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S76 An Interim Analysis of 2 Years of Continuous Ozanimod Treatment From the True North Open-Label Extension Study

2022· article· en· W4310871171 on OpenAlexaff
María T. Abreu, Parambir S. Dulai, Axel Dignaß, Edoardo Savarino, David Hudesman, Anita Afzali, Vipul Jairath, Mark T. Osterman, Lucy Akukwe, W. Jerry Liu, Arteid Memaj, AnnKatrin Petersen, Anjali Jain, James B. Canavan, Séverine Vermeire

Bibliographic record

VenueThe American Journal of Gastroenterology · 2022
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicInflammatory Bowel Disease
Canadian institutionsLondon Health Sciences Centre
Fundersnot available
KeywordsMedicineInternal medicineClinical trialPopulationSurgery

Abstract

fetched live from OpenAlex

Background: The phase 3 True North (TN) study demonstrated the efficacy and safety of oral ozanimod 0.92 mg once daily (equivalent to ozanimod HCl 1 mg) in patients with moderately to severely active ulcerative colitis (UC). The ongoing TN open-label extension (OLE) study is exploring longer-term efficacy and safety of ozanimod in the treatment of UC. This interim analysis of the TN OLE evaluated the efficacy and safety of ozanimod in patients who received 98 weeks of continuous ozanimod treatment. Methods: Patients in clinical response after 52 weeks of continuous ozanimod therapy during TN who rolled over into the OLE were included (data cutoff: September 30, 2020). Endoscopy was performed annually throughout the OLE and was scored by Mayo endoscopic score. Efficacy data (clinical remission, clinical response, endoscopic improvement, and corticosteroid-free remission) were analyzed using observed cases (OC) and nonresponder imputation (NRI). Safety data were also recorded. Results: Of 131 patients in clinical response at TN Week 52, 83 (63%) were in clinical remission and 48 (37%) were in clinical response only (but not clinical remission) upon entry to the OLE. Nearly 73% of the overall population of clinical responders, including 69% of patients who achieved clinical remission and 79% of patients who achieved clinical response only, completed Week 46 of the OLE (ie, Week 98 of continuous ozanimod therapy) at the time of data cutoff when outcomes were measured (NRI group). Baseline demographic and clinical characteristics were similar for patients in clinical remission and in clinical response only, except more patients with clinical response only at OLE entry were exposed to prior immunomodulators or tumor necrosis factor inhibitors at TN baseline. A high proportion of the overall population sustained clinical remission (67%), clinical response (97%), endoscopic improvement (74%), and corticosteroid-free remission (63%) on ozanimod at OLE Week 46 (OC analysis); NRI values were 44%, 64%, 58%, and 42%, respectively. There were higher rates of clinical remission (73% vs 55%), endoscopic improvement (82% vs 58%), and corticosteroid-free remission (71% vs 50%) among patients entering the OLE in clinical remission versus clinical response only (OC analysis). In the overall population of clinical responders, the mean partial Mayo score stabilized by Week 18 (mean, 1.3 points; range, 0-6 points) of the maintenance period and was maintained through OLE Week 46 (mean, 0.9 points; range, 0-4 points) in patients treated with continuous ozanimod. No new safety findings emerged from this extended analysis; 1 sudden death occurred during the OLE and was determined to be unrelated to ozanimod. Conclusion(s): This interim analysis of the TN OLE found that patients who achieved clinical response or clinical remission after 52 weeks of ozanimod had a high rate of sustaining clinical response, clinical remission, and endoscopic improvement for another year with continued use of ozanimod. Patients who were in clinical response after 52 weeks of ozanimod could achieve clinical remission with continued ozanimod therapy. No additional safety signals were observed.

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)0.012
metaresearch head score (Gemma)0.008
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: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.012
Threshold uncertainty score0.062

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0120.008
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0020.004
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0010.001
Open science0.0010.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0090.001

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 head0.019
GPT teacher head0.289
Teacher spread0.271 · 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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Citations0
Published2022
Admission routes1
Has abstractyes

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