Safety and Efficacy of Long-Term Treatment with Ozanimod, an Oral S1P Receptor Modulator, in Moderate to Severe Ulcerative Colitis: Touchstone Extension
Bibliographic record
Abstract
Introduction: Ozanimod (RPC1063) is an oral, selective sphingosine 1-phosphate (S1P) 1 and 5 receptor modulator in clinical development for the treatment of Inflammatory Bowel Disease (ulcerative colitis [UC] and Crohn's disease) and relapsing multiple sclerosis. The objective of the open-label extension (OLE) of the TOUCHSTONE trial is to evaluate the long-term efficacy and safety of daily 1 mg ozanimod in patients with moderate to severe UC who had initially participated in the TOUCHSTONE trial. Methods: A total of 197 patients were randomized (1:1:1) and treated with daily ozanimod at 0.5 mg, 1mg (n=67), or placebo in the TOUCHSTONE trial. Of the initial 197 patients randomized, 170 (86%) entered the OLE and received daily 1 mg ozanimod, 131 (77%) completed the Week 44 assessments, and 109 (64%) remained in the OLE as of the data cut-off (March 2016). At the data cut-off, all remaining patients had received treatment in the OLE for ≥ 1 year. Results: At entry into the OLE, the partial Mayo Score (pMS) for patients on placebo, ozanimod 0.5 mg, and 1.0 mg was 4.6, 4.5, and 3.3 respectively. The pMS had improved in all groups (1.7, 1.7, and 1.9) at Week 44. The greatest improvement was reported in patients who received placebo or ozanimod 0.5 mg in the TOUCHSTONE trial with a change in pMS at Week 44 of -2.6, -2.7 and -1.3 in the placebo, 0.5 mg and 1 mg groups. Improvement occurred rapidly, in the first 4 to 8 weeks of the OLE with a change in pMS at Week 4 of -1.8, -1.5 and -0.8 and a change in pMS at Week 8 of -2.4, -1.9 and -1.1 in the placebo, 0.5 mg and 1 mg groups. At the Week 44 visit in the OLE, 119/131 (90.9%) had little or no active disease based on the physician global assessment (PGA 0 or 1), 129/131 (98.4%) had little or no blood in their stools (rectal bleeding subscore [RBS] 0 or 1), 111/131 (84.7%) had no blood in the stools (RBS 0). The most common adverse events (AEs) (>2.0%) during OLE were UC flare, anemia, upper respiratory tract infection, nasal pharyngitis, back pain, arthralgia, headache, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevation. The only serious AEs in ≥2 patients were anemia, and ulcerative colitis flare. ALT and AST > 3x upper limit of normal occurred in 4 (2.4%) of the 170 patients in the OLE. All elevations were asymptomatic, < 5xULN, transient, and resolving while receiving continued treatment. Conclusion: Long-term treatment with ozanimod continues to be safe and well tolerated with good compliance and evidence of durable efficacy.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 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".