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S14 Duration of Response After Ozanimod Withdrawal: Phase 3 True North Study Results

2022· article· en· W4310871165 on OpenAlexaff
Bruce Sands, Bincy Abraham, Brian Bressler, Walter Reinisch, Anjali Jain, Arteid Memaj, Lucy Akukwe, W. Jerry Liu, Mark T. Osterman, James B. Canavan, Séverine Vermeire

Bibliographic record

VenueThe American Journal of Gastroenterology · 2022
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicInflammatory Bowel Disease
Canadian institutionsUniversity of British Columbia
Fundersnot available
KeywordsMedicineDiscontinuationInternal medicinePlaceboClinical trialPathologyAlternative medicine

Abstract

fetched live from OpenAlex

Background: The phase 3 True North (TN) randomized trial demonstrated efficacy and safety of ozanimod in patients with moderately to severely active ulcerative colitis (UC). Temporary discontinuation of UC treatment can occur in clinical practice. Understanding the duration of response after treatment discontinuation can assist in clinical decision making. This analysis examined time to disease relapse in patients who discontinued ozanimod and switched to placebo in the TN maintenance period (MP). Methods: In TN, patients were randomized to once-daily oral ozanimod 0.92 mg or placebo or to open-label ozanimod during a 10-week induction period (IP). Patients with clinical response to ozanimod at Week 10 were rerandomized to ozanimod (continuous ozanimod) or placebo (ozanimod/placebo) in the MP through Week 52. Disease relapse was defined as an increase in partial Mayo score (PMS) of ≥2 points versus Week 10 with absolute PMS ≥4, endoscopic subscore ≥2, and exclusion of other causes of increased disease activity unrelated to UC. A subanalysis compared outcomes in continuous ozanimod and ozanimod/placebo patients who entered the MP after achieving clinical remission or clinical response only (excluding patients in clinical remission) at Week 10. Results: In the TN MP, 230 patients continued ozanimod (clinical remission, n = 82; clinical response only, n = 148) and 227 patients switched to placebo (clinical remission, n = 79; clinical response only, n = 148). Baseline characteristics were generally similar between groups, except the group achieving clinical remission had less severe disease at baseline and fewer patients had a history of other prior immunosuppressive medication use than the group achieving clinical response only. Endoscopic disease severity improved from baseline, with all patients in clinical remission and 15.5% in clinical response achieving an endoscopic score of 0 or 1 at Week 10 (ie, MP entry). In the overall MP population, differences in disease relapse between groups became apparent after MP Week 8, after which a significantly higher proportion of patients on continuous ozanimod were without relapse versus those who switched to placebo. Kaplan-Meier (KM) estimates of no relapse at MP Week 42 were 86.1% for continuous ozanimod and 62.6% for ozanimod/placebo groups. Additionally, patients in clinical remission at Week 10 had higher rates of nonrelapse during the MP versus those in clinical response only at MP entry. KM estimates of nonrelapse at MP Week 42 were 90.9% for patients on continuous ozanimod and 67.9% for patients in the ozanimod/placebo group who achieved clinical remission, and 83.4% and 59.7% in the continuous ozanimod and ozanimod/placebo groups with clinical response only, respectively. Conclusion(s): This analysis shows that ozanimod is effective at preventing disease relapse over 42 weeks of maintenance treatment in patients who achieved clinical response at Week 10. These data show that ozanimod maintains disease control even in the event of temporary discontinuation. However, extended discontinuation should be minimized in clinical practice.

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)0.004
metaresearch head score (Gemma)0.003
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 score0.013
Threshold uncertainty score0.043

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0040.003
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.002
Bibliometrics0.0000.000
Science and technology studies0.0000.001
Scholarly communication0.0010.001
Open science0.0010.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0130.001

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 head0.005
GPT teacher head0.248
Teacher spread0.243 · 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".

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Citations0
Published2022
Admission routes1
Has abstractyes

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