Sustained Low Rate of Brain Volume Loss under Long-term Delayed-Release Dimethyl Fumarate Treatment in Relapsing-Remitting Multiple Sclerosis Patients: Results from the ENDORSE Study (P7.243)
Bibliographic record
Abstract
OBJECTIVE: Evaluate the long-term effect on brain volume loss in patients receiving continuous delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) treatment compared with patients switching from placebo or glatiramer acetate (GA) in ENDORSE, an extension of the phase 3 DEFINE and CONFIRM studies. BACKGROUND: Brain atrophy in MS has been shown to correlate with physical disability, cognitive deficits, and quality of life. DESIGN/METHODS: In ENDORSE, patients randomized to DMF 240 mg twice (BID) or three times (TID) daily in DEFINE/CONFIRM continued the same dosage. Patients randomized to placebo (PBO) or GA (CONFIRM only) were re-randomized 1:1 to DMF BID or TID. Data were analyzed (May 14, 2014 cutoff) by treatment in parent/extension study; we report BID data, as this represents the approved dose. At year 3 (week 144) of ENDORSE, BID/BID patients received 蠅5 years continuous DMF treatment; PBO/BID and GA/BID patients received 2 years PBO (DEFINE/CONFIRM) or GA (CONFIRM), respectively, followed by 蠅3 years DMF (ENDORSE). Percentage brain volume change (PBVC) was calculated at year 3 of ENDORSE relative to the predefined baseline for PBVC, week 24 of DEFINE/CONFIRM. RESULTS: This analysis was conducted in the MRI cohort of ENDORSE. Normalized brain volume data was available for 195 (BID/BID), 87 (PBO/BID), and 42 (GA/BID) patients. Mean PBVC at year 3 (over 218 weeks or 4.5 years) of ENDORSE relative to week 24 of DEFINE/CONFIRM was 1.38 (BID/BID), 1.90 (PBO/BID), and 2.05 (GA/BID). In the BID/BID group, the rate of brain volume loss was slowed compared with placebo (P=0.0304) and significantly slowed across all time points compared with PBO/BID and GA/BID. CONCLUSIONS: This analysis suggests a continuous beneficial effect of DMF on brain atrophy and a higher impact of early compared with delayed DMF treatment. Study Supported by: Biogen Idec
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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 | 0.003 | 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 | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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".