bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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phase 2b and phase 3 induction were randomised 1:1:1 (subcutaneous [SC] RZB 180 mg (RZB180), SC RZB 360 mg (RZB360), or withdrawn to PBO [withdrawal, WD]) for 52 wks in COMMAND.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

Abstract

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

Abstract

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 &lt;0.001). Among EOIBD, there were significantly higher rates of malignancy (17% vs 6%, p &lt;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

Abstract

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 &lt;80g/L, at 12 weeks which resolved at 24 weeks), 1 (1.4%) was noted to be lymphopenic (lymphocyte count &lt;0.5x109/L, at 24 weeks), and 1 (limited data) with CK &gt;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

Abstract

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

Abstract

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&lt; 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

Abstract

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&lt;0.001), while significant increases in PRO-C3 were observed in responders vs nonresponders (P&lt;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

Abstract

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 &gt; 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 &lt; 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 &lt; 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 &lt; 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.