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Record W4391161866 · doi:10.1093/ecco-jcc/jjad212.1144

P1014 Faecal loss of vedolizumab is associated with UC severity, lower serum vedolizumab levels and rates of clinical response – Results from the FAVOUR study

2024· article· en· W4391161866 on OpenAlex
M Samaan, Georgina Cunningham, Samuel Lim, Patrick Dawson, Sherine Hermangild Kottoor, Zareen Bheekhun, Simon Anderson, Joel Mawdsley, S Ray, Nick Powell, Robin Dart, Krystal Rawstron, Zehra Arkir, Peter M. Irving

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.

Bibliographic record

VenueJournal of Crohn s and Colitis · 2024
Typearticle
Languageen
FieldMedicine
TopicMicroscopic Colitis
Canadian institutionsSt. Thomas Hospital
Fundersnot available
KeywordsVedolizumabMedicineInternal medicineUlcerative colitisDisease

Abstract

fetched live from OpenAlex

Abstract Background Infliximab is detectable in the faeces of patients with active UC and faecal loss is associated with more severe disease and with primary non-response. Detection of vedolizumab (VED) in faeces and its importance in patients with UC has not been investigated. We conducted a prospective, observational study of patients with UC commencing VED to investigate faecal VED loss as well as its impact on serum VED levels (SVL) and association with treatment outcomes. Methods The FAVOUR study recruited UC patients with moderate to severe UC commencing vedolizumab between April 2019 and May 2022. Patients were treated with 300mg VED IV at weeks 0, 2, 6 and 14. Trough SVL were measured at weeks 2, 6 and 14. Faecal samples at days 1, 4, 7 and at weeks 2, 6 and 14 were homogenised and centrifuged to produce supernatants which were analysed for faecal VED levels (FVL) using a commercially available ELISA (LISA TRACKER, Theradiag, France). Clinical (SCCAI) and biochemical disease activity (CRP and faecal calprotectin) were measured at each infusion. Endoscopy was performed at baseline and week 14 to measure endoscopic (UCEIS/Mayo) and histologic activity (NHI). Correlations were calculated using the Spearman correlation coefficient (r). Categorical variables were compared using Mann-Whitney U. Results 36 patients (median age 34 (range 18-73); 13 Female) were recruited, of whom 33 completed induction therapy (3 withdrew early and were considered non-responders). 26/36 (72%) achieved a clinical response (SCCAI≤5 and reduction of ≥2) and 18/36 (50%) achieved endoscopic remission (UCEIS≤2). Faecal VED was detectable in 80/203 (39%) samples. Statistically significant correlations were observed between FVL and markers of clinical, biochemical, baseline endoscopic and histologic disease activity at day 1, and weeks 2 and 6 (table 1). Week 14 clinical non-responders had higher FVL than responders at that time point (median 1.0 vs 0.0ug/mL, p=0.004) but not at other timepoints. A statistically significant negative correlation was observed between week 2 FVL and SVL measured at weeks 6 and 14 (table 1). SVL did not differ significantly between week 14 responders and non-responders at any time point. Conclusion Active colonic inflammation results in faecal loss of vedolizumab. This appears to correlate with lower SVL and rates of response to treatment. However, SVL were not observed to directly influence rates of response. It is possible that FVL may be a marker of disease activity or that faecal loss results in lower rates of drug exposure at a tissue level and negatively impacts rates of response by this mechanism.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.002
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.440
Threshold uncertainty score0.549

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0020.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.048
GPT teacher head0.365
Teacher spread0.316 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it