S732 Ozanimod Is an Effective Oral Treatment for Patients With Ulcerative Colitis Regardless of Moderate orSevere Endoscopic Disease Activity at Baseline: A Post Hoc Analysis of the Phase 3 True North Study
Bibliographic record
Abstract
Introduction: Ozanimod (OZA), an oral S1P receptor modulator, is effective and well tolerated in the treatment of moderate to severely active ulcerative colitis (UC). OZA is approved in this patient (pt) population based on results of the phase 3, randomized, double-blind, placebo (PBO)-controlled True North (TN) study (NCT02435992). Disease activity may influence treatment outcomes. Consequently, this post hoc analysis of TN explored the effect of baseline endoscopic disease activity on OZA efficacy. Methods: In TN, pts were randomized to oral OZA 0.92 mg once daily or PBO (Cohort 1) or to open-label OZA (Cohort 2) for a 10-week induction period (IP). OZA clinical responders were rerandomized at Week 10 to OZA or PBO for a 42-week maintenance period (MP). Efficacy was assessed at Weeks 10 and 52, subgrouped by endoscopic disease activity at baseline (“moderate,” Mayo endoscopic score [MES]=2, or “severe” [MES=3]). Results: Baseline demographics were similar in pts with moderate or severe disease. OZA was more effective than PBO regardless of baseline endoscopic severity at Weeks 10 and 52 for all evaluated endpoints (Table). Treatment effects at Week 10 (OZA vs PBO; Cochran-Mantel-Haenszel [CMH] test, stratified by corticosteroid [CS] use at screening and prior anti-tumor necrosis factor) were similar in pts with moderate or severe disease: Clinical Remission (CRem; odds ratio [OR] 3.4 [95% CI 1.6-7.2]; P=.0007; and 4.1 [95% CI 1.2-14.1]; P=.0198), Clinical Response (CRes; 2.6 [1.5-4.4]; P=.0006; and 2.7 [1.6-4.4]; P=.0001), Endoscopic Improvement (EI; 2.6 [1.5-4.7]; P< .001; and 3.7 [1.5-9.2]; P=.003), and Mucosal Healing (MH; 3.1 [1.3-7.4]; P=.0066; and 8.0 [1.01-63.2]; P=.0221), respectively (Figure). Tx effects at Week 52 (OZA-OZA vs OZA-PBO; CMH test, stratified by Week 10 CRem and CS use at Week 10) were similar in pts with moderate or severe disease: CRem (OR 3.1 [95% CI 1.7-5.7]; P=.0003; and 2.5 [95% CI 1.3-4.7]; P=.0038), CRes (2.6 [1.5-4.6]; P=.0007; and 2.2 [1.3-3.7]; P=.0043), EI (2.5 [1.4-4.4]; P=.002; and 2.7 [1.5-4.9]; P< .001), CS-free remission (2.7 [1.4-5.1]; P=.0027; and 2.8 [1.4-5.7]; P=.0032), and MH (3.2 [1.6-6.1]; P=.0005; and 2.4 [1.2-4.9]; P=.0182), respectively (Figure). Conclusion: This post hoc analysis of the phase 3 TN study shows that OZA is effective at achieving clinical endpoints at Weeks 10 and 52 in pts with BL moderate or severe endoscopic disease activity. OZA is efficacious in UC pts regardless of BL endoscopic disease activity.Figure 1.: Efficacy of OZA by BL endoscopic disease activity in TN Table 1. - Patients achieving clinical outcomes, n (%) IP: Cohort 1 IP: Cohort 2 MP PBO OZA 0.92 mg OZA 0.92 mg OZA-PBO OZA-OZA Moderate subgroup (n=403) Clinical Remission 10/86 (11.6%) 58/179 (32.4%) 50/138 (36.2%) 23/111 (20.7%) 43/98 (43.9%) Clinical Response 28/86 (32.6%) 101/179 (56.4%) 90/138 (65.2%) 50/111 (45.0%) 67/98 (68.4%) Endoscopic Improvement 20/86 (23.3%) 81/179 (45.3%) 64/138 (46.4%) 34/111 (30.6%) 52/98 (53.1%) Mucosal Healing 7/86 (8.1%) 40/179 (22.3%) 31/138 (22.5%) 19/111 (17.1%) 38/98 (38.8%) Severe subgroup (n=609) Clinical Remission 3/130 (2.3%) 21/250 (8.4%) 27/229 (11.8%) 19/116 (16.4%) 42/132 (31.8%) Clinical Response 28/130 (21.5%) 104/250 (41.6%) 103/229 (45.0%) 43/116 (37.1%) 71/132 (53.8%) Endoscopic Improvement 6/130 (4.6%) 36/250 (14.4%) 36/229 (15.7%) 26/116 (22.4%) 53/132 (40.2%) Mucosal Healing 1/130 (0.8%) 14/250 (5.6%) 11/229 (4.8%) 13/116 (11.2%) 30/132 (22.7%)
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 | 0.004 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.006 | 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".