Efficacy of Delayed-Release Dimethyl Fumarate in Newly Diagnosed Patients with Relapsing-Remitting Multiple Sclerosis Using a Composite Measure of Disability: Integrated Analysis of the Phase 3 DEFINE and CONFIRM Studies (P2.144)
Bibliographic record
Abstract
Objective: Assess the effect of delayed-release dimethyl fumarate (DMF, also known as gastro-resistant DMF) on multi-component composite endpoints in patients newly diagnosed with relapsing-remitting multiple sclerosis (RRMS) from DEFINE/CONFIRM. Background: DMF significantly reduced confirmed disability progression (CDP) as measured by Expanded Disability Status Scale (EDSS) in an integrated analysis of DEFINE/CONFIRM of patients newly diagnosed with RRMS. A composite outcome, using multiple neuroperformance components, can potentially enhance the measurement of CDP. Methods: Eligible patients were randomized to receive DMF 240 mg twice (BID) or thrice daily, placebo, or glatiramer acetate (CONFIRM only) for up to 2 years. Assessments were administered at baseline and 12-week intervals thereafter. Composite-CDP was defined by the first occurrence of worsening from baseline of any one of the following: ≥1.0- or ≥1.5-point increase in EDSS score (>0 or 0, respectively); or ≥20[percnt] on timed 25-foot walk (T25FW), 9-hole peg test (9HPT), or Paced Auditory Serial Addition Test (PASAT); or ≥10-letter on Visual Function Test (VFT), confirmed at 12- and 24-weeks. Statistical comparisons were based on a Cox proportional hazards model adjusted for baseline covariates. DMF BID (approved dosage) results are reported. “Newly diagnosed” was defined as diagnosis within 1 year prior to study entry and treatment-naïve or previously treated with corticosteroids alone. Results: Newly diagnosed population included 221 DMF and 223 placebo patients. Compared with placebo at Year 2, DMF significantly reduced the risk for 12-week composite-CDP (hazard ratio, 95[percnt] confidence interval: 0.68, 0.49-0.94) and 24-week composite-CDP (0.56, 0.37-0.84) as measured by worsening of any of the disability outcomes (EDSS, T25FW, 9HPT, PASAT, or VFT); this represented 32[percnt] (P=0.0198) and 44[percnt] (P=0.0053) reductions vs placebo, respectively. Additional outcomes will also be presented. Conclusions: DMF demonstrated significant reductions compared with placebo on a composite measure of disability progression in newly diagnosed RRMS patients. 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 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.003 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 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".