bluuebunny/crossref_metadata_2025 huggingface dataset:
P571 The Effect of NLRX1 Activation on Eosinophils in Ulcerative Colitis and Inflammation: Translational Learnings Across Diseases and from Mouse to Human
Authors: Verstockt B , Dubinsky M , Peyrin-Biroulet L , Mosig R , Cataldi F , Vermeire S
Published: January 2024

Background

Although the precise role of eosinophils in IBD is debated, elevated eosinophils may influence response to therapy and clinical outcomes1. Thus, therapeutic agents which affect both neutrophil and eosinophil recruitment may provide more robust clinical improvement in patients with UC. NLRX1 is an immunometabolic protein which reduces oxidative stress, shifts cellular metabolism, and decreases inflammation in multiple cell types implicated in ulcerative colitis (UC). Studies of NLRX1 agonists (gut-selective NX-13 & systemic LABP-73) in diverse disease models identified novel cellular targets of NLRX1 activation. We compared NLRX1’s effect on eosinophils in 2 disease states, UC and the more prototypical eosinophilic disease, asthma, and evaluated the findings.

Methods

In the 4-week NX-13 Phase 1b, a double-blind trial of 36 patients with active UC (Total Mayo Score 4-10; Mayo endoscopic subscore 2-3) who were randomly assigned to NX-13 250mg Immediate Release (IR), 500mg IR, 500mg Delayed Release (DR) or Placebo QD for 4 weeks, histology was assessed using the Geboes score by a blinded pathologist2. For allergic asthma models, mice were immunized with ovalbumin or house dust mite followed by antigen challenge concurrent with LABP-73 or vehicle. Cells isolated from the lung were analyzed by flow cytometry using the BD FACS Celesta/Diva. Data are represented as means (standard error).

Results

In the 1b clinical trial, both the Geboes score and neutrophil subscores were reduced in the IR NX-13 group compared to placebo, consistent with the effects seen in preclinical IBD models. Upon examination, eosinophil infiltration was reduced in both the IR dose cohorts compared to placebo (Fig1A). In the subset of patients with active eosinophil infiltration at baseline (defined as Geboes subscore ≥2A.1), eosinophil reduction was seen in all NX-13 doses (Fig1B). Importantly, a numerically increased clinical response rate (decrease in total Mayo score of ≥3 or ≥30%) was seen in patients that demonstrated effective eosinophil reduction, compared to patients without improvement (75% versus 29%; Fisher’s Exact Test, p=0.08). In two allergic asthma models, NLRX1 activation by LABP-73 significantly reduced the fraction of eosinophils within the lung relative to vehicle control (n=7-8; p< 0.05), confirming NLRX1 activation can regulate eosinophilic inflammation in Th2-mediated responses.

Conclusion

Neutrophil and eosinophil infiltration were reduced in UC patients treated with the gut selective NLRX1 agonist, NX-13, and was coupled with better clinical outcomes. The effect of NX-13 on eosinophils will be evaluated further in the ongoing phase 2 NEXUS trial in patients with UC.

1 A Mookhoek, et al. JCC (16).

2 L Peyrin-Biroulet, et al. JCC (17) Supp
P577 Histological Remission Leads to Less Endoscopic Flare-up in Moderate-to-Severe, Biologics Experienced Ulcerative Colitis Patients: A Comprehensive Retrospective Cohort Study
Authors: Wei Z H , Le P H , Chiu H Y , Yeh P J , Chiu C T , Chiu C H
Published: January 2024

Background

In the management of inflammatory bowel disease (IBD), adopting a treat-to-target strategy has proven beneficial. Current therapeutic targets primarily focus on achieving endoscopic remission. However, the significance of histological remission as a potential target. However, it remains underexplored in Asian populations. We aimed to investigate the role of histological remission in clinical outcomes among ulcerative colitis (UC) patients already in endoscopic remission.

Methods

In this retrospective cohort study, we enrolled moderate to severe, biologics experienced UC patients with endoscopic remission, defined as endoscopic Mayo subscore 0 point during June 2017 and September 2023 in Chang Gung Memorial Hospital, Linkou. Then the patients were divided into histological remission (HR) and non-histological remission (non-HR) groups according to histological Nancy index (NI). HR was defined as NI 0 point, and others belonged to non-HR group. Comparative analyses were performed between two groups regarding baseline characteristics, one year follow up and end of follow-up clinical outcomes. The location of biopsy was active inflammatory lesion, if no active lesion, we performed routine biopsy over rectum, 15cm level from anal verge. We took at least 4 pieces biopsy over each location.

Results

We enrolled 42 moderate-to-severe, biologics experienced UC patients (HR group, 23 patients and non-HR group, 19 patients) with endoscopic remission. The average follow-up duration was 17.6 months. In non-HR group, NI scores were categorized as follows: 1 point (42.1%), 2 points (31.6%), 3 points (21.1%), and 4 points (5.3%). Baseline characteristics showed no significant differences between the two groups. In terms of outcomes, the HR group demonstrated a significantly lower endoscopic relapse rate (26.1% vs. 68.4%, P=0.006) and better results in Kaplan-Meier survival analysis (log-rank P=0.015) at the end of the follow-up period. The HR group also exhibited a reduction in clinical relapses, emergency department visits, and hospital admissions. Although these differences did not attain statistical significance, this phenomenon is likely attributable to the study's constrained sample size.

Conclusion

In moderate-to-severe UC patients who are biologics-experienced and in endoscopic remission, achieving histological remission is associated with a reduced rate of endoscopic relapse.
P593 Efficacy of Risankizumab in Patients With Moderately to Severely Active Ulcerative Colitis by Prior Advanced Therapy Failure and Mechanism of Action: Post Hoc Analysis of the INSPIRE and COMMAND Phase 3 Studies
Authors: Panaccione R , Louis E , Colombel J F , D'Haens G , Peyrin-Biroulet L , Dubinsky M , Takeuchi K , Kalabic J , Levine P , Neimark E , Chen S , Cheng L , Duan W R , Vladea R , Hecht P M , Sanchez Gonzalez Y , Schreiber S , Ferrante M
Published: January 2024

Background

Risankizumab (RZB), a monoclonal antibody targeting interleukin-23 p19, demonstrated superior efficacy compared with placebo (PBO) in the induction and maintenance of patients with moderately to severely active ulcerative colitis (UC) in the INSPIRE and COMMAND studies. Here, we evaluated whether RZB was an effective induction and maintenance therapy based on the number (0, 1, ≥ 2) and types of prior advanced therapies (ATs).

Methods

Eligible patients with an Adapted Mayo Score of 5-9 points and endoscopic subscore of 2-3 (confirmed by central reading) were randomised 2:1 (intravenous [IV] RZB 1200 mg [RZB1200] or PBO) for 12 weeks (wks) in the phase 3 induction substudy of INSPIRE. Clinical responders (per Adapted Mayo Score) to RZB IV treatment in phase 2b and phase 3 induction were randomised 1:1:1 (subcutaneous [SC] RZB 180 mg (RZB180), SC RZB 360 mg (RZB360), or withdrawn to PBO [withdrawal, WD]) for 52 wks in COMMAND. Efficacy and safety outcomes were assessed at induction wk 12 and maintenance wk 52 in patients who were non-advanced therapy-inadequate responders (non-AT-IR), had 1 or ≥ 2 AT failures, and among patients previously treated with tumor necrosis factor inhibitors, vedolizumab, or Janus kinase inhibitors.

Results

Proportions of AT-IR patients were similar across treatment groups for the induction (RZB1200 51.2% [333/650]; PBO 52.3% [170/325]) and maintenance studies (RZB180: 74.9% [134/179]; RZB360: 74.7% [139/186]; PBO [WD] 75.4% [138/183]). Significantly greater proportions of patients receiving RZB achieved the primary endpoint of clinical remission per Adapted Mayo Score at wk 12 vs PBO in the non-AT-IR and AT-IR subgroups (RZB1200: 29.7%, 11.4% vs PBO: 8.4%, 4.3%, respectively); consistent results were observed at wk 52 in patients treated with either RZB maintenance dose vs PBO (RZB180: 50.9%, 36.6%; RZB360: 61.7%, 29.5%; vs PBO [WD] 31.1%, 23.2%, respectively) (P ≤ .05, Fig. 1-2). Regardless of the number of prior AT failures or class of prior therapy, numerically higher proportions of patients treated with RZB achieved clinical remission, clinical response, endoscopic improvement, and histologic endoscopic mucosal improvement at wk 12 of induction and wk 52 of maintenance. Rates of treatment-emergent adverse events were similar among subgroups in induction and maintenance.

Conclusion

RZB induction and maintenance therapy was effective and well-tolerated in patients with moderately to severely active UC regardless of a patient’s prior experience with advanced therapies. Numerically higher efficacy was observed in non-AT-IR compared to AT-IR subgroups.
P605 Intravenous Ustekinumab maintenance treatment is effective in patients with Crohn’s Disease
Authors: Wang Y , Chen Y
Published: January 2024

Background

With the usual subcutaneous (SC) doses (90 mg every 8-12 weeks) of Ustekinumab some patients will only partially respond or experience secondary loss of response. Intravenous (IV) dose of Ustekinumab is more affordable than the subcutaneous does in China. However, the evidence of intravenous administration maintenance when shortening subcutaneous dose is not effective enough is limited.

Methods

We conducted a retrospective study to evaluate the effectiveness and safety of IV Ustekinumab in patients with Crohn´s disease (CD). Patients received Ustekinumab with insufficient efficacy or loss of response to 90 mg SC treatment could escalate to IV maintenance at regular intervals through every clinic visit and could deescalate back to SC maintenance when the efficacy is satisfied. We obtained data from 247 patients.

Results

Follow-up data beyond 24 weeks (24w) were available for 229 patients and data beyond 52 weeks (52w) were available for 144. Baseline characteristics of the included patients are shown in Table 1. Complicated forms (B2-B3; 55.6%) predominated and perianal disease was present in 45.3% of patients. 136(58.12%) patients were naïve to biological treatments, 41.8% had received at one and 8.97% more than 2. Steroid-free clinical remission were observed in 88.1%(185/210) patients at 24 weeks.35/104(33.65%) had a normal level of fecal calprotectin(FCP) and 56/115(48.70%) achieved endoscopic remission at 52 weeks. Serious adverse events were reported in 0.81% of patients. Logistic regression demonstrated that 24w C-reactive protein, baseline FCP and frequency of IV treatment were associated with endoscopic remission at 52w (Figure 1).

Conclusion

Patients who lose response to the intensified dose of Ustekinumab SC could benefit from intravenous administration as maintenance treatment.
P607 Increased rates of fractures and malignancy in elderly onset IBD in Singapore
Authors: Tan C K , Ong J , Ang T L , Salazar E , Tan M , Lim C T , Tay S W , Tan Y Y , Chan W
Published: January 2024

Background

Elderly onset inflammatory bowel disease (EOIBD) has variable characteristics in the published literature. We performed this study to report the disease characteristics, treatment exposure, and clinical outcomes of EOIBD compared to adult onset IBD (AOIBD) in Singapore.

Methods

This is a retrospective study involving IBD patients seen at two tertiary hospitals in Singapore from January 2020 to September 2023. Patients were identified from the Singapore National IBD registry. Those with missing data on age of IBD diagnosis were excluded. Data on baseline demographics, disease characteristics, treatment and disease-related complications were collected. EOIBD is defined as age of diagnosis ≥ 60 years old and AOIBD as those diagnosed from age 18 to 59 years old. The characteristics was compared between these two groups. Data was analysed using SPSS version 27.0.

Results

1116 patients were included in the final analysis, 10.6% (n =118) were EOIBD as shown in Figure 1. 50% were male with a mean age of diagnosis at 68 years old. The comparison between EOIBD and AOIBD are shown in Figure 1 and Table 1. There is a higher proportion of Crohn’s disease (CD) (45.7% vs 37.4%) in EOIBD. In terms of treatment, there is significantly lower use of thiopurines amongst EOIBD (34.5% vs 46.8%, p = 0.012). There was a trend of higher use of methotrexate among EIOBD (19.6% vs 10.6%, p = 0.067) although this was not statistically significant and this is similarly observed in the use of biologics (32.8% in EOIBD vs 27.1% in AOIBD, p = 0.205). There were no significant differences in corticosteroids (CS) exposure, CS dependence and mean number of CS courses used. There was a lower proportion of IBD-related surgery in EOIBD (12.1 vs 18.5%, p = 0.094) with EOID having a significantly lower mean number of IBD-related surgery (1.1 vs 1.6, p <0.001). Among EOIBD, there were significantly higher rates of malignancy (17% vs 6%, p <0.001) and fractures (18.1% vs 9.2%, p = 0.02); the latter despite a statistically higher mean level of vitamin D (20.9 ng/ml vs 18.3 ng/ml, p = 0.026). There were no differences in IBD-related hospitalization.

Conclusion

EOIBD is associated with increased rates of fractures and malignancy compared to AOIBD. Therefore, bone health and malignancy screening should be regularly performed in this group of patients to clinical outcomes.
P629 JAK inhibitor safety in Inflammatory Bowel Disease: real-world data comparing the effect of JAK inhibitors on blood parameters and their clinical significance
Authors: Radia C , George R , Campbell S , Abdel-Aziz S , Plewa S , Ratcliff S , Blake T , Medcalf L , Patel M , Dubois P , Pavlidis P , Kent A J
Published: January 2024

Background

Janus kinase inhibitors (JAKi) licensed for the treatment of inflammatory bowel disease (IBD) now include tofacitinib, upadacitinib and filgotinib. JAKi are known to cause abnormalities in a multitude of blood tests. However, whether there are differences in their effects in a ‘real-world’ setting is not known.

Methods

Blood test results for 118 patients treated with a JAKi were collected. A total of 13 parameters known to be affected were included. Percentage change at 12 and 24 weeks from baseline was calculated and compared amongst the different JAKi. The difference between the proportion of patients with abnormal results at each time-point was also reviewed.

Results

The JAKi breakdown included: tofacitinib-64, upadacitinib-35, filgotinib-18. JAKi treatment was associated with a significant rise in cholesterol, bilirubin, ALP and AST at 12 and 24 weeks (table 1), while rises in triglyceride and LDL cholesterol, and haemoglobin reduction were only apparent at 24 weeks. Other parameters showed transient or non-significant changes. Individual analysis of each parameter highlighted only two significant differences amongst JAKi: upadacitinib significantly reduced WCC (p=0.048) and neutrophil count (p=0.044) within the group at 24 weeks, and when directly compared to tofacitinib (p=0.047). However, no patients were neutropenic at 24 weeks and only 5 patients had a low WCC (upadacitinib: 3, tofacitinib: 2, filgotinib: 1). As per Common Terminology Criteria for Adverse Events (CTCAE), adverse events (AEs) in these parameters were low despite the significant percentage change in multiple variables. 1 patient (1.1%) was found to be anaemic (Hb <80g/L, at 12 weeks which resolved at 24 weeks), 1 (1.4%) was noted to be lymphopenic (lymphocyte count <0.5x109/L, at 24 weeks), and 1 (limited data) with CK >5 times upper limit of normal. No patients had a significant hepatic disorder as per CTCAE, though mild liver function changes above the upper limit of normal were seen in 9% of patients. On comparing the proportion of patients with abnormal results at 12 and 24 weeks to baseline, it was only cholesterol (p=0.027) and HDL-cholesterol (p=0.041) that had a significantly higher proportion of patients within the abnormal range at 12 weeks. This did not persist at 24 weeks (p=0.13 and p=0.37 respectively). Two patients were commenced on a statin during JAKi therapy. No abnormalities in these blood parameters caused drug withdrawal.

Conclusion

In this cohort the majority of changes in blood test parameters were transient and/or mild with no AE-related drug withdrawals during JAKi therapy. No clinically significant differences have been appreciated amongst the three JAKi.
P647 Effectiveness of combined treatment with two biologics or advanced molecules in inflammatory bowel disease
Authors: Melcarne L , Laucirica I , Brunet E , Villoria A , Puy A , Llovet L , Garcia-Sagué B , Frisancho L E , Altadill A , López-Sáez B , Del Estal J , Calvet X
Published: January 2024

Background

Treatment with a combination of biologic drugs or advanced molecules represents a seldom-used therapeutic option for inflammatory bowel disease (IBD). Data on the effectiveness of these combinations of treatment are limited.

The objective of this study is to assess the effectiveness of combination therapy in IBD patients.

Methods

A retrospective, single-center observational study was conducted. Patients with IBD treated with a combination of biologic drugs or advanced molecules from January 2020 to September 2023 were analyzed.

Clinical, demographic, and therapeutic variables were collected. The clinical response rate was evaluated using the Harvey-Bradshaw Index for Crohn's disease (CD) and the partial Mayo score for ulcerative colitis (UC) at the initiation and 6 months into treatment.

Bivariate analysis was performed to identify variables associated with clinical response.

Long-term treatment survival was studied using Kaplan-Meier curve.

Results

A total of 9 patients were included: 7 (77.8%) with CD and 2 (22.2%) with UC. The majority (66.6%) had received more than two biologic treatments. Patient characteristics are described in Table 1. Combination treatment was initiated due to partial response to monotherapy in 2 patients (22.2%) and monotherapy failure in 7 (77.8%). The most commonly used combination was ustekinumab-vedolizumab (n=6, 66.6%). Three patients (33.3%) had a clinical response at 6 months, with one patient achieving clinical remission.

In the bivariate analysis, partial response to monotherapy as an indication for a second biologic and elevated PCR at the start of treatment were associated with a higher clinical response (p=0.03 and p=0.04, respectively).

The median survival of the combination treatment was 309 days (±109) (Fig. 1). At the end of the follow-up, 2 patients (22.2%) continued with combination treatment (average of 251 days). In 4 cases the treatment was switched to a JAK inhibitor, one patient required surgery and, finally, two patients needed surgery and treatment change.

Conclusion

The combination treatment have a low long term effectiveness in patients refractory to conventional treatment, although it may be a valid option for that subgroup of patients showing a partial response to monotherapy.
P650 Optimization through iv maintenance with ustekinumab in Inflammatory Bowel Disease. Efficacy and adjusted regimen in real world
Authors: Mínguez A , Coello E , Gomez M , Ripoll P , Garrido A , Aguas M , Iborra M , Cerrillo E , Tortosa L , Bayarri V , Nos P , Bastida G
Published: January 2024

Background

Ustekinumab (UST) is an effective treatment for Crohn's disease (CD) and ulcerative colitis (UC). However, some patients do not respond to conventional subcutaneous (SC) doses and lose response at follow-up. The use of maintenance intravenous (IV) UST could play a role in these patients.

Methods

The aim of the study was to evaluate the effectiveness of IV maintenance UST in patients with failure to subcutaneous UST. Single-center study performed in consecutive patients included in a prospective database. The reduction of activity markers such as C Reactive Protein (CRP) and fecal calprotectin (FC), UST trough levels pre- and post IV maintenance as well as clinical indices of activity were evaluated. IV dose adjustments and their effect on levels were collected. We defined biochemical remission as the percentage decrease FC ≥ 80% and/or final FC ≤ 250.

Results

Of 335 patients in our center under treatment with ustekinumab, 31 patients (9.25%) were included. Baseline characteristics of patients are shown in Table 1. Mean age at the start of UST IV 42.49 years ± 13.23. CD 77.4%; UC 22.6%. Up to 2/3 of patients with CD had a complicated phenotype (B2/B3) and 50% perianal disease (PD). All included patients were bio-exposed and 61.3% had carried ≥ 2 biologics.

The major indication for initiation of UST was secondary failure to previous biologic therapy (74.2%). The most used induction IV dose was 390mg and subsequent SC maintenance was every 8 weeks in 76% (60% were later intensification cases). Re-induction was performed in 36.7% of patients. The median time from drug initiation to IV maintenance was 10.23 [IQR 30.7] months. In 54.8% a higher dose was administered in the first IV maintenance infusion. The most common maintenance regimen was 130mg (64.5%) every 4 weeks (54.8%). Baseline FC decreased significantly (Figure 1) at the end of follow-up (median [IQR]: 809 µg/g [2256] vs 333 µg/g [508], p =0.001). Basal Harvey index was reduced compared to HBI at 24 weeks (mean ± SD: 6.5 ± 4.3 vs 4.1 ± 3.1, p =0.019). Drug levels at the start of IV maintenance were 1.4 µg/ml [IQR 2.3] vs. 4.8 µg/ml [IQR 3.9] at week 24 (p< 0.001) after dose adjustment in 35.5% of patients during IV maintenance.

At the end of follow-up 54% went into biochemical remission. The presence of PD was associated with lower biochemical remission (70.6% vs. 27.3%, p =0.025). The median IV UST maintenance time was 8.55 [IQR 23.9] months. 96.6% are continuing treatment. No serious infections or malignancy were documented.

Conclusion

The use of maintenance IV UST appears to be an effective and safe strategy that can be evaluated as a salvage treatment especially in highly bioexposed patients or with complex CD phenotype.
P653 Impact of ozanimod on type III collagen turnover biomarkers and the association with ozanimod efficacy in patients with moderately to severely active ulcerative colitis: Results from the phase 3 True North study
Authors: D'Haens G , Maddux R , Wu C , Hu Y , Sands B E , Mortensen J H , Zhang J , Petersen A , Harris S
Published: January 2024

Background

Ozanimod (OZA), an oral sphingosine 1-phosphate 1 and 5 receptor modulator, was efficacious and well tolerated for up to 52 wk in adults with moderately to severely active ulcerative colitis (UC) in the phase 3 True North study (NCT02435992). Alterations in the degradation and formation of type III collagens, a major component of the extracellular matrix of the intestinal wall, may play a role in the pathogenesis of UC. The objective of this analysis was to assess the effect of OZA on type III collagen levels and turnover and the association of type III collagen levels with OZA efficacy in the True North study.

Methods

In a 10-wk induction period, patients (pts) in Cohort 1 were randomised to receive oral OZA 0.92 mg (n=429) or placebo (PBO) once daily (n=216) in a double-blind manner and pts in Cohort 2 received open-label OZA at the same daily dose (n=367). At Week (W) 10, pts with a clinical response to OZA in either cohort underwent rerandomisation to receive double-blind OZA (n=457) or PBO (n=69) for 52 wk (maintenance period). Type III collagen biomarker plasma levels were assessed at baseline (BL), W10, and W52. Associations between type III collagen levels and disease activity or efficacy outcomes were assessed using Spearman’s rho correlation and logistic regression, respectively.

Results

At W10, treatment with OZA resulted in significantly decreased collagen type III degradation (C3M) (Figure 1A), increased collagen formation (PRO-C3) (Figure 1B), and decreased collagen turnover (C3M/PRO-C3) (Figure 1C). Significant reductions in C3M and C3M/PRO-C3 were observed in pts with vs without a clinical response in all treatment groups (P<0.001), while significant increases in PRO-C3 were observed in responders vs nonresponders (P<0.001; Cohort 1 only). The significantly greater reductions in C3M/PRO-C3 were observed with OZA vs PBO regardless of prior exposure to biologics or tumour necrosis factor inhibitors. Changes in C3M, PRO-C3, and C3M/PRO-C3 levels from BL to W10 were significantly correlated with improvements in all disease activity scores from BL to W10 with OZA and PBO. These changes in C3M, PRO-C3, and C3M/PRO-C3 continued through W52 (Figure 1D–F) in pts who continued OZA. At W52, significantly greater reductions in C3M/PRO-C3 ratios were observed in responders vs non-responders in pts who continued OZA.

Conclusion

These data show that pts with UC who were treated with OZA had decreased plasma type III collagen degradation and turnover, with greater reductions in OZA responders than nonresponders. This further supports the evaluation of collagen type III fragments as potential markers of treatment response in pts with UC.
P654 Assessing patient-perceived burden of disease in Ulcerative Colitis: a novel scoring approach in a real-world Australasian cohort
Authors: Gu B , Pipicella J L , Palmer L , Connor S J , Wilson W , Andrews J M
Published: January 2024

Background

The prevalence and burden of inflammatory bowel disease (IBD) including ulcerative colitis (UC) is rising globally. We present a novel score to evaluate patient-perceived burden of disease (PPBoD) in UC, which we applied to a large real-world Australasian cohort.

Methods

The Crohn’s Colitis Care (CCCare) Clinical Registry was interrogated in October 2023. Adults with ulcerative colitis (UC) across 17 IBD centres who had an outpatient encounter in the last 14 months were included. A novel PPBoD score was created for UC, including patient-reported components from the Mayo Score (stool frequency and rectal bleeding) as well as general wellbeing, urgency and nocturnal bowel motions. The PPBoD was calculated as detailed in Figure 1. A score of 0 was defined as no PPBoD, 1-2 as mild, 3-4 as moderate and ≥ 5 as significant PPBoD. The correlation between PPBoD and demographics, disease and treatment factors was assessed.

Results

A total of 2507 people with UC (41.0%) were identified with a clinical assessment in the last 14 months; 92.2% of whom (n = 2311) had adequate data to calculate the PPBoD. In this cohort > 80% had either no or only mild PPBoD (Table 1). Age, gender and BMI did not vary significantly between PPBoD categories. People with lower PPBoD were more likely to be on advanced therapies and had lower rates of steroid use. There was no significant difference in the use of immunomodulators and aminosalicylates across PPBoD categories. The cohort was geographically dispersed across Australia (n = 1786, 77.3%) and New Zealand (n = 525, 22.7%). There was significantly higher PPBoD in New Zealand, but notably those in New Zealand were less likely to be on advanced therapies (p < 0.001). In the subset of 780 people (33.8%) who had a recent faecal calprotectin, people with no PPBoD were more likely to have biochemical remission (faecal calprotectin < 100 μg/g). Data were available for endoscopic and radiological remission in 654 people (28.3%); those with no PPBoD were more likely to be in remission (p < 0.001). Over 98% of people with no PPBoD had no days out of role due to disease, whereas those with higher PPBoD had more days out of role (Table 1).

Conclusion

We present a novel consumer-focused score to evaluate PPBoD in UC. Within this geographically dispersed cohort, the majority had either no or mild PPBoD. Advanced therapies were associated with lower PPBoD, and their health economic value could be evaluated using this tool. Further studies are required to validate this novel score to assess BoD in UC.
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

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

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 < 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 < 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 < 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

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

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 < 1), and biochemical remission (BR, 5 mg/l > 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

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

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

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.