Safety and Efficacy of Siponimod (BAF312) in Patients with Relapsing-remitting Multiple Sclerosis: Results from Dose-blinded Extension Phase of BOLD Study (P3.151)
Bibliographic record
Abstract
OBJECTIVE: To present siponimod (BAF312) safety and efficacy results in patients with relapsing-remitting multiple sclerosis during the dose-blinded phase (up to 24 months) of BOLD extension study. BACKGROUND: In the core BOLD study, siponimod showed dose-dependent reduction in MRI-assessed inflammatory lesion activity and annualized relapse rate (ARR) with a manageable safety and tolerability profile, particularly at low doses. DESIGN/METHODS: Patients either continued on siponimod doses assigned in the core phase or were re-randomized from placebo to siponimod 10 (n=33), 2 (n=29), 1.25 (n=43), 0.5 (n=29) and 0.25 (n=50) mg. Dose titration from 0.25 mg over the first 10 days was implemented to reduce the risk of bradycardia during siponimod treatment initiation. MRI was performed at extension baseline and every 6 months thereafter. RESULTS: Of the 184 patients who entered the extension study, 159 completed the dose-blinded phase (overall average exposure, 655 days). The following data pertain to patients taking 10, 2, 1.25, 0.5 and 0.25mg doses, respectively. Mean number of Gd-enhanced T1 lesions by visit: 0.2, 0.5, 0.1, 0.6, 0.7 (Month 12) and 0.0, 0.1, 0.3, 0.6, 1.3 (Months 24) versus 1.7, 1.4, 1.8, 3.1, 1.3 (core baseline). Mean number of new/enlarged T2 lesions: 0.0, 0.5, 0.3, 2.1, 2.9 (Month 24) versus 0.5, 0.6, 0.3, 1.6, 1.7 (Month 12). Annualized confirmed relapse rate (95% CI) remained low: 0.22 (0.12, 0.40), 0.20 (0.10, 0.38), 0.14 (0.08, 0.26), 0.33 (0.19, 0.56), and 0.33 (0.21, 0.50). Seven patients withdrew from study drug due to adverse events (AE). Most common AEs (蠅12% in any dose group) were nasopharyngitis, headache, lymphopenia, decreased lymphocyte count, upper respiratory tract infection, increased alanine aminotransferase, pharyngitis, sinusitis, insomnia and depression. Serious AEs were reported in 9 patients. CONCLUSIONS: Siponimod showed sustained efficacy on MRI and clinical measures with highest effects in the 1.25mg, 2mg, and 10mg dose groups, in line with dose-finding results in the core study. No new safety signals emerged. Study Supported by: Novartis Pharma AG
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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 | 0.000 | 0.001 |
| 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".