAFLD glycoprotein concentrations were the highest (p<0.001) with no overlap with controls (table 3).

Conclusion

This prospective study confirms that glycoprotein concentrations can be a biomarker in IBD and for the first time suggests that it can be a very useful biomarker to identify MAFLD.
P227 High prevalence of mental health illness in IBD patients with high caregiver burden in the developing world: An analysis of risk factors from the IBD Emerging Nations Consortium (IBD-ENC)
Authors: Banerjee R , Pal P , Hilmi I , Rahman M , Aye T T , Joshi N , Ghoshal U , Alavinejad P , Peddi K , Mudigonda S
Published: January 2022

Background

Mental health is an important yet most neglected part of IBD care more so in developing countries.Left unaddressed, psychological factors can portend worse disease outcomes and poor quality of life. Caregiver burden including QOL and coping strategies have not been evaluated.

Methods

The study was conducted under IBD ENC (www.ibdenc.com). Consecutive IBD patients from 8 centers in 6 countries (Nepal, Bangladesh, India, Thailand, Myanmar, Malaysia, Iran) were enrolled after informed consent. For patients, a proforma including demographics, disease severity (Harvey Bradshaw Index: HBI- Crohn’s disease (CD), Simple Clinical Colitis Activity Index: SCCAI- Ulcerative Colitis), Morisky medication adherence scale (MMAS-8), Patient Health Questionnaire 9 (PHQ-9) for depression

Generalised anxiety disorder 7 (GAD7) for anxiety, Short inflammatory bowel disease questionnaire (SIBDQ) for quality of life (QOL) and IBD COPE was used. For caregivers the Zarit Burden Interview (ZBI), the Ferrans & Powers QOL index and Brief COPE survey were analysed.

Results

192 (age 14–79 yrs, median 33, 54% male) IBD patients and 168 (age 18–70, median-45, 41% male) caregivers were recruited. Depression and anxiety were noted in 72% and 67% patients respectively. On multivariate analysis, active disease was associated with increased risk of depression (p <0.001,OR-6.7,95%CI-2.8–16.3); Risk factors for anxiety were higher education (p=0.002, OR-2.17, 95% CI-1.32–3.55), married (p=0.001,OR-6.78, 95% CI- 2.27–20.26), comorbidities (p=0.022, OR- 3.9, 95% CI-1.22–13.12) and active disease (p<0.001, OR-14.2, 95% CI-4.8–41.5). Drug adherence was associated with lower risk of depression (p=0.001,OR-0.59, 95% CI: 0.43–0.87) and anxiety (p=0.002, OR-0.63, 95% CI- 0.47–0.84). Both Depression and anxiety scores (PHQ-9 and GAD-7) correlated negatively with QOL (SIBDQ) (r= —0.653, p<0.001;r=—0.653, p<0.001). but there was no significant association with good or bad coping scores (IBD COPE). Disease activity scores correlated positively with PHQ-9 (r=0.55, p<0.001,CD; r=0.52,p<0.001, UC) and GAD-7 (r=0.47, p<0.001, CD; r=0.36, p=0.001, UC).

66.7% of caregivers reported high care giver burden (ZBI score≥ 21) which correlated with poor QOL (r=—0.373, p<0.001). Higher occupational status was associated with lower care giver burden (p=0.028,OR-0.88, 95% CI-0.79–0.99). Positive reframing and self distraction were the most common adaptive and maladaptive coping strategies.

Conclusion

Depression and anxiety is highly prevalent in IBD patients in developing countries with high caregiver burden. Clinicians need to make assessment of psychiatric comorbidity in IBD patients a priority.
P240 Influence of Covid-19 infection in patients with inflamatory bowel disease with biological and no biological therapy
Authors: Herrador Paredes M , Fernández Cano M C , Sánchez Capilla A D , Martín Rodrírguez M D M , Cabello Tapia M J , Redondo Cerezo E
Published: January 2022

Background

Inflammatory bowel disease (IBD) patients undergoing treatments that act on the inmune system and present an increased risk of infections. For this reason, we could consider that these patients may have an increased risk of severe SARS-CoV-2 infection, however, it remains unclear. We aimed to analyze the cumulative incidence, the severity of the infection and its influence on the natural history of IBD in patients under biological treatment and also evaluating the possible differences with another group without these therapy.

Methods

Retrospective observational study about our IBD patients followed from March 2020 to January 2021 divided into two groups: patients on treatment with biological drugs (anti-TNF, vedolizumab, ustekinumab and tofacitinib) and patients without biological drugs (thiopurines or 5-ASA). We evaluated: the cumulative incidence in 10 months for COVID-19 in the 2 cohorts; clinical variables considered risk factors for the infection, the infection severity and influence on the course of IBD employing Harvey-Bradshaw index in Crohn′s disease and Mayo partial index in ulcerative colitis before and after infection.

Results

It collected 755 IBD patients. 89 were infected by SARS-COV-2, 43 in the biological group and 46 in non biological group. The cumulative incidence in 10 months was 10.85% in the first group (figure 1) and 12.81% in the second group with no significant differences. We verified comparability of the groups discarded the existence of statistical differences in all of the risk factors (sex, age, hypertension, diabetes, dyslipidemia, cardiovascular disease and BMI). In most cases, the infection was mild (94.4%) and the required treatment was symptomatic in 86.4% of the total (Figure 2), without significant differences between groups. Pneumonia was diagnosed in 5 patients, whose required hospital admission (3 belonged to the biological group and 2 to the other). The maximum respiratory support required was FIO2 36%, no patient required admission to ICU and there were no deaths. Additionally, the course of IBD was not affected because of COVID-19, considering no significant differences were observed in clinical scores in each group before and after infection, even taking into account 14 patients discontinued biological therapy temporarily during infection.

Conclusion

Our study suggests that IBD patients under biological therapy do not have an increased incidence of SARS-COV-2 infection and also do not have a higher risk of severe disease than IBD patients without this therapy. Furthermore, COVID-19 does not affect the natural history of IBD. These data go in the same direction as those published to date, however, we need multicentre registries with a larger sample size in the future
P246 Persistent burden of disease in patients with Crohn’s disease treated with biologic therapy: results from a real-world survey in the United States (US), France, Germany, Italy, Spain, and United Kingdom (5EU)
Authors: Sikirica M , Lynch J , Kershaw J , Lukanova R , Baker S , Milligan G
Published: January 2022

Background

Crohn’s disease (CD) requires life-long disease management. The study objective was to investigate the burden of CD in patients who have only partially responded to biologic therapy.

Methods

Data were drawn from two waves (Nov 2014-Mar 2015; Sep 2017-Jan 2018) of the Adelphi Inflammatory Bowel Disease (IBD) Disease Specific Programme™, a point-in-time survey of gastroenterologists (GEs) and their IBD patients, in the US, and 5EU. GEs completed a physician-reported questionnaire (PRF) for 5–10 consecutively consulting patients with CD, covering demographics, clinical characteristics, and health care resource use (HCRU). Same patients completed a voluntary patient-reported questionnaire (PSC) covering the Short IBD Questionnaire (SIBDQ), EuroQol 5-dimension (EQ-5D), and Work Productivity and Activity Impairment (WPAI) questionnaires. Crohn’s Disease Activity Index (CDAI) score, derived per patient from the PRF and PSC, was used to stratify patients into four groups by degree of disease activity (DA). Since clinical remission (CDAI <150) and moderate to severe (mod/sev) (≥221) are well known in clinical trials, we explored stratification in between, creating a ‘mild’ group (CDAI 150 - <180) and a ‘partial responder’ (PR) group (CDAI 180 - 220).

Outcomes were compared between DA groups using linear regression (or logistic for binary outcome) that included the potential confounding variables age, gender, body mass index (BMI), comorbidities (using Charlson Comorbidity Index), and severity at diagnosis. From each regression, least square (LS) means were generated for each DA group and pairwise Wald tests were conducted to compare pairs of DA groups. Base sizes varied due to the voluntary PSC element.

Results

319 GEs and 853 CD patients receiving a biologic for at least 12 weeks at data collection were included in the analysis (mean age 38.1 years, proportion of female patients 52.3%, 65.3% employed, mean BMI 24.1). CDAI groups are reported in Table 1.

Levels of pain, sleep disturbance and fatigue were significantly lower in patients in remission (Table 2).

SIBDQ, EQ-5D, and WPAI Health-Related Quality of Life (HrQoL) measures indicated significantly better outcomes amongst remission patients (Table 3).

HCRU in the past 12 months, in terms of hospitalisations and surgery rates, was significantly lower amongst remission patients (Table 4).

Conclusion

Patients in remission showed significantly better outcomes compared with mild, PR and mod/sev. Patient stratification by CDAI demonstrated that patients in remission may considerably benefit from fewer symptoms and improved HrQoL, even vs ‘mild’ patients. The latter had unaddressed symptoms, which may negatively impact their wellbeing.
P247 Comparison of discontinuation/switching between infliximab biosimilar and originator among Inflammatory Bowel Disease patients: a real-world analysis of two Canadian cohorts
Authors: Moura C S , Lukusa L , Wong E C , Lakatos P L , Afif W , Narula N , Bernatsky S
Published: January 2022

Background

Biosimilar infliximab (INF-B) has been approved in Canada for Inflammatory Bowel Disease (IBD) for over five years, but real-world descriptions of therapy persistence (discontinuation/switching) comparing INF-B to bio-originator (INF-O) are still scarce. Our objectives are to describe and compare therapy discontinuation/switching of INF-B and INF-O in IBD.

Methods

We used data from two IBD tertiary care clinics in Canada, in Montreal (QC) and Hamilton (ON). We studied biologic-naïve and biologic-experienced IBD adult initiating INF-B or INF-O between Jan. 2015 and Jul. 2020. We assessed time to discontinuation/switching through Kaplan-Meier curves (right-censoring due to loss to follow-up or end of the observation period). Reasons for discontinuation were assessed. Multivariable Cox regression models were performed to assess difference in time to discontinuation/switching between the two infliximab types. Model variables included age at infliximab initiation, sex, underlying condition (Ulcerative Colitis or Crohn’s Disease), disease duration, race/ethnicity, calendar year of infliximab start, current smoking, clinical centre, and previous use of other biologics, as well as previous/current use of corticosteroids, non-biologic immunosuppressants, budesonide, or 5-aminosalicylates.

Results

We studied 306 patients followed an average of 1.4 (standard deviation, SD=0.99) years. Patients were 46.7% female, with median age at infliximab initiation of 32 (interquartile range, IQR 21 to 47) years and median disease duration of 3.5 (IQR 0.9 to 11.7) years. Age, sex, and other baseline characteristics were comparable between the two groups, though there was a trend towards more INF-B initiation in recent years (Table 1). We identified 70 discontinuation/switching events; the main reasons for discontinuation/switching were adverse events (37.1%) and secondary loss of response (28.6%). The median time to discontinuation/switching was 4.1 (95% confidence interval, CI 3.4–5.5) years among INF-O and 3.0 (95% CI 2.2–3.5) years in the INF-B group. In the multivariate model, risk of the main outcome was not clearly different between the two groups (hazard ratio, HR 1.21, 95% CI 0.64–2.32 – Table 2). Older age and corticosteroids were significantly associated with discontinuation/switching of the initial infliximab therapy.

Conclusion

In this real-world analysis, we were unable to demonstrate differences in risk of discontinuation/switching among initiators of infliximab biosimilar or originator in IBD.