4-Year Follow-up of Delayed-Release Dimethyl Fumarate Treatment in Relapsing-Remitting Multiple Sclerosis (RRMS): Integrated Magnetic Resonance Imaging (MRI) Outcomes From DEFINE, CONFIRM, and the ENDORSE Extension Study (P3.160)
Bibliographic record
Abstract
OBJECTIVE: Report 4-year interim MRI outcomes with delayed-release dimethyl fumarate (DMF) from DEFINE/CONFIRM and ENDORSE. BACKGROUND: Delayed-release DMF demonstrated efficacy and safety in RRMS patients in the 2-year, Phase 3 DEFINE/CONFIRM studies. ENDORSE is an ongoing, 5-year, dose-blind extension study of DEFINE/CONFIRM evaluating long-term safety and efficacy. DESIGN/METHODS: In ENDORSE, patients randomized in DEFINE/CONFIRM to delayed-release DMF 240 mg twice- (BID) or three-times daily (TID) continued on the same dosage. Patients randomized to placebo (PBO) or glatiramer acetate (GA) were re-randomized 1:1 to delayed-release DMF BID or TID. Brain scans were obtained yearly in the ENDORSE MRI cohort. Efficacy was analyzed (June 12, 2013 cutoff) by parent/extension study arm: BID/BID, TID/TID, PBO/BID, PBO/TID, GA/BID, GA/TID. RESULTS: 718 of the 982 MRI cohort patients who completed DEFINE/CONFIRM were dosed in ENDORSE (n=206 [BID/BID], 215 [TID/TID], 96 [PBO/BID], 93 [PBO/TID], 48 [GA/BID], 60 [GA/TID]). Among patients continuing delayed-release DMF treatment, during Year 1 and Year 2, respectively, in ENDORSE: 64% and 68% (BID/BID) and 60% and 61% (TID/TID) were free of new/enlarging T2 lesions; 72% and 76% (BID/BID) and 67% and 70% (TID/TID) were free of new T1-hypointense lesions; 89% and 88% (BID/BID) and 85% and 84% (TID/TID) were free of gadolinium-enhancing lesions at 1-year and 2-year assessments. For patients switching from PBO, no new/enlarging T2 lesions were observed in 31% and 33% (PBO/BID) and 18% and 31% (PBO/TID) during Year 1 and Year 2 on placebo in DEFINE/CONFIRM, and in 43% and 73% (PBO/BID) and 47% and 77% (PBO/TID) during Year 1 and Year 2 on delayed-release DMF in ENDORSE. CONCLUSIONS: Reduced frequency of new MRI lesions is maintained over 4 years among patients continuing therapy. Switching from placebo to delayed-release DMF, patients demonstrated MRI outcomes similar to those with delayed-release DMF in DEFINE/CONFIRM. Together with clinical efficacy and an acceptable safety profile, results support delayed-release DMF as a potential long-term treatment option for relapsing MS. 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 | 0.004 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 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".