bluuebunny/crossref_metadata_2025_split huggingface dataset:
P915 Multi-Omics Biomarkers for the Prediction of Response to Biologics in Patients with Inflammatory Bowel Disease
Authors: Chen L , Zhang C , Niu R , Mao R , Qiu Y , Feng R 
Published: January 2024

Abstract

Background
The treatment concept for inflammatory bowel disease (IBD) has been transformed with biologics now recommended as the first-line therapy for moderate-to-severe patients. However, the significant heterogeneity among IBD patients has limited the efficacy of selected biologics based on traditional clinical factors. Therefore, it is imperative to molecularly stratify patients to match them with the most appropriate biologics. In this study, we systematically reviewed baseline omics biomarkers that have the potential to predict response to biological therapies, aiming to facilitate precision medicine in IBD.

Methods
We conducted a comprehensive literature search using PubMed by which we included studies that explore the role of omics biomarkers in predicting the efficacy of various biologics including anti-TNFα, anti-integrin, anti-IL-12/23P40 and anti-IL-23 P19 in patients with IBD.

Results
Our review included 110 studies. Of these, 86 studies focused on anti-TNFα, 17 focused on anti-integrin and 7 focused on anti-IL-12/23P40 and/or anti-IL-23P19. These studies investigated multi-levels baseline biomarkers, including genomics, transcriptomics (bulk RNA and sc-RNA sequence), proteomics, microbiome, and metabolomics (derived from serum, urine, or stool). Furthermore, recent studies already focused on integrating multiple omics analysis and showed that the predictive model based on multi-omics data could significantly enhance their performance. Among the available biomarkers, mucosal transcription of OSM (AUROC = 0.83), IL-13RA2 (AUROC = 0.90), and TREM-1 transcription in mucosal biopsy (AUROC = 0.77) as well as in PBMC ( AUROC varies between 0.78 and 0.94) could accurately predict the response to anti-TNFα. The mucosal IL-23A transcription could discriminate responders from non-responders to anti-IL-12/23P40 with an AUROC of 0.90. OSM, biomarkers of intestinal collagen turnover like C4M, IL-17, IL-22, and TNFα in serum also showed significant potential in predicting the response to anti-TNFα, anti-integrin and anti-IL-12/23P40. In addition, single-cell molecular signatures with sc-RNA sequencing provided more profound insights into predicting the response to biologics. The lack of reproducibility in results across different groups may be due to the disparity in patient selection, methodology, and study designs among different investigations.

Conclusion
Numerous omics markers have shown great potential in predicting the efficacy of biologics. However, it is crucial to explore and validate these novel biomarkers in larger cohorts using harmonized protocols to facilitate their evaluation into actual clinical practice, especially for newer biologics like anti-IL-12/23P40 and anti-IL-23P19.
P959 Dose escalated vedolizumab in Inflammatory Bowel Disease - Crohn's Colitis Cure (CCC) Data Insights Program
Authors: Mcnamara J , Alshiwanna B , Wilson W , Pipicella J L , Ghaly S , Gearry R , Begun J , Ng W , Lynch K , Lawrance I , Schultz M , Walker G , Radford-Smith G , Andrews J A , Connor S J 
Published: January 2024

Abstract

Background
Vedolizumab is a gut specific integrin antagonist with established efficacy in inflammatory bowel disease (IBD). Many people with IBD fail to achieve adequate or sustained response to standard dosing, thus requiring dose escalation (DE). We aimed to explore the need for escalated dosing and subsequent outcomes in a large real-world cohort.

Methods
We utilised data from the CCC registry entered during routine clinical care at 14 centres across Australia and New Zealand. Data were extracted in October 2023 and included patients on intravenous (IV) and subcutaneous (SC) therapy. DE was defined as maintenance dosing &gt; 108mg SC fortnightly, &gt; 300mg IV Q8weekly and/or additional induction doses. We examined data prior to and at 12 months post DE.

Results
919 people with IBD received Vedolizumab, with 28% (n=261) receiving DE therapy. Median age for the DE cohort was 40 years (IQR 29-56) with median age at diagnosis 26 (IQR 19-39). Median age, age at diagnosis, disease duration and BMI did not vary significantly between the DE and standard dosing cohorts. Most of the DE cohort had Crohn’s (60%) followed by ulcerative colitis (38%) and IBD-unclassified (2%). Half the DE cohort was female (49.8%) with median time to dose escalation being 6 months. 57% (n=111) continued on DE Vedolizumab after 12 months.
Median drug level (where measured) increased from 10.3mg/L pre-DE to 19.8mg/L post. Rates of faecal calprotectin (FCP) remission, (FCP &lt;250ug/g) increased at 12 months post DE as did rates of PRO2 and endoscopic remission (p=0.007, 0.034 & 0.016 respectively). Improved remission rates coincided with decreased systemic steroid requirements, which fell by &gt;50% at 12 months post DE (p=0.001). Hospital admissions and radiological investigations were unchanged over the study period, however the need for endoscopic assessment decreased 12 months post DE. Patients receiving DE therapy had increased encounters healthcare providers, with more clinical assessment and Healthline calls at 12 months post DE (p=0.001 & 0.001 respectively).

Conclusion
In an Australasian cohort of people with IBD, over a quarter of individuals receiving Vedolizumab therapy required DE. DE Vedolizumab correlated with improved endoscopic, PRO2 and FCP remission rates at 12 months with reduced steroid use. As biosimilars reduce the cost of DE therapy, further research beyond 12 months examining remission rates, healthcare utilisation and cost analysis in more detail is needed.
P974 Incidence of Perianal Complications in Clinical Trials for Therapies for Moderate to Severe Inflammatory Bowel Disease
Authors: McDonald B , Choi N , St-Pierre J , Klein J , Rubin D 
Published: January 2024

Abstract

Background
Crohn’s disease (CD) and ulcerative colitis (UC) are chronic inflammatory bowel diseases (IBDs) with distinct clinical consequences. Distinct from patients with UC is that nearly 25% of patients with CD patients have or will develop perianal disease. Predictors for the development of new perianal disease or complications from existing perianal disease are not well described but such occurrences are included as adverse events (AEs) in clinical trials for IBD. We performed a systematic review and meta-analysis of perianal AEs in pivotal trials of therapies for IBD.

Methods
We conducted a search of PubMed, EMBASE, MEDLINE, Medline Plus, and CDSR library databases for registry and pivotal Phase II-III clinical trials of therapies for IBD. Safety data from clinicaltrials.gov was reviewed to identify incidence of perianal AEs using the terms "abscess" and "fistula." Reported perianal AEs included the following: anal abscess, fissure, fistula; perianal abscess, fistula; perineal abscess; perirectal and rectal abscess; subcutaneous (gluteal) abscess.

Results
Perianal AE incidence across all trials reviewed was 0.47% (91/19,327 patients). Perianal AEs were more likely to occur in patients with CD (0.77%, 70/9,046) than UC (0.20%, 21/10,281). Perianal AEs occurred more frequently in populations of drug-exposed patients than in patients exposed to placebo. In drug-exposed patients with UC, 0.22% (16/7,415) of patients experienced a perianal AE vs 0.17% (5/2,935) of patients exposed to placebo. In drug-exposed patients with CD, 0.76% (55/7,271) of patients experienced a perianal AE vs 0.61% (15/2,465) of patients exposed to placebo. The results are summarized in Table 1.

Conclusion
We found that perianal AEs occur in pivotal UC and CD clinical trials. Expectedly, the frequency of perianal AEs was higher in trials of CD than those for UC. However, the development of perianal AEs in trials of UC suggests that these patients may have been misclassified and have CD. Available data do not allow distinction between development of a perianal AE in a patient with known perianal disease or progression of undiagnosed clinical or subclinical perianal disease, nor does it allow for distinction in a patient not responding to the experimental agent. The finding that perianal AEs occurred more frequently with drug exposure than placebo may be due to fistula healing with consequential abscess formation or unique mechanistic effects that worsen perianal disease. These results highlight a probable rate of misclassification of patients with UC in pivotal trials, and suggest the possibility of subclinical perianal disease in some patients. Further clarification and study of these AEs and their implications are warranted.
P1037 Treatment sequences and time on specific treatments in patients with inflammatory bowel disease under advanced treatment – a German claims data analysis
Authors: Dignass A , Teich N , Kudernatsch R , Sünwoldt J , Grellmann C , Sende F , Kaiser S 
Published: January 2024

Abstract

Background
The number of advanced therapies (ADT) approved for the treatment (Tx) of inflammatory bowel disease (IBD) in is increasing, however, yet no guidance on optimal sequencing of treatments is available in Germany (and elsewhere). This study aims to investigate applied Tx sequences of ADT in claims data based on real-world setting across Germany in patients (pts) with IBD.

Methods
A retrospective healthcare claims data analysis was conducted using claims data from approx. 4.5 Mio pts within German statutory health insurance, including pts diagnosed with Crohn’s disease (CD) and ulcerative colitis (UC) from 2014 to 2021. Pts were followed up for at least 6 months after the first prescription of ADT (index date) if not deceased. A pre-index period of at least 12 months was applied to only include pts naïve to ADT. The study assessed Tx sequences and time to next treatment (TTNT) among other parameters. Data was not adjusted to disease severity and only descriptively reflects real world Tx patterns within the database.

Results
The database included 15.041/18.361 pts with CD/UC. Pts with CD/UC starting ADT between 2014 to 2021 received either Adalimumab (ADA: 923/337), Infliximab (IFX: 616/419), Ustekinumab (UST: 113/25) or Vedolizumab (VDZ: 139/248). In an analysis of ADT sequences and TTNT defined as start of first line (1L) Tx to start of second line (2L) Tx we found that during the observation period the majority of pts (71.4%) have not switched to 2L Tx yet. In 1L, ADA was observed as the preferred Tx in CD pts (51.5%) followed by IFX (34.4%), VDZ (7.8%) and UST (6.3%), in UC pts IFX (40.7%) was mostly prescribed as 1L followed by ADA (32.8%), VDZ (24.1%) and UST (2.4%). The proportion (%) of pts not switched to 2L Tx within one year for CD/UC were: ADA (83.6/70.3), IFX (79.0/73.1), UST (93.5/96.0) and VDZ (85.4/86.6). Within three years proportions of pts not switched to 2L Tx changed for CD/UC: ADA (68.1/54.5), IFX (57.8/56.8), UST (82.5/72.0) and VDZ (72.7/73.0) (table1). For pts who had a switch to a different ADT, the switch occurred within one year in over 50% of all pts. Most Tx switches (45.8%) were observed in pts who received IFX as 1L Tx, both in the UC and CD population. The majority of CD pts that received 2L Tx were switched to UST (35.7%), while in UC, a high proportion of pts were switched to VDZ (44.3%). Further Tx pathways and proportions of switches are summarized in Figure 1.

Conclusion
The study found that most IBD pts started ADT with ADA or IFX, but unadjusted time on 1L data may suggest a trend towards superior TTNT of VDZ and UST in UC and CD. Data should be interpreted carefully, as pts for &gt;1L are limited and UST and VDZ were approved during the study period.
P1057 Upadacitinib as Salvage Therapy for Acute Severe Ulcerative Colitis: A Single-Center Experience
Authors: St-Pierre J , Choi D , Krugliak Cleveland N , Miyatani Y , Friedberg S , Choi N K , Picker E A , Fear E , Fine Z , Han J , Labas J , Rubin D T 
Published: January 2024

Abstract

Background
Ulcerative colitis (UC) often leads to hospitalization and may be resistant to standard treatments, necessitating colectomy. Upadacitinib (UPA), an oral selective Janus kinase 1 inhibitor, offers a novel mechanism and the benefit of rapid and predictable pharmacokinetics which suggest it may be efficacious in acute severe UC (ASUC). However, there are a limited number of cases using different dosing regimens describing the potential of this treatment for ASUC. We describe the efficacy and safety of UPA in hospitalized patients with ASUC at our center.

Methods
We conducted an observational cohort study of patients hospitalized for ASUC treated with UPA 45 mg/d as a rescue therapy after failure or incomplete response to other therapies, including corticosteroids. Patient demographics, disease characteristics, and clinical data were collected. The Simple Clinical Colitis Activity Index (SCCAI) was used to monitor clinical response. Clinical outcomes, including loss of response and colectomy, were collected.

Results
Ten patients (ages 21-78, 40% female) hospitalized for ASUC were treated with UPA (population characteristics and clinical summarized in Table 1). The majority of patients (8/10) had prior exposure to two or more advanced therapies. The median SCCAI score at the time of UPA initiation was 8.5, with improvement in five patients on upadacitinib at week 2 (Figure 1). Six of 10 patients discontinued UPA, 3 of whom underwent colectomy during the same hospitalization due to inadequate response. Two patients underwent surgical intervention after discharge from the hospital. Patients who underwent colectomy had a significantly lower albumin level at the time of UPA initiation compared to patients who didn’t undergo colectomy (3.0 and 4.2 g/dL, respectively; p = 0.005), but not CRP (28.5 and 29.8 mg/L, respectively; p = 0.48). One patient had discontinuation of upadacitinib during the induction phase due to elevated liver enzymes. The median time to discontinuation was 7.5 days. Of the 4 patients on ongoing therapy with UPA after initiation in hospital, 2 have been on the maintenance dose for over 6 months with ongoing remission.

Conclusion
Our experience with UPA 45 mg/d for salvage therapy in ASUC patients demonstrated a higher colectomy rate than reported in earlier studies, which . Although some patients benefited from UPA with an improvement in SCCAI scores by week 2, the colectomy rate highlights the need for further research to identify which patients are most likely to benefit from UPA therapy. Our findings underscore the importance of personalized approaches to ASUC treatment and warrant further investigation in larger, controlled studies.
P1069 One-year clinical outcomes of switching to subcutaneous infliximab in patients with inflammatory bowel disease on maintenance of intravenous infliximab therapy with or without remission: A multicentre cohort study
Authors: Bae J H , Park J B , Baek J E , Lee Y J , Kim K O , Kim E S , Jo H H , Hong S W , Park S H , Yang D H , Ye B D , Byeon J S , Myung S J , Yang S K , Kim E Y , Hwang S W 
Published: January 2024

Abstract

Background
An elective switching to the subcutaneous (SC) formulation of infliximab (IFX) has shown effectiveness and safety in patients with inflammatory bowel disease (IBD) on intravenous (IV) IFX maintenance therapy. However, data on long-term outcomes in patients not in clinical remission during maintenance therapy is limited. This study aims to evaluate the long-term outcomes of SC switching in patients who were in clinical remission and not in remission during IV IFX maintenance therapy.

Methods
This retrospective multicentre study was conducted from January 2021 to October 2023. Clinical remission was defined as Crohn’s Disease Activity Index (CDAI) &lt;150 for Crohn’s disease (CD) and partial Mayo score &lt;2 for ulcerative colitis. Biological remission was defined as faecal calprotectin (FC) &lt;250 µg/g and C-reactive protein (CRP) &lt;0.5 mg/dL. The primary outcome measure was 1-year treatment persistence of SC IFX.

Results
Among 127 patients included in the study, 80 (62.9%) had CD, and 47 (37.1%) had UC. At the time of switching, 90 patients (70.9 %) were in clinical remission; whereas, 37 (29.1 %) were in a non-remission state. The treatment persistence rate at 1 year was high at 92.9%. Treatment persistence rates between the clinical remission and non-remission groups did not differ significantly (94.4% vs. 89.2%, p=0.287). In both groups, IFX pharmacokinetics and biomarkers between baseline and 12 months (p&lt;0.01) significantly improved. The median infliximab levels increased from a baseline of 3.3 µg/mL (interquartile range [IQR] 1.3–5.1) to 14.4 µg/mL (IQR 9.4–23.0, p&lt;0.001) at 12 months. Disease activity index was stable in the remission group, and decreased in the non-remission group (partial Mayo score, p&lt;0.001; CDAI, p=0.063). At the one-year follow-up, clinical remission and biological remission were achieved in 86.6% and 60.6%, respectively, an increase from baseline (70.9% and 48.0%, respectively). Biologics exposure before IFX was the only significant variable associated with treatment persistence (odds ratio 5.138, 95% confidence interval 1.150–22.951, p=0.032). The concomitant use of immunomodulators was not associated. The incidence of IFX-related adverse events was 14.2%, with only three patients discontinuing treatment.

Conclusion
Switching to SC IFX from IV IFX maintenance therapy demonstrated high treatment persistence and favourable safety profiles, irrespective of remission status at the time of switching. Patients in both remission or non-remission states showed significant improvement in pharmacokinetics and biomarkers, and/or stable disease activity indices.
P1089 Disease characteristics at time of diagnosis of adult onset inflammatory bowel disease and the risk of venous thromboembolism in the modern era – A Swedish nationwide cohort study 2007-2021
Authors: Bröms G , Forss A , Eriksson J , Linder M , Eriksson C , Askling J , Halfvarson J , Ludvigsson J F , Olen O 
Published: January 2024

Abstract

Background
Studies from mainly before the wide use of targeted therapies and guidelines for thromboprophylaxis indicate that patients with inflammatory bowel disease (IBD) are at a doubled risk of venous thromboembolism (VTE). We studied the risk of VTE in a modern-day cohort of patients with IBD, overall and in subgroups of disease characteristics.

Methods
Using Swedish healthcare registers, we identified a nationwide population-based cohort of 55,252 patients with incident IBD between 2007 and 2021 with a median follow-up time of 6.5 years. Patients were matched by age, sex, calendar year and county of residence with up to ten reference individuals from the general population (N=536,067). The primary outcome was VTE, including pulmonary embolism and deep vein thrombosis. Incidence rates per 1,000 person-years and hazard ratios (HR) were calculated for IBD in general and according to disease subtype, sex, age and disease characteristics at diagnosis. HRs stratified by matching variables (model 1) and additionally adjusted for comorbidities and socioeconomic factors (model 2) were estimated by using Cox regression.

Results
The incidence rate of VTE among patients with IBD was 5.03 per 1,000 person-years compared with 2.34 per 1,000 person-years among reference individuals (Table 1). This corresponded to a doubled incidence of VTE (HR=2.18, 95% confidence interval (CI)=2.07-2.29, model 1). Adjusting further for covariates in model 2 had only minor effects on the HR. The HR was consistent across IBD subtypes and sex. The relative risk was higher for those with younger age (18-39 years) at IBD diagnosis (HR 2.52, 95% CI: 2.22-2.83) with a risk difference of 1.25 per 1,000 person-years. The IR, 10.64 per 1,000 person-years, and risk difference, 5.42 per 1,000 person-years, was the highest for those with elderly onset (≥60 years) IBD. There was a stronger association for those with extensive ulcerative colitis (E3), primary sclerosing cholangitis, extraintestinal manifestations and perianal disease. HRs for VTE were persistently elevated across follow-up time, but was higher during the first year of follow-up (Figure 1).

Conclusion
The risk of VTE was doubled in these modern-day data and remained elevated across follow-up time. Disease characteristics associated with higher inflammatory burden at diagnosis and older age are markers of increased risk. This underscores the importance of continuous vigilance and individual assessment of risk factors for VTE in patients with IBD.
P1101 Patient-reported physical activity of IBD patients is of concern when weighed with the international physical activity questionnaire regardless of disease activity and IBD phenotype: barriers and facilitators emerged from the extended "BE-FIT-IBD" cross-sectional study
Authors: Gravina A G , Pellegrino R , Palladino G , Imperio G , D'Onofrio R , Arboretto G , Romeo M , Ciamarra P , Dallio M , Federico A 
Published: January 2024

Abstract

Background
As the World Health Organization recommends, regular physical activity (PA) determines quality of life. The qualitative/quantitative characteristics of ideal PA to be suggested for inflammatory bowel diseases (IBD) nor the relationship with disease activity are not yet well defined. This study aimed to weigh PA levels and barriers/facilitators to PA in a cross-sectional group of patients with IBD.

Methods
Consecutive Italian non-severe IBD patients (assessed with partial Mayo score for and Harvey-Bradshaw index) received an anonymous online questionnaire to assess PA levels using the International Physical Activity Questionnaire (IPAQ), disease activity as Patient-Reported Outcomes 2 (PRO-2), and finally habits, beliefs, and barriers in conducting regular PA. Clinical, anthropometric, and demographic data were also collected. PA was processed as continuous units of resting metabolic rate in minutes/week (Met min/wk). Three PA groups were identified: inactive (&lt; 700 Met min/wk), sufficiently active (700-2500 Met min/wk) and Health Enhancing PA (i.e., HEPA active, &gt; 2500 Met min/wk) patients.

Results
The 219 patients enrolled exhibited overall PA levels of 834.5 Met min/wk, with a large proportion (94, 42.9%) classified as inactive. Only a minority (9, 4.1%) resulted as health-enhancing PA. Patients with a non-dyslipidaemia metabolic profile (p &lt; 0.0001) or on biologics therapy (p=0.022) showed better IPAQ scores in moderate activities. PRO-2 correlated negatively with IPAQ intense activities scores (τ= -0.156, p=0.038) in ulcerative colitis patients. PRO-2 did not show notable sensitivity/specificity in predicting IPAQ inactivity (AUC &lt; 0.6). IPAQ showed no notable differences when related to disease activity categories according to PRO-2 (p &gt; 0.05). Physically active patients were more willing to discuss their PA with their IBDologists. Several barriers (e.g., diagnosis of IBD and fear of flare-ups after PA) are firmly rooted in physically inactive patients. Evacuation urgency (rectal syndrome) is the IBD-related barrier most physically inactive patients reported. Some fears about PA were worse felt in the absence of a stable partner (i.e., fear of worsening or recurrence of IBD, p &lt; 0.05).

Conclusion
Many Italian IBD patients show a worrying rate of physical inactivity, depriving themselves of the multidimensional benefits that regular PA can bring. There is a need for IBDologists to act by removing barriers to PA and engaging in a regular discussion on the importance of PA with IBD patients. IPAQ has shown good feasibility and patient acceptance in this setting.