P031 Impact of Prior Biologic Exposure on Response to Ozanimod for Moderate-to-Severe Ulcerative Colitis in the Phase 3 True North Study
Bibliographic record
Abstract
BACKGROUND: Ozanimod, an oral sphingosine 1-phosphate (S1P) receptor modulator selectively targeting S1P1 and S1P5, demonstrated superior efficacy and safety vs placebo for up to 52 weeks in adults with moderately to severely active ulcerative colitis (UC) in a phase 3 study (True North). In this post-hoc analysis, we evaluated the impact of prior biologic exposure on response to ozanimod. METHODS: True North consisted of two cohorts. In cohort 1, patients with UC received double-blind treatment with once-daily ozanimod 0.92 mg (equivalent to ozanimod HCl 1 mg) or placebo. In cohort 2, patients received open-label once daily ozanimod 0.92 mg. Ozanimod responders after a 10-week induction were re-randomized to double-blind maintenance with ozanimod 0.92 mg or placebo through week 52. Outcomes based on prior biologic exposure (biologic-naïve, 1 biologic, and 2+ biologics) and prior biologic type (anti-tumor necrosis factor [TNF] agents, vedolizumab, or both) were analyzed for clinical remission, clinical response, endoscopic improvement, and mucosal healing. Patients exposed to only a JAK inhibitor were excluded from the analysis. RESULTS: A total of 992 patients (n = 213 placebo and n = 426 ozanimod in cohort 1, n = 353 ozanimod in cohort 2) were included in the analysis for induction; 616 were biologic-naïve, 162 had exposure to 1 biologic, and 214 were exposed to 2 or more biologics. At baseline, biologic-exposed patients had more prior corticosteroid use, longer disease duration, and more extensive disease than biologic-naïve patients. During induction, greater therapeutic effects of ozanimod were generally seen in biologic-naïve vs biologic-exposed patients, and ozanimod-treated patients had greater responses on nearly all reported endpoints at week 10 (cohort 1). Clinical remission was achieved in 23% vs 6.6% of patients on ozanimod vs placebo who were biologic naïve, 17.2% vs 8.3% on 1 prior biologic, and 3.7% vs 2.5% on 2 or more biologics. Clinical response was reached in 53% vs 28% of patients on ozanimod vs placebo who were biologic naïve, 50% vs 33% on 1 biologic, and 27% vs 15% on 2 or more biologics. During maintenance, ozanimod-treated patients had greater responses on all endpoints versus placebo, with similar proportions of patients achieving clinical response to ozanimod regardless of prior biologic exposure (61% for biologic naïve, 60% for 1 biologic, and 55% for 2 or more biologics). At week 52, the proportion of patients on ozanimod with clinical remission was similar in the 1-biologic and 2+-biologic exposure groups (28% and 26%, respectively), and proportions of patients on ozanimod with endoscopic improvement and mucosal healing were similar for the 1-biologic and biologic-naïve groups (47% and 50%, 30%, and 33%, respectively). Among patients with inadequate response to prior anti-TNF agents, vedolizumab, or both at baseline, treatment effects favored ozanimod vs placebo on these endpoints in all three groups during both induction and maintenance. CONCLUSION: Ozanimod improved clinical, endoscopic, and histologic outcomes in both biologic-exposed and -naïve patients. Patients with prior biologic use may require additional time to respond to treatment. Outcomes were improved with ozanimod regardless of prior use of anti-TNF agents and vedolizumab.
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 | 0.003 | 0.002 |
| 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 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 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".