Pooled Safety Data From Four Placebo-Controlled Teriflunomide Studies (P2.203)
Bibliographic record
Abstract
OBJECTIVE: To report safety results from pooled analyses of the teriflunomide clinical trial database. BACKGROUND: Teriflunomide is a once-daily oral immunomodulator approved in several countries for treatment of relapsing-remitting MS. In phase 2 and 3 studies, teriflunomide has shown beneficial effects on relapse rate and disability progression, with a consistent, manageable safety profile across studies. DESIGN/METHODS: Data were pooled from four double-blind studies: phase 2 (NCT01487096); TEMSO (NCT00134563); TOWER (NCT00751881); and TOPIC (NCT00622700). Patients were randomized to receive teriflunomide 14mg, 7mg, or placebo. Safety assessments included treatment-emergent adverse events (TEAEs), laboratory parameters, and physical examinations. Patients with confirmed alanine aminotransferase (ALT) >3x upper limit of normal (ULN) or neutrophil count <1000 cells/μL were required to discontinue study treatment. RESULTS: This analysis included 3044 patients with cumulative treatment exposure >1500 patient-years per group. Common TEAEs reported more frequently in teriflunomide-treated patients were hair thinning, diarrhea, ALT elevation, headache, and nausea. Most events were mild to moderate and many resolved on therapy. Discontinuations owing to TEAEs were more frequent with teriflunomide (14mg, 12.5%; 7mg, 11.2%; placebo, 7.5%). In all groups, the most common reason for treatment discontinuation was ALT increased, driven by protocol requirements. Asymptomatic, transient ALT elevations were more frequent in teriflunomide-treated patients; however, incidence of ALT>3x ULN and serious hepatic disorders was similar across groups. Mean absolute neutrophil and lymphocyte counts remained within normal ranges, and not associated with increased infections. Serious infections were infrequent (<=2.7% of patients; all groups). TEAEs related to malignancy occurred in <=0.5% patients in any group (14mg, n=3; 7mg, n=2; placebo, n=5); no hematological or lymphoproliferative malignancies were reported. There were five deaths (teriflunomide: motor-vehicle accident, suicide, sepsis; placebo: respiratory infection, suicide). CONCLUSIONS: Results of this pooled analysis of >3000 patient-years of teriflunomide exposure were consistent with those of individual studies and no new safety signals were identified. Both doses of teriflunomide had similar, manageable safety profiles. Study Supported by: Genzyme, a Sanofi company
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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 | 0.035 | 0.045 |
| Meta-epidemiology (narrow) | 0.003 | 0.001 |
| Meta-epidemiology (broad) | 0.008 | 0.021 |
| Bibliometrics | 0.004 | 0.004 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.001 | 0.002 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.011 | 0.002 |
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".