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S1470 Matching-Adjusted Indirect Comparison of Etrasimod Versus Ozanimod for Clinical Response and Remission Among Patients With Moderately to Severely Active Ulcerative Colitis

2024· article· en· W4403722163 on OpenAlexaff
Vipul Jairath, Thomas P. Leahy, Ravi Potluri, Karolina Wosik, David Gruben, Joseph C. Cappelleri, Peter Hur, Lauren Bartolome

Bibliographic record

VenueThe American Journal of Gastroenterology · 2024
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicInflammatory Bowel Disease
Canadian institutionsPfizer (Canada)Western University
Fundersnot available
KeywordsMedicineUlcerative colitisMatching (statistics)Internal medicineGastroenterologyPathologyDisease

Abstract

fetched live from OpenAlex

Introduction: Etrasimod (ETR) and ozanimod (OZN) are selective sphingosine 1-phosphate receptor modulators targeting the S1P1,4,5, and S1P 1,5 receptors, respectively, for the treatment of moderately to severely active ulcerative colitis (UC). While network meta-analyses have been conducted that included both ETR and OZN, differences in populations and trial designs can impact outcomes. The aim was to conduct matching-adjusted indirect comparisons (MAIC) between ETR and OZN to compare clinical response and remission after the induction period and among induction phase responders following the maintenance period. Methods: Data from phase 3 clinical trials of ETR and OZN that reported data on both induction and maintenance were included in the analyses, namely ELEVATE UC 52 and TRUE NORTH. Patients (pts) in ELEVATE UC 52 received 2mg ETR or placebo (PBO) throughout induction and maintenance, in a treat-through trial design, while pts in TRUE NORTH received 1mg equivalent dose of OZN or PBO during induction, OZN pts with clinical response after induction were further rerandomized to PBO or OZN for maintenance. A PBO anchored approach was used for induction results, while an unanchored approach was conducted for maintenance due to differences in the maintenance PBO arms resulting from the distinct trial designs. Patient level data from ELEVATE UC 52 were weighted using MAIC methodology to match the TRUE NORTH population. Pts were matched on age, sex, corticosteroid use, duration of UC, previous biologic exposure, modified Mayo Score, and presence of left-sided disease, all measured at baseline. Results: After MAIC weighting, matched characteristics were similar with standardized mean differences < 0.1. There were no significant differences between ETR and OZN after the induction period for the outcomes of clinical response and remission (Table 1). However, following the maintenance period, for both clinical response and remission among induction phase responders, a significantly greater proportion of ETR pts achieved clinical response and remission compared to OZN (relative risk 1.19 (95% CI, 1.06-1.31), P < 0.05 and 1.34 (95% CI, 1.11-1.55), P < 0.05 respectively) at 52 weeks. Conclusion: MAIC results suggest superiority of ETR over OZN in terms of clinical response and remission at the end of the maintenance period (52 weeks), while both treatments are similar after the induction period (10-12 weeks). Additional comparisons of other efficacy and safety outcomes will further facilitate treatment decisions. Table 1. - Summary of the data and results of the matching-adjusted indirect comparisons for the clinical response and remission outcome over induction and maintenance periods Treatments Number of patients with the outcome (prior to weighting) Number of patients in the arm (prior to weighting) Unadjusted relative risk (95% CI) (prior to weighting) Adjusted relative risk (95% CI) (post MAIC weighting) ESS Induction Clinical response Etrasimod 2 mg/PBO 171/46 274/135 0.99 (0.70, 1.41) P-value = 1 0.99 (0.77, 1.34) P-value = 1 360.114 Ozanimod 1 mg/PBO 205/56 429/216 Clinical remission Etrasimod 2 mg/PBO 74/10 274/135 1.19 (0.51, 2.77) P-value = 0.6968 1.37 (0.79, 3.25) P-value = 0.3875 360.114 Ozanimod 1 mg/PBO 79/13 429/216 Maintenance Clinical response among induction phase responders Etrasimod 2 mg 123 171 1.20 (1.04, 1.38) P-value = 0.011 1.19 (1.06, 1.31) P-value = 0.001 237.405 Ozanimod 1 mg 138 230 Clinical remission among induction phase responders Etrasimod 2 mg 84 171 1.33 (1.06, 1.67) P-value = 0.014 1.34 (1.11, 1.55) P-value = 0.001 237.405 Ozanimod 1 mg 85 230 PBO, placebo; CI, confidence interval; ESS, effective sample size.Analysis matched on age, sex, baseline corticosteroid use, duration of ulcerative colitis, biologic exposure, modified Mayo Score, and extent of left-sided disease.

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)0.007
metaresearch head score (Gemma)0.013
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Simulation or modeling · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.007
Threshold uncertainty score0.039

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0070.013
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0030.010
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)0.0070.000

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 head0.022
GPT teacher head0.327
Teacher spread0.305 · 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 designSimulation or modeling
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
Published2024
Admission routes1
Has abstractyes

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