bluuebunny/crossref_metadata_2025_split huggingface dataset:
P890 Usefulness of subcutaneous Infliximab in patients with Inflammatory Bowel Disease in clinical practice: are increased levels associated with clinical benefit?
Authors: De La Filia Molina I Garcia , Gismero F Mesonero , Cardona J López , Aldehuelo R Sánchez , De la Serna Gamboa Á , Gramage Caro T , Fernández Fernández C , Garbiñe R A , Agustín A M , San Román A López 
Published: January 2024

Abstract

Background
Switch from intravenous Infliximab (IFXiv) to subcutaneous Infliximab (IFXsc) in Inflammatory Bowel Disease (IBD) has been associated with an increase in trough levels. However, whether this increase is correlated with additional clinical benefit has not thus far been evaluated in clinical practice.

Methods
Single-center retrospective study of IBD patients who switched from IFXiv to IFXsc (for at least 3 months), between July 2021 and August 2023, due to unfavorable pharmacokinetics (IFX serum levels &lt;3 +/- anti-IFX antibodies). Disease activity was defined as clinically: Simple Clinical Colitis Activity Index (SCCAI) ≥2 for Ulcerative Colitis (UC), Harvey Bradshaw Index (HBI) ≥5 for Crohn´s Disease (CD) or perianal fistulae with active drainage; and biochemical: C-reactive protein (CRP) &gt;5 mg/L and/or fecal calprotectin (FC) &gt;250 µg/g in UC and &gt;150 µg/g in CD. Primary endpoint was to evaluate the effectiveness of IFXsc switch: achieving clinical response (decrease of SCCAI ≥2, IHB ≥3 or ≥50% in fistula drainage) or remission (SCCAI ≤1, IHB ≤4 or absence of active fistula drainage) with biomarkers normalization, or maintenance of remission, in patients with and without previous activity, respectively. Secondary endpoints were to assess IFX levels change and safety of IFXsc switch.

Results
Twenty-five patients (23 CD, 2 UC) were included (Table 1). Previous IFXiv therapy lasted for a median of 55 (20.6-74.1) months (100% with intensified dose and 48% with combined therapy). Median baseline IFX level was 1.7 (0.4-3) μg/mL, with anti-IFX antibodies in two cases. At baseline, 7 patients were in remission and 18 had active disease: 15/18 clinical or both clinical and biochemical (3/15 luminal, 11/15 perianal or 1/15 both), and 3/18 biochemical only. Median follow-up was 15.2 (10.2-19.2) months. After IFXsc switch, an increase of IFX level was achieved in 96% of cases, with a median final level of 12.4 μg/mL (9.2-18) (Figure 1). None of the patients in remission at the beginning relapsed during follow-up. Of patients with previous clinical activity, 66.6% achieved clinical remission (53.3%) or response (13.3%), which was seen in 50% of patients with luminal and 66.7% with perianal activity, after a median of 79 (75-210) days. CRP and FC normalization was reported in 53.3% of patients with previous biochemical activity. Treatment was discontinued only in one patient due to inefficacy. IFXsc was intensified in 8% and concomitant treatment could be withdrawn in four patients. No adverse events we reported.

Conclusion
Switching to IFXsc in patients with previous therapy with intensified IFXiv is not only associated with a more favorable pharmacokinetic profile but also with a greater effectiveness.
P893 Transition from intravenous to subcutaneous infliximab: effectiveness in a cohort of patients with inflammatory bowel disease
Authors: Todeschini A , Geccherle A , Signoretto P , Colaci N , Barugola G , Variola A 
Published: January 2024

Abstract

Background
Inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohn’s disease (CD), is a group of chronic inflammatory disorders. Biologics are indicated for patients failing conventional maintenance therapy with moderate to severe activity. Different routes of administration, intravenous (IV), subcutaneous (SC) or oral have been approved. For chronic diseases such as IBD, some patients may prefer self-administered SC dosing to IV dosing as a less time-intensive and more convenient treatment option. This study aims to evaluate evaluate the success of infliximab subcutaneous administration after switching from intravenous administration in IBD patients.

Methods
The transition from IV to SC administration was proposed to 60 IBD patients in clinical remission. Data on medical history and laboratory tests were collected from electronic health records. Moreover, patients filled a paper questionnaire 8 weeks after the switch focused on the level of satisfaction and onset of adverse event (AE).

Results
Overall 60 patients were enrolled for switching from IV to SC therapy. Most of patients (&gt;80%) did not experience any difficulties in handling the device and respected the correct time-table of administration. The switch was a complete success in 50 out of 60 patients (83.3%). Ten patients stopped subcutaneous formulation: five of these switched back to intravenous formulation for adverse event or patient’s preference, four swap or swop to other therapy and one withdraw from biologic. No predictor of loss of response was found at multivariate analysis. Faecal calprotectin and C-reactive protein values significantly improve after the switch at 3, 6 and 12 months (p= 0.03, p= 0.004, p = 0.01 and p= 0.06, p= 0.001, p= 0.007 respectively). About 16.7 % of patients had at least one side effect after switching. Local pain and swelling at site of injection were the most common AEs. The vast majority of AE were mild and lasted only a few days. No serious AEs were reported and no patient was hospitalized.

Conclusion
Effectiveness of switching from intravenous to subcutaneous infliximab administration in IBD patients is confirmed in our real world cohort of patients.
P896 You Can Lead a Horse to Water But You Can’t Make it Drink: A Study on Medication Adherence of Inflammatory Bowel Disease Patients in Ireland
Authors: Kumar L , Hanly M , Drudy A , Girod P , Fennessy A , Mulcahy H , Horgan G , McDermott E , Buckley M , Sheridan J , Cullen G , Doherty G 
Published: January 2024

Abstract

Background
Medication adherence is important in ensuring adequate treatment of Inflammatory Bowel Disease (IBD). The High Tech Hub (HTH) is an online system used in Ireland to prescribe and monitor the ordering of High-Tech Medication, specifically oral small molecules and subcutaneously-delivered biologics. We aimed to observe compliance rates of treatment in our centre, observe trends between different medication and identify factors associated with adherence.

Methods
We extracted prescribing and medication dispensing information from the HTH database for our centre between May and November 2023. We collected information on patient demographics such as age and gender, patient disease subtype, medication class and duration of prescription given against the duration of prescription collected by the patient with an 85% threshold as a marker of compliance to treatment. Statistical analysis was used to compare differences in adherence between subsets of the population and a multivariate regression model was used to identify factors associated with adherence.

Results
We extracted information from 824 prescriptions from 644 unique patients. The median age was 42 years (IQR 32-52) with 52.2% males. 60.7% (n=391) had Crohn’s Disease, 33.4% (n=215) had Ulcerative Colitis and 3.1% (n=20) had IBD-U. Majority of patients, 77.3% (n=498), were on Anti-TNF medication, followed by 13.2% (n=75) on anti-Interleukins, 6.2% (n=40) on JAK Inhibitors and 3.3% (n=21) Anti-Integrins.
6.5% (n=42) of patients required dose optimization during the 6-month observation and 1.7% (n=11) required a change of medication. 9.5% (n=61) of patients collected prescriptions for steroids. Further analysis demonstrated no significant difference in adherence within gender (Male: 61.0% vs. Female 53.6%, p=0.056), age (&lt;25 years: 66.2%, 25-39 years: 55.0%, 40-54 years: 58.6%, ≥55 years: 54.6%, p=0.346), disease type (Crohn’s: 58.6%, Ulcerative Colitis: 56.7%, IBD-U: 50%, p=0.776), medication class (Anti-TNF: 56.4%, Anti-Interleukin: 65.9%, Anti-Integrin: 57.1%, JAK Inhibitor: 52.5%, p=0.378).
However, we found significant lower adherence rates in patients who required dose optimization (21.4% vs. 60.0%, p&lt;0.001) and those who required a change in medication (18.2% vs. 58.1%, p=0.008) in the observation window. There was also a lower rate of adherence noted in those who received prescriptions for steroids (45.9% vs 58.9%, p=0.051).

Conclusion
There was a high rate of non-adherence noted in our IBD population, worse in those who ended up requiring dose optimization or change in therapy. Addressing compliance by monitoring the online dispensing of medication may be a useful way to ensure adequate treatment and avoid unnecessary treatment escalation.
P899 Inflammatory Bowel Disease Patients Show More Recognizable Digestive Symptoms of COVID-19: A Questionnaire Study
Authors: Xu Z , zhimin M , lujia J 
Published: January 2024

Abstract

Background
It's important to manage IBD patients in the era of coronavirus pandemic (COVID-19). However, there is few studies on the clinical symptoms and prognosis of COVID-19 in IBD patients.

Methods
A web-based survey concerning symptoms of COVID-19 in people with or without IBD was designed. A pilot-test was carried out to ensure the feasibility of the questionnaire. Propensity score matching (PSM) was used to compensate for differences in baseline characteristics. Wilcoxon rank-sum test and Chi-square test were used to compare the clinical and prognosis differences between two groups.

Results
A total of 1274 individuals (including 631 with IBD) completed the questionnaire. After the use of PSM, 786 cases including 393 of IBD and non-IBD individuals respectively were included in the analysis. Fever and nasal congestion were the most common clinical manifestations of COVID-19 in our study. As for gastrointestinal (GI) symptoms, more IBD patients presented with new-onset abdominal pain (26.7% vs. 12.7%, p&lt;0.001), diarrhea (22.4% vs. 14.5%, p&lt;0.005) and altered bowel habits (38.7% vs. 24.9%, p&lt;0.001).

Conclusion
COVID-19-related GI symptoms are more common in IBD patients. It is important to rule out COVID-19 infection in patients experiencing recurrence or exacerbation of GI symptoms.
P906 The drug-survival of low-dose thioguanine in patients with inflammatory bowel disease. A retrospective observational study
Authors: Karling P , Werner M , Gensmyr-Singer H 
Published: January 2024

Abstract

Background
Thiopurines are commonly used to treat inflammatory bowel disease but withdrawal due to side-effects are common. Thioguanine has been suggested to be better tolerated than conventional thiopuries. We aimed to study drug-survival of low-dose of thioguanine in real-life clinical practice in comparison to conventional thiopurines.

Methods
All patients born in the year 1956 and later, and who at least once started thiopurine treatment between the years 2006-2022 were included. A medical chart review was performed that noted drug-survival for every thiopurine treatment attempt. Mantel-Cox rank test was used to test differences in drug-survival for different thiopurines. Blood chemistry analysis and faecal calprotectin levels was registered the first five years of treatment.

Results
In the study population there was 379 initiated thiopurine treatments (210 for Crohns disease and 169 for ulcerative colitis) in 307 patients with IBD. Low-dose thioguanine (median dose 11 mg; 25-75th percentile 7-19 mg) had been initiated in 31 patients. Overall, when including all thiopurine attempts, the median time on treatment for the different thiopurine treatments were for azathioprine 24 months (25th-75th percentile 3-59 months), for 6-mercaptopurine 15 months (3-59 months), for azathioprine/allopurinol 22 months (1-25 months) and for thioguanine 33 months (11-64 months). Thioguanine had longest drug-survival (Mantel-cox rank test: thioguanine versus azathioprine p=0.014; thioguanine versus 6-mercaptopurine (6-MP) p&lt;0.001). For second line thiopurine treatment, the median time on treatment for 6-mercaptopurine were 13 months (2-69) and for thioguanine 33 months (11-64). Thioguanine had longer drug-survival than 6-MP (Mantel-Cox rank test: p=0.006) (Figure). At 60 months, 86% of the patients who started low dose thioguanine was still on treatment compared to 42% of the patients who started 6-MP (p=0.022). The median 6-TGN levels in patients treated with thioguanine was 364 pmol/8x108. Patients on thioguanine treatment showed significantly lower values of median mean corpuscular volume at follow-up than patients treated with azathioprine and 6-MP. Patients treated with 6-MP had signficantly lower levels of F-calprotectin at year three and year four compared to patients treated with azathioprine. Overall there was a similar response on inflammatory markers the first five years from starting treatment with thioguanines compared to conventional thiopurines.

Conclusion
Treatment with a low-dose of thioguanine is well tolerated in patients with IBD and have a significantly higher drug survival than conventional thiopurines.
P928 "Metabolism and Response to Stress" (MARS) gene signatures reveal heterogeneity in patients with Ulcerative Colitis and identify characteristics of patients with increased response to therapy
Authors: Linggi B , Sangiorgi B , Smith M I , Teft W , Jairath V , Ma C , Vande Casteele N 
Published: January 2024

Abstract

Background
Ulcerative colitis (UC) therapies lead to variable remission in participants in clinical trials likely due to interindividual variability, differences in active biological pathways, feedback, and/or resistance mechanisms. We sought to characterise these differences using mucosal biopsy transcriptomics datasets from two recent UC clinical trials.

Methods
Two clinical trial datasets including patients with moderate to severe UC with mucosal biopsy RNA-Sequencing analysis were used: a phase 2/3 study of andecaliximab (anti-matrix metalloproteinase-9, NCT02520284) and a phase 3 study of ustekinumab (anti-interleukin-12/23, UNIFI, NCT02407236). Samples were scored for enrichment of ~5200 MSigDB signatures using Geneset Variation Analysis and were evaluated for correlation to the sample Robarts Histopathology Index (RHI) (Figure).

Results
From the andecaliximab baseline and follow-up samples, 11 Reactome pathways were specifically selected that were moderately correlated with RHI (r=~0.4) and had low correlation to each other (r&lt;0.7). The 11 genesets, called Metabolism and Response to Stress (MARS) signatures, can generally be sorted into 2 categories: 5 metabolism-related and 6 related to stress response. Clustering of baseline andecaliximab samples scored with MARS signatures revealed 3 major sample groups (baseline and follow-up samples). Group 1 had low metabolism/high stress scores, group 2 had high metabolism/low stress scores, and group 3 had a mixture of samples that had high metabolism/low stress and low metabolism/high stress. Group 2 was associated with a lower proportion of current smokers (p=.04), and group 3 had a higher proportion of immunomodulator failure (p=.03), but not associated with disease duration or prior biologic use. Group 2 had lower Geboes score for epithelial neutrophils (p=.02), lamina propria neutrophils (p=.002), and inflammatory infiltrate (p=.03), while eosinophils increased (p=.01). To evaluate prediction of response to therapy, we evaluated the UNIFI dataset baseline samples using the MARS signatures and identified 4 groups. Group 2 had low metabolism/high stress response, group 3 had high metabolism/low stress response, and groups 1 and 4 had a mixture. The mucosal healing response rate was 3- to 4-fold lower for group 2 than other groups (5.3% [group 2] and 19%, 23%, and 21% for other groups, p=.0009).

Conclusion
We describe the MARS signatures which characterise the heterogeneity of participants with UC clinical trials and identify participants most likely to respond to ustekinumab at baseline. These signatures may be generally useful to predict patient response, match therapeutics to patient profiles, or identify pathways to target in difficult-to-treat patients.
P935 Remission rates of biologics and small molecules in extension studies of moderate to severe Ulcerative Colitis; A systematic review and Network Meta-analysis
Authors: Godfrey D , Parkash N , Segal J 
Published: January 2024

Abstract

Background
Ulcerative colitis is a relapsing and remitting inflammatory bowel disease characterised by symptoms of bloody diarrhoea and abdominal pain. In recent years, newer therapies have emerged such as biologics and small molecule therapies. However, these therapies have not been compared head-to-head in the longer term, and the choice in clinical practice is often at the discretion of the clinician. In this study we aim to compare these biologics and small molecule therapies across outcomes such as remission (as defined by the Mayo score) as well as histological, endoscopic and corticosteroid free remission in data beyond 52 weeks of medication administration.

Methods
Medical databases including MEDLINE, EMBASE and Cochrane were searched for phase III and IV randomised control trials examining efficacy of biologic and small molecule therapies in adults with moderate to severe ulcerative colitis beyond 52 weeks. A network meta-analysis was performed using the frequentist model to compare the aforementioned outcomes with pooled relative risk, heterogeneity and P values used to rank treatments.

Results
13 randomised control trials (RCT) were included for analysis from a screen of 2516 abstracts. Of these 13 RCTs, there were 8 treatments directly compared to placebo beyond week 52. In terms of remission as defined by the Mayo score, Upadacitinib 30mg was found to be the best treatment for moderate-severe ulcerative colitis when compared to Upadacitnib 15mg, Vedolizumab and Etrolizumab in consecutive order. In achieving histological remission, Upadacitinib 30mg was superior to Upadacitinib 15mg, Filgotinib (200mg and 100mg) and Etrolizumab. For endoscopic remission, Upadacitinib 30mg was superior to Upadacitinib 15mg, Filgotinib (200mg and 100mg), Vedolizumab, Etrolizumab and Golimumab. For corticosteroid free remission, Filgotinib 200mg was superior to Golimumab, Upadacitinib (30mg and 15mg), Vedolizumab and Etrolizumab.

Conclusion
Large head-to-head trials of biologic and small molecule therapies in the treatment of moderate to severe ulcerative colitis beyond 52 weeks have not been performed. However, our results show Upadacitinib 30mg to be efficacious in terms of remission defined by the Mayo score as well as histologic, endoscopic and corticosteroid free remission when compared to other biologics and small molecule therapies. Whilst these newer therapies show promise, their overall performance over an extended period remains unclear and their use often precludes the efficacy of subsequent biologic or small molecule therapies. As such, the first choice of therapy must be made carefully to increase the probability of remission whilst also balancing the burden of adverse events.
P945 Crohn´s disease response to ustekinumab measured by bowel ultrasound
Authors: Navarro-Gerrard C , Bastón Rey I , González López J , Ferreiro Iglesias R , Sequeiros Portela M D , Dominguez Munoz J E , Barreiro de Acosta M 
Published: January 2024

Abstract

Background
After the STRIDE-II update for patients with Crohn’s disease (CD) one of the new possible adjunct treatment goals was transmural healing, yet its assessment is still not fully cost/risk-benefit proven. A valuable tool to assess this adjunct goal is bowel ultrasound. For this reason, our aim was to evaluate the bowel ultrasonographic response to ustekinumab at one year.

Methods
Retrospective, observational, single center study was designed. All adult patients with CD who were treated with ustekinumab and had a bowel ultrasound just before the induction dose with ustekinumab and who repeated the bowel ultrasound one year after it were included. Examination was done by ultrasound machine (Hitachi Avius) with low frequency curved-array (1-5 MHz) and high-frequency linear-array (5-13 MHz) transducers. The measured bowel ultrasonographic variables were: wall thickness, Doppler activity (Limberg index) and fatty striation. Ultrasonographic response was defined as a reduction in wall thickness of at least 25%, 2mm or 1mm plus 1 Doppler sign. Remission was defined as wall thickness less than 3mm plus absent Doppler sign. Patient demographics and disease characteristics were also collected: age, sex, extension of CD, previous biologic treatments and ustekinumab trough levels. Demographic and clinical characteristics were compared using χ2 analysis (or Fisher’s exact test), Student’s t test or Spearman correlation. All statistical analyses were performed using the STATA Statistical Software.

Results
A total of 41 patients (56.1% female) with a mean age of 57.9 years (SD ±2.7) were included. 63.4% had ileal disease and 36.6% ileocolonic involvement. Ustekinumab was first line of biologic treatment in 7.3%, second line in 61.0%, third line in 29.3% and fourth line in 2.4% of patients. 63.4% of patients were on ustekinumab 90mg subcutaneous every 4 weeks at one year with a median trough level of 8.6 (range 7.9-10.6). The median wall thickness measured by bowel ultrasound before induction was 5.5 mm (range 5.0-6.4) and after one year it was 5.0 mm (4.1-5.7) (p=0.47) Figure 1. Before treatment Limberg index was 3 in 26.8% and after treatment it was 3 in 4.9% (p=0.052). Fatty striation was present in 90.2% of patients at the beginning of treatment and in 63.4% at one year (p=0.013). Ultrasound response was achieved in 36.6% of patients while transmural remission was achieved in 12.2% of patients in the first year. No association between ustekinumab trough levels and response/remission were found (p=0.70/p=0.83)

Conclusion
Treatment with USK was related with an ultrasonographic response in one third of patients with refractory CD at one year. No association between ustekinumab trough levels and ultrasonographic response/remission were found