bluuebunny/crossref_metadata_2025 huggingface dataset:
P408 Faecal infliximab and disease activity in Acute Severe Ulcerative Colitis
Authors: Shields S , Dunlop A , Gerasimidis K , Nichols B , Galloway P , Macdonald J , Hansen R , Seenan J P
Published: January 2022

Background

Infliximab (IFX) is increasingly used in the management of moderate to severe ulcerative colitis (UC) and as a ‘rescue’ treatment for acute severe UC (ASUC) but primary non response (PNR) and colectomy rates remain significant. Reasons for IFX treatment failure in ASUC are multifactorial but immunogenicity and faecal loss of drug are thought to be important factors. Emerging evidence suggests accelerated ‘rescue’ IFX dosing may be more effective. The aim of this work was to establish if a relationship exists between faecal IFX levels, disease activity, and clinical outcomes early in IFX treatment.

Methods

Patients with UC were prospectively recruited following initiation of IFX and designated as ASUC or non-ASUC based on Truelove and Witt’s criteria. Stool and serum were collected on days, 0, 7, 14, 28 and, 42 after initiation of IFX. Additional samples on days, 1–5 after IFX were obtained from inpatients. Albumin and CRP results were extracted from electronic patient records. Faecal calprotectin (FC) was measured using ELISA (CALPROLAB). Faecal IFX within the first, 2 weeks of treatment was analysed using a Promonitor-IFX-1DV ELISA assay, performed on the Triturus ELISA instrument. R studio was used to calculate areas under the curves of the time series. Spearman’s rank correlation test was used for correlation analysis.

Results

20 patients were recruited, 12 with ASUC. Faecal IFX correlated strongly with FC (ρ=0.793;p<0.001) (Fig., 1), and moderately with CRP (ρ=0.51;p=0.02), and serum albumin (ρ=-0.51;p=0.02). The correlation was strongest between faecal IFX and FC within in the first week (ρ=0.93;p<0.001), and less strong for crp (ρ=0.481;p=0.037) and albumin (ρ=-0.474;p=0.04). Higher faecal IFX was associated with increased colectomy and PNR rates but this did not reach statistical significance (p=0.098). A rapid decline in median FC was seen after initiation of IFX with a rebound rise in FC observed at day, 3 of IFX treatment (Fig. 2).

Conclusion

In this small cohort, faecal loss of IFX was associated with increased markers of systemic and luminal inflammation. Its role as a biomarker for disease severity, treatment response and clinical outcomes warrants further investigation. The rapid fall but early rebound rise in FC may support the need for earlier accelerated dosing in ASUC. However, larger studies are needed to establish the optimal early IFX regime to improve clinical outcomes.

References

Papamichael et al. Aliment Pharmacol Ther, 2018;47:478–484.

Hindryckx et al. Aliment Pharmacol Ther., 2017 March;45(5):, 617–630

Brandse et al. Gastroenterology., 2015 Aug;149(2):350–5
P409 FMT induced increase in gut microbial diversity and Clostridia is associated with clinical response in patients with ulcerative colitis – results from STOP Colitis trial
Authors: Quraishi M N , Quince C , Hewitt C , Beggs A , Gerasimidis K , Sharma N , Hawkey P , Oo Y , Ives N , Manzoor S , Loman N , Hansen R , Hart A , Gaya D , Iqbal T
Published: January 2022

Background

Findings from five randomised trials using faecal microbiota transplantation (FMT) in adults with ulcerative colitis (UC) demonstrate therapeutic potential. The optimum methodology for administration of FMT is unclear. We describe a prospective, three centre, open-label randomised trial (STOP-Colitis pilot) that compared tolerability and efficacy of nasogastric (NG) versus colonic (COLON) routes of administration and identified potentially important host microbial interactions.

Methods

Adult participants with active UC (partial Mayo score of ≥4 and ≤8) were randomised for administration of, 8 infusions of FMT over an, 8 week period either via the naso-gastric (NG) or colonic (COLON) route. Each patient was matched to a single FMT donor. Clinical response was defined as ≥3 point and ≥30% reduction in full Mayo score at week, 8 compared to baseline. Changes in faecal gut microbial diversity (Shannon’s diversity) and composition before/after FMT were analysed with, 16S rRNA sequencing. Correlation between datasets was evaluated with Kendall’s Tau coefficient.

Results

Sixteen patients were randomised to NG;, 14 to COLON FMT. Seven participants in the NG and, 2 in the COLON arm withdrew before completion. Clinical response was achieved in, 9/12 [75%] for COLON vs, 2/8 [25%] for NG)., 12/14 (86%) COLON participants were protocol-adherent compared with, 8/16 (50%) for NG. For the COLON patients (N=8) an increase in alpha diversity was observed (P=0.01). For those patients that responded to FMT overall (N=9) there was a significant increase in alpha diversity (P<0.005) and lower faecal calprotectin levels in responders vs. non-responders (week, 4 to week, 8 mean, 508.6 ug/g vs, 853.6 ug/g respectively; P=0.03). Overall, there was a negative association between calprotectin levels and alpha diversity (tau =-0.29; P <, 0.005). Operational taxonomic units belonging to Clostridia deriving from the Christensenellaceae and Lachnospiracae families correlated with both reduced calprotectin and had high engraftment frequency (both false discovery rate corrected P<0.10). In a cohort of patients with mucosal immune cell analysis Clostridia positively correlated with gut homing Treg populations and negatively correlated with Th17 cells populations (P<0.005), suggesting that this group may play an important role in the immune response to FMT in UC.

Conclusion

This pilot study suggests that in participants with active UC, FMT delivered via the colonic route appears to be better tolerated than via NG with a greater efficacy signal. There are signals linking gut microbial diversity and taxa belonging to Clostridia (short chain fatty acid producers) with clinical response, calprotectin and a shift towards an immunoregulatory phenotype.
P440 Loss of response and dose escalation of infliximab and adalimumab in Ulcerative Colitis patients: A Systematic Review and Meta-analysis
Authors: Savelkoul E , Thomas P , Derikx L , Den Broeder N , Römkens T , Hoentjen F
Published: January 2022

Background

Anti-Tumour necrosis factor agents are essential therapeutics in moderate-to-severe Ulcerative Colitis (UC). Annual loss of response (LOR) and dose escalation (DE) risk in UC patients have not been systematically evaluated. This study aimed to assess the annual LOR rate and DE rate for infliximab (IFX) and adalimumab (ADA) in UC.

Methods

A systematic search of PubMed, EMBASE and Cochrane Library was conducted from January, 2000 to July, 2021. Clinical trials and cohort studies assessing IFX and/or ADA use in adult UC patients were included if these reported LOR rates or DE rates. The primary outcomes included (1) the annual LOR per patient-year of IFX and ADA in UC patients and (2) the annual DE rates per patient-year of IFX and ADA. LOR was only assessed in patients who had primary response to IFX or ADA as defined by the authors. LOR was reported as defined by the authors and then categorized in three definition groups:, 1) treatment discontinuation due to LOR, 2) treatment intensification defined as dose escalation and/or treatment switch and/or surgery, because of LOR and, 3) increase of clinical, biochemical and/or endoscopic disease activity. Dose escalation was defined as any dose increase or interval shortening as reported by the authors. Summary estimates were calculated using random effects models.

Results

Our search yielded, 26,320 potentially relevant articles. We analysed, 50 unique studies (IFX (n=35) or ADA (n=23)) assessing LOR (IFX:, 24 cohort studies, ADA:, 21 cohort studies) or DE (IFX:, 21 cohort studies, ADA:, 16 cohort studies). Follow-up among all studies ranged from, 38 to, 350 weeks. The pooled annual LOR for IFX was, 11.2% (95% CI [0.082–0.153], Figure, 1). LOR per category was as follows:, 8.3% (95% CI [5.3–13.3]) for discontinuation (n=16), 18.6% (95% CI [11.5–29.8]) for treatment intensification (n=6), 19.3% (95% CI [14.3–26.0]) for increase in clinical/biochemical/endoscopic activity (n=2). The pooled annual LOR for ADA was, 15.1% (95% CI [0.103–0.220], Figure, 2). LOR per category was as follows:, 12.0% (95% CI [7.1–19.9]) for discontinuation (n=16), 43.6% (95% CI [21.8–87.2]) for treatment intensification (n=3), 11.6% (95% CI [4.0–33.9]) for increase in clinical/biochemical/endoscopic activity (n=2). Annual pooled DE rates were, 14.7% (95% CI [10.4–20.7]) for IFX and, 21.3% (95% CI [15.6–29.0]) for ADA.

Figure, 1 - Infliximab

Figure, 2 - Adalimumab

Conclusion

The overall pooled annual LOR in UC patients was, 11% for IFX and, 15% for ADA. LOR rates varied among different used definitions. Annual dose escalation rates were, 15% for IFX and, 21% for ADA. Future studies in this field should focus on a universal definition of LOR and report time to loss of response.
P451 Evaluating drug sustainability, efficacy and safety of biologic agents in elderly patients with Inflammatory Bowel Disease: a single center retrospective study
Authors: Golovics P , LeBlanc J F , Drügg Hahn G , Wetwittayakhlang P , Qatomah A , Wang A , Boodaghians L , Liu J , Al Ali M , Wild G E , Afif W , Bitton A , Lakatos P L , Bessissow T
Published: January 2022

Background

Despite the advancement in pharmacological management of Inflammatory Bowel Disease (IBD), the efficacy and the side effects of the biologics are rarely studied in the elderly population. Our aim was to evaluate retrospectively the drug sustainability, efficacy, and safety of the biologic therapies in the elderly IBD population.

Methods

Consecutive elderly (> 60 years old) IBD patients, treated with biologics (infliximab, adalimumab, vedolizumab, ustekinumab) followed at the McGill University IBD Center were included between January 2000 and 2020. The efficacy of treatment was measured using clinical and biochemical parameters. Response and remission variables were measured at three distinct time points from the start date of the biologic agent, as in 3, 6–9 and 12–18 months. Patients required a minimal follow-up period of three months. Adverse events (AE) or serious adverse events (SAE) occurring within three months of the last biologic dose were considered to be related to the biologic agent.

Results

We identified a total of 147 elderly patients with IBD treated with biologic agents (109 Crohn’s disease (CD) and 38 ulcerative colitis (UC)). Disease location was predominantly ileocolonic (47.7%) in CD and pancolitis(63.2%) in UC. 47.6% of elderly IBD patients had attempted at least 1 biologic agent (Table1). The mean duration of biologic treatment was 157.5 (SD:148)weeks. Steroid exposure varied from 34% at the start of biologic therapy to 19% at 3 months, 16.3% at 6–9 months and 6.5% at 12–18 months.’ The remission rates at 3, 6–9 and 12–18 month were not significant between the biologic therapies. Kaplan-Meyer analysis did not show statistical difference for drug sustainability (p=0.195)(Figure1), time to adverse event (p=0.158) (Figure2) or infection rates (p=0.973) (Figure3) between all four biologics studied. The most common AEs led to discontinuation were loss of response, infusion or injection reaction and infection.

Conclusion

Current biologic therapies were not different with regards to drug sustainability and safety in the elderly IBD population. Based on these results, we are not able to suggest a preferred sequencing order among biologicals.
P459 High inadequate surveillance rates in colitis-associated advanced neoplasia: a multicenter retrospective cohort study
Authors: Te Groen M , Derks M E , Peters C P , Dijkstra G , De Vries A C , Römkens T E , Horjus C S , De Boer N K , De Jong M E , Nagtegaal I D , Derikx L A , Hoentjen F
Published: January 2022

Background

Although colorectal cancer (CRC) surveillance is embedded in IBD practice, a subset of patients still develops advanced neoplasia (AN; high-grade dysplasia (HGD) and/or CRC). We aimed to determine the most plausible explanations for AN in IBD patients through assessment of inadequate surveillance.

Methods

A search of the nationwide histopathology registry of the Netherlands (PALGA) was used to identify IBD patients with AN in seven hospitals. Patients with ulcerative colitis (UC), Crohn’s disease (CD), or IBD-unclassified (IBD-U) from 1 January 1991 until 1 October 2020 were eligible for inclusion. Exclusion criteria comprised familial CRC or AN prior to IBD diagnosis. A root-cause analysis based on the World Endoscopy Organizations’ recommendations was performed to determine inadequate surveillance prior to the first AN, including lack of cecal intubation, insufficient bowel preparation (BBPS<6 or according to colonoscopy report) and active endoscopic inflammation. Interval inadequacy was assessed according to most recent BSG guideline including a six month margin. Associations were assessed with a binary regression model.

Results

We included 179 patients with AN (figure 1). Of these, 22 patients (12.3%) were diagnosed with AN before surveillance was indicated. Inadequate surveillance was present in 122 patients (68.2%, n=50 HGD, n=72 CRC), of whom 47 patients (26.3%) did not receive any surveillance colonoscopy before AN diagnosis. A delayed surveillance interval was identified in 44 patients (24.6%), with a median deviation from surveillance recommendations of 19.0 months (IQR 9.5–28.5 months). Furthermore, 56 patients (31.3%) had active inflammation, three had insufficient bowel preparation, and two patients had an incomplete colonoscopy. Younger age at diagnosis (annual OR 0.96, 95% CI 0.94–0.98, p<0.01) and post-inflammatory polyps (OR 2.14 95% CI 1.06–4.32, p=0.03) were independently associated with inadequate surveillance. By contrast, prior indefinite for dysplasia or low-grade dysplasia was associated with adequate surveillance (OR 0.36, 95% CI 0.17–0.76, p<0.01). Finally, 35 patients (19.6%) had interval or surveillance AN despite adequate surveillance (diagnosed during a diagnostic procedure or surveillance colonoscopy, respectively).

Figure 1. Root-cause analysis flowchart

Conclusion

The majority of IBD patients with AN in our cohort had prior inadequate surveillance. This observation underlines the importance of adequate surveillance and guideline adherence.
P463 Serum and mucosal Serpin E1 concentration correlates with endoscopic activity in inflammatory bowel disease - potential new activity marker
Authors: Jójárt B , Molnár T , Kata D , Szabó V , Varga Á , Resál T , Bacsúr P , Szántó K , Földesi I , Molnár T , Maléth J , Farkas K
Published: January 2022

Background

Inflammatory bowel disease (IBD) is characterized by an unregulated immune response generating unbalance cytokine homeostasis. Analysis of patient-specific cytokine profiles may open new therapeutic targets or identify biomarkers that distinguish responders from non-responders before initiating therapy. Therefore, the aim of the present study was to determine cytokine profile of IBD patients and identify cytokines with predictive potential.

Methods

Blood and biopsy samples were obtained from 79 clinically active IBD patients and 28 controls without IBD. Inclusion criteria included change of therapy or initiation of new treatment for IBD patients. Organoid culture (OC) was generated from 5 clinically active IBD patients and 5 controls. Cytokine Array was used to analyse cytokine expression patterns. Total protein and mRNA were isolated from biopsies and from OCs. Protein levels were measured by ELISA and gene expression by qRT-PCR in serum, mucosa and in OCs.

Results

Pro-inflammatory cytokines were not detected in control samples, whereas in IBD biopsies the cytokine profiles enabled the discrimination between inflamed or non-inflamed areas. The mucosal expression of Serpin E1 was detected in all inflamed biopsy samples, whereas it was below the detection limit in healthy subjects. In responders Serpin E1 gene expressions were significantly (p<0.001) lower than in non-responders. On the other hand, we were not able to detect significant changes between responders and non-responders in gene expression of TNF-α, IL-1β, IL-6 and TGF-β. In responders, mucosal Serpin E1 concentration significantly decreased (p<0,05) after the initiation of therapy compared to non-responders. Serum and mucosal Serpin E1 concentrations were significantly higher in patients with endoscopically and clinically active disease compared to inactive (endoscopic: p<0.0001, clinical: p<0.05). Correlation analysis revealed that serum Serpin E1 level correlates with disease activity (p<0.01). In OCs the level and expression of Serpin E1 was lower in healthy organoids compared to OCs generated from inflamed samples.

Conclusion

Our results suggest that serum and mucosal Serpin E1 expression reflects endoscopic activity in IBD, which could be used to follow-up disease activity and possibly therapeutic response. Organoids mimicked the expression of Serpin E1 in the original biopsies suggesting that OCs can be used to study the effect of Serpin E1 inhibition.
P479 Trends in medication use and treatment patterns in Chinese patients with Inflammatory Bowel Diseases: A multicenter cohort study from 1999 to 2020
Authors: Yao L , Shao B , Cao Q
Published: January 2022

Background

The temporal changes in medication use and therapeutic paradigm in patients with Inflammatory bowel disease (IBD) have not been well elucidated in China over the past two decades. Therefore, we aimed to identify the temporal changes in medication use and treatment patterns for Chinese patients with IBD and to evaluate the factors associated with initial drug strategies.

Methods

A multicenter retrospective cohort study was conducted among Chinese patients newly diagnosed with Crohn’s disease (CD) and ulcerative colitis (UC) from January 1999 to December 2019. Medication utilization, treatment patterns, and associated factors with initial drug strategies were investigated.

Results

Prescriptions of 5-aminosalicylates (ASA) and corticosteroids (CS) gradually decreased, whereas prescriptions of immunosuppressants (IMS) and infliximab (IFX) increased in patients with CD. Except for stable prescriptions of ASA and CS, IMS and IFX increased since 2007 in patients with UC. Subgroup (N=957) analyses revealed that treatment patterns went through notable changes from ASA to IMS or IFX in patients with CD, while ASA and CS were still steadily prescribed in patients with UC. Logistic regression analyses revealed that perianal and gastrointestinal surgeries before diagnosis, disease behavior, and disease location were associated with different initial therapeutic strategies in patients with CD. However, medications before diagnosis, disease location, and diagnostic year might affect initial strategies in patients with UC.

Conclusion

Parallel to increasing uses of IMS and IFX in IBD over past two decades, a significant decrease in uses of ASA and CS were observed in CD, but not in UC. Treatment strategies analyses provided a unique insight in understanding long-term therapeutic patterns in the Chinese population.
P489 Temporal trends of colectomy for ulcerative colitis in the multi-drug era; a population based cohort study
Authors: Jenkinson P , Plevris N , Lyons M , Gros B , Derikx L , Constantine-Cooke N , Jones G , Lees C
Published: January 2022

Background

We are now in the multi-drug era for ulcerative colitis (UC). The use of advanced therapies for UC has dramatically increased over the last 6 years. NICE approvals of anti-TNF and anti-α4β7 therapy (both in 2015) were followed by IL12/23 (2019) and janus kinase inhibitors (2020). The aim of this study was to describe the impact of this change in patterns of advanced therapy prescribing on colectomy rates for UC within a well defined population-based cohort.

Methods

The Lothian IBD registry (LIBDR) is a manually validated, prevalent dataset compiled through capture-recapture methodology (Jones et al. 2018) that is >95% complete for the 907,580 residents of NHS Lothian (mid-2019 population estimates). The LIBDR contains measured prevalence between 2008–2018, estimated prevalence from 2018–2028 (derived from Autoregressive integrated moving average {ARIMA} modelling). All patients with a diagnosis of UC who underwent a colectomy in Lothian, Scotland between 01/01/2005 and 31/102021 were identified by interrogating multiple clinical and administrative databases. Linear and segmental regression analyses were used to identify the annual percentage change (APC) and temporal trends (statistical joinpoints) in colectomy rates.

Results

485 patients underwent colectomy for UC between 2005 and October 2021 (Fig 1). Colectomy rates per 100 UC patients fell from 1.47 colectomies in 2005 to 0.25 in 2021 (p=0.009). The colectomy APC decreased by 4.1% per year between 2005 and 2014 and 18.5% per year between 2014 and 2021 (Figure 2). Temporal trend analysis (2005–2021) identified a significant joinpoint in colectomy rates in 2014 (p=0.009) (Figure 2).

Figure 1 Absolute number of colectomies for UC per year between 2005–2021. Linear regression showing colectomy numbers (solid line) and 95% confidence intervals (dashed lines) constrained at 2014.

Figure 2, Colectomy rates per 100 UC patients from 2005–2021. Joinpoint regression separated at inflection point at 2014 (solid line).

Between 2005 and 2007, 0 / 100 patients undergoing colectomy received maintenance biologic treatment prior to the admission for colectomy. Between 2019 and 2021, 19 / 33 (57.8%) patients received maintenance biologic therapy prior to colectomy (Figure 3).

Figure 3. Percentage of colectomy patients who had been treated with at least 1 maintenance biologic prior to surgery.

Conclusion

This population based cohort study has shown a significant reduction in the rate of colectomy for UC that has coincided with the introduction of biologic medication. Whilst we cannot ascribe causality, within this study the timeline of falling colectomy rates closely parallels the rapid increase in the use of biologic medication.
P493 The synthetic glycan KB295 optimises microbiome composition and function in ulcerative colitis: Results from a proof of principle human study
Authors: Meisner J , Miller K , Lee J , Jose A , Giuggio M , McComb M , Humphries E , Rosini M , Wingertzahn M , Shanahan F , van Hylckama Vlieg J E T , Dowling M
Published: January 2022

Background

Ulcerative colitis (UC) pathogenesis involves genetic susceptibility, immune-mediated tissue injury, and gut microbiota disturbances. Most approved therapies modify host immunity, rather than directly targeting the microbiota. Faecal microbiota transplantation provides encouraging evidence for the therapeutic potential of gut microbiome modulation. Gastrointestinal tract bacteria are ecologically differentiated by their ability to use specific glycans as growth substrates, making glycans a promising and safe alternative to target the microbiome. To explore this, we used an ex vivo faecal microbiota culture system to identify a synthetic glycan (KB295) with desirable microbiological activity and conducted a proof of principle study (NCT04508413) of safety and tolerability of KB295 in patients with UC.

Methods

In ex vivo studies, faecal microbial communities from healthy subjects were incubated anaerobically (negative control) ± KB295. Taxa counts from shotgun metagenomic sequencing data were used to evaluate microbial response to KB295. Short-chain fatty acid (SCFA) levels were also assessed. KB295 was evaluated in an open-label single-arm study in adult patients with mild to moderate UC. KB295 was ingested over an 8-wk period. Objectives included KB295 safety (primary) and effect on gut microbiota composition and faecal biomarkers.

Results

In ex vivo studies, KB295 increased SCFA levels across 10 faecal samples to a median of 47.0 vs 15.2 mM with negative control, including increases in acetate, propionate, and butyrate levels. Metagenomic sequencing showed pathobiont depletion in the family Enterobacteriaceae with KB295 to a median relative abundance of 10.8% vs 38.2% with negative control. Pathobiont depletion was associated with enrichments of diverse genera in the phyla Bacteroidetes and Firmicutes. In patients with UC (n=12), KB295 was well tolerated with generally mild adverse events (AEs). The most frequently occurring AEs were bowel habit changes, flatulence, and headache. Median faecal calprotectin and lactoferrin levels decreased by 69.0% (n=11) and 86.0% (n=6), respectively, from screening to end of the KB295 intake. Consistent with our ex vivo results, of the patients for whom we have data to date, the relative abundance of the faecal pathobiont family Enterobacteriaceae decreased in 5 of 5 participants, and the commensal genus Parabacteroides was enriched in 4 of 5 participants.

Conclusion

Our results establish a proof of principle for the glycan modulation of gut microbiome composition and function and provide insight into the potential utility of this strategy in patients with UC. The safety and tolerability of KB295, along with evidence of reduced inflammation, support a phase 2 study, which is planned.
P494 A serum metabolite panel predicts Crohn’s disease relapse in patients discontinuing infliximab and continuing antimetabolite therapy: sub-analysis of the SPARE Trial
Authors: Radford-Smith D , Satsangi J , Louis E , Laharie D , Ding N , Siegmund B , D’Haens G , Erik H , Yates A , Anthony D , Colombel J F , Probert F
Published: January 2022

Background

Combination therapy with infliximab and anti-metabolites is an effective strategy for maintaining remission in patients with Crohn’s disease (CD); however, the implications of long-term combination therapy has led clinicians to consider discontinuing one of the two agents after sustained remission has been achieved. The SPARE investigators have addressed this in an unblinded clinical trial in which 211 patients were randomised to either continuation of combination therapy, withdrawal of infliximab, or withdrawal of antimetabolite therapy. Here, we aimed to determine whether nuclear magnetic resonance (NMR)-based metabolomics analysis of patient sera at baseline could determine which patients randomised to infliximab withdrawal would relapse over 2-years on anti-metabolite monotherapy.

Methods

The study cohort comprised patients randomised to infliximab cessation who had a serum aliquot available for analysis (n=63). All patients had been treated with a combination therapy of infliximab (IFX) and anti-metabolite >8 months and had been in sustained steroid-free remission >6 months. Disease relapse was defined by CDAI>250 (or between 150–250 with 70 points increase over two consecutive weeks) alongside serum CRP and faecal calprotectin levels. Untargeted metabolomic profiling was carried out using NMR spectroscopy. Key metabolites were identified by their variable importance in projection (VIP) score using orthogonal partial least squares discriminant analysis (OPLS-DA) with 10-fold cross-validation on independent data. Multiple logistic regression on the metabolites with highest VIP score was used to report a receiver operator characteristic (ROC) curve integral (AUC) value after collinear variables were removed.

Results

Of 63 patients, 21 (33%) relapsed. The mean time to relapse after infliximab discontinuation was 7.9 months. Four independent (multicollinearity R2<0.4) serum metabolites (alanine, glutamine, acetoacetate, glucose) identified relapse with an AUC of 0.84 (95% confidence interval 0.74–0.94, p<0.0001). The positive predictive value was 66.7%, and the negative predictive value was 77.1%. All serum metabolites identified were independent of baseline CRP level (p>0.05, Pearson correlation). Patients who relapsed following infliximab discontinuation had significantly elevated serum acetoacetate and decreased alanine and glutamine levels (post-hoc students t-test, p<0.05) at baseline.

Conclusion

Here, we identify a panel of serum metabolites independent of baseline serum CRP, which predict high risk of disease relapse after infliximab discontinuation. These data may help in stratifying patients suitable for drug withdrawal, together with other clinical and multi-omic parameters.
P497 Early improvement in bowel wall thickness on transperineal ultrasonography predicts treatment success in active ulcerative colitis
Authors: Sagami S , Kobayashi T , Aihara K , Umeda M , Odajima K , Morikubo H , Asonuma K , Miyatani Y , Fukuda T , Matsubayashi M , Kiyohara H , Nakano M , Hibi T
Published: January 2022

Background

Bowel ultrasonography is a non-invasive imaging tool that can repeatedly monitor the activity of ulcerative colitis (UC). This study aimed to determine whether early changes in bowel ultrasonographic findings could predict subsequent clinical response to induction treatment in patients with ulcerative colitis.

Methods

This single-center prospective study compared ultrasonographic findings with fecal calprotectin, and C-reactive protein (measured at baseline, week 1, and week 8) in predicting remission (patient-reported outcome-2 ≤ 1 with no rectal bleeding subscore) at week 8 in active UC patients who initiated the remission-induction treatments. Predictive factors were assessed using multivariate regression models and a receiver operating curve analysis.

Results

A total of 100 patients were analysed, of which 54 achieved remission at week 8. Baseline values of biomarkers, and ultrasonographic parameters were not predictive of remission. Bowel wall thickness and bowel wall flow at baseline and week 1 were also not sufficiently predictive. By contrast, changes from baseline to week 1 in bowel wall thickness in the rectum measured by transperineal ultrasonography was an independent predictor of remission by week 8 (adjusted odds ratio associated with 1 mm decrease: 1.90 (95% confidence interval 1.22–2.95)). Predictive value of changes in rectal bowel wall thickness remained high for clinical improvement even among patients who did not achieve remission in 1 week.

Conclusion

Improvement in rectal bowel wall thickness measured by transperineal ultrasonography at week 1 predicts treatment success and thus would help decision making during the early course of induction treatment in UC.
P505 Smoking is associated with the development of adverse events of biological therapy in patients with Inflammatory Bowel Disease
Authors: Theodoraki E , Orfanoudaki E , Foteinogiannopoulou K , Koutroubakis I
Published: January 2022

Background

Smoking has been associated with a reduced response to anti-TNF in patients with inflammatory bowel disease (IBD) as well as with lower serum levels of anti-TNF agents and the development of antibodies against them. The aim of this study was to investigate the association between smoking and the appearance of adverse events (AEs) of biologics in patients with IBD.

Methods

Consecutive patients with IBD who receive biological therapy in a tertiary university hospital were included. The possible association of smoking with the presence of AEs was investigated, using a specially designed questionnaire including a wide range of AEs associated with biologics (infections, skin manifestations, musculoskeletal disorders, general symptoms, hypersensitivity reactions, thromboembololic events and psychological disorders).

Results

A total of 147 patients with IBD under biologics [median age (IQR) 46 (32.5–56) years, Crohn’s Disease (CD) 109 (74%), female 51 (35%), under combination with immunosuppressants 60 (41 %), under intensified biologic therapy 50 (34%), under anti-TNF 132 (89%), vedolizumab 11 (7.5%), ustekinumab 3 (2%)] with completed questionnaire forms available were included in the study. There were 52 (35%) active smokers and 35 patients (24%) ex-smokers. The prevalence of all AEs was 86% in smokers 85% in ex-smokers and 78% in non-smokers. Active smoking was significantly associated with the presence of arthralgias and skin rashes while taking biologics, both in the univariate (P = 0.02 and 0.008 respectively-Figure 1) and in the multivariate analysis (P = 0.02 and 0.007 respectively). These correlations were the same for the two diseases (CD & UC) except for arthralgias where there was a significant correlation only with CD (P = 0.02). There were no other significant associations between smoking and infections (P=0.77) or other AEs (P> 0.05).

Conclusion

Smoking is a predisposing factor for the development of AEs of biologics in patients with IBD. It could be suggested that quit of smoking may lead to the optimal benefit from the use of biologic therapy in IBD.
P509 Biomarkers of neutrophil activity and extracellular matrix turnover predict long-term response to vedolizumab in patients with Crohn’s disease
Authors: Sorokina Alexdóttir M , Bourgonje A R , Karsdal M A , Bay-Jensen A C , Pehrsson M , Loveikyte R , van Dullemen H M , Visschedijk M C , Festen E A M , Weersma R K , Faber K N , Dijkstra G , Joachim H M
Published: January 2022

Background

Crohn‘s disease (CD) is a form of inflammatory bowel disease characterized by high infiltration of immune cells into the intestinal tissue, resulting in increased proteolytic mediated extracellular matrix (ECM) remodeling. Disease management has improved with the use of biologics such as vedolizumab (VEDO). However, considering the high rate of primary non-response to VEDO, there is an unmet need for predictive serum biomarkers capable of determining response to treatment prior to its initiation. This study investigated whether biomarkers of neutrophil activity, mucosal damage, and ECM remodeling could serve as non-invasive tools for predicting long-term response to VEDO in patients with CD.

Methods

Serum biomarkers of human neutrophil elastase (HNE)-derived fragment of calprotectin (CPa9-HNE [serum calprotectin]) and matrix metalloproteinase (MMP)-derived fragments of type I (C1M), III (C3M), IV (C4M), type III collagen formation (PRO-C3), basement membrane turnover (PRO-C4) and T-cell activity (C4G), were measured using protein fingerprint assays in patients with CD (n=32) before VEDO therapy initiation. The ratio C4M/C4G (myeloid/lymphoid mediated degradation) was computed. Long-term response was defined as the continuation of treatment beyond one year after the start of therapy. Baseline biomarker levels were compared between responders and non-responders using Mann-Whitney U-tests, and area under the curve (AUC) values were generated using receiver operating characteristics (ROC) statistics. Biomarker levels were divided into tertiles and chi-square tests were used to investigate the relationship between tertiles and response proportions.

Results

Biomarkers CPa9-HNE, C1M, C3M, C4M, PRO-C3, C3M/PRO-C3, and C4M/C4G were significantly increased at baseline in non-responders compared with responders (all P<0.05). All markers were able to predict response to VEDO at baseline (AUC [95% CI]: CPa9-HNE 0.81 [0.66–0.96]; C1M 0.85 [0.75–0.98]; C3M 0.79 [0.62–0.95]; C4M 0.77 [0.6–0.93]; C3M/PRO-C3 0.78 [0.6–0.95]; C4M/C4G 0.74 [0.56–0.92] all P<0.05). Proportions of long-term VEDO users were highest in the first tertiles for all the markers (73–91%) and decreased in a concentration-dependent manner across the second and third tertiles, indicating that patients with the lowest concentrations of these markers less frequently discontinued treatment at one year after initiation (Figure 1).

Conclusion

Baseline levels of serum biomarkers for neutrophil activity (CPa9-HNE [serum calprotectin]) and mucosal damage (C1M, C3M, C4M, C4G, PRO-C4, and PRO-C3) could predict long-term response to VEDO in patients with CD. Therefore, these biomarkers could aid in early decision making concerning treatment with vedolizumab in patients with CD.
P516 Discrete choice experiment to examine patient preferences for surgical interventions in patients with Crohn’s perianal fistulas: results from a global burden of illness study
Authors: Karki C , Athavale A , Hantsbarger G , Lee K , Milicevic S , Perovic M , Raven L , Sajak-Szczerba M , Abilash V , Tozer P
Published: January 2022

Background

Perianal fistulas (PAF) are a common complication of Crohn’s disease (CD) and patients with Crohn’s perianal fistulas (CPF) experience low health-related quality of life and a higher burden of symptoms than patients with CD without PAF (non-PAF CD). Treatment options for PAF, including medical and surgical interventions, are associated with high rates of relapse or failure. This global study assessed the burden of illness in patients with CPF compared with patients with non-PAF CD. Here, we present data on patient satisfaction with currently available PAF treatments and the attributes that drive treatment choice for patients with CPF.

Methods

This cross-sectional study was conducted in seven countries (France, Germany, Spain, UK, Canada, Australia and Japan) in patients aged ≥21 and ≤90 years with self-reported physician-diagnosed CD. Patients were classified as non-PAF CD (cohort 1) or CPF without PAF-related surgery (cohort 2) or CPF with PAF-related surgery (cohort 3). Using a web-enabled questionnaire, patient satisfaction with current PAF treatment options was recorded using a 1–9 scale and relative treatment attribute preferences were assessed via a discrete choice experiment (DCE) that included six attributes (Figure 1). Patients evaluated two treatment profiles at a time (“choice tasks”) to identify their most preferred treatment of the choices available. Data were analysed using descriptive statistics.

Results

A total of 929 patients were recruited, 620 with non-PAF CD and 309 with CPF. Of those with CPF (cohort 2, n=174; cohort 3, n=135), 68% were male, 65% were aged 21–40 years and 83% were currently taking CD-related medication. The median number of PAF was the same in cohorts 2 and 3 (both 2.0), although cohort 3 had a higher proportion of patients with active PAF (119/135 [88%]) compared with cohort 2 (136/174 [78%]; p =0.022). In cohort 3, 105/135 (78%) patients had ≥3 PAF-related procedures/surgeries, and ≥1 and >3 post-operative complications were experienced by 117/135 (87%) and 34/135 (25%) patients, respectively. Mean satisfaction scores were moderate for the majority of PAF treatment options and similar in both cohorts (range 6.2–6.9), although cohort 3 had significantly less satisfaction with long-term seton placement than cohort 2 (6.2 vs 6.7, respectively; p =0.035). Among the tested attributes, post-operative discomfort and fistula healing rate were the most important attributes influencing treatment choice (Figure 1).

Conclusion

In this study, patients with CPF had moderate satisfaction with PAF treatment options, regardless of surgical intervention. The DCE demonstrated that patients preferred interventions with better healing rates and lower post-operative discomfort compared to other attributes tested.
P520 Very early intestinal ultrasound predicts intravenous corticosteroid failure in hospitalized severe ulcerative colitis patients
Authors: Fremberg Ilvemark J , Wilkens R , Thielsen P , Kirch Dige A , Boysen T , Brynskov J , Tveiten Bjerrum J , Seidelin J
Published: January 2022

Background

Intestinal ultrasound (IUS) is an objective marker for inflammation in ulcerative colitis (UC). Few studies have examined if repeated IUS can predict treatment outcomes in UC. Our aim was to determine if IUS changes after 48±24h of intravenous corticosteroids can predict treatment outcomes in hospitalized patients with severe UC.

Methods

We performed a blinded observational multicenter study at three university hospitals in Denmark. Bowel wall thickness (BWT), colour doppler signals (CDS), inflammatory mesenteric fat (I-fat), haustration, and bowel wall stratification (BWS) were assessed before treatment initiation and after 48±24h. Treatment response was assessed with a partial Mayo score (pMayo) at day 6±1, defined as a ≥30% and ≥3 point reduction with either a rectal bleeding subscore of 0 or 1 OR a decrease in rectal subscore ≥1 point. If infliximab was administered earlier (≥3 days), pMayo was evaluated at administration. The treating physician was blinded to the IUS findings, and the IUS examiner was blinded to all non-IUS disease parameters.

Results

Fifty-six patients were recruited between February 2019 and March 2021 (Table 1). Thirty-seven (66%) responded to intravenous corticosteroid therapy within seven days of treatment, while 19 (34%) did not. There was no difference in baseline BWT between groups. However, at follow-up, significant differences between responders and non-responders were identified in both absolute BWT (median 3.1mm vs 4.9mm), absolute reduction ΔBWT (median -1.9mm vs -0.2mm), and percentage reduction (median -35.9% vs -4.1%) all p<0.005, (Figure 1). Receiver operating characteristic curve analysis for BWT at 48±24h to predict non-response showed an area under the curve of 0.85. BWT ≥4mm had a sensitivity of 84.2 (95% CI 60.4–96.6), specificity of 75.7 (95% CI 58.8–88.2), a negative predictive value of 90.3 (95% CI 74.2–98.0), and a positive predictive value of 64 (95% CI 42.5–82.0) for determining non-response. The absence of I-fat, and the presence of BWS and haustration all had significant odds ratio (OR) for detecting response at follow-up. However, BWT was the only significant parameter in the multivariable analysis and, thereby, the most important parameter for response assessment (BWT >20% reduction adjusted OR 10.8 (95% CI 2.5 - 56.6) and BWT ≤4mm adjusted OR 8.8 (95% CI 1.9 - 51.3), both p<0.01).

Conclusion

Changes in IUS BWT after 48±24h following intravenous corticosteroid treatment in hospitalized severe ulcerative colitis patients, identify responders with high accuracy. IUS might be utilized as an early corticosteroid non-response marker to guide accelerated rescue infliximab regimes.
P534 Effectiveness and safety of Adalimumab switch from originator to biosimilar in patients with inflammatory bowel disease in clinical remission
Authors: Gros B , Soto Escribano P , Marín Pedrosa S , Medina Medina R , Benítez J M , Iglesias-Flores E
Published: January 2022

Background

Multiple adalimumab (ADA) biosimilars are now available since they were first commercialized in 2019 after having proved their safety and effectiveness in rheumatoid diseases. However, real data in inflammatory bowel disease (IBD) remain scarce.

The main aim was to evaluate the remission rates after switching from ADA originator (Humira) to biosimilar (Hyrimoz) in a cohort of patients in remission at time of inclusion as well as to describe any safety issues.

Methods

We performed a prospective, observational cohort in a tertiary IBD referral centre.

All patients on Humira who were in clinical remission (defined as Harvey-Bradshaw score ≤4 or partial Mayo score ≤2) +/- biological remission (faecal calprotectin <250 μg/gr and C-reactive protein [CRP] <5gr/L) +/- endoscopic/radiologic remission at time of switch were included and followed-up for at least 9 months.

Data on IBD phenotype, CRP, ADA drug and antibody levels and faecal calprotectin were collected.

Results

A total of 40 patients were included, 53.7% (22) men. Median follow-up 10.6 months (IQR 10–11.1). Regarding IBD type, 85.4% (35) suffered from Crohn′s disease (CD) and 14.6% (6) from ulcerative colitis (UC). Table 1 shows the baseline characteristics of patients.

Prior to switch, adalimumab levels were 7.7 mg/mL (5.9–11.2), CRP 0.4 (0–1.7) gr/L and faecal calprotectin 140 μg/gr (69–180). One patient stopped the drug (2.5%) as per personal reasons and 5% (2) flared during the follow-up but no drug cessation was needed. At the end of follow-up 94.9% (37) patients remained in clinical remission. No severe adverse events were reported. Statistical differences were found in ADA levels prior and after switching (7.7 vs 5.9 mg/mL, p=0.001), CRP levels (0.4 vs 0.7 g/L; p=0.016) and albumin levels (4.4 vs 4.6 g/L, p=0.015).

Conclusion

Switching from Humira to Adalimumab biosimilar appeared to be effective and safe with most patients being in clinical remission at the end of follow-up. Statistical differences were found in adalimumab levels, CRP after switching and albumin, however, the impact of these differences was not noticeable.
P535 Association of anti-Infliximab antibodies and HLADQA1*05 variant in ulcerative colitis: a retrospective single centre study
Authors: Aleman Gonzalez H , Sankaranarayanan R , Pattinson A , Turnbull J , Katie S , Whitehead E , Talbot A , Myers S , Sebastian S
Published: January 2022

Background

The genetic variation HLADQA1*05 has been reported to be associated with anti-Infliximab antibody in CD. The relevance in UC patients receiving infliximab is uncertain. We aimed to evaluate the association of HLADQA1*05 and infliximab antibody formation, treatment changes and infliximab persistence in a real world setting of single centre cohort

Methods

Infliximab treated UC patients (n=94) were retrospectively screened for HLDqA1*05. The risk of anti-infliximab antibody formation, absent drug levels in presence of antibody, change in therapy from infliximab were assessed in variant carrying patients in comparison to those without the variants. The proportion of patients needing dose optimisation of infliximab also evaluated

Results

Anti-infliximab antibodies were detected in 41.5% of patients in a median follow up of 14.75 (IQR 9–29) months. HLA DQAI*05 was positive in 39.13% of patients. 52.2 % of patients were on concomitant immunomodulators. Higher proportion of patients with HLADQA1*05 developed anti-Infliximab antibodies (59% Vs 24%, p=0.002). Eighty percent of patients who had anti Infliximab antibodies with absent drug levels were positive for HLADQA1*05 with Hazzard Ratio (HR) for development of anti-Infliximab antibodies of 4.54 (95% CI 1.73–11.89) and for antibodies with absent infliximab drug levels 9.86 (95% CI 2.43 -40.01). Higher proportion of HLADQA1*05 patients required dose escalation (78% vs 31%, p=0.001). After adjusting for age, initial infliximab dose and concomitant immunomodulator use, there was no difference anti TNF persistence in patients with HLADQA1*05 variant (HR 2.36, 95% CI 0.89–6.25, p=0.06)

Conclusion

Determination of HLADQA1*05 status may identify patients at higher risk of anti-infliximab antibodies in ulcerative colitis. Early intervention with dose optimisation and concomitant immunomodulation may avoid loss of response and facilitate treatment persistence