P789 Impact of risk factors for Janus kinase inhibitor use identified by the Pharmacovigilance Risk Assessment Committee on the safety and efficacy of ozanimod in patients with moderately to severely active ulcerative colitis
Bibliographic record
Abstract
Abstract Background With the emergence of oral small molecule therapies for ulcerative colitis (UC), there is a need for identification of favourable safety and efficacy profiles for these therapies. The Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency reassessed the benefit–risk of Janus kinase inhibitor (JAKi) use based upon data showing increased risk of major adverse cardiovascular (CV) events (MACE) and cancer with tofacitinib. Accordingly, the PRAC identified criteria for which a JAKi should be used only if no alternatives are available or used with caution. This analysis of the phase 3 True North (TN) study (NCT02435992) evaluated the safety and efficacy of ozanimod (OZA) by the presence of JAKi PRAC criteria in patients with moderately to severely active UC. Methods Analyses were performed in TN patients comparing those with ≥1 vs no JAKi PRAC criteria at TN baseline (BL). The criteria included age ≥65 y, history of major CV problems, history of CV risk factors (eg, hypertension, high-density lipoprotein cholesterol <40 mg/dl, diabetes mellitus), current or former smoker, and history of cancer. Safety was monitored through Week (W) 52 and efficacy endpoints were assessed at W10 and W52 in patients receiving OZA or placebo (PBO). Results At TN BL, 491 patients had ≥1 JAKi PRAC criteria and 521 had no JAKi PRAC criteria. BL patient characteristics were generally similar across groups, but the ≥1 JAKi PRAC criteria group was older (46-48 y vs 36-37 y), with more male patients (62-72% vs 52-61%) and longer UC disease duration (7-9 y vs 6-7 y) vs the no JAKi PRAC criteria group. Treatment-emergent adverse events (TEAEs) occurring during the induction and maintenance periods are shown in Table 1. Overall, TEAE rates were slightly higher in patients with ≥1 vs no JAKi PRAC criteria; however, rates of serious TEAEs and TEAEs leading to treatment discontinuation were similar. Bradycardia and hypertension rates were slightly higher in patients with ≥1 vs no JAKi PRAC criteria; rates of other CV and thromboembolic events and cancer were similar between groups. At W10, OZA was more effective than PBO for clinical remission and response, with slightly greater treatment differences in patients with ≥1 vs no JAKi PRAC criteria (Figure 1A). At W52, more OZA/OZA pts achieved all endpoints vs OZA/PBO pts, with slightly greater treatment differences in patients with ≥1 vs no JAKi PRAC criteria (Figure 1B). Conclusion In patients with UC, JAKi PRAC criteria were not associated with greater rates of MACE or cancer with OZA for up to 52 wk, nor did they affect OZA efficacy, suggesting that OZA is a safe and tolerable oral small molecule treatment option for such patients.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".