bluuebunny/crossref_metadata_2025_split huggingface dataset:
P656 Plasma Inflammation-related Proteins Predict the Therapeutic Effect of 5-ASA in Patients with Ulcerative Colitis
Authors: Dang Y , Xu X , Zhou M , Xu C , Huang X , Xu F , Wang Z , Wang C , Zhu S , Li P , Zhang S , Shi H 
Published: January 2024

Abstract

Background
5-aminosalicylate acid (5-ASA) is the first line therapy for mild to moderate ulcerative colitis (UC). However, up to 56% of patients on 5-ASA treatment could not achieve mucosal healing, which is the therapeutic target of UC. At present, predictors for patients’ response to 5-ASA are lacking. Our aim was to identify circulating markers to predict the therapeutic effect of 5-ASA in patients with UC.

Methods
Plasma samples were collected from patients with active UC at baseline and analyzed using the OLINK panel (Target 96 Inflammation). Effective therapy was defined as achieving clinical remission within 8 weeks or mucosal healing within 1 year of 5-ASA treatment. Orthogonal Projections to Latent Structures Discriminant Analyses (OPLS-DA) were implemented to correlate patient groups to plasma proteins in linear multivariate models. Machine learning models (ML) were constructed to predict ineffective therapy in UC patients.

Results
Among the 36 UC patients involved (media age 38.5 years old, men 61.6%), 18 patients belonged to the effective group and the ineffective group, respectively. In multivariate analysis, circulating inflammatory protein profiles could distinguish the patients who did not respond well to 5-ASA treatment (Figure 1A). Elevated levels of Axin 1 (p=0.012), sulfotransferase 1A1 (ST1A1) (p=0.032) and interleukin 15 receptor subunit alpha (IL-15RA) (p=0.022), and decreased level of interleukin 2 (IL-2) (p=0.036) were observed in UC patients refractory to 5-ASA therapy (Figure 1B). Receiver operating characteristic curves (ROC) for predicting the therapeutic efficacy of 5-ASA were constructed. The areas under ROC (AUC) of Axin 1, ST1A1, IL-15RA and IL-2 for the prediction of ineffective 5-ASA therapy were 0.744 (p=0.012, sensitivity 83.3%, specificity 72.2%), 0.710 (p=0.031, sensitivity 94.4%, specificity 55.6%), 0.704 (p=0.037, sensitivity 88.9%, specificity 50%) and 0.704 (p=0.037, sensitivity 77.8%, specificity 61.1%), respectively (Figure 1C). Combination of the four protein markers improved the performance of prediction (AUC 0.860 to 1.000, sensitivity 72.2%-100%, specificity 83.3%-100% across all machine learning classifiers) (Figure 1D).

Conclusion
We identified four plasma inflammation-related proteins associated with the therapeutic effect of 5-ASA in UC. The ML models demonstrated excellent performance in predicting the therapeutic effect of 5-ASA, which could help clinicians identify UC patients who are refractory to 5-ASA in the early course of disease and timely initiation of treatment escalation.
P671 Patient perspectives on symptoms and impacts in Crohn’s disease: Results from qualitative research
Authors: Gibble T H , Kosa K , Basnyat B , Martin S , Moses R , Dubinsky M 
Published: January 2024

Abstract

Background
Patients’ perspectives on their Crohn’s disease (CD) symptoms and the impacts of CD on their daily lives can be used to inform clinical care and treatment development. This study aimed to elicit in-depth qualitative information on the symptom burden of CD and to quantify which symptoms patients considered most bothersome and most important to improve.

Methods
Individual, web-based interviews were conducted in adults and adolescents (aged 15–17 years) with moderately to severely active CD. Participants were asked open-ended questions to elicit their experiences with CD and CD-related impacts on their daily lives. Participants were then probed about symptom- and impact-related concepts of interest that they did not spontaneously report. Participants were asked which symptoms they considered most bothersome and which symptoms they considered most important to improve. Interview transcripts and field notes were analyzed using a standard thematic analysis approach.

Results
17 adults and 3 adolescents participated between May and July 2023. Participants were 17–60 [mean=38] years old; 70% were female [n=14]; 70% were White [n=14]. Participants had been diagnosed, on average, 10 (range: 0.5–29) years ago. Over half (n=13, 65%) reported moderate CD severity. Nearly all participants reported fatigue (n=19, 95%), bowel urgency (n=18, 90%), diarrhea (n=18, 90%), abdominal pain (n=17, 85%), and frequent bowel movements (n=15, 75%). About a third reported nausea (n=7, 35%), bloating (n=6, 30%), joint pain (n=6, 30%), or blood in their stool (n=6, 30%). In total, nine different most bothersome symptoms or treatment priorities were reported across participants (Figure 1). Participants most commonly reported abdominal pain (n=6, 30%), bowel urgency (n=4, 20%), and diarrhea (n=4, 20%) as their most bothersome symptoms; these were also the symptoms most commonly reported as the most important to improve (abdominal pain: n=7, 35%; bowel urgency: n=5, 25%; diarrhea: n=4, 20%) (Figure 1). All participants reported that CD hinders their daily activities, and nearly all reported that CD affects their mood or emotions (n=19, 95%), social activities or relationships (n=19, 95%), work or school (e.g., loss of productivity) (n=18, 90%), and sleep (n=15, 75%) (Table 1). Participants described "feel[ing] left out", "want[ing] to stay home", and having to cancel or leave activities because of their CD. Several participants indicated that they "plan their day around [their CD]".

Conclusion
Patients with moderately to severely active CD were burdened by a variety of symptoms. Patients commonly considered abdominal pain, bowel urgency, and diarrhea symptoms to be the most bothersome and the most important to improve.
P673 Accelerated intravenous ustekinumab dosing as rescue therapy in Moderate- Severe Ulcerative Colitis
Authors: Muñoz Villafranca M D C , Arreba P , Buendia L , Higuera R O , López M L , Prado N F , Irusta L , Jiménez M A , Aldama M , Santacruz M , Perez A , Rodriguez P , Bilbao A , Ortiz de Zárate J 
Published: January 2024

Abstract

Background
Ustekinumab (UST) is an accepted treatment for patients with moderate- severe Ulcerative Colitis (UC) following failure with corticosteroids and/or anti-TNF. Some studies suggest that intravenous (IV) administration, in an accelerated schedule, could improve outcomes in this difficult-to-manage group with a high risk of colectomy.

Methods
We conducted a retrospective analysis in patients with moderate-severe UC who received UST (IV) as rescue treatment, following failure with corticosteroids and infliximab. UST was administered intravenously, with an initial dose of 6mg/Kg followed by 130mg every four weeks. Clinical activity was determined by the Partial Mayo Score (PMS), and endoscopic activity by the Mayo Score (SM). Clinical Remission (CR) was defined as PMS&lt;2, and Clinical Response (CRp) as a reduction in activity of ≥30%.

Results
The study included 17 patients, 8 (47%) women, 9 (52.9%) of whom were hospitalized at baseline, and 11/17 required transfusion or intravenous iron. According to PMS, clinical activity was severe in 16 (94.12%) and moderate in one. Endoscopic activity according to SM was severe in 13 (76.4%). Clinical remission and response were as follows: 1 (5.8%) / 7 (41.1%) patients respectively at week 4; 8 (47%) / 16 (94.1%) patients at week 12; and at week 26, 15 patients had completed the study, 10 (66.6%) in CR, and 12 (80%) in CRp. Ustekinumab was withdrawn in one case due to an infusion reaction, and one patient underwent colectomy. No independent predictors of response to UST were found in this study.

Conclusion
Intravenous ustekinumab in an accelerated dosing schedule is effective in moderate-severe UC, achieving clinical response in more than two-thirds of patients at week 26.
P684 Using a pharmacokinetic simulation model to determine the optimal infliximab intensification strategy to address loss of response in inflammatory bowel disease
Authors: Srinivasan A , Upton R 
Published: January 2024

Abstract

Background
The optimal dose intensification strategy to address loss of response associated with low infliximab levels remains uncertain. Favorable associations between higher infliximab levels and objective endpoints imply that post-intensification trough and treatment targets may have utility. This simulation study aimed to identify intensification strategies capable of achieving post-intensification trough thresholds associated with aspirational treatment targets in Crohn’s disease (CD) and ulcerative colitis (UC).

Methods
A previously published infliximab pharmacokinetic model, applied to 200 simulated patients, identified those with subtherapeutic(&lt;3.00mg/L) trough levels after 30-weeks of standard dosing, and subsequently applied ten dose intensification strategies (Figure 1) over a further 32 weeks. The proportion of simulations achieving infliximab trough thresholds associated with endoscopic remission (CD &gt;9.7mg/L; UC &gt;7.5mg/L) was the primary outcome, with clinical improvement (CD &gt;7.0mg/L; UC &gt;3.7mg/L) and perianal fistula healing (CD &gt;10.1mg/L) representing secondary outcomes. Outcomes were stratified by intensity of dose intensification, with five deemed intensive (&gt;10mg/kg 8-weekly). The impact of pre-intensification antibodies to infliximab (ATI) on post-intensification trough levels was also evaluated.

Results
The median pre-intensification infliximab trough level was 0.91mg/L (IQR 1.31). Intensive intensification strategies were more likely to achieve infliximab trough concentrations associated with endoscopic remission (UC: 34.76 v 10.56%, CD: 25.80 v 4.92%), clinical improvement (UC: 61.40 v 34.52%, CD: 39.58 v 12.12%) and perianal fistula healing (24.70 v 4.50%, all p&lt;0.01) than standard intensification strategies (Figure 2). When controlling for cumulative (mg/kg) infliximab dose over 32 weeks, strategies that concurrently dose increased and interval shortened achieved the highest trough levels (all p&lt;0.01). Patients simulated to have ATI prior to dose intensification had lower median infliximab trough levels at weeks 30/32 (3.38 mg/L, IQR 5.52 mg/L) compared to those without ATI (3.89 mg/L IQR 6.14 mg/L) across all dose intensification strategies (p=0.015).

Conclusion
This simulation-based analysis highlights the potential of using post-intensification trough level targets to guide dosing strategy and intensity. Combined high-dose, interval-shortened strategies appear to achieve higher infliximab levels, which may be important in the pursuit of stringent endpoints such as endoscopic remission and fistula healing. These findings require validation across real-world cohorts.
P700 The efficacy of adalimumab combined with surgery for rectovaginal fistula in Crohn's disease：a single-center retrospective study
Authors: Yan Y , Liu X , Yi J , Luo D , Gen J , Wang H 
Published: January 2024

Abstract

Background
To assess the efficacy of adalimumab(ADA)combined with surgery in the treatment of Crohn's disease patients with rectovaginal fistulas.

Methods
A single-center retrospective study. The baseline data of patients with Crohn’s rectovaginal fistulas who visited the Anorectal Department of the Affiliated Hospital of Nanjing University of Chinese Medicine from January 2020 to July 2022 and accepted ADA combined with surgery treatment were included. Crohn’s disease Activity Index(CDAI), perianal disease activity index(PDAI) and inflammatory parameters, including Erythrocyte sedimentation rate(ESR) and C-reactive protein(CRP), were statistically analyzed at weeks0, 48. Follow-up was performed every 8 weeks. The outcomes included clinical response, clinical remission, fistula response, fistula remission, fistula remission under MRI, endoscopic response and endoscopic remission.

Results
A total of 43 RVF patients were included, 53.4% (23/43) patients were treated with Seton,44.1% (19/43) patients were treated with Advancement flap and 2.3%(1/43) patient was treated with Fecal diversion, with a median follow-up of 11.0 (2.5-15.0) months. After 48 weeks of treatment, CDAI[325(262,397)vs.197(134,396)], PDAI[8(6,9) vs. 5(3,6)], ESR[31(8,50) mm/h vs. 10(4,28)mm/h]and CRP[4.62(0.85, 14.45)mg/L vs.0.5(0.5,2.14)mg/L] were significantly lower than 0 week (Table 1) . CDAI, PDAI, ESR and CRP at the 48th week of treatment were significantly lower than those before treatment (p&lt;0.05). At the last follow-up, 62.7%(27/43) patients achieved clinical response, 30.2%(13/43) achieved clinical remission. Meanwhile 69.7%(30/43) of patients achieved fistula response,32.5%(14/43) achieved fistula remission(Table 2),and 25.5%(11/43) achieved fistula remission under MRI; A total of 37 patients completed endoscopic re-examination, including 54.0% (20/37) of patients with endoscopic response and 24.3%(9/37) with endoscopic remission.

Conclusion
ADA combined with surgery is effective in the treatment of patients with Crohn’s rectovaginal fistulas.
P711 Outcomes of Outpatient Biologic Exposed Patients Hospitalized with Severe Ulcerative Colitis
Authors: Al-Bawardy B , Al Sulais E , Mukhtar M , Hart A , Raine T 
Published: January 2024

Abstract

Background
Up to 20% of patients with ulcerative colitis (UC) will require hospitalization for an acute severe flare. It is unclear whether outpatient exposure to biologics alters the outcomes of inpatient severe UC. We aimed to assess the outcomes of hospitalized severe UC patients exposed to biologics in the outpatient setting.

Methods
This was a multicenter, retrospective study of adult patients hospitalized with severe UC at University of Cambridge, Cambridge, St. Mark’s Hospital, London and Yale University, Connecticut (from 1/1/2012-11/1/2021). We included adult patients (age ≥ 18 years) who were hospitalized for a severe UC flare as determined by the treating clinician. The primary outcome was need for colectomy among outpatient biologic exposed vs biologic naïve patients. Secondary outcomes stratified by outpatient biologic exposure included length of hospitalization and need for rescue medical therapy.

Results
A total of 382 patients (53.2% male) with a median age of 35 years [interquartile range (IQR) 25-53] were reviewed. Outpatient biologic exposure was noted in 23.2% (n=86, 52 exposed to infliximab) while 76.8% (n=284) were naïve to biologics. Median disease duration was longer in the biologic exposed group at 6 years (IQR 2-11) compared to 2 years (IQR 1-8) in the biologic naïve group (p &lt; 0.001). Biologic exposed group was more likely to have pancolitis (70.2% vs. 54.7%; p=0.04). The C-reactive protein (CRP) to albumin ratio was higher in the biologic naïve group was higher at 12.8 (IQR: 3.2-35) vs. 8 (IQR: 1-21.5) (p=0.004).
The biologic exposed group was more likely to undergo colectomy at 25% (n=21) vs. 9.3% (n=26) in the biologic naïve group (p&lt;0.001). The median hospital length of stay was 6 days (IQR: 4-9) in both groups (p=0.96). Need for rescue medical therapy 37.7% (n=107) in the biologic naïve group vs. 41.9% (n=36) in the biologic exposed group (p=0.49).
Colectomy was associated with outpatient biologic exposure (44.7% vs. 19.9%, p=0.0002), Mayo UC endoscopic sub-score of 3 (81.6% vs. 55.1%, p=0.002), higher median CRP [70.6 (IQR:26.8-126.3) vs. 38.8 mg/dL (IQR: 9.7-94.7), p=0.04], lower median albumin [3 (IQR: 2.7-3.6) vs. 3.5 (IQR: 3-4) g/dL, p=0.0002], and female sex (61.2% vs. 44.8%, p=0.03). On multivariable analysis, only low albumin was independently associated with risk of colectomy (odds ratio: 3.31, 95% confidence interval 1.59-6.87, p=0.0005)

Conclusion
In our multicenter cohort, outpatient biologic exposure was associated with increased risk of colectomy among hospitalized patients with severe UC but on multivariable analysis only low albumin was independently associated with risk of colectomy. Further study of larger cohorts is warranted.
P715 Multiparametric assessment of IBD and SpA-IBD patients to explore disease biomarkers and response predictors
Authors: Privitera G , Parisio L , Perniola S , Varca S , Alivernini S , Tolusso B , Petito V , Napolitano D , Schiavoni E , Scaldaferri F , Gasbarrini A , Armuzzi A , Gremese E , Guidi L , Pugliese D 
Published: January 2024

Abstract

Background
Immune-mediated inflammatory diseases (IMID) are an emerging problem in Western world. Despite being traditionally considered nosologically distinct entities, two or more IMID can coexist within the same patient and their pathogenesis overlap to a certain extent. Two IMID, inflammatory bowel disease (IBD) and spondylarthritis (SpA), often associate, but their pathogenesis remains unknown and disease biomarkers are not fully characterized. This project aims to investigate pathogenic and predictor markers of response

Methods
A collaborative study, enrolling IMID patients (pts) starting a target therapy, was performed. We focused on 2 cohorts: IBD and IBD-SpA. At baseline, serum (to measure CRP, IL17A, TNFα, and TREM1), intestinal biopsy and stools were collected. Clinical response was assessed at 4 months. The exploratory outcome of this preliminary analysis was to investigate whether serum, immunohistochemical and microbiological markers correlate with each other and with response to therapy

Results
We enrolled 60 pts (36 IBD, 24 IBD-SpA): 61.7% were female, median age was 46 years (IQR 30-57.3). At 4 months, 52.8% and 41.7% of the IBD and IBD-SpA cohorts showed clinical response. A nearly significant correlation between increased intestinal CD68+ cell infiltrate and higher baseline CRP levels (R=0.52, p=0.06), and between increased CD21+ cell infiltrate and CRP drop at 4 months (R=0.47, p=0.09) was observed. Lower baseline TNFα levels correlated with CRP drop at 4 months (R=0.35, p=0.02); higher baseline TNFα levels correlated with a reduced intestinal infiltrate of CD20+ and CD21+ cells (R=0.67, p=0.04; R=0.69, p=0.04). In the IBD-SpA cohort, a trend towards higher mean TREM1 levels was observed in non-responders vs responders (389.0 pg/mL vs 276.4 pg/mL, p=0.09); ROC curve identified a cut-off of 361.0 pg/mL to predict nonresponse (sensitivity 66.6%, specificity 75.0%, p=0.09). IBD patients had a reduced α-diversity compared to healthy controls (HC) and SpA patients; IBD and SpA patients had an increased β-diversity compared to HC. IBD pts had increased Proteobacteria and decreased Bacteroidetes compared to HC. Agathobacteria, Bacteroides, Faecalibacteria and Prevotella genera were significantly decreased in IBD vs HC, whereas Streptococci and Escherichia-Shigella were significantly increased

Conclusion
Baseline TNFα may correlate with specific immune signatures of the intestinal infiltrate. Baseline TREM1 may help predicting response in the specific setting of concomitant IBD and SpA. Gut microbiome composition is altered in IBD pts compared to HC, comprising more pathogenic and fewer protective bacteria. Further analyses will be needed to confirm such observations and explore additional features and predictive biomarkers
P734 Super-responders in patients with moderate-to-severe Crohn’s disease treated with subcutaneous infliximab maintenance therapy: A post hoc analysis of the LIBERTY-CD study
Authors: Schreiber S W , Sands B E , Hanauer S B , Danese S , Loftus Jr E V , Jeong A L , Kim D H , Lee Y N , Colombel J F 
Published: January 2024

Abstract

Background
The LIBERTY-CD study demonstrated a broad level of benefit for subcutaneous (SC) infliximab (IFX) maintenance therapy compared with placebo in patients (pts) with moderate-to-severe active Crohn’s disease (CD) who responded to intravenous IFX induction. Characterising subgroups of pts with different levels of response could help to better position SC IFX therapy.

Methods
This was a post hoc analysis of 231 pts from the CT-P13 SC arm of the randomised, parallel-group, placebo-controlled LIBERTY-CD study (NCT03945019). Unsupervised group-based trajectory modelling (GBTM) was conducted to deconvolute cohort-level data into response trajectories. Longitudinal patient reported outcomes (PRO-2: abdominal pain and stool frequency) were used to investigate whether pts who received SC IFX maintenance therapy cluster into response trajectories. Efficacy endpoints (clinical remission, endoscopic response and remission, corticosteroid-free remission and comprehensive disease control [CDC] rate) were analysed and compared between different trajectories. Trough levels of IFX (TLI) were evaluated by trajectory throughout the treatment period. Baseline characteristics were analysed in a descriptive manner to explore predictors for super-response.

Results
Four distinct trajectories were clearly separated and stabilised around Week (W) 10–14 (Figure): rapid and sustained improvement (super-responders, n=61), rapid, but slightly less drastic than super-responders, then sustained improvement (fast responders, n=56), gradual then sustained improvement (slow responders, n=63) and partial improvement during the maintenance phase (limited responders, n=51). Super-responders had the highest rates of W54 clinical remission (73.8%; p=0.002), endoscopic response (63.9%; p=0.009), corticosteroid-free remission (63.6%; p=0.007), endoscopic remission (42.6%; p=0.094) and CDC (37.7%; p=0.013) among trajectories (Table). Super-responders also maintained the highest TLI from W10 throughout the maintenance period. Super-responders showed a trend towards lower baseline body weight, body mass index and oral corticosteroid use, but higher Crohn’s Disease Activity Index score and prior biologic/Janus kinase inhibitor use compared to other trajectories.

Conclusion
Distinct subpopulations with different levels of responses were detected by GBTM using data from a large group of pts with moderate-to-severe active CD who were treated with SC IFX for 1 year. Super-responders with rapid and sustained improvements during SC IFX therapy had a higher likelihood of achieving desirable long-term outcomes, with substantial individual benefit (CDC). Baseline characteristics and TLI were associated with super-response.