bluuebunny/crossref_metadata_2025_split huggingface dataset:
P659 Prognostic markers in Treat-to-Target for Crohn’s Disease- an Asian institution’s experience
Authors: Jiang B , Leong J , Ong J , Ang T L , Wang L M , Tan C K 
Published: January 2024

Abstract

Background
Endoscopic healing (EH) is a long-term treatment target in the Treat-to-Target approach for Crohn’s Disease (CD). However, not all patients with CD will achieve this treatment target due to a combination of factors. This study aims to evaluate the proportions of patients with CD who achieve EH at 24 months from diagnosis. Secondary aims include proportion of patients who achieve corticosteroid free clinical remission (CSFR), biomarker (BM) normalization and predictors of failure to achieve EH.

Methods
This is a retrospective study of all patients with Crohn’s disease seen at a tertiary hospital in Singapore from January 2010 to December 2021. Patients with a confirmed diagnosis of CD based on endoscopic, clinical and histological findings were identified from existing IBD registry. Those with a follow-up period of less than 12 months, no repeat endoscopy and missing data were excluded from analysis. We collected data on baseline demographics, disease characteristics and treatment received. Treatment targets were assessed in terms of CSFR, biomarkers normalization, EH and transmural healing (when available). We defined these targets as outlined in the selecting therapeutic Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) II initiative. Statistical analysis was performed in Python using statsmodels 0.14.0.

Results
We identified a total of 86 CD patients. After excluding 29 patients, 59 patients were included in the final analysis.Mean age at diagnosis was 33 years old, and 69.5% were males. Table 1 demonstrates the baseline demographics and disease characteristics of all patients. The median follow-up period was 101 months. Out of 59 patients, 88% (n=52) and 80% (n=47) achieved CSFR and biomarker normalization respectively at 12 months. At 24 months of follow up, EH was achieved in 54% (n =32) of all patients. Of those who achieved EH, 22 had repeat imaging and transmural healing was documented in 14 patients. On multivariate logistic regression, Montreal B3 (penetrating type) disease was predictive of failure to achieve EH (OR 9.8, p= 0.036). Use of biologics also showed a trend for failing to achieve EH though this was not statistically significant (OR 3.5, p = 0.075).

Conclusion
A vast majority of CD patients were able to achieve corticosteroid free clinical remission and biomarker normalization. Penetrating disease was predictive of failure to achieve EH at 24 months. This study provides additional evidence in determining treatment targets for CD patients based on their disease phenotypes. These findings could be further validated in larger cohort, prospective studies.
P660 Serum Leucine-rich Alpha-2 Glycoprotein Can be a Biomarker for Selecting Anti-Cytokine Biologics in Patients with Inflammatory Bowel Disease: A Multicentre Prospective Cohort Study
Authors: Amano T , Yoshihara T , Shinzaki S , Sakakibara Y , Yamada T , Osugi N , HIyama S , Murayama Y , Ogiyama H , Nagaike K , Tujii Y , Asakura A , Tashiro T , Tani M , Otake-Kasamoto Y , Inoue T , Yonezawa A , Iijima H , Hayashi Y , Takehara T 
Published: January 2024

Abstract

Background
Serum leucine-rich alpha-2 glycoprotein (LRG) is a biomarker reflecting endoscopic activity in patients with inflammatory bowel disease (IBD). However, it remains unclear whether serum LRG can predict the effectiveness of anti-cytokine biologics (biologics) in patients with IBD. This study aimed to evaluate whether serum LRG could predict the effectiveness and serum trough concentrations of biologics in patients with IBD.

Methods
This was a multicentre prospective cohort study including patients with IBD (including ulcerative colitis [UC] or Crohn’s disease [CD]) who received the biologics [ustekinumab (UST), anti-tumor necrosis factor (anti-TNF)] from January 2019 to March 2023 at 15 hospitals participating in the Osaka Gut Forum. The effectiveness of biologics was evaluated by clinical remission (CR) at week 8. We defined CR as a partial Mayo score of 2 or lower, with each subscore of 0 or 1 for UC and a CD activity index of &lt; 150 for CD. Factors associated with CR at week 8 such as backgrounds, disease activities and concomitant medications at week 0 were analyzed by Cox proportional hazards model. For each biologic, we compared the effectiveness of biologics in the high LRG group with that in the low LRG group divided by the median serum LRG levels at week 0 (cut-off = 18.2 μg/mL).

Results
A total of 184 patients with IBD (UC, 80; CD, 104) were enrolled (UST/ anti-TNF, 119/ 65; biologic exposure, 31.5%; median disease duration, 6 years [Interquartile range (IQR) 1-14]). Median serum LRG levels at week 0 and serum C-reactive protein levels at week 0 were 18.2 μg/mL [IQR 12.5-28.1] and 0.19 mg/dL [IQR 0.03-0.77], respectively. At week 0, 63 (34.2%) and 64 (34.8%) patients concomitantly received corticosteroids and immunomodulators, respectively. In 184 patients with IBD, multivariate analysis revealed that serum LRG level at week 0 &lt; 18.2 μg/mL was extracted as a significant factor for CR at week 8 (Odds ratio: OR 2.70, 95% confidence interval: CI 1.22-5.96). In patients who received UST, the proportion of CR at week 8 in the low-LRG group (76.9%) was significantly higher than that in the high-LRG group (59.3%, P = 0.038). In patients who received anti-TNF, however, the proportion of CR in the low-LRG group (84.6%) was not differ from that in the high-LRG group (82.1%, P = 0.781). Median serum trough concentrations of UST at week 8 in the low-LRG group (10.9 μg/mL, IQR 6.7-13.4) was significantly higher than that in the high-LRG group (5.3 μg/mL, IQR 2.4-8.3, P &lt; 0.001).

Conclusion
Serum LRG could predict the effectiveness and serum trough concentrations of UST and be a biomarker for selecting biologics in patients with IBD.
P667 Benefit of 5-ASA continuation on UC disease outcomes following initiation of a biologic
Authors: Tomasic V , Biscanin A , Cacic P , Babic F , Burcul I , Dorosulic Z , Kralj D , Ogresta Kordej D , Hrabar D 
Published: January 2024

Abstract

Background
In the era of advanced therapeutics for treatment of ulcerative colitis (UC) the benefit of routinely prescribed concomitant 5-aminosalicylate (5-ASA) compounds is still unclear.

Methods
A single centre, noninterventional retrospective cohort review study was performed on real-life data of adult patients with moderate-to-severe UC who were treated with biologics (infliximab, vedolizumab, ustekinumab) for a minimum of 6 months with or without concomitant use of 5-ASA. The difference in further treatment failure defined as a clinical negative composite outcome (need for steroid rescue therapy, biologic switch, IBD-related hospitalization and/or surgery) in two groups (5-ASA + biologic combination therapy vs biologic monotherapy) was assessed. Participants’ characteristics were assessed using descriptive statistics. Normal distribution was assessed using Kolmogorov-Smirnov and Shapiro-Wilk tests. Categorical variables were analysed using Chi-square test and continuous variables with Mann-Whitney test. Kaplan-Meier analysis and log-rank test were used in order to assess difference in therapy duration between two groups.

Results
Total of 104 patients (47.1% females; smokers 17.6%; concomitant stable dose oral 5-ASA 33%) were included. There were no differences in key baseline characteristics such as age, sex, smoking status, extraintestinal manifestations, serum albumin and CRP as well as fecal calprotectin levels between groups of patients receiving 5-ASA co-treatment and patients without 5-ASA. Median duration of therapy was 21 months (IQR 9-40). Concomitant use of 5-ASA was not associated with improved clinical outcomes; there was no statistically significant difference in the occurrence (χ2(1, N =102)=2.2, p=0.14) or time to develop (χ2(1, N =102)=1.12, p=0.29; Figure 1.) negative composite outcomes.

Conclusion
In our cohort we have failed to detect any benefit of 5-ASA continuation on significant clinical adverse events or hospitalisations in UC following initiation of a biologic.
P674 Real-world experiences of switching to subcutaneous formulation in IBD patients on maintenance vedolizumab treatment
Authors: Bacsur P , Resál T , Farkas B , Sarlós P , Iliás Á , Kata D , Bálint A , Fábián A , Bor R , Szepes Z , Molnár T , Farkas K 
Published: January 2024

Abstract

Background
Usability of subcutaneous vedolizumab (SC VDZ) in inflammatory bowel diseases (IBD, ulcerative colitis [UC], Crohn’s disease [CD]) have proved via clinical trials, while real-world data collection is ongoing. Experiences of Central-European population and assessment of patient’s perspectives are lacking. Our study aimed to evaluate the real-world efficacy, safety and patient’s preferences of SC VDZ maintenance treatment after switching from intravenous (IV) formulation in a Hungarian IBD cohort.

Methods
In this prospective, multicenter cohort study, IBD patients on maintenance IV VDZ treatment were enrolled, who switched to SC administration. Baseline was the day of the switch, while 52-week follow-up was set. Clinical and demographic data were collected, while serum VDZ level and CRP was measured at baseline and at w52. A non-validated questionary was filled by patients who were on drug at w12 recording patient’ satisfaction. Primary outcome was the drug survival rate at one year, while secondary outcomes were change in corticosteroid-free clinical (CSFR, based on physicians’ global assessment score PGA &lt; 1), and biochemical remission (BR, 5 mg/l &gt; CRP) rates to w52, safety issues and patients’ preferences and change in serum drug levels.

Results
In total, 37 IBD patients were followed (Table 1., 15 CD and 22 UC, male/female ratio 45.9 %, median age 42.0 [IQR 34-49] years). In CD group, 66.7 % were in CSFR and 60 % in BR, while in UC group 63.6 % were in CSFR and 68.2 % in BR (p = 0.55 and p = 0.61). Overall, 29.7 % of patients ceased SC VDZ treatment after a median of 20 (IQR 6-26) weeks. Cessation was due to secondary response losing in 3/6 and 4/5 patients in CD and UC group. In case of 2 and one patients, SC treatment was terminated due to local reactions. One patient was fear of needle. Severe adverse event did not occur. Factors associated with discontinuation did not identify. The mean serum VDZ level has higher at w52 compared to baseline in CD and UC patients (CD: 8.9 ± 6.9 to 30.6 ± 17.8 ug/mL, p = 0.047; UC: 13.6 ± 13.8 to 33.6 ± 17.6 ug/mL, p = 0.001, Figure 1.), while disease activity was stable. 84 % of the patients who filled the questionnaire were satisfied with injection, while only one patient found it difficult to inject.

Conclusion
Transition from IV to SC maintenance VDZ treatment is effective at one year, the overall survival rate is high presumably due to the elevated serum drug levels. Severe safety issue did not raise. Satisfaction of switched patients is high, which may improve treatment adherence and save resources.
P675 Comparative efficacy of Infliximab, Adalimumab, and Ustekinumab in patients with biologics naive Crohn's disease：a retrospective observational single-center study
Authors: Sakurai K , Takahashi S , Fujihata K , Watanabe R , Nishimura Y , Yamada R , Sawada K , Sano I , Oda H , Miyagishima T 
Published: January 2024

Abstract

Background
The number of biologics available for Crohn's disease (CD) has increased dramatically, but there is no established standard of selection and few direct comparisons of efficacy among the agents. In this study, we compared the efficacy of infliximab (IFX), adalimumab (ADA), and ustekinumab (UST) in biologics naive CD patients.

Methods
A retrospective analysis of clinical data from CD patients who received IFX, ADA, and UST as 1st biologics during the period 2014-2023 was performed.

Results
Of 137 CD patients, 8 patients who received IFX, 17 patients who received ADA, and 10 patients who received UST as 1st biologics were included. Patient background (IFX/ADA/UST group) was as follows: median age was 32/21/22 years, median disease duration was 1/2/2 years, median HBI was 5/6/6, median SES-CD was 9/6/9, median CRP was 1.59/0.49/1.03 mg/dl, median albumin was 3.7/4.3/4.2 g /dl. Prednisolone or budesonide was concomitantly administered at induction in 5 (62.5%)/4 (23.5%)/0 (0%) patients.The cumulative remission rate (IFX/ADA/UST group) was 62.5%/58.8%/85.7% at 52 weeks after biologics induction in all patients, with a higher rate in the UST group. The steroid-free remission rates at 52 weeks (IFX/ADA/UST group) were 50.0%/58.8%/90.0%, which were higher in the UST group. For patients with HBI≥5 at the biologics induction, the remission rate after 8/16 weeks was 83.3% (5/6)/66.7% (4/6) in the IFX group, 54.5% (6/11)/63.6% (7/11) in the ADA group and 75.0% (6/8)/100% (8/8) in the UST group. There were no significant differences among all groups. Regarding adverse events, one case of skin rash and one case of dizziness were observed in the IFX group, one case of skin rash was observed in the ADA group, and no adverse event was observed in the UST group. One case of intestinal obstruction occurred in the IFX group and two cases in the ADA group, but not in the UST group.

Conclusion
Induction of UST in biologics naive CD patients may be as effective as anti-TNFα antibodies.
P691 Intestinal ultrasonography accuracy in the evaluation of patients with moderate to severe ulcerative colitis starting infliximab therapy
Authors: Albshesh A , Melnik P , Dotan A , Lahat A , Ungar B , Ben-Horin S , Carter D , Kopylov U 
Published: January 2024

Abstract

Background
The diagnostic accuracy of detecting active ulcerative colitis (UC) by transabdominal intestinal ultrasonography (IUS) is well described. However, the value of repeated IUS measurements in tight monitoring during treatment remains to be established. The aim of the study is to evaluate the utility of IUS for monitoring biologic therapy in UC. Additionally, to establish the correlations between IUS findings and the endoscopic Mayo score (EMS), as well as clinical and biochemical severity indices.

Methods
In a prospective open-label study, individuals with moderate to severe ulcerative colitis who were initiating infliximab therapy were included, excluding those with proctitis. Patients were evaluated at baseline and after 3 months of biologics induction by means of clinical, biochemical, endoscopic mayo score, and IUS assessments. A Paired Wilcoxon analysis was conducted to compare data before and after therapy induction. The correlation between bowel wall thickness (BWT) and the endoscopic mayo score (EMS), C-reactive protein (CRP), calprotectin, and the Simple Clinical Colitis Activity Index (SCCAI) was analyzed across both visits.

Results
Thirty-two patients were enrolled and completed baseline evaluations and 21 completed follow-up assessments. The median age was 38 years (IQR 29-60), with 53% male, a median disease duration of 7 years (6-9), 41% having left-sided colitis, and 59% with pancolitis. All patients were treated with infliximab. No significant differences were observed at both time points in terms of BWT, EMS, CRP, and calprotectin (5.5 vs 4.4, p=0.2; 2 (2-3) vs 2 (1-3), p=0.4; 9.4 vs 9.6, p=0.4; 979 vs 394, p= 0.1, respectively). The only significant improvement was in terms of SCCAI (7 (4.8-8) vs 3 (1-5), p=0.009). BWT showed significant correlations with EMS (r= 0.43, p= 0.0015) (figure 1), CRP (r= 0.40, p= 0.007), and SCCAI (r= 0.28, p= 0.03), while no correlation was found with calprotectin (r= 0.19, p= 0.25).

Conclusion
Intestinal ultrasonography could serve as a substitute for lower endoscopy in evaluating disease activity.
P695 Untargeted proteomics analysis of baseline serum samples prior to biologic therapy initiation
Authors: Rauch M , Laponogov I , van Welsen I , Quinn A , Joustra V , Paulich H , Camesella Perez B , Ramkisoen R , Noble A , Satsangi J , D’Haens G , Williamson A , Veselkov K , van 't Wout A 
Published: January 2024

Abstract

Background
Biologic drugs such as anti-TNFα antibodies are predominantly used in a step-up setting and prescribed for Crohn’s disease (CD) patients who have failed, or are contraindicated for, first-line therapies. However, patient response to biologics is highly variable, with only a minority benefitting from a strong and sustained clinical response. Presently, there is no operationally effective means in clinical care to stratify patients on individual biologic drugs. Consequently, standard of care for those with CD remains inadequate and inefficient. To identify protein biomarkers associating with treatment outcomes, we performed an untargeted proteomics analysis of baseline serum samples from individuals with moderate to severe CD starting anti-TNFα treatment.

Methods
Biobanked serum samples from 47 (42 from Amsterdam, 5 from Oxford) moderate to severe CD patients starting anti-TNFα treatment (adalimumab, infliximab or their biosimilars) with documented 12 and 26-week treatment response were used for untargeted serum proteomic analysis using SomaLogic’s SomaScan® technology platform. Data was checked for outliers using robust principal component analysis. Supervised machine learning (ML) was used to predict treatment outcome.

Results
There were 29 responders and 18 non-responders to anti-TNFα treatment (week 26). Untargeted proteomics profiles passing SomaLogic’s quality controls were generated for all samples with 7,596 proteins detected in each sample. Robust principal component analysis for anomaly detection did not reveal any substantial outliers (see Figure 1). Five different ML algorithms independently generated mean AUCs and balanced accuracies from 5x 5-fold cross-validation ranging from 0.47 to 0.53 (see Table 1) indicating no reliable signal in the data. Notably, applying the ML algorithms to detect sample origin, samples from the 2 different clinical sites (Oxford or Amsterdam) could be confidently distinguished suggesting careful protocol alignment for serum collection is essential. Of 26 proteins previously reported to be associated with biologic treatment outcome, only PF4 was found to be significantly different between anti-TNFα responder and non-responders (P=0.0043). Overall, these metrics all fall well below what would be needed for a predictor to have value in the clinic.

Conclusion
ML analysis of serum proteomics profiles for 47 CD patients did not identify any strong and reliable biomarkers of biologic treatment response suitable for clinical applications. This small study suggests serum proteins are not suitable for anti-TNFα response prediction in this population. In addition, the serum proteomic profile is highly susceptible to differences in serum collection and storage methods.
P707 Real-world Long-term efficacy of ustekinumab in the treatment of Perianal Fistulizing Crohn's disease: Results from a single-center retrospective study
Authors: Chen Q , Gong Y , Yang F , Qiao L , Wang H , Zhang D , Wang C , Zhu Z , Yang B 
Published: January 2024

Abstract

Background
The efficacy of ustekinumab (UST) in treating perianal fistulizing Crohn's disease (PFCD) remains inconclusive. This study aimed to investigate the long-term efficacy and prognostic factors of UST in the treatment of PFCD patients.

Methods
This is a retrospective single-center analysis of PFCD patients who had at least one year of follow-up and began UST treatment between November 2020 and September 2022. The primary outcome was fistula clinical remission at any time point. Secondary outcomes included fistula clinical response, intestinal clinical remission, and response. Factors associated with long-term fistula clinica remission were screened using the univariate analysis, LASSO regression and extreme gradient boosting (XGBoost) model, and visualized using SHAP.

Results
A total of 131 patients were included in the study, the mean follow-up was 70.39 weeks. Among these patients, 51 (38.9%), 72 (55.0%), and 82 (62.6%) achieved clinical fistula remission at weeks 24, 52, and the last follow-up, respectively. 111 patients (84.7%) achieved intestinal clinical remission and 119 patients (90.8%) achieved intestinal clinical response. Ninety-one patients (69.5%) had prior exposure to other biologics. This study did not ascertain a significant difference in the outcome of UST for CD between biologics Naïve and biologics Exposure patients. The XGBoost model integrated eight independent variables: Montreal L3, Montreal A2, CDAI, PDAI, ESR, body mass index, simple fistula, and re-operation events. The model revealed a favourable discrimination ability with AUC was 0.798 in the internal cohorts.

Conclusion
This study defined the effectiveness and eight risk factors of UST in long-term clinical fistula remission in PFCD patients, which is helpful for early identification of UST beneficiaries.
P732 Lack of concordance between patient-reported, physician-reported and objective criteria-based identification of suboptimal control in IBD patients: IBD PODCAST study results
Authors: D'Amico F , Gomollón F , Bamias G , Magro F , Heatta-Speicher T , Michelena N , Leitner C , Dignass A 
Published: January 2024

Abstract

Background
Crohn’s disease (CD) and ulcerative Colitis (UC) are inflammatory bowel diseases (IBD) characterized by chronic inflammation of the digestive tract. Increasing evidence highlights the unmet need, the burden of disease, the progressive nature of the disease and subsequent intestinal damage, limited efficacy of current treatments and suboptimal disease management. The IBD-PODCAST study estimates the proportion of patients with CD and UC with suboptimal disease control (DC) in a real-world setting. Criteria for suboptimal control were largely based on STRIDE-II and modified by an expert panel (Tabel 1). We previously reported that a large proportion of patients were identified with suboptimal DC. The aim of the current analysis was to compare the patients’ and physicians’ opinion to these objective criteria of suboptimal DC in this cohort.

Methods
A non-interventional, cross-sectional, multi-center study was conducted. In total 2185 patients were recruited across 103 sites in 10 countries. Details on the subjective evaluation of DC from patients and physician questionnaires were compared to the objective disease criteria identifying patients with suboptimal DC.

Results
While 52.2% and 44.3% of patients with suboptimal DC in CD and UC, respectively, were identified based on objective criteria; only a limited proportion of patients with CD (10.9%) and UC (13.0%) reported their DC as suboptimal. Similarly, a suboptimal DC was identified by a low rate of physicians (15.7% in CD and 17.9% in UC). Impaired QoL was the main reason for suboptimal DC among CD (46.1%) and UC (51.9%) patients. Conversely, lack of biochemical lab parameter normalization was the main reason for suboptimal DC for physicians (46.6% in CD and 51.8% in UC). An aligned definition of suboptimal DC between physicians and patients was found in a quarter of patients with CD (22.3%) and in a third of cases with UC (33.0%). A concordance of suboptimal DC between patient-reported, physician-reported and objective criteria based on STRIDE-II was identified in 7.5% of CD and 12.0% of UC patients (Figure 1).

Conclusion
There is a high percentage of suboptimally-controlled IBD patients in this large multinational real-world cohort suggesting a large disease burden in IBD patients. There is a disconnect between objective criteria for suboptimal DC and the evaluation by the patient and the physician. Objective criteria (incl regular disease monitoring) may be essential to improve alignment in disease management and treat to target approaches. There is a strong need to improve patient-physician communication and to standardize the definition of disease control in order to improve patient management, patient-physician communication2 and the patients’ quality of life.