Related Experiment Video
Updated: Jun 23, 2025
A Method of Trigonometric Modelling of Seasonal Variation Demonstrated with Multiple Sclerosis Relapse Data
Published on: December 9, 2015
Diroximel Fumarate in Patients with Relapsing-Remitting Multiple Sclerosis: NEDA-3 After Re-Baselining in the Phase 3
James D Bowen1, Jessica Stulc2, Samuel F Hunter3
1Swedish Neuroscience Institute, Seattle, WA, USA.
Introduction:
Diroximel fumarate (DRF) and dimethyl fumarate (DMF) are orally administered fumarate disease-modifying therapies (DMTs) for multiple sclerosis (MS). The safety, tolerability, and exploratory efficacy of DRF were evaluated in the phase 3 EVOLVE-MS-1 study. No Evidence of Disease Activity (NEDA-3) is a composite efficacy endpoint used in clinical trials for MS defined as no relapse, no 24-week confirmed disability progression (CDP), no new/newly enlarging T2 lesions, and no new gadolinium-enhancing lesions. As NEDA outcomes in studies may be confounded by initial disease activity, the objective of this analysis was to evaluate NEDA-3 in EVOLVE-MS-1 for newly enrolled patients and patients who were re-baselined after approximately 7 weeks.
Methods:
Patients entered EVOLVE-MS-1 as either newly enrolled or having completed the 5-week phase 3 EVOLVE-MS-2 study of DRF and DMF. Magnetic Resonance Imaging (MRI) was performed at baseline before each study (approx. 7 weeks apart) and at weeks 48 and 96 in EVOLVE-MS-1. Therefore, patients entering from EVOLVE-MS-2 were re-baselined after approximately 7 weeks. NEDA-3 outcomes on DRF are reported for prior DRF, prior DMF, and de novo patient groups.
Results:
Of 1057 patients in EVOLVE-MS-1, 239 (22.6%) had rolled over from receiving DRF in EVOLVE-MS-2 ("prior DRF"), 225 (21.3%) had rolled over from receiving DMF in EVOLVE-MS-2 ("prior DMF"), and 593 (56.1%) were newly enrolled ("de novo"). At week 48, Kaplan-Meier estimates of NEDA-3 were 72.3% (prior DRF), 72.1% (prior DMF), and 62.1% (de novo); at week 96, estimates were 50.2% (prior DRF), 48.2% (prior DMF), and 36.5% (de novo).
Conclusions:
In EVOLVE-MS-1, after re-baselining at approximately 7 weeks, approximately half of DRF-treated patients achieved NEDA-3 at week 96, compared with 36.5% of patients who were not re-baselined. Re-baselining may be useful for assessing efficacy of DMTs by mitigating the influence of disease activity prior to the onset of efficacy.
Clinical Trial Registrations:
NCT03093324 (EVOLVE-MS-2); NCT02634307 (EVOLVE-MS-1).
Insights
Diroximel fumarate (DRF) demonstrated efficacy in multiple sclerosis (MS) patients. Re-baselining patients approximately 7 weeks into the study improved assessment of NEDA-3 outcomes for DRF treatment.
Area of Science:
- Neurology
- Clinical Pharmacology
Background:
- Diroximel fumarate (DRF) and dimethyl fumarate (DMF) are oral fumarate disease-modifying therapies (DMTs) for multiple sclerosis (MS).
- The EVOLVE-MS-1 study evaluated the safety, tolerability, and efficacy of DRF.
- No Evidence of Disease Activity (NEDA-3) is a key composite endpoint in MS clinical trials.
Purpose of the Study:
- To evaluate the impact of re-baselining on NEDA-3 outcomes in the EVOLVE-MS-1 study.
- To assess NEDA-3 achievement in newly enrolled patients versus those re-baselined after prior treatment.
Main Methods:
- Patients in EVOLVE-MS-1 were either newly enrolled or rolled over from EVOLVE-MS-2 (prior DRF or DMF treatment).
- Patients from EVOLVE-MS-2 were re-baselined approximately 7 weeks after their previous study baseline.
- Magnetic Resonance Imaging (MRI) was used for assessments at baseline and weeks 48 and 96.
Main Results:
- At week 96, NEDA-3 was achieved by 50.2% of prior DRF patients, 48.2% of prior DMF patients, and 36.5% of de novo patients.
- Re-baselining patients (prior DRF/DMF groups) resulted in higher NEDA-3 achievement at week 96 compared to de novo patients.
- Approximately half of re-baselined DRF-treated patients achieved NEDA-3 at week 96.
Conclusions:
- Re-baselining patients in the EVOLVE-MS-1 study may provide a more accurate assessment of DRF efficacy.
- This approach helps mitigate the influence of prior disease activity on NEDA-3 outcomes.
- Approximately 50% of re-baselined patients achieved NEDA-3 at 96 weeks, suggesting sustained treatment benefits.
More Related Videos
Related Concept Videos
01:11Renal Failure: Dose Adjustments
Reduced renal clearance and elimination rate are common outcomes of renal impairment. These alterations lead to a prolonged elimination half-life and an altered apparent volume of distribution for drugs. As a result, dosage adjustments are typically necessary to maintain optimal drug levels in the body.
However, dosage adjustments...
01:20Antiepileptic Drugs: Potassium Channel Activators
Ezogabine has gained approval as an adjunctive treatment...