4-Year Follow-up of Delayed-Release Dimethyl Fumarate Treatment in Relapsing-Remitting Multiple Sclerosis (RRMS): Integrated Clinical Efficacy Data From DEFINE, CONFIRM, and the ENDORSE Extension Study (P3.173)
Bibliographic record
Abstract
OBJECTIVE: To report 4-year interim clinical efficacy outcomes with delayed-release dimethyl fumarate (DMF) from DEFINE, CONFIRM, and ENDORSE. BACKGROUND: Delayed-release DMF demonstrated efficacy and safety in patients with RRMS in the 2-year, Phase 3 DEFINE and CONFIRM studies. ENDORSE is an ongoing, 5-year, dose-blind extension study 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. Efficacy was analyzed (June 12, 2013 cutoff) according to treatment arm in parent/extension study: BID/BID, TID/TID, PBO/BID, PBO/TID, GA/BID, GA/TID. RESULTS: Of 2,079 patients completing DEFINE/CONFIRM, 1,736 were dosed in ENDORSE (n=501 [BID/BID], 502 [TID/TID], 249 [PBO/BID], 248 [PBO/TID], 118 [GA/BID], and 118 [GA/TID]). Both BID/BID and TID/TID patients showed consistent efficacy over 4 years (2 years in parent studies, 2 years ENDORSE). Adjusted annualized relapse rate (ARR) (95% confidence interval [CI]) during Year 1 and Year 2 in parent studies and Year 3 and Year 4 in ENDORSE were: 0.202 (0.162-0.252), 0.163 (0.128-0.208), 0.138 (0.104-0.183), and 0.142 (0.108-0.187) for BID/BID, and 0.239 (0.195-0.294), 0.123 (0.094-0.162), 0.167 (0.128-0.217), and 0.198 (0.155-0.252) for TID/TID, respectively. For patients switching treatment from PBO or GA, ARR (95% CI) in Year 4 (second year of delayed-release DMF treatment) was 0.126 (0.083-0.194) for PBO/BID and 0.138 (0.092-0.209) for PBO/TID, and 0.128 (0.070, 0.233) for GA/BID, and 0.184 (0.105, 0.325) for GA/TID patient groups. Disability progression remained low among patients who continued treatment with delayed-release DMF. CONCLUSIONS: Treatment with delayed-release DMF resulted in low relapse rates and disability progression sustained over 4 years. Along with neuroradiologic efficacy and an acceptable safety profile, results support its potential as a 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 | 0.006 | 0.005 |
| 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 | 0.001 |
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".