bluuebunny/crossref_metadata_2025 huggingface dataset:
P627 HLA DQA1*05 was not associated to primary non-response or loss of response to first anti-TNF in real world Inflammatory Bowel Disease patients.
Authors: Pascual Oliver A , Cuarán C , Casas-Deza D , García-López S , Corsino-Roche P , Sierra Moros E , Julián-Gomara A B , Vicente-Lidón R
Published: January 2023

Background

Biologics have been a breakthrough in the management of patients with inflammatory bowel disease (IBD). However, we lack predictors of response to these drugs. A recent study has shown a significant association between HLA DQA*105 mutations and the development of loss of response to anti-TNF mediated by immunogenicity. The high quality of the study and the wide differences found, have led to its quick practical implementation in the choice of biological agent. However, the supporting evidence is limited in clinical practice.

Methods

Retrospective cohort study, carried out at the Miguel Servet Hospital, Zaragoza, Spain. We included IBD patients who had received anti-TNF therapy as first biologic and whose HLA DQA1*05 had been determined. Primary non-response and secondary failure (assessed by survival analysis) has been evaluated as well as safety outcomes.

Results

199 IBD patients [161 (81%) Crohn′s disease (CD) 38 (19%) ulcerative colitis (UC)] were included. 42.4% had HLA DQA1*05 mutation and 60% received combination therapy with immunomodulators at the start of anti-TNF treatment. Median follow-up was 24 months (IQR 11-66). No statistically significant differences were found in primary non-response to anti-TNF (87,8% vs 12,2%, p = 0,825), depending on the presence or absence of HLA mutation. No differences in secondary loss of response according to HLA mutation in any of the analyses performed (full cohort, according to IBD or anti TNF type) were observed (Figure 1). Secondary loss of response has also been assessed according to the use or non-use of concomitant immunomodulator. Again, no differences were observed in this analysis (Figure 2). Multivariate analysis, like the univariate analyses, showed that the presence of the HLA-DQA1*05 mutation was not associated with a higher rate of secondary loss of response or shorter time to failure. In terms of safety, no significant differences were found in the rate of infusion reactions or serious adverse events between carrier and non-carrier patients.

Conclusion

In our real-life cohort of IBD patients treated for the first time with anti-TNF, the presence of the HLA-DQA1*05 mutation did not act as a predictor of response failure, either primary or secondary. The safety of anti-TNF treatment has also not been influenced by the mutation. More data is needed to incorporate HLA DQA1*05 determination into routine clinical practice as a key factor in individual decision making.
P641 Bowel Doppler Signal, the most important ultrasonographic feature in clinical practice in managing Inflammatory Bowel Diseases patients
Authors: Les A , Cotruta B , Iacob R , Saizu R , Gheorghe L , Gheorghe C
Published: January 2023

Background

IBD are chronic diseases that require multiple endoscopic and imaging assessments, being diseases that not only involve a multitude of medical resources but patient compliance too. Bowel ultrasound (BUS) is a useful imaging tool in monitoring inflammatory bowel diseases (IBD) patients. Current guidelines recommend BUS altogether with other cross-sectional imaging methods to diagnose, monitor IBD patients and also for detecting complications and post-surgery recurrence. A multitude of ultrasonographic features are used to describe pathologic findings related to IBD but not all of them are easy to integrate in clinical practice, especially in unexperienced hands.

Methods

Our study included 117 IBD patients of which 28 were diagnosed with ulcerative colitis and 89 with Crohn’s disease. Diagnosis was established endoscopically and histologically and both patients with active and inactive disease were included. Exclusion criteria consisted in patients with other causes of inflammatory syndrome, patients with solely rectal localization of the disease or a surgical history. Subjects were prospectively evaluated using BUS and several sonographic aspects of the bowel wall were monitored: bowel wall thickness, bowel echo pattern, Doppler signal (DS) presence, hypertrophic mesenteric fat, and the presence of lymph nodes. Biological markers of inflammation were obtained including faecal calprotectin. Patients were followed up for the next 6 months and data regarding treatment intensification was noted. All patients signed an informed consent, and the study was approved by the Ethics Committee of the Fundeni Clinical Institute.

Results

Significantly higher values of clinical and biological markers were associated with the presence of parietal DS (p<0.0001) suggesting that this BUS feature is an important bowel wall inflammation surrogate. Higher Limberg scores (a subjective Doppler signal score used in BUS) correlated with increased values of biological markers of inflammation (p=0.002). A multivariate analysis showed that DS and a thicker than 5 mm bowel wall were independent predictors of step-up therapy. The presence of parietal DS raised the patient risk of switching therapy 7.6 times, while bowel wall thickness only 2.4 times, making DS the most useful BUS feature in evaluating inflammatory activity and predicting the need for step-up therapy.

Conclusion

DS is one of the most important BUS features to use in evaluating and monitoring IBD patients and could have a role in disease decision making. This finding should advocate for this imaging method in clinical practice, and even low BUS-experience practitioners are encouraged to use it.
P644 Leucine-rich alpha 2 glycoprotein- A useful biomarker to discriminate small intestinal mucosal healing in asymptomatic CRP-negative Crohn’s disease
Authors: Tanaka A , Kanmura S , Maeda N , Kuwazuru K , Komaki F , Komaki Y , Ido A
Published: January 2023

Background

The long-term treatment goals for inflammatory bowel disease including Crohn’s disease (CD) have shifted from clinical remission to mucosal healing. However, frequent endoscopies are a great burden on the patients. Leucine-rich alpha 2 glycoprotein (LRG) is produced by hepatocytes, neutrophils, and the intestinal epithelium. Therefore, it is speculated to be more gut-specific than C-reactive protein (CRP) level. This study examined whether LRG could be used as a biomarker to determine the presence or absence of small intestinal mucosal healing in asymptomatic patients with CRP-negative CD.

Methods

The subjects of this study were asymptomatic CRP-negative CD patients who visited our department from May 2021 to October 2022, had their LRG measured, and underwent imaging evaluation by capsule endoscopy or balloon-assisted endoscopy. We analysed the patients’ clinical background, the ROC-AUC of LRG for mucosal healing, the cut-off value of LRG to discriminate mucosal healing. Endoscopic evaluation was performed within 3 months before and after the LRG measurement. Mucosal healing was defined as the absence of open ulcers. Clinical remission (no subjective symptoms) was defined as a Harvey-Bradshaw index (HBI) ≤4 points. The upper limit of the normal CRP value was set to <3 mg/L.

Results

A total of 28 cases were analysed; 13 (46%) were men. The median age (range) of onset was 21.2 years (7-52 years). The median disease duration (range) was 6.4 years (0-27). B1 was established in 13 (45%) cases, B2 in 7 (25%) cases and B3 of Montreal Classification in 8 (29%) cases. The median (range) of the HBI score was 2 (0-4). The median (range) of LRG was 12.3 g/ml (7.6-20.5 μg/ml). The ROC-AUC of LRG for mucosal healing was 0.743 (95% confidence interval 0.559-0.927). The cut-off value of LRG for discriminating mucosal healing was 12.2 μg/ml (sensitivity 0.769, specificity 0.682).

Conclusion

In asymptomatic CRP-negative CD patients, when LRG was 12.2 μg/ml or more, it was suggested that they might have small intestinal ulcers.
P648 Effectiveness of Biologic Therapies in Decreasing Risk of Hospitalization and Surgery, Maintaining Steroid Free Remission and Achieving Mucosal Healing in Inflammatory Bowel Disease; Real World Data.
Authors: Shehab M , Abdullah I , Alostad W , Marei A , Alfadhli A
Published: January 2023

Background

Several biologic therapies are currently available for the management of inflammatory bowel disease (IBD) rendering the choice and sequencing between them as a first line under question. In our study, we evaluated the effectiveness of biologic therapies in achieving important clinical and endoscopic outcomes in biologic naïve patients with IBD.

Methods

Electronic medical records of patients with moderate to severe IBD, who were previously naïve to biologics, were reviewed and evaluated retrospectively in a tertiary care gastroenterology center, Haya Alhabib Center. Patients who were on infliximab, adalimumab, ustekinumab and vedolizumab for 12 months were included. The primary end points were percentage of hospitalization, surgery, steroid free remission, and mucosal healing, defined as Mayo score less than 1 in ulcerative colitis and SES-CD score less than 3 in Crohn’s disease. Descriptive analysis was performed to measure outcomes.

Results

A total of 335 biologic naïve patients with IBD were included; 262 (78.2%) patients with ulcerative colitis and 73 (21.8%) patients with Crohn’s disease. Regarding hospitalization, 25 (14.7%) out of 170 on adalimumab,12 (10.7%) out of 112 on infliximab, and one (6.25%) on vedolizumab were hospitalized. None of the patients on ustekinumab were hospitalized. 9 out of 171 (4.7%) patients on adalimumab underwent surgery, while none of the patients on the other biologics underwent IBD related surgery. Regarding steroid free remission, 29 (16.9%) out of 171 patients on adalimumab received steroid courses, 15 (13.3%) out of 113 patients on infliximab, 4 (11.4%) out of 35 patients on ustekinumab, and 1 (6.3%) out of 16 patients on vedolizumab. A total of 159 out of 171 patients (93.0%) on adalimumab achieved mucosal healing. While 100 out of 113 patients (88.5%) on infliximab, 26 out of 35 patients (74.3%) on ustekinumab, and 7 out of 16 patients (43.8%) on vedolizumab achieved mucosal healing.

Conclusion

Adalimumab, infliximab, and ustekinumab and vedolizumab were all effective in inducing steroid free remission. However, patients on vedolizumab had numerically lower percentages of mucosal healing than other biologics. Percentage of hospitalizations and IBD related surgeries were higher in patients on infliximab and adalimumab. Future Larger prospective comparative studies are needed.
P650 Integrin expression patterns of patients with IBD treated with vedolizumab.
Authors: Kokkotis G , Chalakatevaki K , Papathanasiou E , Tzanoudaki M , Kane R , Liatsis M , Zampeli E , Michopoulos S , Bamias G
Published: January 2023

Background

Anti-α4β7 integrin monoclinic antibody vedolizumab is an effective treatment for moderate and severe Ulcerative Colitis and Crohn’s Disease. Occasionally vedolizumab-treated patients experience articular extraintestinal manifestations, in the form of arthralgias, which could be attributed to lymphocyte tracking modification caused by vedolizumab. This study aims to describe α4β7 andα4β1 integrin expression on circulating lymphocytes and the effect of vedolizumab on integrin expression, as well asto identify expression patterns associated with arthralgias under vedolizumab.

Methods

A cross-sectional study was conducted. Peripheral blood was collected in EDTA-coated bottles before a scheduled drug administration. Expression of α4β7 and α4β1 integrins on CD4+T, CD8+T, B and plasma cells was studied by flow cytometry (DX Flex, BC), using CD3, CD4, CD8, CD19,CD138, CD49d (α4), β7, CD29 (β1). Kaluza C software and SPSS23 were used for analysis.

Results

In total, 40 IBD patients (16 of them treated withvedolizumab) and 8 healthy controls were included. There was a higher percentage of α4β1expressing lymphocytes compared to α4β7+ ones (P<0.001) (figure 1).

Vedolizumab-treated patients had lower percentages of integrin-expressing B cells (α4β7 P=0.001 vs controls, α4β7 P=0.052 vs non-vedolizumab IBD, α4β1 P=0.002 vs controls, α4β1 P=0.015 vs non-vedolizumab IBD) and α4β1 plasma cells (P=0.013 vs non-vedolizumab IBD) (figure 2).

In patients treated with vedolizumab with arthralgias, α4β7 expression on B-cells was more suppressed, whereas α4β1 expression on plasma cells was less suppressed, compared to those that had not developed arthralgias, but not in a statistically significant level (figure 3).

Conclusion

Patients treated with vedolizumab presented different patterns of integrin expression on circulating B cells. Manifestation of arthralgias under vedolizumab may be associated with a disruption of α4β7/α4β1 proportion.

Funding: This study was funded through a research grant from the Greek IBD study group (EOMIFNE) to G.B. EOMIFNE Grant: 2020EOMIFNEp1
P652 Therapeutic drug monitoring during induction therapy with Ustekinumab in patients with Crohn’s disease: the key to early identification of patients with inadequate response.
Authors: Mínguez A , Bastida G , Terol I , Argumánez V , Iborra M , Aguas M , Moret I , Cerrillo E , Garrido A , Tortosa L , Nos P
Published: January 2023

Background

Ustekinumab (UST), an inhibitor of the p40 subunit of interleukins 12 and 23, is approved for the treatment of moderate and severe Crohn disease (CD) but a significant number of patients either partially respond or do not benefit at all. Therapeutic drug monitoring can be used to optimize the efficacy of biological drugs by ensuring adequate exposure to these drugs.

The aim of our research was to identify the relationship between serum concentrations of UST during the induction and biochemical remission at week 16 in patients with CD.

Methods

All CD patients treated with UST included in a local database were identified. Only patients with a fecal calprotectin (FCP) > 250 mg/g were selected. All patients were treated with an initial intravenous induction therapy of UST, followed by subcutaneous maintenance therapy. Disease activity was assessed retrospectively by clinical (Harvey–Bradshaw Index [HBI]) and biochemical parameters (FCP; C-reactive protein (CRP) and Albumin) at Week 0, Week 4, week 8 and week 16. UST trough levels were measured at 4, 8 and 16 weeks using a commercially available validated enzyme-linked immunosorbent assay (ELISA).

Main outcome was biochemical remission, defined by a decreased of calprotectin levels more than 80% or an absolute value less than 200 mg/g at week 16.

Results

Seventy-six patients were included. Patients’ Characteristics at baseline are listed in table 1. Median [IQR] HBI was 5,5 [3-8] at the beginning of treatment. Evolution of biochemical parameters throughout induction is showed in table 2. At the end of the induction phase (week 16), HBI, CRP and FCP decreased significantly from baseline. At this moment HBI was less than 2 in 51% of patients. FCP was available in 63 patients. Biochemical remission was observed in 26/63 (41,3%) patients. Median [IQR] UST serum concentrations were 20,9 μg/mL [13,7–26,3] at w4, 10,1 μg/mL [3,5–7,4] at w8 and 4,1 μg/mL [1,4–3,9] at w16. Quartile analysis demonstrated that 100% and 66% with an UST serum concentration in the highest quartile [Q4], at w4 and w8, achieved a biochemical remission by w16 [p = 0.05 and p <0,02 respectively]. The area under the receiving operating characteristic curve (AUROC) of UST levels to predict biochemical remission at week 4 and week 8 were 0,84 CI95% (0,62-1) and 0,74 CI95% (0,57-0,91) respectively.

Conclusion

Serum concentrations of UST at week 4 and 8 after intravenous infusion could be used to stratify patients according to the probability of achieving remission. This measurements during induction could be used to optimize treatment of CD.
P653 Tight control and Treat to target increase the rates of Transmural remission and Transmural response in Crohn’s disease
Authors: Fernandes S R , Bernardo S , Rita Gonçalves A , Moura dos Santos P , Valente A , Tato Marinho R , Correia L
Published: January 2023

Background

increasing evidence support the use of Transmural remission as a treatment target in Crohn’s disease (CD) but few patients can reach it with currently available therapies. Treat-To-Target (T2T) and Tight-Control (TC) strategies may potentially improve these results.

Methods

Methods: single-center retrospective study including 123 CD patients with active colonoscopy (CN) and magnetic resonance enterography (MRE) at baseline and with available follow-up CN and MRE for reassessment of remission. We evaluated the effects of T2T and TC strategies on the rates of Transmural remission and Transmural response. Patient submitted to bowel surgery between examinations were excluded.

Definitions

CN activity: ulcers in non-operated patients or Rutgeerts score> i1 in operated patients; MRE activity: bowel thickness >3 mm and enhancement on T1/T2 sequences. Transmural remission: inactive CN and MRE at reassessment; Transmural response: improvement from baseline in either examination. T2T: treatment decisions resulting in both clinical remission (Harvey-Bradshaw <5) and fecal calprotectin remission (Fc <250 ug/g) at reassessment. TC: treatment decisions resulting in persistent Fc remission (≥ 2 consecutive results, including reassessment).

Results

48.0% and 42.3% of patients followed a T2T and TC strategy, respectively. Transmural remission and Transmural response were reached by 33.3% and 69.1% of patients, respectively. T2T resulted in higher rates of Transmural remission (55.9% vs 12.5%, P<0.001) and Transmural response (91.5% vs 48.4%, P<0.001). TC was also associated with higher rates of Transmural remission (51.9% vs 19.7%, P<0.001) and Transmural response (90.4% vs 53.5%, P<0.001). In multivariate regression, T2T (OR 9.30 95%CI 2.85-30.30, P<0.001), TC (OR 3.85 95%CI 1.18-12.54, P=0.025) and starting biologic treatment (OR 3.63 95%CI 1.36-9.70, P=0.010) were independent predictors of reaching Transmural response. T2T was the only independent predictor of reaching Transmural remission (OR 6.540 95%CI 2.41-17.74, P<0.001).

Conclusion

Patients following a T2T and TC strategy presented higher rates of Transmural remission and Transmural response.
P657 Current landscape of the real-world utilization of Interleukins 22, 23 and Interleukin 22 binding protein as biomarkers for Inflammatory Bowel Disease (IBD): A targeted literature review
Authors: Dolin P , Evans K , Castañeda J , Udayachalerm S , Cabrera C
Published: January 2023

Background

Precision medicine is an active area of IBD research. Evidence underpinning the role of IL-22, IL-23, and IL-22 binding protein (BP) as biomarkers of mechanistic pathways, diagnosis, disease severity, and treatment response has been accumulating. Little is known about the applications of these ILs as biomarkers in real-world studies. The aim of this literature review was to describe the current landscape of assessing IL-22, IL-23 and IL-22BP in real-world studies.

Methods

A search was undertaken in MEDLINE and Embase to identify English-language manuscripts (2018-2021) and conference abstracts (2019-2021) of real-world studies in adult IBD, measuring IL-22, IL-23, or IL-22BP. One reviewer screened titles/abstracts for eligibility using a standardized form. A second reviewer independently screened a random sample of publications and disagreements were resolved by a third reviewer.

Results

Titles and abstracts of 369 studies were screened. Forty-two studies met the eligibility criteria and were included for full-text screening. Seventeen studies were then excluded because they lacked key information such as the study design or the clinical application. A total of 25 studies were included. Of those, three were conference abstracts. Nine (36%), eight (32%), and eight (32%) studies included patients with CD only, UC only, and both CD and UC with/without their comparison groups, respectively. Eleven studies (44%) were conducted in Europe, 10 (40%) in Asia, two (8%) in North America, and one (4%) each in Africa and the Middle East.

Twelve (48.0%) studies reported on IL-23, 11 (44.0%) on IL-22 and one (4.0%) on IL-22BP. Most publications reported on more than one IL with multiple applications. Eight (28%) studies examined diagnostic applications, 11 (38%) prediction of severity, and 10 (34%) prediction of treatment response. Multiple sampling sources were used, including tissue (38%), serum (34%), cell (16%), blood(9%), and plasma (3%). IL-23 levels were consistently correlated with IBD severity when comparing IBD with healthy controls, but the data was less consistent for IL-23 as a diagnostic test or predictor of treatment response. The reported correlations for IL-22 and IL-22BP varied across studies. This was potentially due to heterogeneous study methodologies.

Conclusion

This literature review shows that IL-22, IL-22BP and IL-23 have been studied in the real world for diagnosis, prediction of disease severity, and treatment response in IBD; however, there was heterogeneity in methodologies, ethnic composition, and sample types across studies. The correlation of IL-22 level with the studied outcomes was qualitatively inconsistent across studies and applications, whereas IL-23 was found to be consistently associated with IBD severity.
P662 Pre-treatment vitamin D concentrations do not predict therapeutic outcome to anti-TNF therapies in biologic-naïve patients with active luminal Crohn’s disease
Authors: Lin S , Chanchlani N , Smith R , Roberts C , Nice R , McDonald T J , Hamilton B , Bewshea C , Kennedy N A , Goodhand J R , Ahmad T ,   PANTS consortium
Published: January 2023

Background

Vitamin D has a regulatory role in innate and adaptive immune processes. Previous small studies have reported that low pre-treatment vitamin D concentrations are associated with primary non-response and shorter drug persistence to anti-TNF therapy. We sought to assess whether pre-treatment 25-hydroxyvitamin D concentrations predicted primary non-response and non-remission to infliximab and adalimumab in patients with Crohn’s disease recruited to the PANTS (Personalised Anti-TNF Therapy in Crohn’s disease) study.

Methods

We used composite endpoints using the Harvey Bradshaw Index (HBI) in adults and the short paediatric Crohn’s disease activity index (sPCDAI) in children, corticosteroid use, and C-reactive protein (CRP) to define primary non-response (Figure 1). Remission was defined as CRP of ≤3 mg/L and HBI of ≤4 points (short paediatric Crohn’s disease activity index ≤15 in children), without corticosteroid therapy or exit for treatment failure. 25-hydroxyvitamin D concentrations were measured in stored baseline serum samples and cut-offs for vitamin D status were: deficiency < 25nmol/L, insufficiency 25-50nmol/L and adequacy/sufficiency > 50nmol/L.

Results

Samples from 659/898 infliximab (526 Remicade; 133 biosimilar CT-P13) and 448/605 adalimumab (448 Humira) treated patients included in the effectiveness analysis of the PANTS study were included. Overall, 17.1% (189/1107; 95% confidence interval [CI] 15.0 - 19.4%) and 47.7% (528/1107; 95% CI 44.8 - 50.6%) patients had vitamin D deficiency and insufficiency, respectively. At baseline, 22.2% (246/1107) patients were receiving some form of vitamin D supplementation.

Multivariable linear regression analysis confirmed that baseline sampling during non-summer months (Figure 2), South Asian ethnicity, lower serum albumin concentrations, higher HBI and nontreatment with vitamin D supplements were independently associated with lower vitamin D concentrations (Figure 3).

Primary non-response at week 14 and non-remission at week 54 occurred in 19.3% (116/600; 95% CI 16.4 - 22.7%) and 58.8% (351/597; 95% CI 54.8- 62.7%) patients treated with infliximab and 25.3% (100/396; 95% CI 21.2- 29.8%) and 65.3% (246/377; 95% CI 60.3- 69.9%) of patients treated with adalimumab, respectively.

Pre-treatment vitamin D status did not predict response or remission status to anti-TNF therapy at week 14 (infliximab Ppnr = 0.87, adalimumab Ppnr = 0.18) or non-remission at week 54 (infliximab P = 0.12, adalimumab P = 0.59) (Figure 4).

Conclusion

Vitamin D deficiency is common in patients with active Crohn’s disease. Unlike previous studies, pre-treatment serum 25-hydroxyvitamin D concentration did not predict primary non-response to anti-TNF treatment at week 14 or non-remission at week 54.
P665 Social Media Listening to better Understand the Lived Experience of Individuals With Ulcerative Colitis
Authors: Auriat O , Lucats L , Badalamenti S , Kruger A , Wiekowski M , Glotfelty L , Van Hoogstraten H , Coulouvrat C
Published: January 2023

Background

Lived experience is a depiction of a person’s experiences and decisions, as well as the knowledge gained from these experiences and choices. Despite a wealth of clinical studies and real-world data on ulcerative colitis, large-scale and comprehensive insights into the lived experience are lacking. This study aimed to explore how the lived experience of UC is described on social media.

Methods

All English-language posts from the UC open-access forums of Reddit.com, Inspire.com and Everyday Health.com were extracted and anonymized with Synthesio. Concept occurrence and sentiment analysis were performed using Luminoso, a natural language processing (NLP) platform. NLP is the ability of a computer program to interpret human language as it is spoken and written.

Results

A total of 29,250 comments posted between July 01, 2018 and January 01, 2021 were extracted and analyzed. The first 40 concepts were manually reviewed to remove the synonyms of UC and high level health-related concepts (e.g., illness, doctor, treat…) and several concepts were manually merged (eg, stomach and gut). The most common topic expressed in the posts was feeling (n=4,749, 16%), two thirds reporting negative sentiment (68%). Symptom analysis revealed the highest occurrence in pain (n = 4,085, 14%), rectal bleeding (n = 3,385, 12%), toilet frequency (n = 2,003, 7%) and fatigue (n = 626, 2%). These symptoms were associated with negative sentiments (58% to 89%). Among pain, a quarter of the posts were related to stomach or intestinal pain (n = 1,097, 27%). Further sub-concept analysis related to pain revealed topics on pain related to disease flare (n = 711, 17%), joint pain (n = 394, 10%) and bone pain (n = 124, 3%). Notably, patients did not post frequently about their medication (<1%), but surgery was mentioned in 1,494 posts (5%). Sentiment analysis again outlined the dominance of negative feelings whether the comment was related to fear of this definitive procedure or to life post-surgery. Lastly, anxiety (n = 1,019, 3%) and concerns about sleep (n = 857, 3%) were less frequently identified, but still meaningful, concepts.

Conclusion

NLP analysis of posts on UC in unmonitored social media forums demonstrates that patients are firstly concerned by pain and its impact that is strikingly not part of the Mayo score and not routinely assessed in large clinical trials. While social media-based retrospective data collection inherently limits the amount of demographic or clinical description, social media listening studies offer the potential to sample spontaneous patient concerns from large numbers of individuals. Analysis of these data may lead to the development of patient-centered endpoints to be incorporated into clinical studies in the future.
P666 Effect of anastomotic configuration on Crohn’s Disease recurrence after primary ileocolic resection. A comparative monocentric study of end-to-end versus side-to-side anastomosis.
Authors: Bislenghi G , Vancoillie P J , Fieuws S , Verstockt B , Sabino J , Wolthuis A , D'Hoore A
Published: January 2023

Background

There is an ongoing debate whether the type of anastomosis following intestinal resection for Crohn’s disease (CD) can have an impact on complications and postoperative recurrence. The aim of the present study is to describe the outcome of side-to-side (S-S) versus end-to-end (E-E) anastomosis after ileocolic resection for CD.

Methods

A retrospective single center comparative study was conducted in consecutive CD patients who underwent primary ileocecal resection between 2005 and 2013. All patients underwent colonoscopy 6-months postoperatively to assess endoscopic recurrence, defined as modified Rutgeerts’ score >i2b. Surgical recurrence implied reoperation due to CD activity at the anastomotic site. Modified surgical recurrences was defined as the need for re-operation or balloon-dilation. Perioperative factors related to recurrence were evaluated.

Results

Of the128 patients included, 52 (40.6%) received an E-E anastomosis. Median follow-up was longer in the E-E group (8.62 vs 13.68 years, p<0.001). Apart from the primary anastomosis, patient, disease and surgical characteristics were similar between both groups. Postoperative complications and anastomotic leak were comparable (S-S 6.6% vs E-E 7.7%, p=1.00). During the entire postoperative follow-up, biologicals were used in 55.3% and 63.5% (p=0.37) in S-S and E-E patients, respectively. Endoscopic recurrence did not differ between S-S and E-E patients (40.8% vs 49.0%, p=0.37). However, at ten years follow-up, surgical and modified surgical recurrence rate were significantly higher in the E-E group (19.7% vs 7.4%, p=0.02 and 39.2% vs 14.1%, p=0.001). Type of anastomosis was the only independent risk factor for surgical and modified surgical recurrence.

Conclusion

The type of anastomosis did not influence endoscopic recurrence and immediate postoperative disease complications. However, the wide diameter and the morphologic characteristic of the stapled S-S anastomosis result in a lower risk for balloon dilatation and surgical reintervention in the long-term.
P673 The safety of rapid versus standard infliximab infusions in children with inflammatory bowel disease: a multi-centre retrospective cohort study
Authors: Jagt J , Galestin S , Benninga M , de Boer N , de Meij T
Published: January 2023

Background

Rapid infliximab (IFX) infusions have shown to be safe in adults with inflammatory bowel disease (IBD), but data on its safety in paediatric IBD is limited. This study aimed to assess the frequency and timing of infusion reactions (IR) in children with IBD who received rapid (1-h) vs. standard (2-h) IFX infusions.

Methods

This retrospective cohort study included IBD patients 4-18 years old, treated with IFX between January 2006 - November 2021 at two tertiary centres (AMC and VUmc) in Amsterdam, the Netherlands. The AMC protocol was adjusted from standard to rapid infusions with a 1-h post-infusion observation period in July 2019, whereas in VUmc only standard infusions were administered without a post-infusion observation period. After merging both departments in 2022, VUmc patients were allocated from standard to rapid infusions. The primary outcome was the frequency of acute IR amongst rapid vs. standard infusions. Secondary outcomes were the timing, severity and management of IR.

Results

Totally, 297 (150 VUmc, 147 AMC) patients (221 Crohn’s disease; 65 ulcerative colitis; 11 IBD-unclassified) were included, with a total of 7500 maintenance IFX-infusions. No differences were found in the frequency of IR between the patients receiving standard infusions (16/115, 13.9% of patients), rapid infusions (1/31, 3.2%) and both infusion rates (11/151, 7.3%) (p= 0.105). No difference in the frequency of IR was found between standard infusions (26/4383, 0.6% of infusions) and rapid infusions (9/3117, 0.3%) (p= 0.083). Twenty-six of 35 IR (74.3%) occurred during infusion, while nine occurred post-infusion (25.7%). All post-infusion IR were mild, requiring no intervention or oral medication.

Conclusion

Rapid IFX infusions did not result in an increased frequency of IR compared to standard infusions. The IR that occurred post-infusion were mild. Our data have resulted in adjustment of the protocol to rapid infusion without a post-infusion observation period for all IFX patients.
P676 Intestinal ultrasound accurately predicts therapy failure in Crohn's disease patients during a biologics-induced remission
Authors: Albshesh A , Abend A , Margalit Yehuda R , Mahajna H , Ben-Horin S , Kopylov U , Carter D
Published: January 2023

Background

Intestinal Ultrasound (IUS) is a non-invasive modality that can assess disease activity, complications, and treatment follow-up in Crohn's disease (CD) patients. IUS is reliable, patient-friendly, and allows frequent monitoring of disease activity. While 3mm bowel wall thickness (BWT) was repeatedly found to correlate with intestinal inflammation, whether this threshold also best predicts clinically relevant future outcomes is still largely unknown.

We aim to investigate the role of IUS to predict the risk of therapy failure in biologics-treated CD patients in clinical remission.

Methods

Our analysis included a retrospective cohort of CD patients in clinical remission (HBI≤4) induces by biologic drugs, who underwent IUS 12 (±2) months after induction. We examined the correlation of IUS activity parameters with future therapy failure (defined as drug discontinuation, dose escalation, new corticosteroid use, CD-related hospitalization, or surgery).

Results

A total of 57 patients (58% male), with ileal (65%) or ileocolonic (35%) CD, on biological therapy (28% infliximab, 51% adalimumab, 10.5% vedolizumab, 10.5% ustekinumab) were included. Therapy failure occurred in 54.3% (32.2% drug discontinuation, 45.2% dose escalation, 16.2% corticosteroid use and 6.4% hospitalization) during a median follow-up of 12 (IQR 5-22) months after IUS. Of all IUS parameters examined, therapy failure was associated only with increased BWT; BWT > 5mm (hazard ratio (HR) 2.3 [confidence interval (CI) 1.03-5.3], p= 0.041). Interestingly, there was risk plateauing with increased BWT above this cutoff (>5.5 mm (HR 2.2 [CI 1-5.10], p=0.048); >6mm (HR 2.6 [CI 1.17-6.12], p=0.019); >6.5 mm (HR 2.5 [CI 1.08-5.83], p=0.032)) (Figure 1). A BWT cutoff of 3mm could not discriminate patients with future treatment failure.

Conclusion

Our findings suggest that BWT of > 5 mm during clinical remission can predict subsequent treatment failure in CD patients treated with biologics. Our results support the use of IUS in monitoring CD during remission, and may point to a novel threshold predicting disease reactivation.
P677 Combination of vedolizumab and exclusive enteral nutrition in patients with moderate to severe Crohn’s Disease
Authors: Kang J , Wang J , Lu Y , Li J , Su J , Ying A , Ren H , Zhou Q , Wang Y , Ding Y , An P
Published: January 2023

Background

Crohn’s disease (CD) is an incurable chronic inflammatory condition of the gut. It causes severe gastrointestinal and extraintestinal complications and is associated with high morbidity, poor quality of life and increased health expenditure. Although increasing randomized controlled tests (RCT) studies demonstrated the premise of efficacy of biologics including vedolizumab in adult patients with active CD, there’re still 60% of patients hard to achieve clinical and endoscopic remission in real-world studies. Here, we investigated the efficacy of combination strategy of vedolizumab and exclusive enteral nutrition (EEN) in moderate to severe active CD treatment.

Methods

Twenty-eight patients with moderately to severely active CD patients treated with vedolizumab in IBD medical center of Renmin Hospital of Wuhan University in Hubei Province were retrospectively enrolled in this cohort. All patients received EEN for 16 weeks with concomitant vedolizumab standard induction. The clinical response, clinical remission, and fecal calprotectin (FC) normalization was evaluated in short- (week 16) and moderate-term (week 32 and 48). Endoscopic response and mucosal healing were assessed at week 16 and 48 (Figure 1).

Figure 1: Study design

Results

Following vedolizumab intravenous induction and 16-weeks EEN treatment, patients achieved 71.4% (20/28) of clinical remission, 73.1% (19/26) of endoscopic response and 71.4% (20/28) FC normalization at week 16. For moderate-term assessment at week 32, sustainable efficacy of current treatment induced 19/24 (79.2%) of clinical response, 15/24 (62.5%) of clinical remission and 16/24 (66.7%) of FC normalization. Clinical response (15/22, 68.2%) and mucosa healing (14/22, 63.6%) were also observed in over 60% of patients at week 48 since treatment induction (Figure 2,3).

Figure 2. Clinical and biochemical endpoints

Figure 3. Endoscopic endpoint

Conclusion

Combination of Vedolizumab and 16-weeks EEN increased clinical and endoscopic outcomes in short and moderate term for patients with moderate to severe Crohn’s Disease.
P679 Is the burden of obesity in IBD bigger than just weight?
Authors: Madigan S , Mountifield R , Barnes A ,   M
Published: January 2023

Background

In the past IBD has been thought to cause low body weight however current estimates show that 15-40% of those with IBD are obese. Obesity is a pro-inflammatory state and has been linked to disease processes such as psoriasis and rheumatoid arthritis. There is some limited data to suggest that obesity also affects disease activity in IBD. In addition, medical therapy for IBD such as corticosteroids and TNF-alpha inhibitors are associated with weight gain. The aim was to determine the relationship between obesity and IBD disease severity. And also to determine the relationship between obesity, depression, anxiety and QoL in those with IBD.

Methods

As part of the IBD-SLEEP study a survey was emailed to patients via tertiary hospital IBD unit email lists, private gastroenterology group email lists and advertised online. IBD activity was assessed using the Harvey Bradshaw Index and the Simple Crohn’s Colitis index as appropriate. The survey included measures of clinically significant depression (PHQ9>10) and anxiety (GAD7>10), as well as disability (IBD-DI reduced form) and quality of life (EQ-5D-5L).

Results

They were 585 responses with mean age of 42 years (SD 13). The majority were female (80%) and had Crohn’s disease (61%). Mean weight of cohort was 79.2kg (SD 20), mean BMI was 28 (SD 7), with 61% overweight (BMI > 25), and 38% obese (BMI>30). People with obesity were more likely to have active disease (HBI or SCCAI > 5) in those with Crohn’ disease (OR 2.39 (1.47-3.89), p<0.001) but not ulcerative colitis (OR 1.26 (0.68-2.31), p=0.46). Obese patients were also found to have higher levels of disability (IBD-DI reduced form, p<0.001) and lower quality of life (EQVAS, p<0.001). Interestingly there was an association between obesity and depression (PHQ9>10, OR 2.06 (1.42-2.99), p<0.001) but not obesity and anxiety (GAD7>10, OR 1.03, (0.74-1.45), p=0.16).

Conclusion

Obesity is not only a risk factor for metabolic disease but is also associated with active IBD in those with Crohn’s disease. Obesity was also associated with clinically significant depression, increased disability, and lower quality of life. Although causation is not established, consideration should be given to more aggressive management of obesity in an IBD outpatient setting.
P683 Risk factors for fatigue in IBD patients.
Authors: Sina M , Djegsi A , Pemaj X , Telaku* S , Babameto A , Prifti S
Published: January 2023

Background

Fatigue is a common symptom, in IBD patients, ranging from 40% to 86% in patients with active disease, and 20% to 48% in those in remission. The aim was to determine the degree of fatigue and to identify possible factors associated to its presence in our patients.

Methods

Consecutive patients presented at our outpatient IBD clinic from 2021 to 2022 were included. Demographic data, disease activity scores, endoscopic scores, disease duration, localization, hospitalization, laboratory data, were collected for each patient. Working status was determined on the patient’s actual ability to work. Total Mayo score (TMS) and Crohn’s disease activity index (CDAI) were used to assess disease activity in patients with ulcerative colitis (UC) and Crohn’s disease (CD) respectively. Clinical remission was defined as TMS ≤ 2 points, or CDAI < 150 points. Presence of inflammation was defined C-reactive protein ≥ 5.1 mg/L. Presence of anxiety and depression was evaluated using Hospital Anxiety and Depression Scale HADS and fatigue was assessed with self-administered questionnaire IBD Fatigue Rating Scale (FRS). Based on FRS, 2 groups of patients were created: group A with slight to moderate fatigue (1-60 points) and group B patients with severe fatigue (61-120 points).

Results

A total of 48 IBD patients were included; mean age was 40.9±16.0 years, 60.4% females; 89.6% UC. Mean disease duration was 5±4.6 years. Of UC patients, 44.2% were in clinical remission, 16.3% had mild disease, 30.2% moderate disease, and 9.3% severe disease. Of CD patients, 40% were in clinical remission and 60% had active disease.

Severe fatigue was found in 8/48 (16.7%) of patients, and was significantly higher in those with active disease (p=0.039), presence of inflammation (p=0.018), and anxiety (p=0.059). Mean fatigue score was 35.4±22.4 points with no statistical difference between CD and UC (p=0.404). Higher fatigue scores were observed among patients with presence of active disease (p=0.036); among patients with higher TMS scores (p = 0.022); in patients with anxiety (p=0.01), and in patients with depression (p=0.004).

On multiple linear regression, only vitamin D levels and working status were associated with fatigue severity (p= 0.052; p= 0.049, respectively R2 =0.062).

Conclusion

Our study findings confirm that the most important factors associated with fatigue during IBD course, are disease activity, presence of inflammation, presence of anxiety and/or depression. Low vitamin D level and working status were predictive factors for fatigue severity. These results highlight the complexity and variability of fatigue in IBD patients.
P684 Extra intravenous reinduction of ustekinumab on an already shortening interval is an effective optimisation strategy for patients with refractory Crohn’s disease
Authors: Yao J , Liu T , Min Z
Published: January 2023

Background

Designing treatment optimisation strategy for ustekinumab (UST) is challenging. We aimed to evaluate the efficacy and safety of extra weight-based intravenous reinduction of UST on an already shortening interval in patients with refractory Crohn’s disease (CD). To the best of our knowledge, this is the first study to report optimised UST treatment in a Chinese population.

Methods

This was a single-center retrospective observational study. Dosing optimisation strategies were designed for CD patients showing partial or loss of response to standardised UST with a shortened interval of every-8-week (q8w) dosing, or an extra weight-based intravenous reinduction followed by q8w subcutaneous administration. Clinical, biochemical, and endoscopic findings and trough concentrations of UST were analyzed.

Results

Dose optimisation strategies were developed for 27 out of 64 patients; 13 patients required a shortened q8w interval and 14 patients required intravenous reinduction. Crohn’s disease activity index [96.5 (39.8,156.3) vs. 158.0 (101.5,175.3), P=0.009] and C-reactive protein [3.3 (1.1,7.0) vs. 4.8 (0.5,15.1), P=0.023] levels decreased significantly after intravenous reinduction, while the trough concentration of UST increased [1.8 (1.2,8.6) vs. 1.1 (0.2, 6.4), P=0.009]. Clinical and endoscopic remission was achieved in 57.1% (8/14) and 33.3% (2/3) of patients, respectively, while 53.8% (7/13) and 25.0% (2/8) of patients achieved clinical and endoscopic remission at around week 8 in the q8w cohort, respectively. The incidence of patient-reported adverse effects was 3.7%. (Figure 1)

Conclusion

Intravenous reinduction improved clinical and endoscopic remission safely and effectively in patients showing poor response to standardised UST treatment, which should be an optimal rescue optimisation strategy before switching to biologics targeting other pathways.
P685 Early use of infliximab after seton technique for patients with Crohn’s disease who initially presented with perianal fistulas
Authors: Lim K Y , Hwang D Y , Lee J K
Published: January 2023

Background

Widespread early use of biologic agents cannot be recommended for all Crohn’s disease patients, but for patient subgroups with a predicted disabling course such as perianal fistulas, the early introduction of a biologic agent can be considered. The aim of this study was to assess the outcome of the early use of infliximab after seton technique for patients with Crohn’s disease who initially presented with perianal fistulas

Methods

We retrospectively reviewed charts of patients with Crohn's disease who initially presented with perianal fistulas between January 2020 and December 2021. After confirm diagnosis of CD by endoscopic examination, all patients underwent both seton procedure and infliximab therapy by single colorectal surgeon. After third injection of infliximab, we removed silastic seton at once, or, in the case of active fistula, replaced it with nylon, and then removed it when the fistula was in remission. Outcomes included clinical remission based on physical examination with radiologic examination (including sonogram and MRI) and endoscopic findings up to last follow up.

Results

Overall, 31 patients were identified, [29 males (94%), mean age at diagnosis of Crohn’s disease 21.2 (9-32) years]. Half of patients (15/31) showed moderate to severe bowel severity at pre-treatment colonoscopy. Mean number of fistulas was 1.6 (1-4). The overall number of primarily placed setons was 70, of which 33 were inserted through the primary opening and the other 37 were placed between secondary openings. The mean interval between seton insertion and introduction of infliximab was 17.2 (7-30) days. The number of patients who changed silastic seton to nylon was 11. The mean follow-up was 24 months. In 27 patients, Setons were completely removed until last follow up. Interval between seton insertion and complete removal was 7 months ranged from 3 to 24 months. In colonoscopy performed 1 year after infliximab introduction, luminal Crohn's disease of most patients was in endoscopic remission (20/31) or improved (11/31) and there were no case of exacerbation. In 3 patients, because of local sepsis or pain after seton removal, seton procedure was performed again. 30 patients were in clinical remission and had no anal discomfort.

Conclusion

Early use (within 30 days) of infliximab after seton technique was very effective for patients with Crohn’s disease who initially presented with perianal fistulas. Seton removal should be started at least after remission induction. And replacing silastic seton with nylon was a simple and effective method.