Diroximel Fumarate in Patients with Relapsing–Remitting Multiple Sclerosis: NEDA-3 After Re-Baselining in the Phase 3 EVOLVE-MS-1 Study
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| Titel: | Diroximel Fumarate in Patients with Relapsing–Remitting Multiple Sclerosis: NEDA-3 After Re-Baselining in the Phase 3 EVOLVE-MS-1 Study |
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| Autoren: | James D. Bowen, Jessica Stulc, Samuel F. Hunter, Hailu Chen, James B. Lewin, Matthew Scaramozza, Ivan Bozin, Florian Then Bergh |
| Quelle: | Adv Ther |
| Verlagsinformationen: | Springer Science and Business Media LLC, 2024. |
| Publikationsjahr: | 2024 |
| Schlagwörter: | Adult, Male, Brief Report, Dimethyl Fumarate, Middle Aged, Magnetic Resonance Imaging, Multiple Sclerosis, Relapsing-Remitting, Treatment Outcome, Fumarates, Double-Blind Method, Disease Progression, Humans, Female, Double-Blind Method [MeSH], Female [MeSH], Disease Progression [MeSH], Adult [MeSH], Diroximel fumarate, Disease-modifying therapies, Humans [MeSH], Dimethyl fumarate, Treatment Outcome [MeSH], Fumarates/therapeutic use [MeSH], Middle Aged [MeSH], Dimethyl Fumarate/therapeutic use [MeSH], Efficacy, Re-baselining, No Evidence of Disease Activity (NEDA), Magnetic Resonance Imaging [MeSH], Multiple sclerosis, Male [MeSH], Multiple Sclerosis, Relapsing-Remitting/drug therapy [MeSH], Fumarates/pharmacology [MeSH], Immunosuppressive Agents/therapeutic use [MeSH], Immunosuppressive Agents |
| Beschreibung: | 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.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.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).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.NCT03093324 (EVOLVE-MS-2); NCT02634307 (EVOLVE-MS-1). |
| Publikationsart: | Article Other literature type |
| Sprache: | English |
| ISSN: | 1865-8652 0741-238X |
| DOI: | 10.1007/s12325-024-02901-1 |
| Zugangs-URL: | https://pubmed.ncbi.nlm.nih.gov/38878121 https://repository.publisso.de/resource/frl:6501302 |
| Rights: | CC BY NC URL: http://creativecommons.org/licenses/by-nc/4.0/Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/ (http://creativecommons.org/licenses/by-nc/4.0/) . |
| Dokumentencode: | edsair.doi.dedup.....cdfcf77281a4695cd54aab329161724f |
| Datenbank: | OpenAIRE |
Nájsť tento článok vo Web of Science | Abstract: | 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.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.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).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.NCT03093324 (EVOLVE-MS-2); NCT02634307 (EVOLVE-MS-1). |
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| ISSN: | 18658652 0741238X |
| DOI: | 10.1007/s12325-024-02901-1 |