bluuebunny/crossref_metadata_2025 huggingface dataset:
P0774 Key elements of high quality and sustainable IBD care: the common eye from an inter-, and intra stakeholder perspective
Authors: Thomassen B , Hendrix E , Mujagic Z , Smeets F , De Jong M , Gevers T , Veldhuijzen G , Van der Horst D , Scherpenzeel M , Dijkstra G , Kimman M , Ament S , Pierik M
Published: January 2025

Background

In the Netherlands, the growing burden of IBD, driven by a rising prevalence, a shift to new expensive treatments, and lifelong tight monitoring of mucosal inflammation, necessitates redesigning care processes to ensure accessible and high quality care in the future. Successful innovation requires engagement from all stakeholders within the healthcare system. In this study, we aimed to identify key elements of IBD care from an inter-, and intra-stakeholder perspective in the Dutch setting, exploring shared and unique elements to inform future healthcare improvements.

Methods

This study included all stakeholders involved in Dutch IBD care: 1) patients, 2) informal caregivers (ICs), 3) healthcare professionals (HCPs), 4) managers of gastroenterology departments, and 5) national stakeholders, e.g. pharmaceutical companies, healthcare insurers, eHealth providers, and the IBD patient organization. Participants were recruited from outpatient clinics and through networks, using purposive, convenience, and snowball sampling. In Phase 1, key elements of IBD care were identified through semi-structured interviews. These elements were prioritized within each group in Phase 2 and Phase 3 convened all stakeholders to discuss shared values, differences, and future implications (Figure 1).

Results

A total of 78 participants contributed to the study; 21 patients, 10 ICs, 27 HCPs, 8 managers and 12 national stakeholders. Key elements for each stakeholder group (Phase 1) and their rankings (Phase 2) are shown in Figure 2. Patients and ICs mainly identified micro-level elements of IBD care, while managers and national stakeholders focused on meso- and macro-level elements. HCPs addressed elements across all levels. Key elements prioritized across groups for the group discussion (Phase 3) included: accessible and affordable IBD care, adequate information and support, regular follow-up, holistic care with sufficient time and attention, achieving remission, patient autonomy and self-management, shared decision-making, remote monitoring, IBD care at home, easy access to HCPs, HCP’s expertise, scientific research, and a trustful relationship between HCPs, patients and ICs. In Phase 3, stakeholders acknowledged the importance of the identified elements, but revealed differing interpretations of shared concepts, like remote monitoring. Preserving personalized care and a trusting relationship between patients and HCPs were emphasized as key priorities in this.

Conclusion

Our study shows shared values but also significant differences between stakeholders in IBD care. Shared values can be priorities in redesigning care processes, but innovators should be aware of the elements valued by specific stakeholders based on their unique perspectives.
P0776 EVOKE - Evaluation of the long-term outcomes of Crohn’s disease complicating intra-abdominal abscess - retrospective, multicentre cohort study
Authors: Bacsur P , Nemeczek S , Filip R , Fotios F , Mpakogiannis K , Pastras P , Blesl A , Vieujean S , Gatt Y , Brinar M , Kagramanova A , Iliás Á , Gönczi L , Miheller P , Resál T , Ivány E , Farkas B , Bálint A , Fábián A , Bor R , Rutka M , Bősze Z , Szepes Z , Farkas K , Molnár T ,   Collaborators: Katsanos Konstantinos, Christos Triantos, Pierre Ellul, Zeljko Krznaric, Magdalena Gawron-Kiszka
Published: January 2025

Background

Crohn’s disease (CD) complicated with intra-abdominal abscess often requires surgical intervention. Image guided percutaneous drainage (PD) can help to avoid surgical interventions, however there is limited evidence on the optimal management after PD. Our study aimed to analyze the long-term outcomes of CD complicated with intra-abdominal abscess after intervention.

Methods

In this multicenter, multinational retrospective trial penetrating CD patients with simplex intra-abdominal abscess were enrolled and followed. Baseline was defined as the day of the first detection of simplex abdominal abscess, while follow-up period of 12-24 months was set. Patients with urgent resection were excluded. Patients were grouped based on elective surgical need during follow-up after a successful PD, while a control group of patients after resection without PD is created. Primary outcome was the abscess recurrence, while stoma rate, post procedural complications rate (<30 days), and postoperative luminal recurrence were analyzed as secondary outcomes. Logistic regression and Cox-regression models were created, while descriptive statistics, Welch’s test, and Fisher’s exact test were used to compare groups, with p-values <0.05 considered significant.

Results

A total of 131 CD patients from 7 countries were recruited (Table 1., 58% were male, the median age at inclusion was 31.4 [IQR25-40] years) and 74/131 patients had PD due to simplex abdominal abscess during a median follow-up of 104 (74-104) weeks. Abscess recurrence rates did not differ between groups (p=0.155, Figure 1.); however baseline SES-CD score was coupled with increased risk of recurrence (HR=1,17, 95% CI 0.993-1.389). Need for re-drainage was more common amongst PD patients (OR=0.092, 95% CI=0.012-0.732), while new stoma was created more frequently in patients without prior PD (OR=2.50, 95% CI=1.034-6.034). Postoperative luminal recurrence was similar between groups based on PD. Surgical complications were coupled with increased odds in patients without prior PD (OR=8.609, 95% CI=1.825-40.616), septic complications, perforation and new fistula formation were reported the most, while PD associated complication did not occur.

Conclusion

However, abscess recurrence did not differ between groups, PD prior to surgery strongly correlated with less stoma creature. Furthermore, surgical treatment of intra-abdominal abscess alone may be coupled with post procedural complications.
P0778 Exploring the impact of personalised and curated educational videos delivered via an online platform to paediatric IBD patients
Authors: Tucknott S , Rose J , Sivananthan A , Glemas C , Heuschkel R , Zilbauer M
Published: January 2025

Background

Paediatric IBD patients and families want reliable, easily accessible information from sources they trust. Appointment time is limited and teams spend much of that time repeating basic information. Families often struggle to remember/process information imparted in appointments, and have no way to check details/ask further questions, resulting in misunderstanding, anxiety and information being sought from unregulated sources. Patients and families feel isolated and unsupported between appointments.

In this study we looked at 12 months use of IBDmate, an online platform for patient education and present initial results of a high-level survey.

Methods

IBDmate is an online education platform (figure 1) featuring over 150 videos filmed with healthcare professionals and patients. It offers ‘prescribable information about all aspects of IBD, including patient and family members’ stories.

During a 12 month period, 104 paediatric IBD patients under the care of Addenbrooke’s Hospital in Cambridge were signed up to IBDmate. They were prescribed educational video modules at diagnosis and at appropriate times during following appointments. Over the 12 months, a total of 1,116 videos were watched by these patients (average >10 per patient) for a total of 64 hours (average >36mins per patient). At the end of this period we conducted a survey to gather feedback from patients and families using IBDmate. We asked the following questions assessed on a 5-point scale (table 1).

Results

43 patients of 104 asked (41%) and family members responded to the survey over a period of 72 hrs.

• 83.72% (n=36) of respondents strongly agreed or agreed that IBDmate helped them understand their/their child’s disease better.

• 86.05% (n=37) of respondents strongly agreed or agreed that IBDmate helped them understand treatments available to them/their child and make better informed decisions about their care.

• 88.37% (n=38) of respondents strongly agreed or agreed that having access to patient/family stories in IBDmate helped them feel less alone.

• 88.37% (n=38) of respondents strongly agreed or agreed that having access to IBDmate had been beneficial to them/their family.

Conclusion

Paediatric patients and families who use IBDmate are better informed and better equipped to manage their disease. They feel more confident making decisions about their care, and feelings of isolation are significantly reduced. Anecdotally IBDmate reduced the need for in-person consultations, especially for routine education about treatments and disease management. This represents a key next step for the impact assessment of IBDmate.
P0784 Independent association between baseline simple endoscopic score for Crohn’s disease and C-reactive protein with Crohn’s disease-related complications: An analysis of the Randomized Evaluation of an Algorithm for Crohn’s Treatment – Study 2 (REACT2)
Authors: Jairath V , Joshi N , Clark R , Kristina K , Xuan S , Zou G , Peng Y , Dubcenco E , Feagan B , Dulai P S , Sedano R , Ma C
Published: January 2025

Background

Endoscopic improvement in the validated Simple Endoscopic Score for Crohn’s disease (SES-CD) is associated with better long-term outcomes in CD; however, a relationship with CD-related complications is not clear. Elevated biomarkers, such as C-reactive protein (CRP) also are associated with adverse long-term outcomes. We assessed the relationship between baseline (BL) SES-CD score, elevated CRP, and CD-related complications and identified the threshold for SES-CD score associated with an increased risk of complications.

Methods

Pooled data from REACT2 (NCT01698307) was analysed. SES-CD at BL was categorized as inactive disease (0–2), mild (3–6), moderate (7–16) and severe disease (>16). Elevated BL CRP was defined as >5mg/L. CD-related complications (ie, hospitalisation, surgery, medications-related, and non-surgical CD events) were assessed from BL through 24 months. Exposure-adjusted incidence (EAI) of CD-related complications was analysed as incidence rates. Adjusted analyses compared time to the first occurrence of CD-related complication, with Cox proportional hazard regression used to adjust for clustering effects and key patient characteristics. The BL SES-CD threshold that was associated with complications was determined using receiver operating curve (ROC) approach.

Results

Of 502 patients (pts) reporting BL SES-CD, 21.9% had inactive disease, 32.7% had mild disease and 45.4% had moderate-to-severe disease. A greater proportion of pts in the moderate-to-severe group (50.0%) had ≥1 CD-related complication vs those with inactive disease (32.0%; P=.0004). More pts with moderate-to-severe disease (20.6%) had CD-related hospitalizations vs those with inactive disease (5.8%; P=.0002). The EAI rate of CD-related complications was higher with moderate-to-severe vs inactive disease (0.4347 vs 0.2239; P=.0003). The adjusted risk of CD-related complications was higher in moderate-to-severe SES-CD vs inactive disease (HR=1.72; P=.0058). The ROC approach suggested SES-CD ≥7 was associated with CD-related complications.

The proportion of pts with ≥1 CD-related complication was higher in those with elevated CRP at BL (48.6%) vs not (34.6%; P<.0001). Similar trends were observed for CD-related hospitalization. The adjusted risk of CD -related complications was higher among pts with elevated CRP vs not (HR=1.48; P=.0016); results were similar for CD-related hospitalizations (HR=1.75; P=.0013).

Conclusion

Elevated SES-CD and CRP are independently associated with a higher risk of complications in pts with CD. These findings point to the importance of controlling mucosal healing and inflammation to reduce risk of complications.
P0789 Combined inhibition of TL1A and integrin β7 is superior to either monotherapy in mouse models of colitis and coadministration of SPY001 and SPY002 demonstrates no drug-drug effects on exposure in non-human primates
Authors: Siegel M , Friedman J , Nguyen D , McNally J , Kennedy M , Ballew O , Rose M , Spencer A
Published: January 2025

Background

Advanced treatments for IBD typically have placebo-adjusted clinical remission rates of only 10 to 25%. The combined use of targeted biologic agents could break through this efficacy ceiling while avoiding the risks associated with broad immunosuppression. Spyre Therapeutics is developing fully human half-life extended IgG1 antibody drug candidates that can be used in combination against clinically validated IBD targets, including α4β7 integrin (SPY001) and TL1A (SPY002). The efficacy of combined inhibition of integrin β7 and TL1A was tested in proof-of-concept mouse colitis models. In advance of clinical assessment, it is essential to assess potential drug-drug effects on pharmacokinetics (PK). Accordingly, the clinical-stage antibodies SPY001 and SPY002 were evaluated in non-human primate (NHP) PK studies independently and in combination.

Methods

The efficacy of mouse surrogate anti-β7 or anti-TL1A antibodies used alone or in combination was assessed in the TNBS and anti-CD40 mouse models of colitis. Mice were treated with the antibodies or isotype control on Day -1 and Day 2. Body weight, stool consistency, blood in stool, and disease activity scores were recorded daily until the end of the study on Day 6. Colon weight and length were measured at the conclusion of the study. In separate experiments, SPY001 and SPY002 PK were measured in NHP following individual or combination dosing.

Results

In the murine TNBS model, combination therapy with anti-β7 and anti-TL1A antibodies significantly reduced body weight loss, improved body weight gain, and reduced disease activity to a greater extent than either monotherapy alone. In the anti-CD40 model, anti-β7 and anti-TL1A monotherapy increased weight gain and improved disease scores. Combination therapy reduced weight loss through Day 3, improved weight gain, improved disease activity, and reduced the colon weight-to-length ratio, all to a greater extent than either monotherapy. In NHPs, PK profiles of SPY001 and SPY002 were similar whether they were dosed individually or in combination.

Conclusion

Combined anti-β7 integrin and anti-TL1A therapy showed additive or greater than additive in vivo biological activity relative to either monotherapy in the TNBS and anti-CD40 mouse colitis models. Coadministration of SPY001 and SPY002 in NHPs demonstrated no drug-drug effects on PK. These preclinical results support the advancement of the combination of SPY001 and SPY002 into clinical trials.
P0793 Correlation between patient centred disease control versus biochemical parameters in IBD
Authors: Aliu A , Mujagic Z , Jeuring S , Pierik M
Published: January 2025

Background

Subjective patient experiences related to treatment are frequently underreported by healthcare providers, leading to potential discrepancies between patients and physicians in defining remission. This can influence patient expectations, engagement behaviours, and ultimately clinical outcomes. Based on these findings, the treatment approach for IBD has evolved, with the STRIDE-II consortium incorporating disease control from the patient perspective into the long-term treatment goals established in STRIDE-I. This study aims to compare subjective disease control assessed with patient reported outcome measures (PROMs) to objective biochemical parameters after starting Vedolizumab or Ustekinumab for the treatment of active disease.

Methods

Patients with IBD starting Vedolizumab or Ustekinumab included in the remote monitoring care-path with myIBDcoach were eligible for inclusion. Follow-up was 48 weeks and patients completed questionnaires at least once every 16 weeks. The IBD-control questionnaire and Monitor IBD At Home (MIAH) questionnaire were used as PROMs for disease control and clinical disease activity. The cut-off value of disease activity assessed with the MIAH questionnaire was >3.5 for ulcerative colitis and >3.6 for Crohn’s disease. Biochemical parameters C-reactive protein (CRP) and faecal calprotectin (FCP) were also measured every 16 weeks. The correlation per follow-up moment between IBD control and clinical remission measured with MIAH questionnaire, CRP and FCP was analysed with bivariate correlation tests. The longitudinal correlation between IBD control and clinical remission was assessed with linear mixed models (LMM).

Results

70 patients were included in the analyses. 25 and 46 patients started Vedolizumab or Ustekinumab, respectively (Table 1). At baseline, the mean IBD-control score was 8.5 (SD 4.7). 38% of the patients had active disease based on the MIAH questionnaire and median FCP and CRP at baseline were 369 (929) and 4 (15), respectively. IBD-control showed a moderate correlation of -0.50 with MIAH score at baseline (P=0.001). There was a weak and non-significant correlation of 0.10 and -0.09 between IBD-control with both FCP (P=0.459) and CRP (P=0.508), respectively. The LMM showed a fixed longitudinal effect between IBD-control and MIAH (P=0.006), whereas there was no fixed effect between FCP (P=0.221) and CRP (P=0.222).

Conclusion

In this explorative study, a significant correlation between IBD-control and a PROM for clinical disease activity was seen, whereas the correlation between IBD-control and objective biochemical parameters was low and not statistically significant. Treating physicians should be aware of the discrepancy between clinical and biochemical indicators of disease activity in IBD.
P0798 Forty-eight months outcomes of Teduglutide in adult stable patients with short bowel syndrome and home parental nutrition dependence: a real-world italian single center observational cohort study
Authors: Guglielmi F W , Regano N , Lamacchia S , Silvestri A , Mazzuoli S
Published: January 2025

Background

This real-life study is designed to investigate the short and long-term efficacy and safety of teduglutide (TED) and its effects on quality of life (QoL) in a cohort of adult, stable patients with short bowel syndrome and chronic intestinal failure (SBS-CIF) receiving a long term parenteral support (PS).

Methods

A prospective, single-center study was conducted for individuals who began using TED between March 2017 and August 2023.

Results

Ten patients were included in the analysis, among which the median duration of teduglutide administration was 48 (range, 12-

71) months. Data relative to short-term clinical outcomes demonstrate that 4 of 10 (40%) patients were early responders to teduglutide therapy, defined as a ≥20% reduction in PS requirement at 3 months. Six of 10 (60%) were no-responders. Data relative to 48 months long-term clinical outcomes demonstrated the absence of late responder patients and underline that all of 4 early TED responder patients continued to mantein a sustained reductions in PS. Two of the 4 patients (50%) responding to TED discontinued PS while the other 2 patients (50%) reduced the number of weekly PS infusions by approximately 50%. The physical and mental components of QoL improved significantly (p<0.05) in responsive patients while they did not change in non-responsive ones. Predictibility of response to TED therapy in this study seems to be linked to: i) SBS type 3 that is completely absent in the no-responder patients (p<0.0001), ii the residual small bowel length significantly (p<0.02) higher in the responder (102=18 cm) compared to no-responder patients (67=27 cm), and i11) SBS type 1 and 2, enterostomy, surgical complications are significantly predictive of no response. Crohn's disease is equally present in both responder and non-responder patients. The number of side effects observed in our experience is extremely rare both at the 3th (0.01 n°/day/patients) and at the 48th months (0.001 I°/day/patients). No endoscopic neoplastic lesions were observed up to the 48th month of TED therapy.

Conclusion

This real-world experience allows us to state that, after 48 months of treatment, TED: a) is a safe therapy with minimal side effects: b) produces a rapid reduction in PS volumes in 40% of treated patients; c) consents to weaned off PS in 20% of enrolled patients; d) maintains a stable nutritional state and, finally, e) significantly improves Qol.
P0806 Monitoring of vedolizumab therapy using fecal calprotectin, abdominal ultrasound, and drug levels in ulcerative colitis: a predictive algorithm
Authors: Helwig PD U , Sobotzk C , Plachta- Danielzik S , Schreiber S
Published: January 2025

Background

Ulcerative colitis (UC) is a chronic inflammatory bowel disease with a relapsing course. Vedolizumab, an anti-integrin, induces clinical remission in UC, but response is typically evaluated after 14 weeks. Earlier predictive markers could optimize treatment. This study aimed to develop an algorithm using baseline and week 6 data (especially abdominal ultrasound, fecal calprotectin, and drug levels) to predict clinical response and remission at week 14.

Methods

In this prospective study, 37 UC patients were recruited from 2018 to 2024, and 17 were included in the final analysis. The primary endpoint was clinical response or remission at week 14, based on significant changes from baseline to week 6 in at least two markers (vedolizumab ≥ 24 µg/ml, ≥ 25% reduction in colon wall thickness, or ≥ 50% reduction in fecal calprotectin). Secondary endpoints included outcomes at week 22. Statistical methods included among others Mann-Whitney U-tests, Fisher’s exact tests, and logistic regression.

Results

Vedolizumab levels at week 6 were the most reliable individual marker for predicting clinical response at week 14, with 0.67 sensitivity and 0.62 specificity. In addition, leukocytes and pancreatic elastase were negatively associated with clinical response, while zonulin showed a positive association (p < 0.001). For clinical remission, colon wall thickness reduction and the combined predictive marker demonstrated perfect sensitivity (1.00) and negative predictive value (1.00). A significant association was found between reduced colon wall thickness and clinical remission (OR = 13.91, 95% CI: 1.13–1986.85).

Conclusion

Early changes in vedolizumab levels, fecal calprotectin, and colon wall thickness can predict clinical response and remission in UC. Colon wall thickness proved the strongest predictor of remission. Larger studies are needed to validate and refine this algorithm for personalized vedolizumab therapy.
P0807 Impact of Risankizumab on Patient-reported Outcomes and Biomarkers Over Time: Post-Hoc Analysis of Phase 3 INSPIRE and COMMAND Studies
Authors: Lindsay J , Ferrante M , Armuzzi A , Peyrin-Biroulet L , Dubinsky M C , Danese S , Garrison A , Yafei Z , Kalabic J , Remple V , Vladea R , Sharma D , Panaccione R
Published: January 2025

Background

Patients with ulcerative colitis (UC) may experience debilitating symptoms that impact their quality of life. This post hoc analysis evaluates changes in patient-reported outcomes (PROs) and biomarkers over time during maintenance treatment with risankizumab (RZB), a specific inhibitor of IL-23, among patients who responded to RZB induction treatment.

Methods

Patients with a clinical response to 12 weeks of intravenous (IV) RZB treatment from the Phase 2b and Phase 3 INSPIRE induction studies were randomised 1:1:1 to subcutaneous (SC) placebo (PBO) withdrawal, 180 mg RZB SC, or 360 mg RZB SC every 8 weeks during maintenance (COMMAND). Individual PROs were examined as no bowel urgency, no abdominal pain, no nocturnal bowel movements, no tenesmus, no faecal incontinence, no UC-related sleep interruption, and no fatigue (Functional Assessment of Chronic Illness-Fatigue [FACIT-F] ≥ 40). Biomarkers examined were faecal calprotectin (FCP) and high-sensitivity C-reactive protein (hs-CRP). Results were reported as the percentage of patients achieving each outcome for all PROs and median values for biomarkers at Week (wk) 0 of induction and every 8 wks from wk 0–52 of maintenance, unless otherwise stated for FACIT-F ≥ 40.1, hs-CRP and FCP. Non-responder imputation with no special data handling for missing data due to logistic restrictions (COVID-19 or the geo-political conflict in Ukraine and surrounding impacted regions) was used for missing data.

Results

In total, 548 patients (PBO SC, n=183; RZB 180 mg SC, n=179; RZB 360 mg SC, n=186) were randomised into the maintenance study. A higher proportion of patients achieved PROs at maintenance wk 0 compared to the induction baseline (Figures 1 and 2). Throughout maintenance, achievement of PROs persisted in patients receiving RZB, regardless of dosage, except for no nocturnal bowel movements, no fecal incontinence, and no UC-related sleep interruption, which showed a slight decrease in response for all treatment groups. A decline in achievement of all PROs in the PBO withdrawal arm was seen from wk 32 onwards. Both biomarkers showed a decrease in median levels from induction wk 0 to maintenance wk 0. During maintenance, median FCP levels were lower for both RZB doses compared to PBO. Lower median hs-CRP levels persisted during maintenance but were similar among all treatment groups.

Conclusion

Improvements in most PROs and biomarkers were sustained throughout maintenance, with declines seen in the PBO maintenance group likely due to the withdrawal of RZB from RZB induction treatment. These findings show that RZB may decrease common UC-related symptoms and may improve patients’ quality of life and inflammatory burden.
P0808 Early Top-down treatment improves transmural remission rates in Crohn's disease - a risk-adjusted propensity score matched analysis
Authors: Fernandes S R , Rodrigues I B C , Da Silva Neves A , Saraiva S , Rita Gonçalves A , Valente A , Moura Santos P , Correia L , Cortez-Pinto H , Magro F ,   Grupo de Estudos de Doenças Inflamatórias do Intestino
Published: January 2025

Background

top-down treatment with biologics has been associated with higher rates of endoscopic remission compared to step-up treatment in Crohn’s disease (CD). We evaluated the benefits of this strategy in respect to transmural remission.

Methods

case-cohort study including CD patients naïve to immunosuppressants and with endoscopic and radiologic evidence of active disease.

Rates of transmural remission were compared between patients receiving early top-down treatment (immediate start of biologics or within 6 months of immunomodulators) and conventional step-up treatment (start of biologics > 6 months after immunomodulators). A propensity score matched analysis was performed adjusting for variables associated with disabling disease (age at diagnosis, disease duration, smoking, phenotype, perianal disease, extensive small bowel disease). Transmural remission was defined as combined endoscopic and radiologic remission. Endoscopic remission was defined as a SES-CD ≤ 3 (non-operated patients) or a Rutgeerts score <i2 (operated patients). Radiologic remission was defined as a simplified Maria score ≤1.

Results

327 patients were included in the analysis, 52.3% receiving conventional step-up treatment and 47.7% early top-down treatment. Rates of transmural remission decreased from 40% to 14.3% in patients with 0 and 5 risk factors for disabling disease, respectively. Early top-down treatment resulted in higher rates of transmural remission (33.3% vs 18.1%, P= 0.002) with similar results in the propensity score matched analysis (34.9% vs 18.5, P= 0.002). In multivariate analysis, early top-down treatment increased the chances of obtaining transmural remission (OR 2.187 95%CI 1.270-3.665, P= 0.005).

Conclusion

Early top-down treatment with biologics improves the rates of transmural remission in CD. Risk factors for disabling disease influence the chances of obtaining transmural remission.
P0822 Comparative Effectiveness and Safety of Upadacitinib and Vedolizumab in Anti-TNF Experienced Patients with Ulcerative Colitis: A Retrospective Study
Authors: Sror N , Leibovitzh H , Hirsch A , Thurm T , Ron Y , Maharshak N , Cohen N A
Published: January 2025

Background

Upadacitinib (UPA) and vedolizumab (vedo) are approved for use in patients with moderate to severe ulcerative colitis (UC). Data comparing these therapies as second line in Anti-TNF experienced patients are limited yet important to aid in determining therapeutic positioning.

Methods

This was a retrospective study conducted between 2015-2024. Patients receiving vedo or UPA for at least 14 weeks following anti-TNF failure were included. Clinical response was defined as a decrease in the Partial Mayo Score by two or more points from baseline, and remission as a score less than two. Clinical response and remission rates at weeks 14 and 52 were compared between the two groups.

Results

Eighty-eight patients, 66 treated with vedo and 22 with UPA were included in this study. The mean ages of the vedo and UPA cohorts were 45.7 ±19 years, and 39.4 ± 12.8, respectively. Thirty-one males (46.9%) were treated with vedo, and nine (40.9%) with UPA. Patients treated with vedo had significantly higher rates of cardiovascular comorbidities (30.3% vs 0%, p<0.001), a higher rate of never smokers (86.8% Vs 63.6%, p=0.018), and shorter disease duration (8.9 years Vs 13.2, p = 0.03). (Table 1). There was no significant difference in terms of clinical response or remission although there was a trend towards a higher likelihood of both in patients receiving UPA (clinical response: adjusted odds-ratio (aOR)=6.85, P=0.09, 95% confidence interval (CI):0.74-62; clinical remission: aOR=3.7, P=0.14, 95% CI: 0.6-21.6). There was a greater decrease in fecal calprotectin in patients receiving UPA during follow-up although this was not significant (mean change of 1,750 ± 2,284 Vs 771 ± 1,727, P=0.13). Patients treated with UPA were significantly more likely to experience adverse events (AE) (aOR 8.72, CI: 1-65, P=0.04) (Table 2). Two patients treated with vedo had treatment discontinuation, one due to pulmonary embolism, and the other by the patient’s request with no objective AE. In the UPA cohort, there were no major AE resulting in treatment discontinuation. One patient in the UPA cohort had mild cutaneous herpes which required a temporary pause in therapy. No patients were hospitalized during the treatment period.

Conclusion

Clinical effectiveness of UPA and vedo were comparable in anti-TNF experienced patients with UC although there was a trend towards greater clinical response, remission and biochemical improvement in patients receiving UPA. Patients receiving UPA experienced a significantly higher incidence of AE. These data suggest that decision making based on disease severity and co-morbidities can help guide positioning of these therapies.
P0824 Patient-Reported Outcomes in Chinese Patients with Inflammatory Bowel Disease treated with Vedolizumab: A subgroup analysis of second interim analysis of VALUE study
Authors: Gao X , Ge W , Yu J , Wang X , Feng X , Qian X , Gu L , Chen M
Published: January 2025

Background

Vedolizumab (VDZ), a gut-selective monoclonal antibody for α4β7 integrin, approved in China for treating inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD). Here, we assess the improvements in symptomatic relief and quality of life (QoL) by patient-reported outcomes (PROs) from the second interim analysis of VALUE study (NCT04872491).

Methods

VALUE study is a prospective, multicenter, single-arm observational study. Enrolled patients with UC/CD aged >18 years, were treated with 300mg VDZ at week 0, 2, 6, and every 8 weeks until 54 weeks. This second interim subgroup analysis was conducted 2 years after the first subject enrolment (data cutoff: 21 Oct’ 2023), which assessed the QoL using partial Mayo score [a composite index of rectal bleeding sub-score (RBS) and stool frequency sub-score (SFS)]for the patients with UC, and abdominal pain sub-score (APS), loose stool frequency sub-score (LSFS) for pts with CD at baseline, days 3, 7 and 14. IBD questionnaires (IBDQ), EuroQol - 5 Dimensions – 5 Levels index (EQ-5D-5L), EuroQol – Visual Analogue Scale (VAS) scores from baseline to week 14. Descriptive statistics summarized the effectiveness.

Results

Of 500 pts (UC: 409, CD: 91), 61.60% were males (61.60%) with a mean partial Mayo score of 5.2±2.09 and Harvey-Bradshaw Index (HBI) score of 5.6±3.35 in pts with UC and CD, respectively. After the treatment with VDZ in 315 pts with UC, the RBS and SFS score decreased(Figure 1), 34.92% (110 pts) achieved RBS=0 and SFS≤1 at baseline, which further increased to 51.69% (168 pts) and 64.19% (190 pts) by in day 7 and 14 respectively. Compared to baseline, the RBS = 0 and SFS≤1 scores improved by 30% (34.92% to 64.19%) at day 14, demonstrating the rapid onset effect of VDZ (Table 1A). In the pts with UC, mean IBDQ, EQ-5D-5L and EQ-VAS scores showed improvement from baseline (148.3 ±37.88, 0.890±0.157 and 76.1±15.56, respectively) to week 14 (186.7±26.30, 0.948±0.105 and 85.5±11.74, respectively) (Table 1B).

The mean pro scores from baseline to day 14 in patients CD are presented in Figure 1. APS≤1 and LSFS≤3 scores in pts with CD treated with VDZ improved from 75% at baseline to 78.08%, 82.19% and 85.51% on days 3, 7 and 14, respectively (Table 1A). Improvement in IBDQ scores was observed from baseline (161.8±37.53) until week 14 (177.4±24.43). Similarly, the mean EQ-5D-5L and EQ-VAS scores from baseline (0.908±0.1126 and 77.2±15.68) to week 14 (0.942±0.0586 and 82.4±10.98) were also improved in CD pts (Table 1B) signifying improved QoL.

Conclusion

VDZ treatment was associated with significant symptomatic relief and improved quality of life in Chinese patients with IBD.
P0829 ‘Temporary’ faecal diversion in refractory Crohn’s Disease: too good to be true? A retrospective, single centre analysis
Authors: Alliet B , Bislenghi G , Vermeire S , Guedelha Sabino J P , Ferrante M , D’Hoore A , Verstockt B
Published: January 2025

Background

Refractory Crohn’s disease (CD) is associated with high morbidity and significantly impaired quality of life. Similarly, perianal fistulising disease is a debilitating condition for a subset of CD patients. As the faecal stream is believed to play an important role in disease pathophysiology, a diverting (ileo)stomy, is sometimes considered as a therapeutic option in patients with extensive colitis and/or refractory anal disease. Long-term outcomes of temporary faecal diversion are limited. We aimed to assess the long-term effect of faecal diversion in CD patients with refractory colon and/or perianal disease, and identify factors associated with successful ostomy reversal.

Methods

We conducted a single centre, retrospective observational cohort study in a large IBD referral centre. We included all CD patients who underwent an ileostomy as a temporary measure for managing their refractory disease between 2019 and 2023, enabling at least 12 months follow-up.

We evaluated the clinical impact of faecal diversion, and explored the rate of (successful) restoration of transit. Clinical improvement was defined as significant symptomatic improvement, according to physician global assessment. Resolution of perianal disease was defined as the absence of perianal fistula at the time of the multidisciplinary assessment for transit restoration.

Results

A total of 42 patients, with a median age of 31.5 (interquartile range, IQR 24.2–40.9) and median disease duration of 12.4 (IQR 5.8-18.4) years at time of diversion were included. Patients were followed up for a median of 46.5 (IQR 30.2-67.5) months after ileostomy. Indication for faecal diversion was refractory colitis in 26.2% (n=11), and/or severe perianal disease in 73.8% (n=31). Advanced IBD therapy was restarted in 78.6% (n=33) of patients following diversion.

Faecal diversion resulted in clinical improvement in 57.1% of patients (n=24), of whom 70.8% received advanced therapy (n=17/24), and resolution of perianal disease in 35.5% (n=11/31). A total of 14 patients (33.3%), of whom 7 with a perianal phenotype, were proposed for restoration of transit by the multidisciplinary team. Ultimately, in 9/14 patients, including 4 with perianal disease, the ileostomy was reverted with a persistent bowel continuity of 89.9% after 19.0 (IQR 10.7-27.2) months of follow-up.

Conclusion

Temporary faecal diversion in patients with severe refractory Crohn’s colitis and/or anal disease resulted in significant clinical improvement in almost two thirds of patients, but is often a bridge to a permanent stoma as stoma reversal could only be considered in one third of patients. In these selected cases where the transit was restored, persistent bowel continuity was high.
P0830 Use of FK-adalimumab biosimilar (MSB 11022) in context of biologic switch in Inflammatory Bowel Diseases : 6 months data of the real-world IDEA study
Authors: Peyrin-Biroulet L , Bouhnik Y , Hebuterne X , Fumery M , Taxonera C , Gutierrez-Casbas A , Howaldt S , Stein J , Lindsay J , Monnet J , Simoes E , Dolfi F
Published: January 2025

Background

Biosimilars offer similar efficacy and safety when compared to their originators, thereby enhancing patient access to more affordable treatments. FK-adalimumab (FK-ada) is an adalimumab biosimilar approved for the treatment of Crohn’s disease (CD) and ulcerative colitis (UC). FK-ada development included 1,234 subjects treated up to 52 weeks (total 420 patients-year). Since first approval, there have been no unexpected safety signals despite more than 115,000 patient-years of exposure. IDEA is an ongoing real-world study aimed to assess persistence with FK-ada and develop a predictive model of persistence at 12 months. In this study, adult patients with IBD who switched from adalimumab originator or another adalimumab biosimilar to FK-ada are followed up to one year.

Methods

Data collected include patient characteristics, reasons for treatment switch, clinical status at each follow-up visit including disease activity scores (Harvey-Bradshaw Index (HBI) and Montreal classification), and faecal calprotectin results. Adult patients with either CD or UC were included, those receiving treatment outside of routine clinical care were excluded. Data are presented using descriptive statistics and a logistic regression model will be employed to identify potential predictive factors at 12 months. We present here the baseline characteristics of IBD patients, and the 6 months intermediate results.

Results

A total of 136 IBD patients (CD: 112, UC: 24) were recruited across France, Germany and Spain, 57% being males, median age of 43 years and median BMI of 25.2 kg/m2. At the time of switch 97.3% of patients with CD and 87.5% with UC were in clinical remission or had mild to moderate disease activity. 54.4% of patients switched to FK-ada from originator, and 45.6% from another biosimilar, with most switches occurring for administrative reasons. A total of 103 IBD patients (CD: 87, UC: 16) completed the 6 months visit. Patients and disease status are summarized in Table 1. The persistence rate of FK-ada at 6 months was 76.4% (CD: 79%, UC: 65.2%). Most permanent treatment discontinuations occurred around 3 months after switch (median 3.6 months), primarily due to adverse events. Since the start of the study 46 patients (34%) experienced at least one adverse event (AE); 16 (12%) had at least one moderate to severe AE and 30 (22%) had AE(s) attributable to FK-ada.

Conclusion

6 months after the switch, FK-ada persistence rate was 76,4%. The majority of patients were still in remission or experiencing mild to moderate disease activity. Treatment and tolerance data from the study completion (52-week) will be critical for identifying predictive factors influencing drug persistence after the switch.
P0835 AI-guided generation and development of HXN-1001, a highly potent and half-life extended anti-TL1A antibody
Authors: Huang J , Ran H , Li S , Su C , Chen C , Liu D , Pan Y , Xu X , Chen X , Fei K , Tian J , Wang M , Tian L , Peng J , Zhu Z
Published: January 2025

Background

TL1A, a member of the TNF family, is genetically associated with several human autoimmune diseases, including IBD, psoriasis, and RA. TL1A-blocking antibodies have demonstrated clinical efficacy in patients with UC and CD. HXN-1001 is a novel humanized anti-TL1A antibody with strong blocking activity and extended in vivo half-life.

Methods

Affinity for soluble TL1A was assessed using SPR, while binding to membrane TL1A was measured with flow cytometry. The activity of HXN-1001 was validated through various in vitro experiments, including blocking TL1A binding to DR3-overexpressing cells, TL1A-induced TF-1 apoptosis, DR3-NFκB-Luc reporter assays, and IFN-γ release from primary T cells. In vivo efficacy was demonstrated in DSS-induced colitis and IMQ-induced psoriasis models using hTL1A, hTL1A/hα4β7, or hTL1A/hIL23 transgenic mice. The in vivo half-life was studied in hFcRn transgenic mice and rhesus monkeys.

Results

HXN-1001 is a humanized antibody that binds to TL1A via unique epitopes, exhibiting sub-nanomolar affinity for both TL1A trimer and monomer. It shows significantly stronger binding to TL1A-overexpressing cells compared to MK-7240 and RVT-3101. HXN-1001 effectively inhibits TL1A-induced NF-κB activity, apoptosis of TF-1 cells, and IFN-γ secretion in human primary T cells, with superior potency to both RVT-3101 and MK-7240. In a DSS-induced colitis model in transgenic mice, HXN-1001 demonstrated superior anti-inflammatory effects compared to RVT-3101, MK-7240, and the α4β7 antibody Vedolizumab. In an IMQ-induced psoriasis model, HXN-1001 exhibited better therapeutic effects than the marketed anti-IL-23 monoclonal antibody Risankizumab. The in vivo half-life of HXN-1001 is approximately 18 days in Tg32 hFcRn-transgenic mice and 23 days in Rhesus monkeys, supporting a clinical dosing frequency of at least every 8 to 12 weeks or even longer.

Conclusion

HXN-1001 is a next-generation antibody targeting TL1A, offering significant advantages in efficacy and in vivo half-life. It has strong potential to enhance clinical efficacy and dosing convenience. HXN-1001 is anticipated to enter clinical development in Q2 2025.
P0838 The clinical outcomes of Inflammatory Bowel Disease after liver transplantation for primary sclerosing cholangitis: a systematic review and meta-analysis
Authors: Zhou J , Sneek D , Hansen B , den Hoed C , de Jong M , Pan Q , van der Meer A J , Li P , de Vries A C
Published: January 2025

Background

The clinical course of inflammatory bowel disease (IBD) associated with primary sclerosing cholangitis (PSC) after liver transplantation (LT) varies significantly across studies. This study aims to provide a comprehensive estimation of incidence rates (IR) for colorectal cancer (CRC) or high-grade dysplasia, bowel surgery, IBD exacerbation, and newly diagnosed IBD in PSC-IBD patients post-LT.

Methods

Online databases were searched from inception till January 2024 for studies reporting on patients who underwent LT for PSC with IBD diagnosed either before or after LT. The pooled IR were calculated with the "meta" package (R Studio [V.4.2.764] ) using a random effects model.

Results

Of 5,324 studies initially identified, 97 underwent full-text review, and 34 retrospective cohort studies were included in the meta-analysis. These cohorts encompassed 3,672 patients with LT for PSC, of whom 63% had concomitant IBD. The mean follow-up period across studies ranged widely from 2.46 years to 17.3 years.

A pooled analysis of 21 studies reporting on colorectal neoplasia revealed an overall IR of CRC or high-grade dysplasia post-liver transplantation of 6.7 cases per 1,000 person-years (95% CI 4.3-9.0) (Figure 1A). Across 18 studies, 17.8% (n=195/1094) patients with concomitant IBD at the time of LT experienced clinical exacerbation, defined as worsening of IBD symptoms, increased inflammatory activity at endoscopy, or required optimization of IBD treatment post-transplantation. The pooled IR of clinical exacerbation was 34.1 cases per 1,000 person-years (95% CI 22.7-45.5), though heterogeneity was high (I² = 76%). Notably, meta-regression revealed a decline in IR of clinical exacerbation over time exclusively within European countries, with no observed change elsewhere. Additionally, 16 studies reported on newly diagnosed IBD in PSC patients without pre-existing IBD at LT, with pooled IR of 12.6 cases per 1,000 person-years (95% CI 9.7-15.5) (Figure 1B). The overall bowel surgery rate post-LT was 20.2 cases (95% CI 16.9-23.4) per 1,000 person-years within 23 studies. More specifically, pooled colectomy rates for neoplasia and therapy refractory IBD were 10.5 cases (95% CI 6.7-14.2) in 16 studies, and 13.8 cases (95% CI 9.4-18.3) per 1,000 person-years in 10 studies, respectively.

Conclusion

This meta-analysis provides a thorough assessment of IBD outcomes in PSC-IBD patients following liver transplantation, highlighting the considerable incidence rates of colorectal neoplasia and newly diagnosed IBD. Close clinical follow-up and regular endoscopic surveillance remain essential in PSC patients post-LT.
P0844 Real-world effectiveness of vedolizumab in managing refractory pouchitis: a multicenter study on intravenous to subcutaneous transition
Authors: Gimeno-Pitarch L , Minguez A , Cespedes E , Ferreiro-Iglesias R , Martín-Arranz M D , Sicilia B , Lorca I , Huguet J M , Mesonero F , Vicente R , Nos P , Iborra M
Published: January 2025

Background

Chronic refractory pouchitis (RP) is a complication of ileal pouch-anal anastomosis (IPAA). Vedolizumab (VDZ) has been used in RP management, but real-world data on its effectiveness are limited. Additionally, information on switching from intravenous (IV) to subcutaneous (SC) VDZ in this context is scarce.

Aims

To evaluate the efficacy and safety of VDZ in RP treatment in a real-world clinical setting, to assess outcomes following a transition from IV to SC VDZ, and to compare treatment persistence and safety between IV and SC administration.

Methods

A multicenter Spanish study was conducted in patients with RP receiving VDZ for active pouchitis. Clinical outcomes were evaluated using the modified Pouch Disease Activity Index (mPDAI), and biomarkers such as faecal calprotectin (FC), C-reactive protein (CRP), and VDZ serum levels were monitored over one year. Patients who transitioned from IV to SC VDZ were assessed post-switch.

Results

A total of 47 patients were included (31 (66%) male; median age 51 [43, 64] years). Of these, 25 (53%) switched from IV to SC administration. Baseline characteristics are shown in Figure 1.

Significant reductions in mPDAI scores were observed with IV VDZ, from 5 (3-7) at baseline to 3 (2-5), 3 (2-5), (2-5.8) at weeks (W) 12, 24 and 52 respectively (p<0.05). FC decreased significantly over time, from 443 µg/g (213, 746) to 329 µg/g (145-701), 193 µg/g (91-412) and 178 µg/g (101-640) at W12, 24 and 52, respectively (p<0.05), although no significant changes were observed in CRP levels. VDZ serum levels were 16,9 μg/dl (10.3-25.7), 12 μg/dl (7.3-23), 9 μg/dl (6.7-13.9) at W12, 24 and 52 respectively. After switching from IV to SC VDZ, there were no significant differences in terms of mPDAI, FC and CRP at W12 and W24. However, a significant decrease in mPAI (p=0.04) and FC levels (p=0.038) was observed at W52. FC levels also dropped significantly from 550 µg/g (145-1163) pre-swich to 264 µg/g (52-989), 129 (101-448) and 62 (31-211) at W12, 24 and 52, respectively. Notably, SC VDZ serum levels increased significantly, from 8.5 μg/dl (7.2-14) at time of switch to 22.7 μg/dl (21-27.3), 19.6 μg/dl (16.5-21), 21.6 μg/dl (17-26.2) over time. Fewer prior advanced therapies correlated with better outcomes, whereas use of corticosteroids and immunosuppressants at baseline did not. VDZ persistence was high (Figure 2) and adverse event rates were similar for IV and SC VDZ (8.5% and 12%, respectively).

Conclusion

VDZ was effective in achieving clinical and biological remission in patients with RP following IPAA for ulcerative colitis, particularly with early intervention. Switching from IV to SC VDZ effectively sustained long-term remission, demonstrating safety and persistence in routine clinical practice.