S933 Durability of Symptomatic and Clinical Outcomes in Ozanimod-Treated Patients by Endpoints of Increasing Objectivity at True North Week 52: Interim Analysis of the True North Open-Label Extension Study
Bibliographic record
Abstract
Introduction: Ozanimod (OZA) is approved for the treatment (tx) of moderately to severely active ulcerative colitis per results of the phase 3 True North (TN) study. Data from the ongoing open-label extension (OLE) demonstrated durability of efficacy in symptomatic, clinical, and mucosal endpoints up to 3 y with continuous OZA tx in patients (pts) who were clinical responders at TN Week (W) 52. Methods: This interim analysis of the TN OLE (cutoff: 10Jan2022) explored whether achieving endpoints at TN W52, examined by increasing objectivity, would impact the durability of symptomatic and clinical outcomes with continuous OZA tx up to OLE W94. OZA clinical responders at TN W52 who continued in the OLE were included in this analysis (N=131). These pts were categorized into subgroups based on achieved endpoints of increasing objectivity (ie, clinical response [CRes], clinical remission [CRem], endoscopic improvement, complete endoscopic healing [endoscopy score=0], histologic remission, mucosal healing, and stringent mucosal healing) at TN W52 to determine whether these endpoints at TN W52/OLE baseline influence the proportion of pts maintaining symptomatic (ie, total/partial Mayo scores and symptomatic CRes) and clinical (ie, CRes, CRem, or corticosteroid [CS]–free remission) outcomes in the OLE. OLE outcomes were assessed up to OLE W94 using observed case (OC) and nonresponder imputation (NRI) analyses. Results: Of 131 pts in this analysis, 114 (87%) completed OLE W46 and 94 (72%) completed OLE W94. OC analyses showed that partial and total Mayo scores and symptomatic CRes were similar and sustained over 94 wk of continuous OZA tx during the OLE, regardless of endpoint achieved at TN W52. Likewise, maintenance of CRes at OLE W46 and OLE W94 was not impacted by the achievement of endpoints of increasing objectivity at TN W52 (Table 1). Achievement of CRem at TN W52 had an incremental benefit over CRes at TN W52 for the maintenance of CRem and CS-free remission at OLE W94, but other endpoints of higher objectivity had no additional benefit (Table 1). A similar pattern was observed for NRI analyses. Clinical outcomes were sustained from OLE W46 to OLE W94 regardless of endpoint achieved at TN W52: CRes: 71.4%–78.4%; CRem: 65.2%–70.0%; and CS-free remission: 63.6%–70.6%. Conclusion: Symptomatic response and clinical outcomes with OZA were durable up to OLE W94. Maintenance of these long-term outcomes was not notably impacted by the achievement of increasingly more objective measures of responsiveness at TN W52. Table 1. - Endpoints (increasing in objectivity) at TN W52 (OC analysis) Endpoint, % (n/N) CResa CRemb CS-free remissionc OLE W46 OLE W94 OLE W46 OLE W94 OLE W46 OLE W94 CResa (N=131) 95.9 (93/97) 91.4 (74/81) 72.2 (70/97) 69.1 (56/81) 70.1 (68/97) 67.9 (55/81) CRemb (N=83) 97.0 (64/66) 94.4 (51/54) 81.8 (54/66) 75.9 (41/54) 80.3 (53/66) 74.1 (40/54) Endoscopic improvement (MES ≤1; N=93) 97.3 (73/75) 95.2 (60/63) 78.7 (59/75) 73.0 (46/63) 77.3 (58/75) 71.4 (45/63) Complete endoscopic healing (MES=0; N=50) 97.6 (40/41) 90.9 (30/33) 82.9 (34/41) 69.7 (23/33) 80.5 (33/41) 66.7 (22/33) Histologic remission (Geboes index score < 2.0; N=68) 98.1 (51/52) 95.3 (41/43) 82.7 (43/52) 74.4 (32/43) 80.8 (42/52) 72.1 (31/43) Mucosal healing (MES ≤1 and Geboes index score < 2.0; N=61) 97.9 (46/47) 94.7 (36/38) 80.9 (38/47) 71.1 (27/38) 78.7 (37/47) 68.4 (26/38) Stringent mucosal healing (MES=0 and Geboes index score < 2.0; N=37) 96.6 (28/29) 91.3 (21/23) 79.3 (23/29) 65.2 (15/23) 75.9 (22/29) 60.9 (14/23) Denominators for the OC analysis were based on the numbers of pts who completed OLE W46 or OLE W94 and had data available for the endpoints in question. aClinical response: reduction from baseline in the 9-point Mayo score of ≥2 points and ≥35%, and a reduction from baseline in RBS of ≥1 point or an absolute RBS of ≤1 point. bClinical remission: RBS=0, SFS ≤1 point (and a decrease of ≥1 point from the baseline SFS), and endoscopy subscore ≤1 point. cCS-free remission: Clinical remission while off CS for ≥12 wk. MES, mucosal endoscopy subscore; RBS, rectal bleeding subscore; SFS, stool frequency subscore.
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 imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.006 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".