bluuebunny/crossref_metadata_2025_split huggingface dataset:
P734 A single measurement of fecal calprotectin, particularly if combined with hemoglobin and C-reactive protein levels, predicts Crohn’s disease prognosis - a prospective study
Authors: Magro F , Estevinho M M , Catalano G , Patita M , Arroja B , Lago P , Rosa I , Tavares-de-Sousa H , Ministro P , Roseira J , Cancela E , Sousa P , Portela F , Correia L , Moreira P , Santiago M , Dias S , Afonso J , Danese S , Peyrin-Biroulet L , Dias C C 
Published: January 2023

Abstract

Background
Early flare prediction is essential for the timely management of Crohn’s disease (CD) patients, allowing to optimize the available therapeutic toolbox and to decrease the disease burden. We aimed to evaluate the performance of readily available biomarkers (when evaluated at least once or more frequently during follow-up) and to develop risk matrices to predict CD progression.

Methods
CD patients receiving infliximab (IFX) as maintenance therapy (n=289) were followed up for 24 months; those patients were enrolled in DIRECT, a prospective, multicenter real-world study. Disease progression was evaluated using two composite outcomes incorporating clinical and drug-related factors, the first including also IFX dose and/or frequency adjustments. Univariate and multivariable logistic regressions were used to calculate the odds ratios (OR) and to develop risk matrices.

Results
The isolated presence of anemia at least once during follow-up was a significant predictor of disease progression (OR 2.436 and 3.396 [p≤0.001] for composite outcomes 1 and 2, respectively), regardless of confounding factors. Levels of C-reactive protein (CRP) above 10.0 mg/L or fecal calprotectin (FC) above 500.0 µg/g, in at least one visit, were also significant predictors, while milder elevations (3.1-10.0 mg/L and 250.1-500.0 µg/g) were only relevant when found in at least two visits (consecutive or not). The risk matrices combining the different non-invasive biomarkers had a good ability to predict CD progression. Indeed, patients simultaneously presenting anemia, CRP&gt;10 mg/dL and FC&gt;500.0 µg/g at least once had a probability of disease progression that ranged between 42 and 63%.

Conclusion
The combined evaluation of FC, hemoglobin, and CRP in at least one time point and their incorporation into risk matrices seems to be the optimal strategy for CD management, as data from additional visits did not meaningfully influence the predictions and may delay decision-making. This is one of the first studies developing risk matrices to predict the occurrence of composite outcomes in CD patients, providing an easily applicable tool for CD clinical management.
P738 Surgery for Crohn’s Disease: Results from a Spanish cohort with 15 years of follow-up
Authors: Elosua Gonzalez A , Rubio S , Irisarri R , Campillo A , Nantes Ó , Vicuña M , Angós R , Zozaya J M , Rodríguez C 
Published: January 2023

Abstract

Background
Crohn’s disease (CD) is a lifelong disease. Knowing the natural history is essential to understand the evolution of the illness, assess the impact of different therapeutic strategies, identify poor prognostic factors and provide patients with understandable information who help them in decision-making. One of the most relevant features in natural history of Crohn’s Disease (CD) are surgery requirements.

Methods
We performed a retrospective study that includes all patients with a definitive diagnosis (DD) of CD in the Navarra Incident Cohort (which includes all patients diagnosed between 2001 and 2003 in Navarra, Spain). Our objectives were to analyze the cumulative incidence of surgical resection and to identify predictive factors for surgery.

Results
We included 94 patients with DD of CD (L1 46.8% / L2 17% / L3 36.2%) 49 were men, median age at diagnosis of 34 years (7-75) and with a median follow-up of 15.6 years.
At the end of the follow-up, 42.5% of the patients had undergone surgery, 33 (35%) intestinal resection, 7 (7.5%) surgery for perianal disease (PAD) and three (3%) for both reasons. In total 59 interventions were performed, 19 of them for PAD.
The cumulative incidence of intestinal resection in our series was 5.3% at diagnosis, 8.5% at one year, 22.4% at 5 years, 29.9% at 10 years, 44.6% at 15 years, and 68.3% at the end of the follow-up (fig A). In 82% of cases a single resection was performed and in 6 patients 2 resections were performed. The surgery was elective in 80% of the cases. Before the intervention, all had received corticosteroids or 5-ASA, 25% (8) immunomodulators and 21% (7) biological agents. The most frequent indication was symptomatic stenosis (45%) followed by inflammatory abscess (25%).
In the univariate analysis, age at diagnosis, sex, L4 involvement, extraintestinal manifestations, and Harvey-Bradshaw index were not associated to the probability of intestinal resection. Disease location and behaviour were associated with more probability of resection (fig B and C). In the multivariate analysis, penetrating behaviour (B3 vs B1) was an independent risk factor associated with resective surgery (HR 14.48; 95% CI 4.17-50.3; p &lt;0.001) while ileocolonic disease (L3) was a protective factor compared with ileal location (L1) (HR 0.32; 95% CI 0.12-0.84; p = 0.02)

Conclusion
- In our cohort 5.3% of patients require intestinal resection at diagnosis and the cumulative incidence at 15 years of 45%
- Penetrating behavior was an independent risk factor for surgery and ileocolonic location a protective factor
P739 Sequential treatment is effective to achieve remission and avoid colectomy in moderate-to-severe Ulcerative Colitis refractory to anti-TNF therapy
Authors: Farkas B , Borsos M , Resál T , Bacsur P , Bor R , Bálint A , Fábián A , Szepes Z , Molnár T , Farkas K 
Published: January 2023

Abstract

Background
The development of anti-TNF agents has brought advances in the treatment of ulcerative colitis (UC). However, many patients require biological treatment sequencing. We aimed to evaluate clinical outcomes, the rate of treatment persistence and colectomy-free survival at second-, third-, and fourth-line therapy after switching from TNF-inhibitor to another treatment and to identify factors predicting the need for colectomy.

Methods
In this retrospective study, we included active UC patients refractory to at least one anti-TNF agent and needed treatment sequencing. The efficacy of therapies of the different lines was assessed by endoscopic or clinical scoring systems and laboratory markers. Kaplan-Meier analysis was performed to investigate the colectomy-free survival. Possible predictive factors were examined by logistic regression.

Results
Data of 90 UC patients were analyzed. The most frequently used first-line biologic therapy was infliximab (83.3%), which was discontinued after an average of 21.3 months. In the second-line vedolizumab (VDZ) was administered in 48.9% of cases, adalimumab in 36.7%. Average time between initiation and discontinuation was 15.7 months. In the third line, VDZ was used in 50%, tofacitinib in 29% of the patients, until an average of 8.7 months. In the fourth line, 53.1% of patients received tofacitinib and it was terminated after an average of 8.9 months. Loss of response, as a reason for treatment discontinuation was more common in the first-, and second-line therapies (58.9% and 46.2%), while primary non-response was more often observed in third-, and fourth-line therapies (52.6% and 63.6%). Fifteen patients underwent colectomy (16.7%). There was a significant increase in the probability of having surgery within 2 years after therapy initiation (p=0.0239) independently from treatment lines. Presence of deep ulcer showed inverse correlation with colectomy-free survival (p=0.0189; OR: 10.414 (95% CI: (1.472; 73.669)). Patients with high partial Mayo score at therapy initiation were more likely to undergo colectomy (p=0.0436, OR: 1.463 (95% CI: (1.011; 2.118)). In contrast, gender, age and disease extent at the time of the diagnosis, and the use of concomitant immunmodulators were not shown to be significant in predicting the subsequent surgical need.

Conclusion
Our results suggest that the remission rate does not decrease considerably as the sequential treatment progresses, more than half of the patients receiving fourth-line therapy were still in sustained remission. The more severe disease activity and deep ulcerations proved to be predictive for colectomy. Further studies in a larger patient population would be required to confirm our data and reveal predictive markers.
P740 Dual biologic therapy for patients with Inflammatory Bowel Disease in a single reference center in Spain
Authors: Diz Lois Palomares M T , Porta Sánchez Á , González Conde B , Estévez Prieto E , Vázquez Rey M T , Elberdin Pazos L , Alonso Aguirre P , Martin Herranz I 
Published: January 2023

Abstract

Background
In the last 5 years, the therapeutic arsenal in IBD has been expanded. Four different groups of effective biologic/new small molecules therapies, according to the target (anti-TNF, anti-integrin, anti-IL-12/23; and JAK inhibitors), are being widely used. There is still a significant number of patients who do not respond. In the last years, in tertiary centers, two simultaneous biologic therapies have been associated in a few IBD patients in clinical practice, in order to treat two different patient profiles: patients with IBD and concurrent extraintestinal manifestations (EIMs) which did not respond to the same biologic treatment, and second, refractory-IBD patients. It seems to add efficacy in case-series. However, safety concerns limit its use. We aim to describe the 6 patients treated in a single reference center in A Coruña, Spain.

Methods
The IBD Unit in A Coruña Universitary Hospital is the reference center for a 550000 patient population. Advance therapy with biologics is centralized in this IBD Unit, with approximately 630 patients having been treated with biologic therapy. Since 2020, we have treated 6 patients with dual biologic therapy (DBT), after discussing the case in the multidisciplinar IBD-Committee and with the informed consent of the patients. We describe this case-series.

Results
Our 6 patients proposed to DBT had long-standing IBD, and presented failure to 3-5 previous advanced lines of therapy. Two had ≥ 2 previous resection surgeries, and for 3 patients the surgery option would include a permanent stoma, or high risk of short bowel syndrome because of extensive disease.
We describe in table 1 patient’s demographics, IBD characteristics, and the DBT combinations.
In table 2 we further describe DBT and response to treatment.

Main indication for DBT was refractory IBD in 5/6 patients. DBT was intensified in all these cases. It added efficacy in 2/5 cases, however without achieving deep remission. Three patients (3/5) were co-treated with steroids. One patient had a serious infectious adverse event that required hospitalisation.
In 1/6 patient the indication for DBT was IBD and concurrent EIMs, each one responding to different biologic, this patient was initially co-treated with IMM and steroids; dual therapy was effective and safe, with standard doses.

Conclusion
Our experience is in line with that described by other authors. DBT in clinical practice is offered to long-standing and refractory IBD. In these cases, effectiveness seems limited, with concerns on infectious adverse events, but surgery probably carries worse prospects. For the indication of IBD with EIMs not responding to the same biologic, DBT seems more effective. More data is needed to know in which cases and what combinations could be beneficial.
P748 Pharmacokinetics, relative bioavailability, and dose proportionality of a tablet formulation of the sphingosine 1-phosphate-1 receptor modulator VTX002 (formerly OPL-002)
Authors: Gregg R , Yun C , Naik S , Huyghe M , Harris J , Mohan R , Nuss J , Sandborn W J 
Published: January 2023

Abstract

Background
VTX002 is an oral selective sphingosine 1-phosphate-1 receptor (S1P1R) modulator in clinical development for treatment of ulcerative colitis (UC). Single and multiple doses of a spray-dried dispersion (SDD) oral suspension of VTX002 were well-tolerated up to 45 mg in a phase 1 study in healthy participants and were accompanied by dose proportional reductions in lymphocyte counts, an expected pharmacodynamic outcome of treatment.1 A separate phase 1 study compared the pharmacokinetics (PK) and pharmacodynamics of the SDD oral suspension and a tablet formulation of VTX002.

Methods
Healthy adult participants (N=12) were randomised (4 per dose group) in an open-label 3-way crossover study to receive single oral doses of 5 mg or 20 mg VTX002 tablets, or 20 mg VTX002 SDD suspension followed by at least a 1-week washout between each dose as shown in Fig. 1. Study assessments included: VTX002 plasma concentrations, PK parameters, change from baseline in absolute lymphocyte count (ALC), and adverse events (AE).

Results
A total of 10 participants completed the study. Mean plasma VTX002 concentrations were greatest with a single oral dose of 20 mg VTX002 SDD suspension (Fig. 2).

The geometric mean peak (Cmax) and total (AUCinf) exposure to VTX002 were lower with the 5 mg (dose normalized to 20 mg tablet) and 20 mg VTX002 tablets compared to the 20 mg VTX002 SDD suspension (Table 1).

Geometric mean ratios for the tablet and SDD formulations of VTX002 are shown in Table 2.

Maximum percent (SD) reduction in ALC from baseline was greatest for the 20 mg VTX002 SDD suspension and was observed at 6 hours post-dose both for the SDD suspension and the 20 mg VTX002 tablet (59.9% [11.0%] and 51.6% [9.4%], respectively). The maximum percent reduction in ALC from baseline for the 5 mg VTX002 tablet was 22.4% (9.2%) which occurred 2 hours post-dose. A total of 23 AEs were reported; of which 19 were considered mild, and 4 were moderate.

Conclusion
All doses and formulations of VTX002 were well-tolerated and associated with ALC reductions. Data from this relative bioavailability study was used to convert the results from the prior phase 1 multiple ascending dose study performed with VTX002 SDD suspension to AUC equivalent tablet doses and enable tablet dose selection for phase 2. A phase 2 study of VTX002 tablets for treatment of UC is underway (ClinicalTrials.gov Identifier:NCT05156125).
1Luo A, et al. 2020 Gastroenterology. 2020;158(6):S1188.
P750 Biosimilar Infliximab Switching is Not Associated with Adverse Outcomes: A Real-World Effectiveness Analyses in a National U.S. Cohort of U.S. Military Veterans with Inflammatory Bowel Disease
Authors: Hou J K , Pham C , Sansgiry S , Modi V , Waljee A K 
Published: January 2023

Abstract

Background
Infliximab (IFX) biosimilars are widely available for Crohn’s disease (CD) and ulcerative colitis (UC). However, implementation of biosimilar switching has been highly variable in the U.S. Barriers to switching include patient and provider concerns of lower efficacy, immunogenicity, and safety. Biosimilar switching in Veterans Affairs (VA) was based on local facility policy rather than patient/provider selection and thus less prone to selection bias. The goal of this study is to evaluate the safety and effectiveness of biosimilar switching in a National U.S. Cohort of Veterans with CD and UC.

Methods
We conducted a retrospective cohort study of CD and UC patients who received maintenance originator IFX from 2017-2019 in the VA. CD and UC patients were identified using a previously validated algorithm and confirmed by chart review. Patents on maintenance IFX originator were identified by dispensed medication from Corporate Data Warehouse (CDW). Patients switched to IFX biosimilar after 2017 were identified in CDW by dispensed medication and confirmed by chart review. Adverse outcomes were defined as infusion reaction, serious infection (intravenous antibiotic, delay of IFX), immunogenicity (anti-IFX antibody or IFX escalation) or disease flare (escalation of steroid, IBD related Emergency department visit, hospitalization) confirmed by chart review. Adverse event rates at 12 months for patients continued on originator IFX were compared to patients switched to IFX biosimilar using univariate and multivariate logistic regression models adjusting for patient and non-patient factors.

Results
A total of 790 patients (492 CD, 298 UC) on originator IFX were identified during the study period. Of these, 380 patients were identified to have switched to IFX biosimilar and 410 patients continued on IFX originator during the study period. Overall adverse outcomes occurred in 35.6% of patients at 12 months (35.6% switch, 35.3% non-switch, p=0.87). No statistically significant difference in rates of infusion reaction, serious reaction, immunogenicity, or IBD flare were identified between switch and non-switch groups. In multivariate logistic regression including age, race, gender, concomitant medication, and VA priority status, no significant differences in adverse outcomes at 12 months were observed between switch and non-switch groups (aOR 1.09, 95% CI 0.76-1.42).

Conclusion
In a real-world national U.S. cohort of patients with CD and UC, we observed IFX biosimilar switching was not associated with adverse events compared to continuation on IFX originator. While this study may be underpowered to detect such a small difference, these findings provide further reassurance that IFX biosimilar switching for CD and UC is safe and effective.
P751 Crohn’s Disease Exclusion Diet: A single centre real-life experience
Authors: Lababidi N E , Pavel F 
Published: January 2023

Abstract

Background
According to ECCO-ESPGHAN consensus guidelines, exclusive enteral nutrition (EEN) is the first line therapy for induction of remission in children with active luminal Crohn’s disease (CD). Steroids may be considered in cases when EEN is not an option. However, adherence to EEN is not ideal. According to various sources it ranges from 50-91 %. This poor adherence is mainly due to palatability and monotony. Many attempts have been made to find an alternative to EEN. One of them is Crohn’s Disease Exclusion Diet (CDED) with partial enteral nutrition (PEN), which shows promising results in efficacy, safety, and adherence. This study evaluates the efficacy of CDED with PEN in a single European centre.

Methods
Retrospective evaluation of prospectively collected dated of children treated with CDED with PEN between 10/19-11/22. Wellbeing, anthropometric data, and laboratory results were evaluated prior to the commencement of CDED with PEN and at the end of both phases 1 and 2. A mean, median and a standard deviation were calculated were applicable. ANOVA was used for evaluation of presence of statistically significant differences and a P-value ≤ 0.05 was regarded as such.

Results
CDED with PEN was used in 24 patients. The mean age at diagnosis was 14.6±3.7 years. At the time of evaluation, 21/24 patients have completed phase 1 and 20/24 have completed phase 2. Three patients were still in phase 1 and 1 in phase 2. One patient decided to quit CDED with PEN at the end of phase 1 and 2 more at the end of phase 2. All patients, who started phase 1 completed it, and 95.2% completed phase 2. Non-adherence was recorded in two patients: once in diet composition and twice in PEN volume.
At commencement of CDED with PEN, dietary intervention was the only treatment in 16/24 patients. Three patients were on Azathioprine (AZA), 2 5-aminosalicylic acid (5-ASA), 1 Methotrexate (MTX) and another Prednisone. At the end of phase 1, 8 patients were on anti-TNF-α, 8 were using AZA, 2 5-ASA and 1 MTX. At the end of the phase 2, anti-TNF-α was used in 12 patients, AZA in 8, MTX in 3 and both anti-IL12/23 and 5-ASA in 1 patient.
CRP and ESR showed a statistically significant decrease (P&lt; 0.01) at the end of phases 1 and 2, Faecal calprotectin (FC) showed so at the end of phase 2 (P&lt; 0.01). Other followed parameters failed to show a significant difference at the end of follow-up.

Conclusion
These data support that CDED with PEN is both well tolerated and has a very high adherence rate. They also confirm that CRP and ESR decrease significantly at the end of both phases and FC at the end of phase 2. CDED with PEN should be considered as an alternative to EEN and steroids in induction of remission of luminal CD in children.
P756 Cumulative adverse events of anti-TNF therapy in IBD patients at a large tertiary centre – a 13-year real-world experience
Authors: Majumder S , Love M , Davis J , Sharma N , Nabil Quraishi M , Cooney R , Ghosh S , Iacucci M , N Shivaji U 
Published: January 2023

Abstract

Background
Anti-TNFα is the first class of biologics approved for treatment of moderate-to-severely active Inflammatory Bowel Disease (IBD). More than two decades on, anti-TNFs remain one of the most commonly used biologics for both Ulcerative Colitis (UC) and Crohn’s Disease (CD), and often as first-line therapy. Although effective, they cause several adverse events (AEs), sometimes requiring withdrawal of therapy. The aim of the study was to record cumulative AEs in IBD patients and report on real-world safety profile of this class of drugs.

Methods
All IBD patients exposed to anti-TNF therapy were identified from EMR at two centres of a large tertiary referral centre between January 2009 and June 2022. All relevant demographic and clinical data were collected for those patients with well recorded AEs and follow-up. Data on cumulative AEs directly attributed to anti-TNFs that ranged from mild reactions to serious AEs (defined as those requiring review/withdrawal of anti-TNF), were collected. Data on malignancies in this cohort was collected separately. The data were analysed and statistical analysis carried out using the IBM® SPSS® Statistics software package Version: 28.0.0.0.

Results
Total of 844 patients (M=408, 48%; median age 37years) were included, of which 61% were Caucasian. Majority had CD (608;72%) with mean age at diagnosis of 27y (SD 15y) and a median disease duration of 12years. About 50% of patients were on monotherapy and adalimumab was most frequently used (52%). A significant proportion of patients (44%) discontinued therapy during the follow-up period covered by the study (median duration 5years); infliximab showed best persistence rate (Fig 1). The commonest AEs were dermatological followed by auto-immune. Infections affected all age groups and bacterial infections were most common. Male sex, age groups of 18-50 years were statistically more likely to develop an AE (Table 1). 16 malignancies and 1 death were recorded in this cohort.

Conclusion
In our cohort, a significant number of AEs to anti-TNFs were noted, frequently resulting in the withdrawal of therapy. Although effective, anti-TNFs related AEs lead to poor persistence rates and contribute to increased risk of infections, particularly in &gt;60y age group. Clinicians must be aware of the wide range of AEs due to anti-TNFs; these risks must be considered, and patients selected carefully to maximize success. With a wider choice of biologics and small molecules currently available, other options with apparently more favourable safety profiles could be considered earlier in the treatment algorithm.