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Record W2791238675 · doi:10.1093/ecco-jcc/jjx180.565

P438 Reinduction with ustekinumab in Crohn’s disease patients with a loss of response to treatment

2018· article· en· W2791238675 on OpenAlexaff
Valérie Heron, Sophie Restellini, Talat Bessissow, Carolyne Lemieux, Péter L. Lakatos, Gary Wild, Ernest G. Seidman, Alain Bitton, Waqqas Afif

Bibliographic record

VenueJournal of Crohn s and Colitis · 2018
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicInflammatory Bowel Disease
Canadian institutionsMcGill University Health Centre
Fundersnot available
KeywordsUstekinumabCrohn's diseaseMedicineCrohn diseaseDiseaseInternal medicineDermatologyInfliximab

Abstract

fetched live from OpenAlex

Ustekinumab (UST), an inhibitor of IL-12 and IL-23, has been shown to effectively induce and maintain remission in patients with Crohn’s disease. However, a significant number of patients do not respond or experience a secondary loss of response to UST. This study aims to assess the role of UST reinduction to achieve clinical and endoscopic response in patients with active Crohn’s disease on UST maintenance therapy. In this retrospective, observational study, patients experiencing a partial response or a secondary loss of response to UST based on clinical and/or endoscopic criteria received intravenous or subcutaneous reinduction of UST. Post-reinduction, clinical remission was defined as an HBI <5 off corticosteroids, endoscopic remission was defined as a SES-CD score of <3 and endoscopic response was defined as a decrease in the SES-CD ≥50%. Adequate drug concentrations were defined as a UST level of ≥1 μg/ml. Twelve reinductions were performed in 11 patients between February 2016 and June 2017. Three reinductions were performed for clinical non-response, 6 for active disease on endoscopy or imaging, and 3 for both these indications. All patients had received their first induction subcutaneously at a dose of either 90 mg at Weeks 0, 1 and 2 (n = 7) or of 270, 180, and 180 mg at Weeks 0, 1, and 2 (n = 4). All were on a maintenance dose of UST 90 mg every 4 weeks, with the exception of one who had a 16-week drug holiday prior to reinduction. The median duration of UST treatment prior to reinduction was 16 months (interquartile ratio [IQR]: 12–32). Eight reinduction doses (67%) were administered intravenously at a dose of 260 mg (n = 2) or 390 mg (n = 6) based on weight, while the remaining 4 (33%) were administered subcutaneously (90 mg every week for three doses (n = 1), or 270–180–180 mg at Weeks 0, 1, and 2 (n = 3)). Clinical follow-up occurred at a mean of 2 ± 0.8 months post-reinduction, while follow-up endoscopy or imaging was performed at a mean of 7 ± 4 months. Five of nine patients (55.5%) achieved endoscopic response (n = 4) or remission (n = 1), while four of six patients (66.7%) achieved clinical remission. Overall, 62.5% of patients who received IV reinduction (n = 8) were in clinical remission or endoscopic response at follow-up. Therapeutic drug monitoring for UST was performed in five patients prior to reinduction, all of whom had a UST level >1 μg/ml (median 5.5, IQR: 5.4–6.99), and three of these patients (60%) achieved clinical remission or endoscopic response. No serious adverse events were reported following reinduction. Ustekinumab reinduction can be used safely to induce clinical and endoscopic response in patients with active Crohn’s disease, even in the context of previously defined adequate UST drug concentrations.

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.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation 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 score0.001
Threshold uncertainty score0.004

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0010.000

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 head0.005
GPT teacher head0.228
Teacher spread0.223 · 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

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

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Citations2
Published2018
Admission routes1
Has abstractyes

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