Rate of Brain Volume Loss with Long-Term Delayed-Release Dimethyl Fumarate Treatment in Patients with Relapsing-Remitting Multiple Sclerosis: 6-Year Results from ENDORSE (P3.061)
Bibliographic record
Abstract
Objective: Evaluate the long-term rate of brain volume loss (BVL) in patients receiving continuous delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) treatment versus those switching from placebo (PBO). Background: DMF demonstrated robust efficacy and a favorable benefit-risk profile in patients with relapsing-remitting multiple sclerosis in the DEFINE, CONFIRM, and ENDORSE studies. Methods: In the ENDORSE extension study, patients randomized to DMF 240 mg twice (BID) or thrice (TID) daily in DEFINE/CONFIRM continued the same dosage. PBO or glatiramer acetate (CONFIRM only) patients were re-randomized 1:1 to DMF BID or TID. Percentage brain volume change (PBVC) was calculated using the SIENA method for each MRI visit relative to baseline. BID data (approved dosage) are reported for patients continuously treated with DMF. BID and TID data were pooled for patients switching from PBO to increase sample size; Years 3-6 (ENDORSE) represent 4 years of DMF after switching. Analyses included only patients with yearly PBVC data from ENDORSE. Results: Among the DEFINE/CONFIRM MRI cohort patients who participated in ENDORSE (n=211 [BID/BID] and 206 [PBO/DMF]), 87 BID/BID and 70 PBO/DMF patients had yearly PBVC data. Using rank analysis, adjusted PBVC at Year 2 relative to DEFINE/CONFIRM baseline was significantly lower with DMF BID (median -0.5) versus PBO (median -0.79; P=0.0110). After 4 years of DMF treatment, PBVC was not significantly different for PBO/DMF versus BID/BID, relative to ENDORSE baseline. In BID/BID patients, a low annualized PBVC was observed over 6 years (mean [95[percnt] confidence interval]: -0.34/year [-0.39, -0.29]). Conclusions: In DEFINE/CONFIRM, patients treated with DMF BID had significantly reduced BVL over 2 years versus PBO. Over 6 years, annual rates of BVL in patients treated continuously with DMF were low and approached rates reported for healthy volunteers, consistent with a sustained beneficial effect of DMF on brain atrophy. Study supported by: Biogen.
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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 | 0.003 |
| 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 | 0.001 |
| 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".