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713 A Randomized, Multicenter, Double-Blind, Placebo-Controlled Study of a Targeted Release Oral Cyclosporine Formulation in the Treatment of Mild to Moderate Ulcerative Colitis: Influence of Immunosuppressants at Baseline

2019· article· en· W2980035932 on OpenAlexaff
Stuart Bloom, Tariq Iqbal, Chuka Nwokolo, Vipul Jairath, Jesse Hall, Bruce Dzyngel, Peter Gardzinski

Bibliographic record

VenueThe American Journal of Gastroenterology · 2019
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicInflammatory Bowel Disease
Canadian institutionsRobarts Clinical TrialsWestern University
Fundersnot available
KeywordsMedicineTolerabilityUlcerative colitisInternal medicinePlaceboClinical endpointGastroenterologyAdverse effectToxicityInflammatory bowel diseaseClinical trialRandomized controlled trialInfliximabSurgeryDiseasePathology

Abstract

fetched live from OpenAlex

INTRODUCTION: Patients (pts) with ulcerative colitis (UC) who have failed immunosuppressants (IM) and biologics have demonstrated poorer response to subsequent therapies. 1 Cyclosporine (CsA) could be an alternative option since it has similar efficacy and safety to infliximab for severe UC, 2 but its use is limited due to concerns regarding systemic toxicity. ST-0529 is a novel oral formulation of CsA that delivers the drug directly to the colon, allowing for precise targeting of the diseased tissue while potentially limiting the risk of systemic toxicity. METHODS: A phase IIa study was conducted in a total of 118 subjects with baseline Disease Activity Index (DAI) < 6 (mild UC) or ≥6 (moderate UC), randomized 1:1 to receive 75 mg ST-0529 once daily (n = 53) or placebo (n = 65) for 4 weeks. The primary endpoint was the induction of clinical remission (DAI score ≤2, with no individual score >1 and rectal bleeding subscore of 0 or 1). The secondary endpoints were safety and tolerability, mucosal healing, clinical response, and histological healing. 3,4 Post-hoc subgroup analysis was conducted in 93 subjects with moderate UC, of whom 75 received at baseline 5-ASA alone or in combination (n = 51, with/without steroids; n = 24, with/without IM) to evaluate the impact of them on clinical improvement (DAI reduction ≥3) and composite subscores (rectal bleeding and stool frequency with or without mucosal appearance evaluation). RESULTS: Table 1 shows the influence of baseline medications on the improvement of DAI scores in subjects with moderate UC, and Tables 2 and 3, the impact of IM on the analyzed parameters. Safety was balanced for the overall population. CONCLUSION: This analysis showed that clinical improvement and composite subscores were influenced by baseline medication in pts with moderate UC. The poorer response in the IM treated group was potentially a function of severity or refractory disease and/or concomitant use of UC medication (prednisone < 10 mg/day, 5-ASAs or purine analogues) at baseline. Concomitant UC medications were not restricted at study entry as long as pts maintained stable dosing regimens throughout. These preliminary data support further investigation of ST-0529 usage as a twice daily treatment for the induction and maintenance of remission in UC pts with moderate disease, which will be the focus of the phase IIb trial.

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)0.002
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Randomized trial · Consensus signal: Randomized trial
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.005
Threshold uncertainty score0.017

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0020.001
Meta-epidemiology (narrow)0.0020.001
Meta-epidemiology (broad)0.0040.002
Bibliometrics0.0010.001
Science and technology studies0.0010.001
Scholarly communication0.0010.001
Open science0.0010.000
Research integrity0.0020.002
Insufficient payload (model declined to judge)0.0050.001

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 head0.010
GPT teacher head0.271
Teacher spread0.262 · 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 designRandomized trial
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".

Quick stats

Citations0
Published2019
Admission routes1
Has abstractyes

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