Effect of Fingolimod on No Evidence of Disease Activity (NEDA-4) and Safety in Young Adult Patients with Relapsing-Remitting Multiple Sclerosis (P3.277)
Bibliographic record
Abstract
OBJECTIVE: To evaluate the efficacy and safety of fingolimod 0.5mg compared to controls in young adults with relapsing-remitting MS (RRMS). BACKGROUND: NEDA-4 as a combined 4-part efficacy measure (no new or enlarging T2 lesions, no confirmed relapses, no 6-month confirmed disability progression, and annualized rate of brain atrophy of <0.4[percnt]) has been proposed as a comprehensive measure of absence of disease activity or worsening at MRI and clinical levels. We evaluated the efficacy and safety of fingolimod compared to controls by analyzing NEDA-4 and reporting on AEs in young adults. DESIGN/METHODS: Post-hoc analysis of NEDA-4 was conducted in the combined FREEDOMS and FREEDOMS II studies (2-year studies versus placebo), and in the TRANSFORMS study (1-year study versus intramuscular interferon beta-1a, IFN). NEDA-4 was analyzed in the intent-to-treat populations using a logistic regression model adjusted for treatment, age at baseline (≤30years and >30years), and treatment-by-age interaction. Proportion of patients with NEDA-4 and odds ratios (OR) versus controls were estimated for ages ≤30years and >30years. Safety in patients ≤30years was evaluated from AEs reported on fingolimod 0.5mg (N=1364) and placebo (N=966) using combined data of all controlled phase II/III studies of the fingolimod RRMS program. RESULTS: In the combined young patients (≤30years) from REEDOMS/FREEDOMS II, 24/153 (15.7[percnt]) had NEDA-4 on fingolimod compared to 4/141 (2.8[percnt]) on placebo (OR=6.37, p<0.001). In TRANSFORMS, 22/105 (21[percnt]) had NEDA-4 on fingolimod 0.5mg compared to 9/103 (8.7[percnt]) on IFN (OR=2.77, p<0.05). Similar effects were seen for patients above 30 years. The fingolimod AE profile in young adults was consistent with the known profile in the overall population. CONCLUSIONS: Young adult patients were more likely to have NEDA-4 on fingolimod compared to placebo or IFN. Efficacy and safety will be further explored in the PARADIGMS study (fingolimod versus IFN in pediatric MS), currently recruiting worldwide.
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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 | 0.002 | 0.002 |
| 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 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".