bluuebunny/crossref_metadata_2025_split huggingface dataset:
P0854 The Effectiveness of Risankizumab as Induction Therapy for Crohn’s Disease: Data from the Sicilian Network for Inflammatory Bowel Diseases (SN-IBD)
Authors: Macaluso F S , Renna S , Fries W , Viola A , Cappello M , Salerno I A , Mocciaro F , Scrivo B , Giangreco E , Ferracane C , Minissale M G , Distefano M E , Tortorella V , Termini A , Bertoncello L , Orlando A ,   Sicilian Network for Inflammatory Bowel Disease (SN-IBD)
Published: January 2025

Abstract

Background
Real-world studies are necessary to complement the evidence from randomized controlled trials. Currently, real-world data on the effectiveness of Risankizumab (RZB) for the treatment of Crohn’s Disease (CD) are scarce.

Methods
We designed a real-world, multicenter, observational study involving CD patients of the cohort of the Sicilian Network for Inflammatory Bowel Disease (SN-IBD) to assess the effectiveness of RZB induction therapy in clinical practice. All consecutive adult (≥18 years) patients with active CD treated with RZB from February 2024 (the date on which RZB became available for clinical practice in Sicily) who completed the induction therapy (12 weeks) were included. The effectiveness of the induction therapy was evaluated at 12 weeks, and all adverse events were reported. The effectiveness outcomes were steroid-free clinical remission (Harvey-Bradshaw Index &lt; 5 and no steroids use) and clinical response (reduction of Harvey-Bradshaw Index ≥ 3 compared with baseline, with a concomitant reduction of at least ≥ 50% of steroid dosage).

Results
74 consecutive CD patients (males: 43.2%; mean age: 43.8 ± 14.9 years) were included. All patients had at least one previous failure with a biological therapy, while 21 (28.8%) and 20 (27.0%) patients experienced three or four previous lines of biologics, respectively. At week 12, steroid-free clinical remission was obtained in 48.6% of patients, clinical response in 17.6% of patients (overall clinical benefit: 66.2%), while nonresponse was reported in 33.8% of patients. No significant difference of clinical benefit was found comparing patients who were previously treated with one or two biologics with those who were previously treated with three or four biologics (75.7% vs. 58.5%; p=0.12). Conversely, the difference of clinical benefit was significant when patients who were previously treated with only one biologic were compared with those who were treated with two or more previous lines (91.7 vs. 61.3%; p=0.04). Two adverse events were reported: one case of mild Covid-19, and one patients who suffered from a generalized edema leading to drug withdrawal.

Conclusion
Our multicenter cohort study confirmed the efficacy of RZB in inducing remission in patients with CD, particularly in those with previous therapeutic failures with biologics. Interestingly, the best results were observed in patients with only one previous therapeutic failure, i.e. as second-line therapy after a failure with one TNF-inhibitor.
P0861 Comparative effectiveness and safety of ustekinumab versus anti-tumour necrosis Factor agents as first- or second-line biologics in Crohn´s disease: a real-world multicentric observational study
Authors: Ferreira S , Serafim Parra R , Yukie Sassaki L , Kurtz de Mello M , Luz Parente J M , Bafutto M , Cancela Penna F G , Penna Pinho L , de Sá Brito Fróes R , Tricarico Gasparetti Junior Gasparetti N L , Andrade Chebli L , Tiburcio Alves Junior A J , Firmino Nóbrega F J , Botelho Quaresma A , Mattioli Nicollelli G , Galhardi Gasparini R , de Medeiros Dutra R , Oliveira Magro D , Gardere Camargo M , Palha Dias Parente L , Féres O , de Almeida Troncon L E , Kotze P G , Fonseca Chebli J M 
Published: January 2025

Abstract

Background
Ustekinumab (UST), an antibody targeting the p40 subunit of interleukin-12/23, has demonstrated efficacy in patients with Crohn’s disease (CD). However, comparative real-world data regarding the positioning of biologic therapies, particularly UST versus anti-tumour necrosis factor (TNF) agents, remain limited. This study aimed to compare the effectiveness and safety of UST and anti-TNF agents in biologic-naïve and biologic-failure CD patients.

Methods
A multicentre retrospective cohort study was conducted, including patients with moderate to severe CD initiating first- or second-line biologic treatment with UST or anti-TNF agents [infliximab (IFX) or adalimumab (ADA)]. Propensity score adjustment (1/PS) was applied to address confounders. Primary endpoints were clinical remission (Harvey-Bradshaw Index ≤3), endoscopic remission (SES-CD ≤3 or Rutgeerts score I0), and steroid-free clinical remission at week 52. Secondary outcomes included clinical response, primary/secondary loss of response, treatment persistence, biochemical remission, adverse events (AEs), hospitalisation, and surgeries.

Results
A total of 536 CD patients (172 IFX, 132 ADA, 236 UST) were analysed. Clinical remission at week 52 was achieved by 78.1% of UST and 75.7% of anti-TNF patients in the biologic-naïve group (p=0.25), and 52.2% of UST and 50.5% of anti-TNF in biologic-failure patients (p=0.31). Steroid-free clinical remission rates were similar between UST and anti-TNF groups: 80.5% vs 80.1% (p=0.99) in biologic-naïve and 81.2% vs 77.3% (p=0.46) in biologic-failure patients. Endoscopic remission was observed in 74.8% of UST vs 68.8% of anti-TNF patients (p=0.81) in biologic-naïve, and 50.6% vs 46.8% (p=0.72) in biologic-failure. Serious AEs were more frequent with anti-TNF agents in biologic-failure patients (28.3% vs 12.5%; p&lt;0.01). UST demonstrated higher treatment persistence in biologic-naïve patients (96.9% vs 80.8%; p=0.029) and lower CD relapse rates (3.08% vs 11.11%; p=0.01).

Conclusion
UST and anti-TNF agents exhibit comparable effectiveness for CD treatment regardless of prior biologic exposure. UST showed superior treatment persistence and a better safety profile, particularly in biologic-naïve patients.
P0862 Elderly-onset inflammatory bowel disease (IBD) differs in disease characteristics and treatment exposures from adult-onset IBD
Authors: Granot M , Kopylov U , Nachum N , Krauthammer A , Tal B , Abitbol C M , Ben-Horin S , Weiss B , Haberman Y 
Published: January 2025

Abstract

Background
Elderly-onset inflammatory bowel disease (IBD) patients (age ≥60 at diagnosis) have unique characteristics and require special considerations. Using a real-life registry-based cohort, we compared disease characteristics and treatment exposures between adult-onset and elderly-onset IBD.

Methods
We analyzed data from a comprehensive IBD registry, comparing demographics, disease characteristics, and treatments between adult-onset (diagnosed at 18≤ age &lt;60 years) and elderly-onset (age ≥60 at diagnosis) IBD patients diagnosed during 2000-2022 and with ≥12 months follow-up.

Results
We included 3307 adult IBD patients diagnosed above the age of 18 years. The median follow-up time was six years. 290 (9%) were elderly-onset IBD. In the elderly-onset group, there was a higher fraction of UC, 38.3% (111/290 IBD), compared with only 31.4% (949/3017) UC cases in the adult-onset group (p=0.02). Similarly, within the CD group, patients with elderly-onset compared to adult-onset CD presented with more colonic L2 disease (21% vs. 12%, p&lt;0.001) and less ileocolonic L3 disease (14% vs. 29%, p&lt;0.001). Additionally, patients with elderly-onset CD compared to adult-onset CD presented less frequently with penetrating B3 phenotype (7.4% vs. 19%, p&lt;0.001) and with less perianal involvement (10% vs. 20%, p&lt;0.001), respectively. Elderly-onset CD and UC patients received significantly more 5ASA (36% vs. 17%, p&lt;0.001 in CD and 75% vs. 63%, p=0.02 in UC) and considerably fewer biologics and/or JAK inhibitors (37% vs. 56%, &lt;0.001 in CD and 20% vs. 34%, p=0.02 in UC). There was no significant difference in surgery rates between the two age groups for CD and UC. Kaplan-Meier curve and Cox proportional hazard analyses showed significantly higher 15-year (180 months) biologic-free survival from diagnoses among elderly-onset compared to adult-onset IBD (p&lt;0.001, Figure 1 for CD and Figure 2 for UC). There were differences between the types of first-line biologics received between the two groups, with adult-onset IBD receiving significantly more anti-TNF class medications (CD: 90% vs. 20%, p&lt;0.001, UC 63% vs. 23%, p&lt;0.001) and elderly-onset IBD receiving more Vedolizumab as first-line biologic (CD: 46% vs. 10%, p&lt;0.001, UC: 68% vs. 38%, p&lt;0.001).

Conclusion
This real-world registry analysis reveals that elderly-onset IBD is characterized by a higher prevalence of UC and colonic-only L2 CD, with less CD B3 penetrating and perianal disease. Treatment strategies in elderly-onset IBD favor 5-ASA and show reduced biologic use, with preferences for Vedolizumab vs anti-TNFs in elderly-onset IBD.
P0865 Impact of assay on the predictive performance of model-informed precision dosing of ustekinumab in patients with Crohn’s disease
Authors: Zhang W , Dervieux T , Thomas D , Ferrante M , Vermeire S , Dreesen E 
Published: January 2025

Abstract

Background
Therapeutic drug monitoring (TDM) concentrations of ustekinumab measured by homogeneous mobility shift assay (HMSA) are significantly higher than those measured by enzyme-linked immunosorbent assay (ELISA) [1]. However, the impact of the assay format on the predictive performance of model-informed precision dosing (MIPD) is unknown.

Methods
Data from 83 patients with Crohn's disease (CD) were repurposed [2]. Patients received an intravenous ustekinumab induction and subcutaneous maintenance injection every eight weeks. Serum samples were collected at week (w)4, w8, w16, and w24. The ustekinumab concentration was measured in each sample using HMSA (Data_HMSA) and ELISA (Data_ELISA). Two corresponding population pharmacokinetics (popPK) models were developed: Model_HMSA (unpublished) and Model_ELISA [2].
Bayesian forecasting was performed with both datasets and models under four scenarios: (1) w8 predicting w16, (2) w8 predicting w24, (3) w16 predicting w24, and (4) w8 and w16 predicting w24. Accuracy and precision were assessed using relative bias (rBias) and relative root mean square error (rRMSE), respectively. Clinically acceptable rBias was ±20% with a 95% confidence interval (CI) including zero. The rRMSE threshold was 30%. Regression and Bland–Altman plots were used to examine correlation and agreement between forecasted ustekinumab clearance estimates.

Results
When datasets and models were matched (Data_HMSA–Model_HMSA, Data_ELISA–Model_ELISA), rBias met clinical standards across all scenarios (Figure 1A). However, accuracy was worse when datasets and models were mismatched (Data_HMSA–Model_ELISA, Data_ELISA–Model_HMSA). Precision was highest using Data_HMSA, irrespective of the assay that was used to build the model (Figure 1B).
Model_HMSA consistently overestimated concentrations in Data_ELISA, with rBias 8.54% [95% CI 0.149%–16.9%], 18.5% [6.81%–30.1%], 27.4% [16.9%–37.8%], and 19.7% [8.88%–30.6%] for scenarios 1, 2, 3, and 4, respectively. In contrast, Model_ELISA underestimated concentrations in Data_HMSA for scenarios 3 and 4, with rBias -11.2% [-17.2%– -5.13%] and -10.8% [-17.2%– -4.45%], though results were clinically acceptable for scenarios 1 and 2.
Clearance estimates were systematically lower using Model_HMSA than Model_ELISA, with high determination coefficients (R² range 0.94–1.00) (Figure 2A). Bland–Altman plots showed poor agreement between clearance estimates obtained from two models (Figure 2B).

Conclusion
This study is the first to assess the impact of the assay format on the performance of MIPD. Our findings highlight the importance of matching the TDM assay format with the assay format used to build the popPK model.

References
[1]Verdon et al.J Can Assoc Gastroenterol. 2020;4(2):73-77.
[2]Wang et al. Br J Clin Pharmacol. 2022;88(1):323-335.
P0867 Persistence of treatment effect in patients with Ulcerative Colitis and Crohn’s disease: Long-term results from the VISIBLE OLE study
Authors: Vermeire S , Jones S , Velazco N , Agboton C , Wojtowicz A M , Young L , Phillips R , Loftus- Jr. E V , Danese S , D’Haens G 
Published: January 2025

Abstract

Background
Vedolizumab (VDZ) is a gut selective, monoclonal anti-α4β7 integrin antibody approved for the treatment of moderate to severe ulcerative colitis (UC) or Crohn’s disease (CD). The subcutaneous (SC) formulation of VDZ was evaluated during the Phase 3 VISIBLE 1 and 2 studies. We report the long-term efficacy among patients (pts) with UC or CD treated with VDZ SC in the VISIBLE open-label extension (OLE) study.

Methods
Pts with UC or CD in VISIBLE 1/2 could enrol in VISIBLE OLE (NCT02620046). Pts in VISIBLE 1/2 who completed 52 weeks(W) of treatment with VDZ or placebo (randomised completers) and pts without clinical response at W6 who responded at W14 (non-randomised responders) received VDZ SC 108mg every 2W (Q2W) in the OLE. Pts with worsening disease were escalated to QW dosing. Clinical remission (partial Mayo score ≤2, no subscore &gt;1 in UC; HBI score ≤4 in CD) up to W168 was assessed (pts with missing data or escalated to QW dosing were imputed as non-response, irrespective of clinical status). The number of pts who regained clinical response when escalated to QW dosing was also assessed. Results were summarized by prior VISIBLE 1/2 treatment groups.

Results
Data from 231 pts with UC and 344 pts with CD were included. In pts with UC, baseline OLE clinical remission rates were 55.0%, 91.3% and 77.1% among randomised completers (N=124) previously treated with placebo, VDZ SC and VDZ IV in VISIBLE 1, respectively. At W168, 40.0%, 56.5% and 62.9%, respectively, were in clinical remission on Q2W dosing. In non-randomised responders with UC (N=107), 57.0% were in clinical remission at baseline and 29.9% at W168 (Figure). In pts with CD, baseline OLE clinical remission rates were 60.3% and 62.0% among randomised completers (N=226) previously treated with placebo and VDZ SC in VISIBLE 2. At W168, 32.4% and 37.3% were in clinical remission on Q2W dosing. In non-randomised responders with CD (N=118), 57.6% were in clinical remission at baseline and 27.1% at W168 (Figure). In pts with UC escalated to QW dosing, 22.2% and 38.1% achieved clinical remission and response at W8 after transitioning to QW. Among pts with CD escalated to QW dosing, 38.6% and 53.5% achieved clinical remission and response by W8 after transitioning to QW. Higher rates of remission and response were noted in VDZ completers than non-randomised responders. No new long-term safety signals were noted with VDZ SC vs IV, except for injection site reactions.

Conclusion
The clinical benefit of VDZ SC was maintained long-term during VISIBLE OLE. A subset of pts who escalated to QW dosing regained response. Findings support VDZ SC as a treatment option for patients with UC or CD who require long-term maintenance therapy.
P0869 Model-informed dosage de-escalation of infliximab in patients with inflammatory bowel diseases
Authors: Wang Z , De Greef I , Kantasiripitak W , Wicha S G , Tops S , Nigro M , Outtier A , Verstockt B , Sabino J , Thomas D , Vermeire S , Ferrante M , Dreesen E 
Published: January 2025

Abstract

Background
Extending the infliximab (IFX) infusion interval has been attempted in patients with Crohn’s disease (CD) and ulcerative colitis (UC) who maintained response following an earlier interval shortening. We compared therapeutic drug monitoring (TDM) and model-informed precision dosing (MIPD) for successful de-escalation of infliximab dosage in these patients.

Methods
MODIFI is a monocentric, open-label, historically controlled Phase 4 trial (NCT04982172). Eligible patients with steroid-free clinical (two-item patient-reported outcome [PRO2] ≤1 for UC and ≤8 for CD) and biological remission(C-reactive protein &lt;5 mg/L and faecal calprotectin &lt;250 mg/kg) on accelerated IFX dosing underwent interval extension to every eight weeks. The extension was guided by either TDM (historical control) or MIPD targeting an infliximab trough concentration (Ctrough) of 5 mg/L (prospective intervention). Bayesian forecasting was performed using the TDMx Infliximab module (www.TDMx.eu). Steroid-free clinical and biological remission and IFX concentrations were measured at each study visit over 52 weeks. The primary endpoint was sustained steroid-free clinical and biological remission over one year.

Results
The study enrolled 52 patients: 21 patients (11 CD, 10 UC) in the TDM arm and 31 patients (19 CD, 12 UC) in the MIPD arm (Table 1).
Although the proportion of patients achieving the primary endpoint was numerically higher in the MIPD arm (52%, n=16/31) compared to the TDM arm (29%, n=6/21), this was not significantly different p=0.17; Figure 1A). However, the proportion achieving sustained steroid-free clinical remission over one year was significantly higher in the MIPD arm compared to the TDM arm (81%, n=25/31, vs. 38%, n=8/21, p&lt;0.01), particularly in the UC subpopulation (100% in the MIPD arm, n=12/12, vs. 30% in the MIPD arm, n=3/10, p&lt;0.01; Figure 1D&F). The proportion of patients achieving sustained steroid-free biological remission over one year did not statistically differ between the MIPD and TDM arms, both in the total population and in the subpopulation analyses (p&gt;0.50; Figure 1G–I).
Following a single model-informed dose at baseline, the IFX Ctrough decreased to median 5.9 mg/L [interquartile range IQR 4.4–7.5 mg/L] with 65% of patients having an IFX Ctrough &gt;5 mg/L. The IFX dose per infusion over the one year period was comparable between the TDM arm (7.5 [IQR 7.4–8.2] mg/kg) and the MIPD arm (8.8 [IQR 6.6–10.9] mg/kg).

Conclusion
MIPD-guided IFX dosage de-escalation resulted in numerically higher rates of sustained steroid-free clinical and biological remission compared to dose de-escalation based on TDM. Future confirmatory studies with randomization and larger sample size are needed to validate our findings.
P0875 Predictors for maintained remission at one year following appendectomy in ulcerative colitis: a post-hoc analysis of the ACCURE trial
Authors: Visser E ,   ACCURE study group
Published: January 2025

Abstract

Background
The ACCURE trial, a randomised controlled trial, demonstrated that appendectomy reduces clinical relapses within one year in patients with ulcerative colitis (UC) in clinical remission without advanced therapies compared to standard medical therapy. We aimed to evaluate predictive baseline characteristics for maintained remission following appendectomy in the ACCURE cohort.

Methods
In this post-hoc analysis, appendectomy patients from the ACCURE trial were included. Patients without endoscopic follow-up or diagnosed with Crohn’s disease were excluded. Maintained remission was defined as the absence of clinical relapse (according to predefined study criteria), with endoscopic confirmation (Mayo subscore ≤1) at one year. Logistic regression was performed to identify baseline characteristics associated with maintained remission at one year, reported as odds ratios (ORs) and 95% confidence intervals (CIs). Associations were also compared to the control group (non-appendectomy patients) to assess differences in baseline predictors for maintained remission between treatment groups and the relative impact of appendectomy on remission.

Results
Of 82 included appendectomy patients, 51 (62.2%) maintained clinical remission up to one year. Baseline characteristics are shown in Table 1. Several numerical trends were observed: patients who maintained remission were younger (40±11 vs 46±14 years), had less previous exacerbations (median 3.5 [IQR, 1.8-5.0] vs 6 [IQR, 4-10]), shorter disease duration (4.7 [IQR, 1.4-12.1] vs 5.5 [2.6-13.2] years), more often proctitis (39.2% vs 32.3%), endoscopic Mayo score of 0 at baseline (52.9% vs 29.0%), and less immunomodulators therapy (3.9% vs 12.9%) when compared to patients who failed maintaining remission. Age (per 10-years: OR 0.68, 95% CI 0.47-0.98, p=0.04) was associated with reduced odds of maintained remission (Figure 1A). This association contrasted significantly with the control group, where older age was associated with greater odds of maintained remission (age per 10-years: OR 1.61, 95% CI 1.10-2.36; Figure 1B), indicating an inverse relationship between age and remission outcomes across treatment groups.

Conclusion
In this post-hoc ACCURE analysis, younger age was significantly associated with higher odds of maintained remission up to one year following appendectomy in UC, contrasting with older age predicting better remission outcomes in the control group. Interestingly, these results align with previous epidemiological studies suggesting appendectomy as a protective factor for the development of UC in younger individuals. Age may therefore serve as an predictor for maintained remission, offering a potential basis for refining patient selection criteria for appendectomy in UC management.
P0881 Effectiveness and Safety of Tofacitinib in Biologic-Naïve Elderly Patients with Ulcerative Colitis
Authors: Singh D.M. A , Midha V , Bhardwaj A , Sharma R , Singh D , Mahajan R , Sood A 
Published: January 2025

Abstract

Background
The prevalence of ulcerative colitis (UC) is increasing in elderly populations, yet real-world data on the efficacy and safety of tofacitinib in this demographic remains limited. This study aimed to evaluate the real-world effectiveness and safety of tofacitinib in elderly patients (≥60 years) with moderate-to-severe UC treated at a tertiary care center in North India.

Methods
This cohort study was conducted at Dayanand Medical College and Hospital, Ludhiana, from July 2022 to June 2024. Elderly patients (aged ≥60 years) with moderate-to-severe UC refractory to conventional therapies were included. Patients received tofacitinib at a dose of 10 mg twice daily for induction, followed by 5 mg twice daily for maintenance, and were assessed at weeks 8 and 52. The primary outcome was steroid-free remission at both weeks 8 and 52. Secondary outcomes included clinical remission (partial Mayo score ≤1), clinical response (≥3-point reduction in partial Mayo score), and steroid-free remission at individual time points. Adverse events were systematically recorded.

Results
A total of 35 patients (median age: 64 years, 40% male) were analyzed. Most patients (80%, n=28) had left-sided colitis. The primary outcome of steroid-free clinical remission at both weeks 8 and 52 was achieved in 9 patients (25.71%). At week 8, clinical remission, steroid-free remission, and clinical response were observed in 18 (51.42%), 15 (42.85%), and 22 (62.85%) patients, respectively. At week 52, clinical remission and steroid-free remission were each achieved in 22 (62.85%) patients, while 27 (77.14%) patients demonstrated a clinical response. The most common adverse events included hair loss (17.14%, n=6), sadness of mood (11.42%, n=4), and dyslipidemia (8.57%, n=3). Three patients developed self-limiting herpes zoster infection, and one patient reported bilateral retinal vein occlusion.

Conclusion
Tofacitinib demonstrated favorable efficacy and safety in biologic-naïve elderly patients with moderate-to-severe UC. These findings highlight its potential as a viable treatment option for this growing and often underrepresented patient population.