bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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 &gt;8 months and had been in sustained steroid-free remission &gt;6 months. Disease relapse was defined by CDAI&gt;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&lt;0.4) serum metabolites (alanine, glutamine, acetoacetate, glucose) identified relapse with an AUC of 0.84 (95% confidence interval 0.74–0.94, p&lt;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&gt;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&lt;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

Abstract

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

Abstract

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&gt; 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

Abstract

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&lt;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&lt;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

Abstract

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 &gt;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

Abstract

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&lt;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 &gt;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&lt;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

Abstract

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 &lt;250 μg/gr and C-reactive protein [CRP] &lt;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

Abstract

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