Long-term Efficacy of Delayed-Release Dimethyl Fumarate for Relapsing-Remitting Multiple Sclerosis According to Prior Therapy: Integrated Analysis of the DEFINE, CONFIRM, and ENDORSE Studies (P7.229)
Bibliographic record
Abstract
OBJECTIVE: To report long-term efficacy of delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) in relapsing-remitting multiple sclerosis (RRMS) patients treated with prior approved interferon β-1a/b or glatiramer acetate (GA) therapy (ABCR). BACKGROUND: DMF demonstrated efficacy and safety in Phase 3 DEFINE and CONFIRM studies; ENDORSE is an 8-year extension of DEFINE/CONFIRM. DESIGN/METHODS: Patients randomized to DMF 240 mg twice (BID) or three times (TID) daily in DEFINE/CONFIRM continued the same dosage in ENDORSE. 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. BID data are reported, as this represents the approved dosage; GA/BID data are not included as patient numbers were low. Minimum follow-up was 5 years in patients remaining on study: BID/BID patients received 蠅5 years DMF; PBO/BID patients received 2 years PBO (DEFINE/CONFIRM) followed by 蠅3 years DMF (ENDORSE). RESULTS: Subgroups included 267 BID/BID and 133 PBO/BID ABCR-naïve patients, 93 BID/BID and 53 PBO/BID with 1 prior ABCR, and 124 BID/BID and 68 PBO/BID with 蠅1 prior ABCR. Over the entire observation period, adjusted annualized relapse rates (95[percnt] confidence interval) for BID/BID and PBO/BID were 0.123 (0.097-0.157) and 0.207 (0.152-0.283) in naïve patients, 0.171 (0.125-0.234) and 0.256 (0.173-0.377) with 1 prior ABCR, and 0.195 (0.151-0.252) and 0.253 (0.181-0.353) with 蠅1 prior ABCR. CONCLUSIONS: Among ABCR-naïve and prior ABCR-treated patients, relapse rates remained low over 5 years with sustained DMF treatment, consistent with beneficial effects of early treatment. Results support the reported clinical efficacy of DMF in patients who previously received ABCR therapy from the integrated analysis of DEFINE/CONFIRM. However, results should be interpreted cautiously as this was a post-hoc analysis and sample sizes were small. 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 | 0.011 | 0.006 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.003 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| 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".